Porcine TLR8 signaling and its anti-infection function are disturbed by immune checkpoint receptor TIM-3 via inhibition of P13K-AKT pathway.

Toll-like receptor 8 (TLR8), an important innate immune receptor recognizing single stranded RNA and the antiviral imidazoquinoline compounds, can activate intracellular signaling pathway and produce an inflammatory response to kill and eliminate pathogens. However, the molecular regulation mechanisms of TLR8 signaling and its anti-infection activity are not fully elucidated. Our previous transcriptome analysis of porcine TLR8 (pTLR8) signaling suggested the immune checkpoint receptor TIM-3 as the potential regulator for pTLR8. Here we investigated TIM-3 in the regulation of pTLR8 signaling and its anti-infection activity. Our results showed that porcine TIM-3 is upregulated by pTLR8 signaling and TIM-3 inhibits pTLR8 signaling activity in a negative feedback way. Accordingly, TIM-3 disturbs pTLR8 mediated anti-bacterial and anti-viral activity. Mechanistically, TIM-3 suppresses PI3K-AKT pathway by inhibiting the TLR8-PI3K p85 interaction and subsequent AKT phosphorylation which is essential for TLR8 signaling and anti-infection activity. Therefore, our study reveals new insights into innate immune TLR8 signaling and its anti-infection function.

Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism.

Glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide hormone that is mainly expressed in the intestine and hypothalamus. In recent years, basic and clinical studies have shown that GLP-1 is closely related to lipid metabolism, and it can participate in lipid metabolism by inhibiting fat synthesis, promoting fat differentiation, enhancing cholesterol metabolism, and promoting adipose browning. GLP-1 plays a key role in the occurrence and development of metabolic diseases such as obesity, nonalcoholic fatty liver disease, and atherosclerosis by regulating lipid metabolism. It is expected to become a new target for the treatment of metabolic disorders. The effects of GLP-1 and dual agonists on lipid metabolism also provide a more complete treatment plan for metabolic diseases. This article reviews the recent research progress of GLP-1 in lipid metabolism.

Pectic polysaccharides from Lilium brownii and Polygonatum odoratum exhibit significant antioxidant effects in vitro.

Two pectic polysaccharides (WLBP-A3-c and WPOP-A-c) were isolated from traditional Chinese medicines Lilium brownii and Polygonatum odoratum, respectively. Monosaccharide composition, FT-IR, NMR and enzymatic analyses indicated that both WLBP-A3-c (59 kDa) and WPOP-A-c (33 kDa) contained homogalacturonan (HG), rhamnogalacturonan I (RG-I), and rhamnogalacturonan II (RG-II) domains, with mass ratios of 76.0: 17.2:6.8 and 76.8:10.6:12.6, respectively. Two RG-I domains WLBP-A3-c-DE1 and WPOP-A-c-DE1, correspondingly obtained from WLBP-A3-c and WPOP-A-c by enzymatic hydrolysis, were composed of repeating units of [→2)-α-L-Rhap-(1 â†’ 4)-α-D-GalpA-(1→] with highly branched neutral sugar side chains at the O-4 position of Rhap, which contained arabinan, galactan, arabinogalactan I and II (AG-I and AG-II) side chains in different proportions. By comparison, WPOP-A-c exhibited higher scavenging effects against DPPH, ABTS and hydroxy radicals than WLBP-A3-c, probably because WPOP-A-c had higher contents of GalA residues and HG domains and lower molecular weight. Among three domains of WPOP-A-c, HG domain possessed the strongest activity in decreasing ROS production and promoting SOD activity, resulting in the effective protection of HepG2 cells against H2O2-induced oxidative stress. Our study provides evidence that pectins rich in HG domains from Lilium brownii and Polygonatum odoratum exhibit significant antioxidant effects, which hold potential for the application in the field of healthcare products.

Magnetic resonance imaging based deep-learning model: a rapid, high-performance, automated tool for testicular volume measurements.

