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Research on coagulation dysfunction following burns is controversial. This study aimed to describe the coagulation changes in severe burn patients by examining coagulation parameters.Patients with third-degree total body surface area (TBSA) burns of ≥30% were enrolled between 2017 and 2020. Platelet (PLT) count and coagulation indexes (including APTT, INR, FIB, DD, and AT Ⅲ) were measured at admission and once weekly for 8 weeks, and statistical analysis was performed. The patient medical profiles were reviewed to extract demographic and clinical data, including TBSA, third-degree TBSA, and inhalation injury. The total intravenous fluids and transfusions of crystalloids, fresh frozen plasma (FFP), and red blood cells (RBC) were calculated during the forty-eight-hour period. The number of sepsis cases was recorded.We enrolled 104 patients , and while the overall coagulation trend fluctuated, inflection points appeared around one week and demonstrated hypercoagulability. INR was significantly higher in the non-survival group than in the survivors' group from admission to three weeks after burn (all p0.01). From post-injury week 1 to post-injury week 3, the APTT in the non-survival group was greater than in the survival group, but the non-survival group's PLT count was lower than that in the survival group (all p0.05). At two and three weeks after burns, the FIB levels in the non-survival group were significantly lower than those of the survival group (both p0.01). The prevalence of inhalation injury and the proportion of sepsis cases were significantly higher in the non-survival group than in the survival group ( p ＜ 0.05, p ＜ 0.001, respectively). At the time of death, APTT, INR, and FDP levels were significantly higher in the non-survival group in the survivor group, and FIB, ATIII, and PLT were significantly lower than in the survivor group (all p0.01). On the day of death, nine of the 12 dead patients had disseminated intravascular coagulation (DIC).Coagulation dysfunction was most prominent in severe burn patients 1 week after injury and presented as hypercoagulability. Large-area burn injury, large amounts of fluid resuscitation, inhalation injury, and sepsis may all contribute to coagulation dysfunction, which can further develop into DIC and even death in severe burns patients.

The function of mitochondrial fusion and fission is one of the important factors causing ischemia-reperfusion (I/R) injury in diabetic myocardium. Aldehyde dehydrogenase 2 (ALDH2) is abundantly expressed in heart, which involved in the regulation of cellular energy metabolism and stress response. However, the mechanism of ALDH2 regulating mitochondrial fusion and fission in diabetic myocardial I/R injury has not been elucidated. In the present study, we found that the expression of ALDH2 was downregulated in rat diabetic myocardial I/R model. Functionally, the activation of ALDH2 resulted in the improvement of cardiac hemodynamic parameters and myocardial injury, which were abolished by the treatment of Daidzin, a specific inhibitor of ALDH2. In H9C2 cardiomyocyte hypoxia-reoxygenation model, ALDH2 regulated the dynamic balance of mitochondrial fusion and fission and maintained mitochondrial morphology stability. Meanwhile, ALDH2 reduced mitochondrial ROS levels, and apoptotic protein expression in cardiomyocytes, which was associated with the upregulation of phosphorylation (p-PI3K

Benign anastomotic stricture remains among the most prevalent complications following surgery for rectal cancer.This study is aimed at identifying risk factors of anastomotic stricture as well as generating an effective nomogram for the stricture.Design: This is a retrospective study.This study was conducted from January 2015 to December 2019 in a single tertiary center for rectal cancer.A total of 117 rectal cancer patients after surgery without recurrence were enrolled in this study, of which 39 with anastomotic stricture and 78 without stricture.Their clinical and pathological data were collected. Multiple logistic regression analysis was conducted to identify risk factors for anastomotic stricture and to generate the nomogram prediction model.Multivariate analysis of the primary cohort led to the identification of LCA (left colic artery) preservation (OR, 0.074; P = 0.0015), protective stoma (OR, 5.353; P = 0.012), anastomotic leakage (OR, 12.027; P = 0.005), and anastomotic distance (OR, 7.578; P = 0.012) as independent risk factors for anastomotic stricture. The following predictive model was derived: Logit (anastomotic stricture) = 0.074∗ LCA + 5.353∗ Protective stoma +12.027∗ Anastomotic leakage + 7.578∗ Anastomotic distance. Assessment of the predictive model revealed that the area under the curve (AUC) was 0.871, while the cutoff value was 15.444 with a sensitivity of 64.1% and a specificity of 94.8%.The main limitation is the research design of a retrospective and case-controlled study with a small sample size from a single center.LCA preservation, protective stoma, anastomotic leakage, and anastomotic distance may affect the occurrence of anastomotic stricture following surgery for rectal cancer. The nomogram model generated in the present study can be valuable in the prediction of anastomotic stricture. This study has been registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/, ChiCTR 2100043775).

