Procine recombinant NK-lysin inhibits hepatocellular carcinoma metastasis by downregulating FKBP3 and inhibiting oxidative phosphorylation and glycolysis: a proteomic analysis / 南方医科大学学报

OBJECTIVE@#To investigate the potential mechanisms that mediate the inhibitory effect of porcine recombinant NKlysin (prNK-lysin) against liver cancer cell metastasis.@*METHODS@#HPLC-tandem mass spectrometry was used to identify the differentially expressed proteins in prNK-lysin-treated hepatocellular carcinoma SMMOL/LC-7721 cells in comparison with the control and PBS-treated cells. GO functional annotation and KEGG pathway analysis of the differentially expressed proteins were performed using GO and KEGG databases. RT-qPCR was used to determine the mRNA expression levels of polypeptide-N-acetylgalactosaminotransferase 13 (GALNT13), transmembrane protein 51 (TMEM51) and FKBP prolyl isomerase 3 (FKBP3) in the cells, and the protein expression of FKBP3 was verified using Western blotting.@*RESULTS@#Proteomic analysis identified 1989 differentially expressed proteins in prNK-lysin-treated cells compared with the control cells, and 2753 compared with PBS-treated cells. Fifteen proteins were differentially expressed between PBS-treated and the control cells, and 1909 were differentially expressed in prNK- lysin group compared with both PBS and control groups. These differentially expressed proteins were involved mainly in the viral process, translational initiation and RNA binding and were enriched mainly in ribosome, protein process in endoplasmic reticulum, and RNA transport pathways. RT-qPCR showed that compared with the control group, prNK-lysin treatment significantly increased the mRNA expressions of GALNT13 (P < 0.05) and TMEM51 (P < 0.01) and lowered FKBP3 mRNA expression (P < 0.05). Western blotting also showed a significantly decreased expression of FKBP3 protein in prNK-lysin-treated cells (P < 0.001).@*CONCLUSION@#Treatment with prNK-lysin causes significant changes in protein expression profile of SMMOL/LC-7721 cells and inhibits hepatocellular carcinoma metastasis by downregulating FKBP3 protein and affecting the cellular oxidative phosphorylation and glycolysis pathways.

multiSero: open multiplex-ELISA platform for analyzing antibody responses to SARS-CoV-2 infection

Serology has provided valuable diagnostic and epidemiological data on antibody responses to SARS-CoV-2 in diverse patient cohorts. Deployment of high content, multiplex serology platforms across the world, including in low and medium income countries, can accelerate longitudinal epidemiological surveys. Here we report multiSero, an open platform to enable multiplex serology with up to 48 antigens in a 96-well format. The platform consists of three components: ELISA-array of printed proteins, a commercial or home-built plate reader, and modular python software for automated analysis (pysero). We validate the platform by comparing antibody titers against the SARS-CoV-2 Spike, receptor binding domain (RBD), and nucleocapsid (N) in 114 sera from COVID-19 positive individuals and 87 pre-pandemic COVID-19 negative sera. We report data with both a commercial plate reader and an inexpensive, open plate reader (nautilus). Receiver operating characteristic (ROC) analysis of classification with single antigens shows that Spike and RBD classify positive and negative sera with the highest sensitivity at a given specificity. The platform distinguished positive sera from negative sera when the reactivity of the sera was equivalent to the binding of 1 ng mL-1 RBD-specific monoclonal antibody. We developed normalization and classification methods to pool antibody responses from multiple antigens and multiple experiments. Our results demonstrate a performant and accessible pipeline for multiplexed ELISA ready for multiple applications, including serosurveillance, identification of viral proteins that elicit antibody responses, differential diagnosis of circulating pathogens, and immune responses to vaccines.

AnmO2l: An open-source pulse-dose oxygen conserving device for the COVID-19 crisis

The surge of COVID-19 cases in India and around the world has resulted in acute oxygen shortage. Oxygen therapy through nasal cannula with flow rates of 1-6 L/min is an effective treatment for many COVID-19 patients in non-critical conditions and may help prevent disease progression. The same treatment is also used in post-acute care for recovering COVID-19 patients. Here we describe a simple, open source, and rapidly manufacturable oxygen conservation device for use with dual-port nasal cannula that can extend the life of current oxygen supply by almost two to three times, which we hope will help towards coping with the ongoing crisis.

