Severe community-acquired pneumonia (SCAP) is associated with a substantial number of hospitalisations and deaths worldwide. Infection or co-infection patterns, along with their age dependence and ...clinical effects are poorly understood. We aimed to explore the causal and epidemiological characteristics by age, to better describe patterns of community-acquired pneumonia (CAP) and their association with severe disease.
National surveillance of CAP was conducted through a network of hospitals in 30 provinces in China from 2009–20 inclusive. Patients with CAP were included if they had evidence of acute respiratory tract, had evidence of pneumonia by chest radiography, diagnosis of pneumonia within 24 h of hospital admission, and resided in the study catchment area. For the enrolled patients with CAP, nasopharyngeal and oral swabs were taken and tested for eight viral pathogens; and blood, urine, or expectorated sputum was tested for six bacterial pathogens. Clinical outcomes, including SCAP, were investigated with respect to age and patterns of infections or co-infections by performing binary logistic regression and multivariate analysis.
Between January, 2009, and December, 2020, 18 807 patients with CAP (3771 20·05% with SCAP) were enrolled. For both children (aged ≤5 years) and older adults (aged >60 years), a higher overall rate of viral and bacterial infections, as well as viral–bacterial co-infections were seen in patients with SCAP than in patients with non-SCAP. For adults (aged 18–60 years), however, only a higher rate of bacterial–bacterial co-infection was observed. The most frequent pathogens associated with SCAP were respiratory syncytial virus (RSV; 21·30%) and Streptococcus pneumoniae (12·61%) among children, and influenza virus (10·94%) and Pseudomonas aeruginosa (15·37%) among older adults. Positive rates of detection of most of the tested pathogens decreased during 2020 compared with the 2009−19 period, except for RSV, P aeruginosa, and Klebsiella pneumoniae. Multivariate analyses showed SCAP was significantly associated with infection with human adenovirus, human rhinovirus, K pneumoniae, or co-infection of RSV and Haemophilus influenzae or RSV and Staphylococcus aureus in children and adolescents (aged <18 years), and significantly associated with infection with P aeruginosa, K pneumoniae, or S pneumoniae, or co-infection with P aeruginosa and K pneumoniae in adults (aged ≥18 years).
Both prevalence and infection pattern of respiratory pathogens differed between patients with SCAP and patients with non-SCAP in an age-dependent manner. These findings suggest potential advantages to age-related strategies for vaccine schedules, as well as clinical diagnosis, treatment, and therapy.
China Mega-Project on Infectious Disease Prevention and The National Natural Science Funds of China.
For the Chinese translation of the abstract see Supplementary Materials section.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
The incidence of well‑differentiated thyroid cancer (WDTC) is rapidly increasing. Poor survival follows distant metastasis (DM) and recurrence. In the present study, we aimed to analyze the ...expression alterations in different stages of WDTC and the regulatory mechanism of DM and the recurrence of DM. A male patient diagnosed with follicular thyroid cancer and distant metastasis in the eleventh thoracic vertebrae received total thyroidectomy and the removal of a metastatic lesion. A local relapse was found in the vertebrae after four‑time iodine‑131 treatment. We performed mRNA and microRNA microarray on the paracancerous, cancerous, metastatic and metastatic recurrent tissue. In combination with the data of The Cancer Genome Atlas (TCGA), we used bioinformatics approaches to analyze the common alterations and microRNA‑mRNA interactions among the processes of tumorigenesis and metastasis. Metastatic lesions and recurrent lesions were used to investigate the molecular mechanism of tumor evolution and recurrence in this case. A total of four mRNAs and two microRNAs were newly found to be related to patient survival in WDTC. The microRNA‑mRNA interactions were predicted for the overlapped mRNAs and microRNAs. Lineage deregulation of genes, such as C‑X‑C motif chemokine receptor 4 (CXCR4) and thyroglobulin (TG) were found from the tumorigenic stage to the metastatic stage. The ribosome pathway was highly enriched in the bone metastasis compared with the cancerous tissue. The downstreaming effects of p53 were impaired in the recurrent lesion due to deregulation of several functional genes. The integrated analysis with TCGA data indicated several prognostic markers and regulatory networks for potential treatment. Our results also provided possible molecular mechanisms in which the ribosome and p53 pathways may respectively contribute to bone metastasis and local recurrence of metastasis.
