The effects of coronaviruses on the respiratory system are of great concern, but their effects on the digestive system receive much less attention. Coronaviruses that infect mammals have shown gastrointestinal pathogenicity and caused symptoms such as diarrhea and vomiting. Available data have shown that human coronaviruses, including the newly emerged SARS-CoV-2, mainly infect the respiratory system and cause symptoms such as cough and fever, while they may generate gastrointestinal symptoms. However, there is little about the relation between coronavirus and digestive system. This review specifically addresses the effects of mammalian and human coronaviruses, including SARS-CoV-2, on the digestive tract, helping to cope with the new virus infection-induced disease, COVID-19.

Background: Acute mountain sickness (AMS) is the mildest form of acute altitude illnesses, and consists of nonspecific symptoms when unacclimatized persons ascend to elevation of ≥2500 m. Risk factors of AMS include: the altitude, individual susceptibility, ascending rate and degree of pre-acclimatization. In the current study, we examined whether physiological response at low altitude could predict the development of AMS.

Methods: A total of 111 healthy adult healthy volunteers participated in this trial; and 99 (67 men and 32 women) completed the entire study protocol. Subjects were asked to complete a 9-min exercise program using a mechanically braked bicycle ergometer at low altitude (500 m). Heart rate, blood pressure (BP) and pulse oxygen saturation (SpO₂) were recorded prior to and during the last minute of exercise. The ascent from 500 m to 4100 m was completed in 2 days. AMS was defined as ≥3 points in a 4-item Lake Louise Score, with at least one point from headache wat 6–8 h after the ascent.

Results: Among the 99 assessable subjects, 47 (23 men and 24 women) developed AMS at 4100 m. In comparison to the subjects without AMS, those who developed AMS had lower proportion of men (48.9% vs. 84.6%, P<0.001), height (168.4±5.9 cm vs. 171.3±6.1 cm, P=0.019), weight (62.0±10.0 kg vs. 66.7±8.6 kg, P=0.014) and proportion of smokers (23.4% vs. 51.9%, P=0.004). Multivariate regression analysis revealed the following independent risks for AMS: female sex (odds ratio (OR)=6.32, P<0.001), SpO₂ change upon exercise at low altitude (OR=0.63, P=0.002) and systolic BP change after the ascent (OR=0.96, P=0.029). Women had larger reduction in SpO₂ after the ascent, higher AMS percentage and absolute AMS score. Larger reduction of SpO₂ after exercise was associated with both AMS incidence (P=0.001) and AMS score (P<0.001) in men but not in women.

Conclusions: Larger SpO₂ reduction after exercise at low altitude was an independent risk for AMS upon ascent. Such an association was more robust in men than in women.

Trial registration: Chinese Clinical Trial Registration, ChiCTR1900025728. Registered 6 September 2019.

Background: p53 and DIRAS3 are tumor suppressors that are frequently silenced in tumors. In this study, we sought to determine whether the concurrent re-expression of p53 and DIRAS3 could effectively induce head and neck squamous cell carcinoma (HNSCC) cell death.

Methods: CAL-27 and SCC-25 cells were treated with Ad-DIRAS3 and rAd-p53 to induce re-expression of DIRAS3 and p53 respectively. The effects of DIRAS3 and p53 re-expression on the growth and apoptosis of HNSCC cells were examined by TUNEL assay, flow cytometric analysis and MTT. The effects of DIRAS3 and p53 re-expression on Akt phosphorylation, oncogene expression, and the interaction of 4E-BP1 with eIF4E were determined by real-time PCR, Western blotting and immunoprecipitation analysis. The ability of DIRAS3 and p53 re-expression to induce autophagy was evaluated by transmission electron microscopy, LC3 fluorescence microscopy and Western blotting. The effects of DIRAS3 and p53 re-expression on HNSCC growth were evaluated by using an orthotopic xenograft mouse model.

