15-Month Health Outcomes and the Related Risk Factors of Hospitalized COVID-19 Patients From Onset: A Cohort Study.

Objective: The long-term impact of COVID-19 on patient health has been a recent focus. This study aims to determine the persistent symptoms and psychological conditions of patients hospitalized with COVID-19 15 months after onset, that patients first developed symptoms. The potential risk factors were also explored. Methods: A cohort of COVID-19 patients discharged from February 20, 2020 to March 31, 2020 was recruited. Follow-ups were conducted using validated questionnaires and psychological screening scales at 15 months after onset to evaluate the patients' health status. The risk factors for long-term health impacts and their associations with disease severity was analyzed. Findings: 534 COVID-19 patients were enrolled. The median age of the patients was 62.0 years old (IQR 52.0-70.0) and 295 were female (55.2%). The median time from onset to follow-up was 460.0 (451.0-467.0) days. Sleep disturbance (18.5%, 99/534) and fatigue (17.2%, 92/534) were the most common persistent symptoms. 6.4% (34/534) of the patients had depression, 9.2% (49/534) were anxious, 13.0% (70/534) had insomnia and 4.7% (25/534) suffered from post-traumatic stress disorder (PTSD). Multivariate adjusted logistic regression analysis showed that glucocorticoid use during hospitalization (OR 3.58, 95% CI 1.12-11.44) was significantly associated with an increased risk of fatigue. The OR values for anxiety and sleep disorders were 2.36 (95% CI 1.07-5.20) and 2.16 (95% CI 1.13-4.14) in females to males. The OR value of PTSD was 25.6 (95% CI 3.3-198.4) in patients with persistent symptoms to those without persistent symptoms. No significant associations were observed between fatigue syndrome or adverse mental outcomes and disease severity. Conclusions: 15-month follow-up in this study demonstrated the need of extended rehabilitation intervention for complete recovery in COVID-19 patients.

Mechanism of Liver Regeneration During ALPPS.

Liver cancer is one of the most lethal malignant tumors in the world, and surgical resection is the main treatment for liver cancer. Liver failure due to insufficient residual liver volume is a fatal complication after hepatectomy. How to effectively increase the residual liver volume after hepatectomy and improve the safety of hepatectomy has always been a problem to be solved in liver surgery. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) effectively reduces the occurrence of liver failure due to insufficient residual liver volume after hepatectomy, thereby increasing the probability of radical resection by inducing rapid proliferation of residual liver tissue. However, the molecular mechanism of residual liver tissue regeneration after primary ALPPS (combined liver partition and portal vein ligation) remains unclear. Here, we found that lots of circular RNAs (circRNAs) are upregulated after ALPPS in pig liver cells; then, we identified the orthologous circRNA in humans and pigs to detect their function in liver regeneration. The results showed that loss of circ-0067724 and circ-0016213 could suppress liver cell proliferation. Together, these findings suggest that circ-0067724 and circ-0016213 play an important role in liver cell proliferation, and this may help us to find new strategies to promote liver regeneration.

Luminescence Enhancement of Mn4+-Activated Fluorides via a Heterovalent Co-Doping Strategy for Monochromatic Multiplexing.

Mn4+ non-equivalent doped fluorides with high color purity red emission and relatively short decay time are crucial for wide color gamut displays and emerging applications, whereas the low quantum efficiency (QE) restrains their further applications. Herein, the luminescence of Mn4+ non-equivalent doped fluoride K2NaAlF6:Mn4+ (KNAF:Mn4+) is significantly enhanced via a heterovalent co-doping strategy, where the luminescence intensity is obviously increased by ∼85%, but the decay time is almost unchanged. The experimental characterization and density functional theory (DFT) calculations provide an understanding of the luminescence enhancement mechanism of heterovalent co-doping, which is enabled by simultaneously improving the stability of Mn4+ and reducing the number of quenching centers (defects and impurities). Combining the short-decay-time (τ = 4.03 ms) emission KNAF:Mn4+, Mg2+ and long-decay-time (τ = 9.23 ms) emission K2SiF6:Mn4+, a novel monochromatic multiplexing mode in the millisecond order is presented, which can be decoded not only in high-efficiency by a digital camera but also with a high security. This work provides a new optical multiplexing for the information security applications and also inspires the design of high-efficiency Mn4+-activated luminescent materials.