Background: Testicular volume (TV) is an essential parameter for monitoring testicular functions and pathologies. Nevertheless, current measurement tools, including orchidometers and ultrasonography, encounter challenges in obtaining accurate and personalized TV measurements. Purpose: Based on magnetic resonance imaging (MRI), this study aimed to establish a deep learning model and evaluate its efficacy in segmenting the testes and measuring TV. Materials and methods: The study cohort consisted of retrospectively collected patient data (N = 200) and a prospectively collected dataset comprising 10 healthy volunteers. The retrospective dataset was divided into training and independent validation sets, with an 8:2 random distribution. Each of the 10 healthy volunteers underwent 5 scans (forming the testing dataset) to evaluate the measurement reproducibility. A ResUNet algorithm was applied to segment the testes. Volume of each testis was calculated by multiplying the voxel volume by the number of voxels. Manually determined masks by experts were used as ground truth to assess the performance of the deep learning model. Results: The deep learning model achieved a mean Dice score of 0.926 ± 0.034 (0.921 ± 0.026 for the left testis and 0.926 ± 0.034 for the right testis) in the validation cohort and a mean Dice score of 0.922 ± 0.02 (0.931 ± 0.019 for the left testis and 0.932 ± 0.022 for the right testis) in the testing cohort. There was strong correlation between the manual and automated TV (R2 ranging from 0.974 to 0.987 in the validation cohort; R2 ranging from 0.936 to 0.973 in the testing cohort). The volume differences between the manual and automated measurements were 0.838 ± 0.991 (0.209 ± 0.665 for LTV and 0.630 ± 0.728 for RTV) in the validation cohort and 0.815 ± 0.824 (0.303 ± 0.664 for LTV and 0.511 ± 0.444 for RTV) in the testing cohort. Additionally, the deep-learning model exhibited excellent reproducibility (intraclass correlation >0.9) in determining TV. Conclusion: The MRI-based deep learning model is an accurate and reliable tool for measuring TV.

Radiological assessment of immunotherapy effects and immune checkpoint-related pneumonitis for lung cancer.

Immune checkpoint inhibitors (ICIs) therapy have revolutionized advanced lung cancer care. Interestingly, the host responses for patients received ICIs therapy are distinguishing from those with cytotoxic drugs, showing potential initial transient worsening of disease burden, pseudoprogression and delayed time to treatment response. Thus, a new imaging criterion to evaluate the response for immunotherapy should be developed. ICIs treatment is associated with unique adverse events, including potential life-threatening immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis) if treated patients are not managed promptly. Currently, the diagnosis and clinical management of ICI-pneumonitis remain challenging. As the clinical manifestation is often nonspecific, computed tomography (CT) scan and X-ray films play important roles in diagnosis and triage. This article reviews the complications of immunotherapy in lung cancer and illustrates various radiologic patterns of ICI-pneumonitis. Additionally, it is tried to differentiate ICI-pneumonitis from other pulmonary pathologies common to lung cancer such as radiation pneumonitis, bacterial pneumonia and coronavirus disease of 2019 (COVID-19) infection in recent months. Maybe it is challenging to distinguish radiologically but clinical presentation may help.

Determination of Paraquat in Arabidopsis Tissues and Protoplasts by UHPLC-MS/MS.

Paraquat is a cost-effective herbicide, widely used in many countries, that can induce severe oxidative stress in photosynthetic tissues. Studying plant herbicide resistance or antioxidant stress mechanisms requires determining the cellular paraquat level when plants are treated by paraquat. The traditional isotopic labeling method has the potential risk to cause problems to both human health and the environment. For radioisotope manipulation, special operation spaces and strict environmental inspection are also required. In addition, the radiolabeled paraquat is increasingly hard to buy due to the extended production cycle. Here, we describe a nonradioactive method to determine the paraquat level in a small number of Arabidopsis tissues or protoplasts, using a high resolution ultra-high-performance liquid chromatography (UHPLC)-mass spectrometry (MS)/MS method. This method is highly selective and sensitive, and more environmentally compatible and technically feasible than the isotope detection method.

Tree-based machine learning model for visualizing complex relationships between biochar properties and anaerobic digestion.

The ideal conditions for anaerobic digestion experiments with biochar addition are challenging to thoroughly study due to different experimental purposes. Therefore, three tree-based machine learning models were developed to depict the intricate connection between biochar properties and anaerobic digestion. For the methane yield and maximum methane production rate, the gradient boosting decision tree produced R2 values of 0.84 and 0.69, respectively. According to feature analysis, digestion time and particle size had a substantial impact on the methane yield and production rate, respectively. When particle sizes were in the range of 0.3-0.5 mm and the specific surface area was approximately 290 m2/g, corresponding to a range of O content (>31%) and biochar addition (>20 g/L), the maximum promotion of methane yield and maximum methane production rate were attained. Therefore, this study presents new insights into the effects of biochar on anaerobic digestion through tree-based machine learning.