Results: TUNEL assay and flow cytometric analysis showed that the concurrent re-expression of DIRAS3 and p53 significantly induced apoptosis (P<0.001). MTT and flow cytometric analysis revealed that DIRAS3 and p53 reexpression significantly inhibited proliferation and induced cell cycle arrest (P<0.001). Mechanistically, the concurrent re-expression of DIRAS3 and p53 down-regulated signal transducer and activation of transcription 3 (STAT3) and upregulated p21^WAF1/CIP1 and Bax (P<0.001). DIRAS3 and p53 re-expression also inhibited Akt phosphorylation, increased the interaction of eIF4E with 4E-BP1, and reduced the expression of c-Myc, cyclin D1, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), epidermal growth factor receptor (EGFR) and Bcl-2 (P<0.001). Moreover, the concurrent re-expression of DIRAS3 and p53 increased the percentage of cells with GFP-LC3 puncta compared with that in cells treated with control adenovirus (50.00%±4.55% vs. 4.67%±1.25%, P<0.001). LC3 fluorescence microscopy and Western blotting further showed that DIRAS3 and p53 re-expression significantly promoted autophagic activity but also inhibited autophagic flux, resulting in overall impaired autophagy. Finally, the concurrent re-expression of DIRAS3 and p53 significantly decreased the tumor volume compared with the control group in a HNSCC xenograft mouse model [(3.12±0.75) mm³ vs. (189.02±17.54) mm³, P<0.001].

Conclusions: The concurrent re-expression of DIRAS3 and p53 is a more effective approach to HNSCC treatment than current treatment strategies.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused millions of infections and deaths worldwide since its emergence in December 2019. As there is little or no natural immunity in the human population or specific anti-COVID-19 drugs, researchers from the government, academia and industry are developing vaccines at an unprecedented speed to halt the pandemic. In this review, the results of animal experiments and clinical trials on several vaccine technical platforms are summarized, and several challenges are also discussed to further promote the development, evaluation and application of vaccines during the challenging situation of the global pandemic.

Compared with non-degradable materials, biodegradable biomaterials play an increasingly important role in the repairing of severe bone defects, and have attracted extensive attention from researchers. In the treatment of bone defects, scaffolds made of biodegradable materials can provide a crawling bridge for new bone tissue in the gap and a platform for cells and growth factors to play a physiological role, which will eventually be degraded and absorbed in the body and be replaced by the new bone tissue. Traditional biodegradable materials include polymers, ceramics and metals, which have been used in bone defect repairing for many years. Although these materials have more or fewer shortcomings, they are still the cornerstone of our development of a new generation of degradable materials. With the rapid development of modern science and technology, in the 21st century, more and more kinds of new biodegradable materials emerge in endlessly, such as new intelligent micro-nano materials and cell-based products. At the same time, there are many new fabrication technologies of improving biodegradable materials, such as modular fabrication, 3D and 4D printing, interface reinforcement and nanotechnology. This review will introduce various kinds of biodegradable materials commonly used in bone defect repairing, especially the newly emerging materials and their fabrication technology in recent years, and look forward to the future research direction, hoping to provide researchers in the field with some inspiration and reference.

Background: Generation of neurons is essential in cell replacement therapy for neurodegenerative disorders like Parkinson’s disease. Several studies have reported the generation of dopaminergic (DA) neurons from mouse and human fibroblasts by ectopic expression of transcription factors, in which genetic manipulation is associated with potential risks.

Methods: The small molecules and protein factors were selected based on their function to directly induce human fetal lung IMR-90 fibroblasts into DA neuron-like cells. Microscopical, immunocytochemical, and RT-qPCR analyses were used to characterize the morphology, phenotype, and gene expression features of the induced cells. The whole-cell patch-clamp recordings were exploited to measure the electrophysiological properties.