Effects of Nano Aluminum Powder on the Mechanical Sensitivity of RDX-Based Explosives.

As nano-aluminum powder (NAP) can improve the detonation performance of aluminum-containing explosives, more and more explosives with NAP as the metal ingredient have been studied. It is believed that the mechanical sensitivity of explosives can be significantly enhanced by the added nano-sized aluminum powder. However, the mechanism for the enhancement has not been clarified. In order to illuminate the effects of NAP on the mechanical sensitivity of explosives, two RDX-based aluminum-containing explosives with the same weight ratio and preparation process were investigated despite the aluminum powders with different nano-size and micron-size. The morphology and surface atomic ratio of the two explosives were examined by scanning electron microscopy with energy dispersive spectroscopy tests. The contact angle and other microstructures properties of the explosives were calculated by Material Studio software. Results revealed that the impact and friction activity was determined by the aluminum particle sizes and explosive components. This paper clarified the mechanism for the increase in explosives sensitivity by the addition of NAP, which provide reference for the scientific and technical design of novel explosives.

Identification of Prognostic Biomarkers for Multiple Solid Tumors Using a Human Villi Development Model.

The processes of embryonic development that rely on epithelial-mesenchymal transition (EMT) for the implantation of trophoblast cells are co-opted by tumors, reflecting their inherent uncontrolled characteristics and leading to invasion and metastasis. Although tumorigenesis and embryogenesis have similar EMT characteristics, trophoblasts have been shown to exhibit "physiological metastasis" or be "pseudo-malignant," resulting in different outcomes. The gene co-expression network is the basis of embryonic development and tumorigenesis. We hypothesize that if the gene co-expression network in tumors is "off-track" from that in villi, it is more likely to develop into malignant tumors and have a worse prognosis, and we proposed the "off-track theory" for the first time. In this study, we examined gene co-expression networks in villi and multiple solid tumors. Through network functional enrichment analyses, we found that most tumors and villi exhibited a significantly enriched EMT, but the genes that performed this function were not identical. Then, we identified the "off-track genes" in the EMT-related gene interaction network using the "off-track theory," and through survival analysis, we discovered that the risk score of "off-track genes" was associated with poor survival of cancer patients. Our study indicated that villi development is a reliable and strictly regulated model that can illuminate the trajectory of human cancer development and that the gene co-expression networks in tumor development are "off-track" from those in villi. These "off-track genes" may have a substantial impact on tumor development and could reveal novel prognostic biomarkers.

Modulation of foreign body reaction and macrophage phenotypes concerning microenvironment.

The foreign body reaction (FBR) is described as a local chronic inflammation after implantation of biomaterials in which macrophages involved intimately. At the stage of acute inflammation, mast cells release histamine, Interleukin-4 (IL-4) and Interleukin-13 (IL-13), enhancing recruitment, and fusion of macrophages in the following phase. As for chronic intensive inflammation, degradation of biomaterials would be promoted by macrophage-derived foreign body giant cells releasing degradative enzymes, acid and reactive oxygen intermediates. Nevertheless, it could be seen as a breakthrough point for regulating FBR, considering the dominant role of the macrophage in the immune response as exemplified by the decrease of IL-4 and IL-13, stabilizing an appropriate balance between two macrophage phenotypes, selectively suppressing some function of macrophages, and so on. Moreover, the relationship between macrophages polarization and the development of a fibrous capsule, which increase the possibility of implantation failure, will be illustrated later. This review aims at providing readers a comprehensive understanding of FBR and its correlative treatment strategy.

Evaluation of epigallocatechin-3-gallate (EGCG)-modified scaffold determines macrophage recruitment.

Biomaterials based on the modulation of macrophages have gained increased attention recently. Macrophages are generally divided into the pro-inflammatory M1 and pro-regenerative M2 phenotypes. Macrophages play a pivotal role in bone regeneration by regulating osteoblast differentiation and secreting pro-regenerative factors. In the present study, epigallocatechin-3-gallate (EGCG)-modified collagen membranes downregulated the expression of inflammatory factors and promoted the recruitment of M2 macrophages, as evidenced by the expression of M2 macrophage markers (CD163 and CD206). It is further demonstrated that the recruitment of M2 macrophages may be involved with CC chemokine receptor type 2 (CCR2) signaling, with a significant downregulation of CD206 following CCR2 knockout. These results suggested that EGCG-modified collagen membranes may modulate the recruitment of macrophages and can be applied to guided bone regeneration and guided tissue regeneration.