The thermal degradation of poly(vinyl chloride) (PVC) is inevitable during its processing and is directly related to the initial stage of the thermal stability of PVC. This paper focuses on the ...influence of the segment structures that include a conjugated polyene sequence structure and internal allylic chloride structure on the initial stage of the thermal degradation of PVC. The conjugated polyene sequence structure and internal allylic chloride structure were the structural models successfully constructed via thermal and alkali treatment methods through the long chain of PVC directly. Ultraviolet-visible spectroscopy (UV-Vis) was used to analyze the type and content of the conjugated polyene structure. Nuclear magnetic resonance spectroscopy ( 1 H-NMR) was used to determine the variation trend in the content of internal allylic chlorine structures because of the oxygen-containing structure excluded by Fourier-transform infrared spectrometer (FTIR) characterization. The thermal stability of the treated PVC was also determined through thermogravimetric analysis (TGA). The comparison between the two structural models revealed that the internal allylic chloride structure greatly influenced the initial thermal stability as an initiation point in the PVC chain, thereby leading to thermal instability.
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•The recombinant Chinese measles virus vaccine strain rMV-Hu191 induced efficient infection and oncolytic effects in human CRC both in vitro and in vivo.•rMV-Hu191 induced the caspase-dependent ...apoptosis and complete autophagy in CRC cells.•Autophagy served as a protective role in human CRC cells’ apoptosis induced by rMV-Hu191.•rMV-Hu191-induced autophagy and apoptosis were regulated by the PI3K/AKT signaling pathway in human CRC.
The potential therapeutic effects of oncolytic measles virotherapy have been verified against plenty of malignancies. However, the oncolytic effects and underlying mechanisms of the recombinant Chinese measles virus vaccine strain Hu191 (rMV-Hu191) against human colorectal cancer (CRC) remain elusive. In this study, the antitumor effects of rMV-Hu191 were evaluated in CRC both in vitro and in vivo. From our data, rMV-Hu191 induced remarkably caspase-dependent apoptosis and complete autophagy in vitro. In mice bearing CRC xenografts, tumor volume was remarkably suppressed and median survival was prolonged significantly with intratumoral treatment of rMV-Hu191. To gain further insight into the relationship of rMV-Hu191-induced apoptosis and autophagy, we utilized Rapa and shATG7 to regulate autophagy. Our data suggested that autophagy was served as a protective role in rMV-Hu191-induced apoptosis in CRC. PI3K/AKT signaling pathway as one of the common upstream pathways of apoptosis and autophagy was activated in CRC after treatment with rMV-Hu191. And inhibition of PI3K/AKT pathway using LY294002 was accompanied by enhanced apoptosis and decreased autophagy which suggested that PI3K/AKT pathway promoted rMV-Hu191-induced autophagy and inhibited rMV-Hu191-induced apoptosis. This is the first study to demonstrate that rMV-Hu191 could be used as a potentially effective therapeutic agent in CRC treatment. As part of the underlying cellular mechanisms, apoptosis and autophagy were involved in the oncolytic effects generated by rMV-Hu191. And the cross-talk between these two processes and the PI3K/AKT signaling pathway was well identified.
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In order to examine the prognostic significance of miR-33a in patients with hepatocellular carcinoma (HCC), total RNA was extracted from 149 HCC biopsies, 36 of which were paired with para-carcinoma ...tissues, and miR-33a expression was measured by reverse transcription-quantitative polymerase chain reaction. The results demonstrated that miR-33a expression was decreased in HCC biopsies compared with normal liver tissue samples. It was also demonstrated that miR-33a expression was significantly associated with tumor foci number. Furthermore, overall and progression-free survival time was decreased in patients expressing low miR-33a with multiple tumor foci. Taken together, the low expression of miR-33a may be a potential risk factor for HCC.
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: COVID-19 has been ravaging the globe for more than three years. Due to systemic immunosuppression of anti-tumor therapy, application of chemotherapy and adverse effects of surgery, the short- and ...long-term prognosis of cancer patients to COVID-19 are of significant concern.
