Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aimed to investigate the factors affecting the ...progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia.
Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher's exact test. Logistic regression analysis was performed to explore the risk factors for disease progression.
Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 51, 70 vs. 37 32, 41 years, U = 4.932, P = 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 37.8, 38.6 vs. 37.5 37.0, 38.4°C, U = 2.057, P = 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ = 5.611, P = 0.028) and respiratory rate (34 18, 48 vs. 24 16, 60 breaths/min, U = 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 14.3, 64.8 vs. 10.6 1.9, 33.1 mg/L, U = 1.315, P = 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ± 6.60 vs. 41.27 ± 4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio OR, 8.546; 95% confidence interval CI: 1.628-44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577-25.000; P = 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036-78.147, P = 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942-40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098-50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224-34.701, P = 0.028) were risk factors for disease progression.
Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature at admission, respiratory failure, albumin, and C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.
The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan, Hubei Province of China since December 2019. This study was performed to analyze the clinical ...characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease (COVID-19).
Clinical data were collected from two tertiary hospitals in Wuhan. A retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19 (death group) and we compare them with recovered patients (recovered group). Continuous variables were analyzed using the Mann-Whitney U test. Categorical variables were analyzed by χ test or Fisher exact test as appropriate.
Our study enrolled 109 COVID-19 patients who died during hospitalization and 116 recovered patients. The median age of the death group was older than the recovered group (69 62, 74 vs. 40 33, 57 years, Z = 9.738, P < 0.001). More patients in the death group had underlying diseases (72.5% vs. 41.4%, χ = 22.105, P < 0.001). Patients in the death group had a significantly longer time of illness onset to hospitalization (10.0 6.5, 12.0 vs. 7.0 5.0, 10.0 days, Z = 3.216, P = 0.001). On admission, the proportions of patients with symptoms of dyspnea (70.6% vs. 19.0%, χ = 60.905, P < 0.001) and expectoration (32.1% vs. 12.1%, χ = 13.250, P < 0.001) were significantly higher in the death group. The blood oxygen saturation was significantly lower in the death group (85 77, 91% vs. 97 95, 98%, Z = 10.625, P < 0.001). The white blood cell (WBC) in death group was significantly higher on admission (7.23 4.87, 11.17 vs. 4.52 3.62, 5.88 ×10/L, Z = 7.618, P < 0.001). Patients in the death group exhibited significantly lower lymphocyte count (0.63 0.40, 0.79 vs. 1.00 0.72, 1.27 ×10/L, Z = 8.037, P < 0.001) and lymphocyte percentage (7.10 4.45, 12.73% vs. 23.50 15.27, 31.25%, Z = 10.315, P < 0.001) on admission, and the lymphocyte percentage continued to decrease during hospitalization (7.10 4.45, 12.73% vs. 2.91 1.79, 6.13%, Z = 5.242, P < 0.001). Alanine transaminase (22.00 15.00, 34.00 vs. 18.70 13.00, 30.38 U/L, Z = 2.592, P = 0.010), aspartate transaminase (34.00 27.00, 47.00 vs. 22.00 17.65, 31.75 U/L, Z = 7.308, P < 0.001), and creatinine levels (89.00 72.00, 133.50 vs. 65.00 54.60, 78.75 μmol/L, Z = 6.478, P < 0.001) were significantly higher in the death group than those in the recovered group. C-reactive protein (CRP) levels were also significantly higher in the death group on admission (109.25 35.00, 170.28 vs. 3.22 1.04, 21.80 mg/L, Z = 10.206, P < 0.001) and showed no significant improvement after treatment (109.25 35.00, 170.28 vs. 81.60 27.23, 179.08 mg/L, Z = 1.219, P = 0.233). The patients in the death group had more complications such as acute respiratory distress syndrome (ARDS) (89.9% vs. 8.6%, χ = 148.105, P < 0.001), acute cardiac injury (59.6% vs. 0.9%, χ = 93.222, P < 0.001), acute kidney injury (18.3% vs. 0%, χ = 23.257, P < 0.001), shock (11.9% vs. 0%, χ = 14.618, P < 0.001), and disseminated intravascular coagulation (DIC) (6.4% vs. 0%, χ = 7.655, P = 0.006).
Compared to the recovered group, more patients in the death group exhibited characteristics of advanced age, pre-existing comorbidities, dyspnea, oxygen saturation decrease, increased WBC count, decreased lymphocytes, and elevated CRP levels. More patients in the death group had complications such as ARDS, acute cardiac injury, acute kidney injury, shock, and DIC.
Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress ...to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.
From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.
Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.
LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
The 2019 novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and ...analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak.
Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were retrospectively collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens.
None of the 137 patients (61 males, 76 females, aged 20-83 years, median age 57 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their conditions. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea.
The majority of patients with 2019-nCoV pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.
Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern ...globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.
We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.
Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.
A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Single‐crystalline Ni‐rich cathode (SC‐NCM) has attracted increasing interest owing to its greater capacity retention in advanced solid‐state lithium batteries (SSLBs), while suffers from severe ...interfacial instability during cycling. Here, via atomic layer deposition, Li3PO4 is introduced to coat SC‐NCM (L‐NCM), to suppress undesired side reaction and enhance interfacial stability. The dynamic degradation and surface regulation of SC‐NCM are investigated inside a working SSLB by in situ atomic force microscopy (AFM). We directly observe the uneven cathode electrolyte interphase (CEI) and surface defects on pristine SC‐NCM particle. Remarkably, the formed amorphous LiF‐rich CEI on L‐NCM maintains its initial structure upon cycling, and thus endows the battery with improved cycling stability and excellent rate capability. Such on‐site tracking provides deep insights into surface mechanism and structure–reactivity correlation of SC‐NCM, and thus benefits the optimizations of SSLBs.
