Novel coronavirus (2019-nCoV), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a pathogen that has caused a rapidly spreading pandemic all over the world. The primary mean of transmission is inhalation with a predilection for respiratory system involvement, especially in the distal airways. The disease that arises from this novel coronavirus is named coronavirus disease 2019 (COVID-19). COVID-19 may have a rapid and devastating course in some cases leading to severe complications and death. Radiological imaging methods have an invaluable role in diagnosis, follow-up, and treatment. In this review, radiological imaging findings of COVID-19 have been systematically reviewed based on the published literature so far. Radiologic reporting templates are also emphasized from a different point of view, considering specific distinctive patterns of involvement.

Multiple myeloma (MM) is the second most common hematologic malignancy, and is characterized by the clonal expansion of malignant plasma cells. Despite the recent improvement in patient outcome due to the use of novel therapeutic agents and stem cell transplantation, all patients eventually relapse due to clone evolution. B cell maturation antigen (BCMA) is highly expressed in and specific for MM cells, and has been implicated in the pathogenesis as well as treatment development for MM. In this review, we will summarize representative anti-BCMA immune therapeutic strategies, including BCMA-targeted vaccines, anti-BCMA antibodies and BCMA-targeted CAR cells. Combination of different immunotherapeutic strategies of targeting BCMA, multi-target immune therapeutic strategies, and adding immune modulatory agents to normalize anti-MM immune system in minimal residual disease (MRD) negative patients, will also be discussed.

On October 5th, 2020, Drs. Harvey J. Alter, Michael Houghton and Charles M. Rice were rewarded with Nobel Prize in Physiology or Medicine for "the discovery of hepatitis C virus (HCV)" . During the past 50 years, remarkable achievements have been made in treatment of HCV infection: it has changed from being a life-threatening chronic disease to being curable. In this commentary, we briefly summarized the milestone events in the "scientific journey" from the first report of non-A, non-B hepatitis and discovery of the pathogen (HCV) to final identification of efficacious direct-acting antivirals. Further, we address the challenges and unmet issues in this field.

In 2019, an outbreak of Mycoplasma pneumoniae (M. pneumoniae) occurred at a military academy in China. The attack rate (10.08%, 60/595) was significantly different among the units. High-intensity training and crowded environments to which cadets are exposed are the high risk factors for the outbreak of M. pneumoniae. In-time prevention and control measures effectively controlled the spread of the epidemic.

In October 2020, Dr. Emmanuelle Charpentier and Dr. Jennifer Doudna won the Nobel Prize in Chemistry for their pioneering work in precise genome editing using the CRISPR technology. Although CRISPR technology has developed rapidly in the last decade, there are still many uncertainties before eventual use in clinical settings. In this mini review, we summarize the current efforts in addressing the limitations of CRISPR technology and future directions.

Background: Our objective was to identify possible associations between clinical and laboratory variables and the risk of developing acute kidney injury (AKI) in severely injured patients admitted to the Intensive Care Unit (ICU) for whom creatine kinase (CK) levels were available.

Methods: For this retrospective observational study, we analyzed adult trauma patients admitted to the ICU from 2011 to 2015 at Fundación Valle del Lili (FVL) University Hospital. Our primary outcome was the incidence of AKI. Multivariate regression analysis was used to assess risk factors for this outcome.

Results: A total of 315 patients were included. The trauma mechanisms were blunt (n=130), penetrating (n=66) and blast (n=44) trauma. The median [interquartile range, IQR) of injury severity score (ISS) was 21 (16–29). AKI developed in 75 patients (23.8%). Multivariate regression analysis revealed that the thoracic abbreviated injury scale (AIS) value (median (IQR) in the AKI group: 3 (0–4)], Acute Physiology and Chronic Health Evaluation (APACHE II) score [median (IQR) in the AKI group: 18 (10–27)], CK greater than 5000 U/L, lactic acid concentration at admission, and dobutamine administration were independently associated with AKI.

Conclusions: We found that age, APACHE II score, thoracic trauma, lactic acidosis, and dobutamine administration were independently associated with AKI. Trauma surgeons need to be aware of the increased odds of AKI if one of these factors is identified during the evaluation and treatment of injured patients.

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.

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: 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: 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.