Pneumask: Modified Full-Face Snorkel Masks as Reusable Personal Protective Equipment for Hospital Personnel

Here we adapt and evaluate a full-face snorkel mask for use as personal protective equipment (PPE) for health care workers, who lack appropriate alternatives during the COVID-19 crisis in the spring of 2020. The design (referred to as Pneumask) consists of a custom snorkel-specific adapter that couples the snorkel-port of the mask to a rated filter (either a medical-grade ventilator inline filter or an industrial filter). This design has been tested for the sealing capability of the mask, filter performance, CO2 buildup and clinical usability. These tests found the Pneumask capable of forming a seal that exceeds the standards required for half-face respirators or N95 respirators. Filter testing indicates a range of options with varying performance depending on the quality of filter selected, but with typical filter performance exceeding or comparable to the N95 standard. CO2 buildup was found to be roughly equivalent to levels found in half-face elastomeric respirators in literature. Clinical usability tests indicate sufficient visibility and, while speaking is somewhat muffled, this can be addressed via amplification (Bluetooth voice relay to cell phone speakers through an app) in noisy environments. We present guidance on the assembly, usage (donning and doffing) and decontamination protocols. The benefit of the Pneumask as PPE is that it is reusable for longer periods than typical disposable N95 respirators, as the snorkel mask can withstand rigorous decontamination protocols (that are standard to regular elastomeric respirators). With the dire worldwide shortage of PPE for medical personnel, our conclusions on the performance and efficacy of Pneumask as an N95-alternative technology are cautiously optimistic. Key pointsFull-face snorkel masks are adapted for use as Personal Protective Equipment during the COVID-19 crisis, using a custom adapter that facilitates the attachment of inline medical-grade respiratory filters or NIOSH industrial respirator filters. This solution was designed as a reusable stopgap solution for healthcare workers to help address the short-term global N95 respirator shortage.

Utah-Stanford Ventilator (Vent4US): Developing a rapidlyscalable ventilator for COVID-19 patients with ARDS

We describe a minimum, rapidly scalable ventilator designed for COVID-19 patients with ARDS. Our design philosophy is not only to try to address potential ventilator shortages, but also to account for uncertainties in the supply chains of parts commonly used in traditional ventilators. To do so we employ a modular design approach and broadly explore taking advantage of parts from non-traditional supply chains. In our current prototype, we demonstrate volume control with assist control on a test lung and present a linear actuator-driven pinch valve-based implementation for both pressure control and volume control with decelerating inspiratory flow. We estimate the component cost of the system to be around $500. We publish our draft design documents and current implementation which is open and accessible in the hope that broadening the community globally will accelerate arriving at a solution and that peer review will improve the final design.

Clinical observation of bortezomib-based combined chemotherapy in treatment of multiple myeloma / 白血病·淋巴瘤

Objective:To observe the efficacy and safety of BD (bortezomib, dexamethasone) regimen and PCD (bortezomib, cyclophosphamide, dexamethasone) regimen in treatment of multiple myeloma (MM).Methods:The clinical data of 31 patients with MM treated in Huangshan People's Hospital of Anhui Province from January 2015 to October 2019 were retrospectively analyzed. The patients were divided into BD group (11 cases) and PCD group (20 cases) according to different treatment schemes. The treatment efficacy and adverse reactions of the two groups were compared.Results:MM patients were treated with BD and PCD regimens for 2-6 courses, with a total response rate of 83.9% (26/31) and a median onset time of 2.5 months (1.3-6.2 months). Among them, there were 2 cases of complete remission (CR), 4 cases of very good partial remission (VGPR), 2 cases of partial remission (PR), 2 cases of stable disease (SD), and 1 case of progression of disease (PD) in the BD group; in the PCD group, there were 6 cases of CR, 8 cases of VGPR, 4 cases of PR, 1 case of SD, and 1 case of PD; there was no statistically significant difference in clinical efficacy between the two groups ( χ2 = 0.186, P = 0.758). There were 1 case of leukopenia, 1 case of anemia, 1 case of thrombocytopenia, 1 case of liver damage, 3 cases of neurological adverse reactions, 2 cases of pulmonary infection, 2 cases of diarrhea in the BD group; there were 3 cases of leukopenia, 1 case of anemia, 3 cases of thrombocytopenia, 1 case of liver damage, 5 cases of neurological adverse reactions, 4 cases of pulmonary infection and 3 cases of diarrhea in the PCD group; there was no significant difference in adverse reactions between the two groups ( P > 0.05). Conclusions:The bortezomib-based combined chemotherapy regimens can achieve CR and VGPR for MM patients in a short time, and effectively delay the disease progression. The efficacy of the three-drug combination regimen may be better than the two-drug combination regimen.