: This research included three parts of data. The first part of the data came from the public database that covered Veneto residents. The second part of the data included participants in Guangzhou. The third part of the data was used for MR analysis. We assessed the associations by logistic, linear or Cox regression when appropriate.
: Lung cancer patients with COVID-19 had shorter progression-free survival (PFS) after COVID-19 (Model II: HR: 3.28, 95% CI: 1.6~6.72; Model III: HR: 3.39, 95% CI: 1.45~7.95), compared with lung cancer patients without COVID-19. Targeted therapy patients recovered from SARS-CoV-2 infection more quickly (Model I: β: -0.58, 95% CI: -0.75~-0.41; Model II: β: -0.59, 95% CI: -0.76~-0.41; Model III: β: -0.57; 95% CI: -0.75~-0.40).
: PFS in lung cancer patients is shortened by COVID-19. The outcome of COVID-19 in lung cancer patients was not significantly different from that of the healthy population. In lung cancer patients, targeted therapy patients had a better outcome of COVID-19, while chemotherapy patients had the worst.
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Highlights
Reduced graphene oxide/carbon foams (RGO/CFs) vdWs heterostructures are efficiently fabricated via a simple mixed-dimensional assembly strategy.
Linkage effect of optimized impedance ...matching and enhanced dielectric loss abilities endows the excellent microwave absorption performances of RGO/CFs vdWs heterostructures.
Multiple functions such as good corrosion resistance performances and outstanding thermal insulation capabilities can be integrated into RGO/CFs vdWs heterostructures.
Considering the serious electromagnetic wave (EMW) pollution problems and complex application condition, there is a pressing need to amalgamate multiple functionalities within a single substance. However, the effective integration of diverse functions into designed EMW absorption materials still faces the huge challenges. Herein, reduced graphene oxide/carbon foams (RGO/CFs) with two-dimensional/three-dimensional (2D/3D) van der Waals (vdWs) heterostructures were meticulously engineered and synthesized utilizing an efficient methodology involving freeze-drying, immersing absorption, secondary freeze-drying, followed by carbonization treatment. Thanks to their excellent linkage effect of amplified dielectric loss and optimized impedance matching, the designed 2D/3D RGO/CFs vdWs heterostructures demonstrated commendable EMW absorption performances, achieving a broad absorption bandwidth of 6.2 GHz and a reflection loss of − 50.58 dB with the low matching thicknesses. Furthermore, the obtained 2D/3D RGO/CFs vdWs heterostructures also displayed the significant radar stealth properties, good corrosion resistance performances as well as outstanding thermal insulation capabilities, displaying the great potential in complex and variable environments. Accordingly, this work not only demonstrated a straightforward method for fabricating 2D/3D vdWs heterostructures, but also outlined a powerful mixed-dimensional assembly strategy for engineering multifunctional foams for electromagnetic protection, aerospace and other complex conditions.
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OBJECTIVES:The present study was designed to explore the efficacy of locally injected thiamine or cobalamin in relieving itch or pain and improving the daily living activities among patients with ...herpetic itching.
METHODS:Eighty eligible patients with herpetic itching with a worst itching score of ≥4 were randomized to receive locally injected thiamine (B1 group), cobalamin (B12 group), lidocaine (LD group), or combination of thiamine and cobalamin (COB group) for 4 weeks. The treatment efficacy was assessed based on the patients’ pruritus and pain severity, global impression of change, and activities of daily living and quality of life.
RESULTS:After 7 days, thiamine yielded a significant itch relief, cobalamin yielded a significant pain relief, and their combination significantly relieved both pain and itch; which all continued till the endpoint (all Ps<0.001). However, lidocaine did not provide significant itch or pain relief than the other groups. Sixteen patients in the thiamine group achieved ≥30% itch reduction; 18 patients in the cobalamin group obtained ≥30% pain reduction; and 18 patients achieved ≥30% itch reduction and 19 patients obtained ≥30% pain reduction in the combination group. The activities of daily living and quality of life data at the endpoint were consistent with a significant benefit in the thiamine (P<0.05), cobalamin, and combination groups (both Ps<0.001).