Evaluation of epigallocatechin-3-gallate (EGCG) modified collagen in guided bone regeneration (GBR) surgery and modulation of macrophage phenotype.

Collagen membranes have been widely applied for guided bone regeneration (GBR), a technique often utilized in dental implant surgery for bone argumentation. However, the implantation of collagen membranes also elicits foreign body reaction (FBR), the imbalance of which may lead to failures of dental implants. Macrophages play a pivotal role in FBR as macrophages can polarize into pro-inflammatory (M1) and pro-regenerative (M2) phenotypes. Therefore, collagen membranes based on modulation of macrophage polarization have gained increased attention. Epigallocatechin-3-gallate (EGCG)-modified collagen membranes have been previously shown to downregulate the expression of inflammatory factors. In the present study, scanning electron microscopy images showed that EGCG-modified collagen membranes prevented the migration of keratinocytes and maintained space for osteoblasts. CCK-8 and live/dead cell assays showed that EGCG-modified collagen membranes unaffected the cell viability of osteoblasts. In addition, immunofluorescent staining and quantitative real-time polymerase chain reaction showed an increased number of M2 macrophages, an upregulated expression of growth factors including vascular endothelial growth factor, bone morphogenetic protein 2, and an upregulation of osteogenic differentiation-related factors including Runt-related transcription factor 2 and osteopontin after implantation of EGCG-modified collagen membranes. Hematoxylin-eosin staining and Micro-CT further demonstrated that the application of EGCG-modified collagen membranes promoted new bone formation in vivo. From these findings it is concluded that EGCG-modified collagen membranes have promising potentials in GBR surgery which served as suitable barrier membranes and promoted bone regeneration in vivo by recruiting M2 macrophages, promoting secretion of growth factors and osteogenic differentiation.

Extracellular vesicle and mesenchymal stem cells in bone regeneration: recent progress and perspectives.

Transplanting mesenchymal stem cells (MSCs) has been widely perceived as an ideal treatment for bone repair and regeneration, owing to their differential potential. However, researchers found that very few intravenous MSCs could stay in the target tissue, whereas the majority of them are trapped in liver, spleen, and lung, largely reducing its therapeutic effects. Recently, extracellular vesicles (EVs) have attracted increased attention due to their function in bone repair and advantages over traditional cell therapy. Also, MSCs-derived EVs are likely to achieve the osteogenic goal via modulating the cells and cytokines involved in bone metabolism. This review aims at summarizing the function of EVs and MSCs in bone metabolism and regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 243-250, 2019.

Research progress on extracellular vesicles and bone regeneration / 口腔疾病防治

@#Extracellular vesicles (EVs) are lipid bilayers secreted by a variety of cells that contain nucleic acids, proteins, etc. They can be used as a carrier for cell-to-cell communication. In related research on bone regeneration, mechanisms for transmitting regeneration signals to target cells to achieve the desired goal of osteogenesis have become one of the most important and unsolved topics. Therefore, this review aims to explore the role of mesenchymal stem cells and EVs derived from osteoblasts in bone regeneration in four processes, immunity, angiogenesis, osteogenesis and mineralization, and to provide new ideas for basic and clinical research.