Insights into the surface mechanism on the single‐crystalline LiNi0.5Co0.2Mn0.3O2 (SC‐NCM) cathode are disclosed by in situ atomic force microscopy in solid‐state batteries. Via atomic layer deposition, the Li3PO4 is introduced to coat SC‐NCM, leading to the uniform formation of LiF‐rich cathode electrolyte interphase and suppression of undesired side reaction, which endows batteries with enhanced interfacial stability, durability and dynamics.
Broadband near‐infrared (NIR) phosphor‐converted light emitting diode (pc‐LED) is demanded for wearable biosensing devices, but it suffers from low efficiency and low radiance. This study reports a ...broadband NIR Ca3‐xLuxHf2Al2+xSi1−xO12:Cr3+ garnet phosphor with emission intensity enhanced by 81.5 times. Chemical unit co‐substitution of Lu3+−Al3+ for Ca2+−Si4+ is responsible for the luminescence enhancement and further alters the crystal structure and electronic properties of the garnet. Using the optimized phosphor, a NIR pc‐LED with photoelectric efficiencies of 21.28%@10 mA, 15.75%@100 mA and NIR output powers of 46.09 mW@100 mA, 54.29 mW@130 mA is fabricated. The high power NIR light is observed to penetrate upper arms (≈8 cm). For application in NIR spectroscopy, the NIR pc‐LED is used as light source to measure transmission spectra of water, alcohol, and bovine hemoglobin solution. These results indicate the NIR garnet phosphor to be a promising candidate for NIR pc‐LED.
Luminescence enhancement of 81.5 times is achieved in Ca3‐xLuxHf2Al2+xSi1‐xO12:0.08Cr3+ garnet phosphor by chemical unit co‐substitution. The near‐infrared phosphor‐converted light emitting diode fabricated by the optimized phosphor shows 46.09 mW output under 100 mA current and is capable of penetrating the upper arm.
Inducing cancer differentiation is a promising approach to treat cancer. Here, we identified chlorogenic acid (CA), a potential differentiation inducer, for cancer therapy, and elucidated the ...molecular mechanisms underlying its differentiation-inducing effects on cancer cells.
Cancer cell differentiation was investigated by measuring malignant behavior, including growth rate, invasion/migration, morphological change, maturation, and ATP production. Gene expression was analyzed by microarray analysis, qRT-PCR, and protein measurement, and molecular biology techniques were employed for mechanistic studies. LC/MS analysis was the method of choice for chemical detection. Finally, the anticancer effect of CA was evaluated both
and
Results: Cancer cells treated with CA showed reduced proliferation rate, migration/invasion ability, and mitochondrial ATP production. Treating cancer cells with CA resulted in elevated SUMO1 expression through acting on its 3'UTR and stabilizing the mRNA. The increased SUMO1 caused c-Myc sumoylation, miR-17 family downregulation, and p21 upregulation leading to G
/G
arrest and maturation phenotype. CA altered the expression of differentiation-related genes in cancer cells but not in normal cells. It inhibited hepatoma and lung cancer growth in tumor-bearing mice and prevented new tumor development in naïve mice. In glioma cells, CA increased expression of specific differentiation biomarkers Tuj1 and GFAP inducing differentiation and reducing sphere formation. The therapeutic efficacy of CA in glioma cells was comparable to that of temozolomide. CA was detectable both in the blood and brain when administered intraperitoneally in animals. Most importantly, CA was safe even at very high doses.
CA might be a safe and effective differentiation-inducer for cancer therapy. "Educating" cancer cells to differentiate, rather than killing them, could be a novel therapeutic strategy for cancer.
Gastric cancer (GC) is a common form of malignant cancer in worldwide which has a poor prognosis. Despite recent improvements in the treatment of GC, the prognosis is not yet satisfactory for GC ...patients. CYT997, a novel microtubule-targeting agent, recently has been identified to be a promising anticancer candidate for the treatment of cancers; however, the effects of CYT997 in GC remain largely unknown.
Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry. The mitochondrial ROS were detected by confocal microscope and flow cytometry. Gastric cancer patient-derived xenograft (PDX) model was used to evaluate its antitumor activity of CYT997 in vivo.
CYT997 inhibited gastric cancer cell proliferation and induced cell apoptosis and triggered autophagy. CYT997 induced apoptosis through triggering intracellular mitochondrial ROS generation in GC cells. ROS scavengers N-acetylcysteine (NAC) and Mitoquinone (MitoQ) distinctly weakened CYT997-induced cell cycle G2/M arrest and apoptosis in GC cells. Pretreatment with autophagy inhibitor 3-MA promoted the effect of CYT997 on cells apoptosis. Mechanistically, CYT997 performed its function through regulation of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in GC cells. In addition, CYT997 inhibited growth of gastric cancer patient-derived xenograft (PDX) tumors.
CYT997 induces autophagy and apoptosis in gastric cancer by triggering mitochondrial ROS accumulation to silence JAK2/STAT3 pathway. CYT997 might be a potential antitumor drug candidate to treat GC.
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