DISCUSSION:Locally injected thiamine had a significant antipruritic effect, cobalamin had an analgesic effect, and their combination had the dual effect with no obvious synergies. This intervention was efficacious, tolerable, and safe for herpetic itching.
Functional elimination of p53 is a common feature of a large percentage of human malignancies. Here, we report the development of a pharmacological strategy aimed at restoring p53 function and its ...use for targeted therapy in p53-deficient mice. Specific inhibition of deubiquitinases ubiquitin-specific peptidase 14 (USP14) resulted in durable tumor regressions of autochthonous lymphomas and sarcomas in p53-deficient mice without affecting normal tissues, and therapeutic response was correlated with an increase in the ubiquitination of constitutive photomorphogenesis 9 (COP9) signalosome subunit 5 (COPS5), a key negative regulatory effector for p53. Inhibition of USP14 resulted in durable tumor regression through COPS5 deubiquitilation and a p53-dependent and -independent regulation mechanism by USP14. This series highlights the utility of proteasome deubiquitinating activity inhibition as a novel treatment paradigm for p53-deficient cancers. In addition, it provides preliminary evidence that inhibition of USP14 resulted in durable tumor regression through COPS5 deubiquitilation and p53-dependent and -independent regulation mechanism by USP14. These findings suggest that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target for patients with p53 deficiency.
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Background
Drugs that promote angiogenesis include statins, recombinant human granulocyte colony-stimulating factor, and stromal cell-derived factor-1. Low doses of atorvastatin could significantly ...increase the vascular expressions of endothelial growth factor, and the number of peripheral blood endothelial progenitor cells (EPCs), thus improving angiogenesis and local blood flow. G-CSF is an EPC-mobilization agent used in ischemia studies for targeting angiogenesis after cerebral ischemia via EPCs. In previous clinical trials, consistent conclusions have not been reached about the effectiveness of G-CSF on ischemic stroke. Therefore, the therapeutic effect of G-CSF and its combination with other medicines need further experimental verification. It is known that atorvastatin, rhG-CSF, and SDF-1 are considered the most promising neuroprotective candidates, but a comprehensive comparison of their effects is lacking.
Aims
To compare the effects of atorvastatin, stromal cell-derived factor-1, and recombinant human granulocyte colony-stimulating factor on ischemic stroke.
Methods
Adult male Sprague-Dawley rats were randomly allocated to three groups: normal, sham-operated, and middle cerebral artery occlusion operated. Middle cerebral artery occlusion operated rats were further allocated into saline, atorvastatin, recombinant human granulocyte colony-stimulating factor, and recombinant human granulocyte colony-stimulating factor + stromal cell-derived factor-1 groups. Neurological function evaluation, cerebral infarction and the blood–brain barrier integrity analysis, identification of angiogenic factors, assessment of angiogenesis, expression of growth-associated protein-43, neuroglobin, glial cell-derived neurotrophic factor, and cleaved caspase 3, were performed.
Results
Compared with atorvastatin or recombinant human granulocyte colony-stimulating factor alone, recombinant human granulocyte colony-stimulating factor + stromal cell-derived factor-1 treatment improved neurological performance, reduced cerebral infarction and blood–brain barrier disruption after stroke, and increased the content of stromal cell-derived factor-1, vascular endothelial growth factor, monocyte chemotactic protein 1, and basic fibroblast growth factor in peripheral blood. In addition, recombinant human granulocyte colony-stimulating factor + stromal cell-derived factor-1 promoted greater angiogenesis than atorvastatin or recombinant human granulocyte colony-stimulating factor alone and increased the expression of growth-associated protein-43, neuroglobin, and glial cell-derived neurotrophic factor, while decreasing the levels of cleaved caspase 3 in the brain after ischemic stroke.
Conclusions
Combination therapy with recombinant human granulocyte colony-stimulating factor and stromal cell-derived factor-1 is more effective than atorvastatin or recombinant human granulocyte colony-stimulating factor alone in protecting against stroke-induced damage and could be an optimal therapeutic strategy for stroke.
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