The hepatitis B virus (HBV) X protein (HBX), a viral macromolecule, plays a vital role in the development of HBV-related hepatocellular carcinoma (HCC). Increased expression of HER2 is linked to HBV infection, and HBX is responsible for HER2 upregulation in HCC. Nevertheless, the underlying molecular mechanisms are not yet fully understood. In the study, we discovered that HBX promoted HER2 expression to facilitate the sensitization of the insulin signaling pathway and enhance the growth and migration of HCC cells. Mechanistically, the viral protein enhanced the stability of HER2 by preventing its ubiquitination-mediated proteasomal degradation through LASP1, which could bind to HER2. Furthermore, increased SUMOylation of LASP1 contributed to the upregulation of HER2 and the interaction of LASP1 with HER2. In addition, RANBP2 and RANGAP1 were found to interact with LASP1 and promote SUMOylation of LASP1 to upregulate HER2 expression in HBX-associated hepatoma cells. In summary, our work provides a novel insight into hepatocarcinogenesis mediated by HBX and estimates the detailed mechanisms related to the increase in HER2 regulated by the viral protein, which might help provide a theoretical basis for identifying novel targets for HBV-positive HCC treatment.

From modular vaccine production to protein assembly on nanoparticles, the SpyCatcher/SpyTag system provides a convenient plug-and-display procedure. Here, we established a general-purpose immunoaffinity chromatography (IAC) method for SpyTagged proteins (SpyIAC). SpyTags are displayed on the surface of nanoparticles to induce high-affinity monoclonal antibodies, allowing the specific capture of the target protein. Taking the key core antigenic regions of two coronaviruses that are currently more threatened in the field of human and animal diseases, the nucleocapsid (N) protein of SARS-CoV-2 and the COE protein of porcine epidemic diarrhea virus (PEDV) as model proteins, a purification model with SpyTag at the N-terminal or C-terminal expressed in E. coli or mammalian cells was constructed. After the efficient elution of SpyIAC, the final yield of several proteins is about 3.5-15 mg/L culture, and the protein purity is above 90 %. Purification also preserves the assembly function and immunogenicity of the protein to support subsequent modular assembly and immunization programs. This strategy provides a general tool for the efficient purification of SpyTagged proteins from different expression sources and different tag positions, enabling the production of modular vaccines at lower cost and in a shorter time, which will prepare the public health field for potential pandemic threats.

Genetic tests have become widely available. We sought to understand the use of genetic tests in the practice of frontline clinicians within the United States Department of Veterans Affairs (VA).We administered a web-based survey to clinicians at 20 VA facilities. Physicians, nurse practitioners, physician assistants, and pharmacists were eligible. We excluded genetics providers and clinicians not seeing patients. We used multiple logistic regression to evaluate the associations between clinician characteristics and experience with genetics.The response rate was 11.3% (1207/10,680) and of these, 909 respondents were eligible. Only 20.8% of the respondents reported feeling prepared to use genetic tests and 13.0% of the respondents were currently ordering genetic tests; although, it was usually only 1 or 2 a year. Delivery of genetic tests without involving genetics providers was preferred by only 7.9% of the respondents. Characteristics positively associated with currently ordering genetic tests included practice in clinical and research settings, believing improving genetics knowledge could alter their practice, feeling prepared to use genetic tests, and referral of at least 1 patient to genetics in the past year.Most VA clinicians don't feel prepared to use genetic tests. Those with genetic testing experience are more likely to consult genetics providers. The demand for genetics providers should increase as frontline clinicians use genetic tests in their practice.

The strikingly rapidly mutating nature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome has been a constant challenge during the coronavirus disease 2019 (COVID-19) pandemic. In this study, various techniques, including reverse transcription-quantitative polymerase chain reaction, antigen-detection rapid diagnostic tests, and high-throughput sequencing were analyzed under different scenarios and spectra for the etiological diagnosis of COVID-19 at the population scale. This study aimed to summarize the latest research progress and provide up-to-date understanding of the methodology used for the evaluation of the immunoprotection conditions against future variants of SARS-CoV-2. Our novel work reviewed the current methods for the evaluation of the immunoprotection status of a specific population (endogenous antibodies) before and after vaccine inoculation (administered with biopharmaceutical antibody products). The present knowledge of immunoprotection status regarding the COVID-19 complications was also discussed. Knowledge on the immunoprotection status of specific populations could help guide the design of pharmaceutical antibody products, inform practice guidelines, and develop national regulations with respect to the timing of and need for extra rounds of vaccine boosters.