Effect of Hypoxia on the Muscle Fiber Switching Signal Pathways CnA/NFATc1 and Myostatin in Mouse Myocytes.

This study investigated the effects of a CoCl2-simulated hypoxic environment on the muscle fiber switching signaling pathways calcineurin A/nuclear factor of activated T cells cytoplasmic 1 (CnA/NFATc1) and myostatin. In this study, C2C12 muscle cells were cultured in vitro under CoCl2-simulated chemical hypoxic conditions, the expression levels of CnA and myostatin were detected through qRT-PCR and Western blot analyses, and a positioning study of NFATc1 was carried out by immunofluorescence labeling. Results showed that CoCl2 treatment significantly increased the expression levels of CnA and myostatin. Moreover, the position of NFATc1 expression changed; actually, its expression in the nucleus considerably increased. Furthermore, CoCl2-induced hypoxia inhibited the differentiation of C2C12 cells and reduced the expression levels of many slow- and fast-twitch muscles marker genes, but immunofluorescence staining results showed that the proportion of MyHC I type muscle fiber increased after CoCl2 treatment. The hypoxic environment simulated by CoCl2 can activate the signaling pathways CnA/NFATc1 and myostatin and increases the proportion of MyHC I type muscle fibers.

A Progress on the Effects of Resveratrol on Tumor Cells / 世界科学技术-中医药现代化

Resveratrol is a natural polyphenolic substance with a variety of bioactivities,such as anti-oxidation,anti-tumor and apoptosis induction.This paper summarized the recent research progress of resveratrol induced cancerous cell apoptosis,including human cervical cancer HeLa cells,leukemia cells,hepatoma cells and gastric cancer cells,and analyzed the molecular mechanism behind resveratrol-induced cell apoptosis in tumor.In addition,resveratrol was investigated by blocking the cell cycle,regulating the expressions of related genes and proteins and mitochondria-induced apoptosis pathways as a potential application of cancer drugs to clinical researches.

Assessment of quality of life for laryngeal cancer patients after laryngectomy / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#This study was designed to develop a rating scale of quality of life (QOL) which fits laryngeal cancer patients after laryngectomy.@*METHOD@#The item pool was developed on the definition of QOL from WHO and the principles and procedures of ddveloping a rating scale. Five methods had been used in the item selection including, such as subjective evaluation methods, discrete tendency, correlation coefficient method, stepwise regression analysis, and factor analysis. The survey was conducted in 126 laryngeal cancer patients after laryngectomy in order to assess the reliability and validity of the rating scale.@*RESULT@#(1) A rating scale of QOL which fits laryngeal cancer patients after laryngectomy including six domains and 27 items is was developed. (2) The split-half reliability coefficient of the scale is 0.802, and the Cronbach' α coefficient is 0.794. (3) It is inferred from the correlation analysis that there are strong correlation between items and their own domains; conversely there are weak correlation between items and other domains. Correlation coefficient is 0.731 between total score and self-rating score.@*CONCLUSION@#The reliability and validity of the rating scale is proved to work well.