Results: Human IMR-90 fibroblasts were rapidly converted into DA neuron-like cells after the chemical induction using small molecules and protein factors, with a yield of approximately 95% positive TUJ1-positive cells. The induced DA neuron-like cells were immunopositive for pan-neuronal markers MAP2, NEUN, and Synapsin 1 and DA markers TH, DDC, DAT, and NURR1. The chemical induction process did not involve a neural progenitor/stem cell intermediate stage. The induced neurons could fire single action potentials, which reflected partially the electrophysiological properties of neurons.

Conclusions: We developed a chemical cocktail of small molecules and protein factors to convert human fibroblasts into DA neuron-like cells without passing through a neural progenitor/stem cell intermediate stage. The induced DA neuron-like cells from human fibroblasts might provide a cellular source for cell-based therapy of Parkinson’s disease in the future.

Background: Plasma expanders are widely used for acute normovolemic hemodilution (ANH). However, existing studies have not focused on large-volume infusion with colloidal plasma expanders, and there is a lack of studies that compare the effects of different plasma expanders.

Methods: The viscosity, hydrodynamic radius (R_h) and colloid osmotic pressure (COP) of plasma expanders were determined by a cone-plate viscometer, Zetasizer and cut-off membrane, respectively. Sixty male rats were randomized into five groups with Gelofusine (Gel), Hydroxyethyl Starch 200/0.5 (HES200), Hydroxyethyl Starch 130/0.4 (HES130), Hydroxyethyl Starch 40 (HES40), and Dextran 40 (Dex40), with 12 rats used in each group to build the ANH model. ANH was performed by the withdrawal of blood and simultaneous infusion of plasma expanders. Acid-base, lactate, blood gas and physiological parameters were detected.

Results: Gel had a lower intrinsic viscosity than HES200 and HES130 (P<0.01), but at a low shear rate in a mixture of colloids, red cells and plasma, Gel had a higher viscosity (P<0.05 or P<0.01, respectively). For hydroxyethyl starch plasma expanders, the COP at a certain concentration decreases from 11.1 mmHg to 6.1 mmHg with the increase of R_h from 10.7 nm to 20.2 nm. A severe ANH model, with the hematocrit of 40% of the baseline level, was established and accompanied by disturbances in acid-base, lactate and blood gas parameters. At the end of ANH and 60 min afterward, the Dex40 group showed a worse outcome in maintaining the acid-base balance and systemic oxygenation compared to the other groups. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) decreased significantly in all groups at the end of ANH. The DBP and MAP in the Dex40 group further decreased 60 min after the end of ANH. During the process of ANH, the Dex40 group showed a drop and recovery in SBP, DBP and MAP. The DBP and MAP in the HES200 group were significantly higher than those in the other groups at some time points (P<0.05 or P<0.01).

Conclusions: Gel had a low intrinsic viscosity but may increase the whole blood viscosity at low shear rates. R_h and COP showed a strong correlation among hydroxyethyl starch plasma expanders. Dex40 showed a worse outcome in maintaining the acid-base balance and systemic oxygenation compared to the other plasma expanders. During the process of ANH, Dex40 displayed a V-shaped recovery pattern for blood pressure, and HES200 had the advantage in sustaining the DBP and MAP at some time points.

Background: Recent studies reported that patients with coronavirus disease-2019 (COVID-19) might have liver injury. However, few data on the combined analysis and change patterns of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) have been shown.

Methods: This is a single-center retrospective study. A total of 105 adult patients hospitalized for confirmed COVID-19 in Beijing Ditan Hospital between January 12, and March 17, 2020 were included, and divided into mild group (n=79) and severe group (n=26). We compared liver functional test results between the two groups. Category of ALT change during the disease course was also examined.

Results: 56.2%(59/105) of the patients had unnormal ALT, AST, or total TBil throughout the course of the disease, but in 91.4%(96/105) cases the level of ALT, AST or TBil ≤3 fold of the upper limit of normal reference range (ULN). The overall distribution of ALT, AST, and TBil were all significantly difference between mild and severe group (P<0.05). The percentage of the patients with elevated both ALT and AST was 12.7%(10/79) in mild cases vs. 46.2%(12/26) in severe cases (P=0.001). 34.6%(9/26) severe group patients started to have abnormal ALT after admission, and 73.3%(77/105) of all patients had normal ALT before discharge.