Research progress in the regulation of macrophages in foreign body reaction in bone tissue repair / 口腔疾病防治

@#The foreign body reaction refers to a chronic inflammatory reaction and a wound-healing reaction that mainly involve macrophages and foreign body giant cells, which occur after a biological material is implanted into the body. Since macrophages in the foreign body reaction are recruited to the surface of the material after implantation of the material, subsequent secretion of a series of inflammatory factors and fusion into foreign body giant cells may lead to the degradation of the biological materials and environmental stress cracking. Moreover, the prolongation of macrophage polarization and the influence of related receptors may also lead to the phenomenon of fiber encapsulation, resulting in poor prognosis. Some scholars are committed to reducing the response of foreign bodies from the perspective of macrophages and foreign body giant cells, specifically by regulating the secretion of related inflammatory factors, reducing the subtypes of M1 macrophages, promoting their polarization to M2 macrophages, and regulating the fusion of macrophages and selective expression of macrophage-associated receptors to regulate fibrosis. The new immunological view holds that macrophages have the potential to repair bone tissue via angioplasts and osteogenesis in foreign body reactions. Therefore, the gold standard that has long been considered in regenerative medicine, which is that an inert material does not cause a foreign body reaction, is expected to be gradually replaced by tissue engineering that regulates tissue activity and function.

Identification of proteins associated with paclitaxel resistance of epithelial ovarian cancer using iTRAQ-based proteomics.

Chemotherapy is an important adjuvant therapy for epithelial ovarian cancer (EOC). The main cause of chemotherapy failure in EOC is paclitaxel resistance. The present study aimed to identify novel biomarkers to predict chemosensitivity to paclitaxel and improve our understanding of the molecular mechanisms underlying paclitaxel resistance in EOC. In the present study, the heterogeneity of EOC was evaluated by adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in vitro. Fresh samples were collected from 54 EOC cases during cytoreductive surgery. Tumor cells were isolated, cultured, and tested for sensitivity to paclitaxel. Proteins that were differentially expressed between paclitaxel-resistant tissues and paclitaxel-sensitive tissues were identified via isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis. Two upregulated proteins, plexin domain containing 2 (Plxdc2) and cytokeratin 7 (CK7), were selected to verify the iTRAQ method using western blot analysis in EOC tissues with different chemosensitivities (sensitive, weakly sensitive and resistant). There was notable heterogeneity of chemosensitivity in the EOC specimens. Highly to mildly-differentiated or early-stage (I/II) EOC specimens had decreased sensitivity to paclitaxel compared with specimens with low differentiation (P<0.05) or an advanced stage (III; P<0.05), respectively. A total of 496 significantly differentially expressed proteins, including 263 that were downregulated (P<0.05) and 233 that were upregulated (P<0.05) in paclitaxel-resistant tissues compared with paclitaxel-sensitive tissues, were identified using iTRAQ in combination with LC-MS/MS. The expression levels of two proteins associated with paclitaxel resistance, Plxdc2 and CK7, were further validated by western blotting, which revealed that they were upregulated in the paclitaxel-resistant tissues. The present study determined candidate proteins associated with paclitaxel resistance in EOC. Plxdc2 and CK7 may be potential makers for distinguishing patients with paclitaxel-resistant EOC from those with paclitaxel-sensitive EOC.

Macrophage phenotype in the epigallocatechin-3-gallate (EGCG)-modified collagen determines foreign body reaction.

Collagen has been widely used in guided bone regeneration, and the implantation of collagen membranes will elicit the foreign body reaction (FBR). The imbalance of FBR often leads to failure of dental implants. Therefore, modulation of the FBR after implantation of collagen membranes becomes increasingly important. Macrophages, pivotal in FBR, have been distinguished into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. Epigallocatechin-3-gallate (EGCG)-modified collagen membranes have been previously shown to regulate secretion of inflammatory factors. In this study, immunohistochemistry of CD31 showed that areas of blood vessels were significantly enlarged after implantation of EGCG-modified collagen membranes compared with those treated with pure collagen membranes. Besides, haematoxylin-eosin staining and immunofluorescence showed an increased number of M2 macrophages after implantation of EGCG-modified collagen membranes. In addition, quantitative real-time polymerase chain reaction showed that after implantation of EGCG-modified collagen membranes, expression of CXCL1 (predominant chemoattractants to neutrophils and inflammation promotors) was significantly downregulated, whereas expressions of STAB1, CCR2, CCR3, CCL2, and CCL3 (related to M2 macrophages) were significantly upregulated. From these findings, we conclude that EGCG-modified collagen membranes were able to regulate the recruitment and polarization of macrophages, so that ameliorate FBR.