Research on the patterns of upper airway obstructive levels by drug-induced sleep endoscopy / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To identify the patterns of airway collapse in patients with obstructive sleep apnea hypopnea syndrome(OSAHS) by dexmedetomidine induced sleep endoscopy.</p><p><b>METHODS</b>Forty-five obstructive sleep apnea patients diagnosed by polysomnography were given dexmedetomidine intravenously. Once the patient was sedated in dorsal position, the electronic nasopharyngoscope was inserted transnasally and positioned on five levels of the upper airway sequentially (velum, oropharyngeal lateral wall, tongue base, epiglottis and larynx) to observe and document the collapse. Each level should be observed no less than three apneas. The degree of airway narrowing was calculated by using the ImageTool. No obstruction was defined when the degree of airway narrowing <50%, and complete obstruction when ≥ 75%.</p><p><b>RESULTS</b>In 45 patients with OSAHS, 1 case showed no obstruction on any level, 6 cases demonstrated obstructions on single level only, and 38 cases demonstrated complete obstructions on multilevel, including 17 cases with complete obstructions on two levels, 15 cases complete obstructions on three levels, and 6 cases complete obstructions on four levels. The patterns of collapse found in the trial were: (1) circumferential stricture by velum collapse was found in 43 patients, and 41 cases showed complete obstructions; (2) the side wall of oropharynx all collapsed in a lateral configuration, and 32 cases showed complete obstructions on this level; (3) anteroposterior swallowing tongue base was common, 11 cases showed partial obstructions on level of tongue base, and 10 cases complete; (4) epiglottic collapses occurred in lateral configuration folding as V shape; in anteroposterior configuration, epiglottis met posterior wall of the pharynx due to swallowing tongue base; the server soften epiglottis obstructed the entrance of the larynx, while the mild soften epiglottis and the collapsed side wall of pharynx came into being obstructions in concentric configuration; (5) the arytenoid area and aryepiglottic fold mucosa inwardly covered the glottis when the obstruction occurred in the larynx.</p><p><b>CONCLUSIONS</b>The patterns of hypopharynx obstructions in OSAHS patients are multifarious. Lateral oropharyngeal wall, epiglottic and tone base collapse play an important role in the obstructions. The laryngeal obstruction can also be observed.</p>

Application Of unilateral multifunctional external fixation apparatus for limb fractures / 中国组织工程研究

There are many methods for internal and external fixation of limbs fractures,such as plaster,splint,and traction.But the disadvantages such as destroyed local blood supply,unreliable fixation,inappropriate dynamic and static combination,postoperative nursing,delayed functional recovery and complications limit their application.Multifunctional external fixation apparatus has been used to treat limbs fractures.It avoids to dissect surrounding tissues and does not damage blood supply out of medullary cavity,which benefits wound treatment,early functional exercise,prevents joint adherence,improves cure rate,reduces complications and avoids second surgery.Moreover,this method is an effective fixation,saves treatment time and prevents adverse results due to treatment for other wounds.In addition.it can also be used to treat bone nonunion,infective fracture,bone defect and other fracture complications.

Association of gene-gene interaction of TNF-? and VDR loci with hepatitis B virus chronic infection of Han population in North China / 基础医学与临床

Objective To determine potential gene-gene interactions of TNF-? and VDR loci with outcomes of hepatitis B virus(HBV) infection.Methods A total of 391 chronic hepatitis B(HB) patients as a case group and 212 HBV self-limited infected subjects as a control group were recruited to conduct a case-control study.TNF-?-238G/A,-857C/T,-863C/A,VDR-TaqⅠT/C and FokⅠC/T gene polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The interactions between TNF-? and VDR genes were analyzed by multiple model.Results There were positive gene-gene interactions between TNF-?-238 GA and FokⅠ CT/CC(ORint=4.04),between-863 CC and-857 CC(ORint=1.26) and between-857 CC and FokⅠ CT/CC(ORint=1.37),respectively,which increase the risk of chronic hepatitis B.There were negative gene-gene interactions between TNF-?-238 GA and-857 CC(ORint=0.92)and between FokⅠ CT/CC and TNF-?-863 CC(ORint=0.95),which decrease the risk of chronic hepatitis B.Conclusion Interaction between TNF-? loci and VDR loci potentially increase the risk of chronic hepatitis B after HBV infection.