Conclusions: Elevated liver function index is very common in patients with COVID-19 infection, and the level were less than 3×ULN, but most are reversible. The abnormality of 2 or more indexes is low in the patients with COVID-19, but it is more likely to occur in the severe group.

Background: The majority of Veterans Affair (VA) hospitals are in urban areas. We examined whether veterans residing in rural areas have lower mental health service use and poorer mental health status.

Methods: Veterans with at least 1 warzone deployment in central and northeastern Pennsylvania were randomly selected for an interview. Mental health status, including posttraumatic stress disorder (PTSD), major depression, alcohol abuse and mental health global severity, were assessed using structured interviews. Psychiatric service use was based on self-reported utilization in the past 12 months. Results were compared between veterans residing in rural and non-rural areas. Data were also analyzed using multivariate logistic regression to minimize the influence by confounding factors.

Results: A total of 1730 subjects (55% of the eligible veterans) responded to the survey and 1692 of them had complete geocode information. Those that did not have this information (n=38), were excluded from some analyses. Veterans residing in rural areas were older, more often of the white race, married, and experienced fewer stressful events. In comparison to those residing in non-rural areas, veterans residing in rural areas had lower global mental health severity scores; they also had fewer mental health visits. In multivariate logistic regression, rural residence was associated with lower service use, but not with PTSD, major depression, alcohol abuse, and global mental health severity score after adjusting confounding factors (e.g., age, gender, marital status and education).

Conclusions: Rural residence is associated with lower mental health service use, but not with poor mental health in veterans with former warzone deployment, suggesting rural residence is possibly protective.

Background: More people ascend to high altitude (HA) for various activities, and some individuals are susceptible to HA illness after rapidly ascending from plains. Acute mountain sickness (AMS) is a general complaint that affects activities of daily living at HA. Although genomic association analyses suggest that single nucleotide polymorphisms (SNPs) are involved in the genesis of AMS, no major gene variants associated with AMS-related symptoms have been identified.

Methods: In this cross-sectional study, 604 young, healthy Chinese Han men were recruited in June and July of 2012 in Chengdu, and rapidly taken to above 3700 m by plane. Basic demographic parameters were collected at sea level, and heart rate, pulse oxygen saturation (SpO₂), systolic and diastolic blood pressure and AMS-related symptoms were determined within 18–24 h after arriving in Lhasa. AMS patients were identified according to the latest Lake Louise scoring system (LLSS). Potential associations between variant genotypes and AMS/AMS-related symptoms were identified by logistic regression after adjusting for potential confounders (age, body mass index and smoking status).

Results: In total, 320 subjects (53.0%) were diagnosed with AMS, with no cases of high-altitude pulmonary edema or high-altitude cerebral edema. SpO₂ was significantly lower in the AMS group than that in the non-AMS group (P=0.003). Four SNPs in hypoxia-inducible factor-related genes were found to be associated with AMS before multiple hypothesis testing correction. The rs6756667 (EPAS1) was associated with mild gastrointestinal symptoms (P=0.013), while rs3025039 (VEGFA) was related to mild headache (P=0.0007). The combination of rs6756667 GG and rs3025039 CT/TT further increased the risk of developing AMS (OR=2.70, P<0.001).

Conclusions: Under the latest LLSS, we find that EPAS1 and VEGFA gene variants are related to AMS susceptibility through different AMS-related symptoms in the Chinese Han population; this tool might be useful for screening susceptible populations and predicting clinical symptoms leading to AMS before an individual reaches HA.

Trial registration: Chinese Clinical Trial Registration, ChiCTR-RCS-12002232. Registered 31 May 2012.