Relationship between T cells and bone regeneration: recent progress and perspectives / 口腔疾病防治

@#Bone is capable of regeneration after injury, but the process of properly restoring form and function is highly complex and prone to failure. The restoration process requires highly ordered and sequential interplay at the injury site between the host immune system and bone tissue. The dynamic process that occurs after bone injury includes the formation of a hematoma, the development of an inflammatory response and callus, and the remodeling of newly formed bone tissue. The inflammatory response at the injury site is essential for the onset of bone regeneration. This inflammatory response is tightly linked with the host immune system, in which various immune cells and molecules are involved. Recently, the relationship between T cells and bone regeneration has become a popular topic; however, currently, there are no summaries of the relationship between T cells and bone regeneration. Thus, this review aimed to elucidate the modulatory functions of T cells in bone regeneration.

Villi-specific Gene Expression Reveals Novel Prognostic Biomarkers in Multiple Human Cancers.

Despite many striking connections, the biological similarities between embryonic development and tumorigenesis have not been well explored. Development of the placental villi is a crucial process involving many cellular activities, including immunity, proliferation, and cell adhesion. In this study, we designed a strategy to identify the gene expression pattern of villi development and to explore the corresponding features in tumors. We discovered villi-specific genes that are highly expressed in the villus as opposed to the mature placenta and then measured the expression levels of these genes in tumors. We found large changes in the expression of villi-specific genes in multiple types of cancer. These villi-specific genes showed distinct expression patterns and were primarily involved in three biological processes: immune-related (5), proliferation-related (6), and focal adhesion-related (8); these genes were extracted from the corresponding enriched Gene Ontology (GO) terms. We observed that these genes were also dysregulated at the transcriptional level across several tumor types. Moreover, the expression of these three gene groups was associated with poor prognosis in a subset of tumors. Based on villi-specific gene expression, this correlation study indicated the existence of common gene expression patterns between embryonic development and tumorigenesis. Therefore, a systematic analysis of villi-specific gene aberrations in various tumors could serve as an indicator for identifying novel prognostic biomarkers.

[Therapeutic effect of endoscopic third ventriculostomy for pediatric hydrocephalus].

OBJECTIVE: To validate the proposed endoscopic third ventriculostomy success score (ETVSS) for predicting successful ETV outcomes for pediatric hydrocephalus on the basis of individual characteristics. METHODS: For 121 cases at our department from June 2007 to June 2010 at both 6 and 24 months, Actual successful rates were compared with Chi-square test and 95% confidence interval for low, moderate and high chance of success strata based on the ETVSS. Long-term successful probability was calculated with Kaplan-Meier methods. RESULTS: The 6-month ETV successful rate was higher than the mean predicted probabilities of success for both moderate and low success strata, but slightly lower for the high chance of success strata. The ETVSS accurately predicted the outcomes at 24 months; the low, medium and high chance of success strata had actual success rates of 74% (37/50), 62% (28/45) and 41% (11/26) and mean predicted successful probabilities of 81.3%, 61.4% and 34.4% respectively. CONCLUSION: ETVSS may accurately predict the overall long-term successful rates in high, moderate and low-risk groups. Thus it will aid clinical decision-making through predicting the therapeutic effect of ETV.

Effect of Strongly Alkaline Electrolyzed Water on Silk Degumming and the Physical Properties of the Fibroin Fiber.

Strongly alkaline electrolyzed water (SAEW) was prepared by electrolysis of tap water in a laboratory-made water electrolyzer. The pH of stored SAEW was stable for more than one month. The hardness of the electrolyzed water was 30% lower and the Na(+) concentration was 18% higher than those of the tap water. Silkworm cocoon shells were boiled in pH 11.50 SAEW at a ratio of 1∶40∼80 (W/V) for 20 min and the sericin layers around the silk fibroin fibers were removed completely. The tensile properties and thermal decomposition temperature of a single filament of silk fibroin obtained by the SAEW method were almost the same as those for the fiber obtained by the neutral soap, and much higher than those for the fiber obtained by Na2CO3 degumming. The results demonstrate that SAEW is an environmentally friendly and pollution-free silk degumming agent that allows highly efficient, low cost recovery of sericin.

Isolation and bioactivities of a non-sericin component from cocoon shell silk sericin of the silkworm Bombyx mori.