The objective of this study was to investigate the characteristics of force degradation and surface morphology of 9 brands of elastic ligatures over 6 weeks, both in vivo and in vitro, to provide some reference for clinical selection of appropriate elastic ligatures and determination of appropriate follow-up visit time.Choosing 9 kinds of brands of elastic ligatures (American Orthodontics, Ormco, 3M Grey, TP Orthodontics, Xihu, Yahong, Creative, Protect, 3M dusty blue), which are common in the market. For the in vivo study, 9 volunteers (5 males, 4 females, aged 22-26 years) were chosen to wear elastic ligature fixators, which were made to fix the elastic ligature in the mouth without bonding brackets on the teeth. The residual force and percentage of force degradation of elastic ligatures were estimated after 0, 1 hour, 2 hours, 8 hours, 1 day, 2 days, 1 week, 2 weeks, 4 weeks, and 6 weeks processed in vivo and in vitro (25°C dry air condition, 37°C artificial saliva, pH = 6.7 and oral environment); A 1-way analysis of variance and t test were used to identify statistical significance (P 0.05). The surface morphology of the initial state and after a 6-week process in vivo and in vitro were observed separately.The characteristics of force degradation and surface morphology of 9 brands of elastic ligatures were different over 6 weeks; With the extension of time, the tensile force declined, and the percentage of force degradation of all groups decreased sharply by about 9.1%-32.3% in the first day, then the rate reduced steadily. In addition, during the first day, the percentage of force degradation declined most sharply in the first hour (4.4%-16.5%). The percentage of force degradation of 9 elastic ligatures was reduced by about 11.3%-37.3% over 6 weeks in all groups. At the same time, the characteristics of force degradation in the same brand are that in vivo artificial saliva air (P 0.05). After a 6-week process, the surface morphologic defects were aggravated under a scanning electron microscope, corresponding to the change of mechanical properties in each brand.The mechanical properties of elastic ligatures are reduced with time extension and decreased greater in vivo than in vitro; According to the characteristics of force degradation of different brands of elastic ligatures, clinicians can choose the proper elastic ligatures at different stages of treatment, and adjust the follow-up visit time appropriately. For example, in alignment and leveling, the elastic ligatures with slow force degradation, such as Ormco, TP, and so on, maybe more suitable to ensure close contact between the archwire and the bracket. In the space-closing stage, the elastic ligatures with fast force degradation may be more appropriate to reduce the friction between the archwire and the bracket, such as 3M Grey, Yahong, Protect, and so on.

Sleep disorders are associated with cognitive impairments, greater amyloid-β (Aβ) burden and increased risk of developing Alzheimer's disease, while the underlying mechanism is unclear. N-methyl-d-aspartate receptors (NMDARs), as vital modulators of cognition, are sensitive to sleep disturbance. Sleep deprivation (SD) could induce the alterations of neuronal NMDAR subunits expression, however the alterations of astrocytic NMDARs in SD have not been reported. Our previous study has demonstrated knockdown of astrocytic Grin2a (gene encoding NMDAR subunit GluN2A) could aggravate Aβ-induced cognitive impairments, but what role astrocytic GluN2A may play in SD is unknown. Here we focused on the changes and roles of hippocampal astrocytic GluN2A in SD. Our results showed SD increased the expression of astrocytic GluN2A. Specific knockdown of hippocampal astrocytic Grin2a aggravated SD-induced cognitive decline, elevated Aβ, and attenuated the SD-induced increase in autophagy flux. Our finding, for the first time, revealed a novel neuroprotective role for astrocytic GluN2A in SD, which may be helpful for developing new preventive and therapeutic targets to sleep disorders.

Obesity impacts multiple sites of the hypothalamus-pituitary gland-ovary axis (HPO axis) and has become a leading cause of female infertility. However, the critical hypothalamic neurons that participate in the development of obesity-induced infertility have not been well defined yet. Previous studies suggested that metabolic-sensing agouti-related peptide-expressing (AgRP) neurons in the arcuate nucleus (ARC) are hyperactive in diet-induced obesity (DIO) mice. We hypothesize that these neurons may convey metabolic dysfunction onto the HPO axis and contribute to obesity-induced infertility's pathophysiological process. To determine if AgRP neurons in obesity play a necessary role in the development of reproductive impairment in obesity, we used the chemogenetic method to normalize the neuronal activity of AgRP neurons in DIO female mice and test if their fertility can be restored. Our results indicated that chemogenetic inhibition of AgRP neurons could fully rescue the reproductive performance of DIO female mice, as manifested by recovered sex hormonal levels, ovulation, and fecundity. Moreover, we assayed serum AgRP levels in normal-weight and obese women and found elevated AgRP levels in obese subjects, suggesting the correlation between obesity and AgRP neuronal hyperactivity. Our results indicated that AgRP neurons constitute a central node connecting metabolism and reproduction, and dysfunctions of these neurons play a crucial role in reproductive impairment induced by metabolic abnormalities.