The cocoon shell of the silkworm Bombyx mori consists of silk fibroin fiber (70%) surrounded by a sericin layer made up of sericin (25%) and non-sericin (5%) components. The non-sericin component which consists of carbohydrate, salt, wax, flavonoids and derivatives is often overlooked in applied research into sericin and its hydrolysate. Here, sericin and non-sericin compounds were obtained from the sericin layer of five types of cocoon shell by means of degumming in water followed by extraction and separation in ethanol. These ethanol extracts were found to mainly contain flavonoids and free amino acids possessing scavenging activities of the 2,2-diphenyl -1-picrylhydrazyl (DPPH) free radical and inhibiting activities of tyrosinase, which were much greater than the corresponding activities of the purified sericin proteins. The extracts also strongly inhibited α-glucosidase while the sericins had no such activity. In particular, the inhibitory activities of the ethanol extract of Daizo cocoons were much greater than those of the other cocoons. The IC(50) values of the Daizo cocoons for DPPH free radicals, tyrosinase, and α-glucosidase were 170, 27, and 110 µg mL(-1), respectively. The bioactivities of the non-sericin component were much higher than the activity of sericin alone. In addition, the in vivo test showed preliminarily that the administration of the non-sericin component had effectively resistant activity against streptozocin (STZ) oxidation and that of the purified sericin could also evidently decrease the induction ratio of diabetic mice induced by STZ. Therefore, ethanol extract protocols of the sericin layer of cocoon shells provide a novel stock which, together with sericin protein, has potential uses in functional food, biotechnological and medical applications.

Bioconjugation of neutral protease on silk fibroin nanoparticles and application in the controllable hydrolysis of sericin.

Bombyx mori silk fibroin is a protein-based macromolecular biopolymer with remarkable biocompatibility. Silk fiber was degummed and subjected to a series of treatments, including dissolution and dialysis, to yield an aqueous solution of silk fibroin, which was introduced rapidly into excess acetone to produce crystalline silk fibroin nanoparticles (SFNs). The SFNs were conjugated covalently with a neutral protease (NP) using glutaraldehyde as the cross-linking reagent. The objective of this study was to determine the optimal conditions for biosynthesis of the SFN-NP bioconjugates. First, SFN-NP was obtained by covalent cross-linking of SFN and NP at an SFN/NP ratio of 5-8 mg:1 IU with 0.75% glutaraldehyde for 6 h at 25 °C. When adding 50 IU of the enzyme, the residual activity of biological conjugates was increased to 31.45%. Studies on the enzyme activity of SFN-NP and its kinetics showed that the stability of SFN-NP bioconjugates was greater than that of the free enzyme, the optimum reactive temperature range was increased by 5-10 °C, and the optimum pH value range was increased to 6.5-8.0. Furthermore, the thermal stability was improved to some extent. A controlled hydrolysis test using the poorly water-soluble protein sericin as a substrate and SFN-NP as the enzyme showed that the longer the reaction time (within 1 h), the smaller the molecular mass (<30 kDa) is of the sericin peptide produced. The SFN-NP bioconjugate is easily recovered by centrifugation and can be used repeatedly. The highly efficient processing technology and the use of SFN as a novel vector for a protease has great potential for research and the development of food processing.

[Protective effect of ligustrazine on insulin resistance after local cerebral ischemia of rat].

OBJECTIVE: To study the protective effect of Ligustrazine on IR after local cerebral ischemia of rat. METHOD: Models of rat IR after local cerebral ischemia were prepared by electrocagulation of the middle cerebral artery, and changes of serum insulin, tomer necrosis factor-alpha (TNF-alpha), plasma endothelin-1 (ET-1), nitric oxide (NO) and nitric oxide synthase (NOS) were observed 2 weeks after the ischemia. RESULT: Ligustrazine could significantly reduce serum insulin (P < 0.01), the content of plasma ET-1 (P < 0.01) and serum TNF-alpha (P < 0.01), the activity of brain tissue NO and NOS (P < 0.01). The drug also increased insulin sensitivity indexes (ISI). CONCLUSION: The protective effects of Ligustrazion on IR cerebral ischemia may be related to decreasing ET-1 content in plasma, TNF-alpha content in serum, NO content and NOS activities in tissue.