A novel urokinase plasminogen activator receptor-targeted peptide-based probe for in-vivo molecular imaging of glioblastoma.

AIM: The urokinase plasminogen activator receptor (uPAR) is a promising biomarker for cancer diagnosis and therapy. We herein fabricated a new type of uPAR-targeted imaging probe Al18F-NOTA-VC and preliminarily evaluated its potential application in PET imaging of the glioma model in vivo. METHODS: Peptide VC was synthesized and identified by MALDI-TOF-MS. The IC50 between VC/precursor NOTA-VC and uPAR was then determined before the synthesis and purification of Al18F-NOTA-VC, followed by further studies of in-vitro properties of Al18F-NOTA-VC. Meanwhile, the AE105-based probe followed a similar procedure in-vitro test. Finally, the PET imaging properties, including uPAR-targeting ability and the metabolism of Al18F-NOTA-VC, were investigated. RESULTS: The VC and NOTA-VC were obtained successfully and demonstrated a good affinity with uPAR. Followed by Al18F labeling successfully, excellent properties, including the serum stability, water solubility, and specificity of Al18F-NOTA-VC, were obtained in-vitro test compared with AE105 based probe. An excellent tumor uptake and renal excretion data of Al18F-NOTA-VC were acquired from in-vivo U87MG tumor model PET imaging, consistent with the subsequent biodistribution study. CONCLUSION: In addition to the excellent specificity and high tumor/normal tissue contrast for uPAR-targeted PET imaging of U87MG tumor, Al18F-NOTA-VC possessed promising clearance ability by renal system route. These excellent properties facilitated Al18F-NOTA-VC to be a promising imaging agent for uPAR high-expressing tumors and, thus, provided a paradigm for developing peptide-based probes for uPAR-associated disease diagnosis.

Accelerated three-dimensional susceptibility weighted imaging of the whole spine of fetus at 3T.

OBJECTIVES: To investigate the image quality and capability of generalized auto-calibrating partially parallel acquisition (GRAPPA) accelerated Three-dimensional (3D) susceptibility weighted imaging (SWI) of the whole spine at 3T. METHODS: A total of 37 pregnant women (gestation age 22 to 39 weeks, average 29 ± 3 weeks) with suspected fetal vertebral anomalies by ultrasound (US) screening underwent 3.0T MR imaging with 3D SWI, conventional two-dimensional (2D) half-flourier acquisition single-shot turbo spin-echo (HASTE) and 3D true fast imaging with steady-state precession (True FISP). The acquisition time of each protocol was recorded. Signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) were determined in representative interest regions of fetal thoracic vertebrae and compared among three pulse sequences. Two radiologists rated image quality independently in random order on a 5-point scale. Kappa coefficients were computed to assess inter-observer reliability. Receiver operating characteristic curves were generated, and the area under the curve (AUC) was used to compare the diagnostic performance of each protocol in vertebral deformities. RESULTS: The acquisition time was 15 s for 3D-SWI and 17 s for 3D True FISP, significantly shorter than conventional HASTE (37 s; both P < 0.01). Of the three protocols, The SNR was highest on 3D True FISP, while the CNR was highest on 3D SWI. Visualization of all segments of the whole spine by 3D SWI was comparable with 3D True FISP. In contrast, 3D SWI and 3D True FISP depicted cervical and sacrococcygeal vertebrae better than HASTE. The weighted kappa statistic was 0.70-0.89 to evaluate the image quality of all segments of the whole spine, indicating good to excellent interobserver agreement. 3D SWI had the highest diagnostic performance for detecting fetal vertebral anomalies (AUC = 0.92). CONCLUSIONS: 3D-SWI is feasible for improved visualization of the whole fetal vertebral column and its congenital malformations with adequate image quality and high accuracy, thereby providing a supplementary method to conventional MR imaging.

Application of computer-aided detection (CAD) software to automatically detect nodules under SDCT and LDCT scans with different parameters.

PURPOSE: To explore the application of computer-aided detection (CAD) software on automatically detecting nodules under standard-dose CT (SDCT) and low-dose CT (LDCT) scans with different parameters including definition modes and blending levels of adaptive statistical iterative reconstruction (ASIR), whose influence was important to optimize radiology workflow serving for clinical work. MATERIALS AND METHODS: 117 patients underwent SDCT and LDCT scans. The comprehensive performance of CAD in detect pulmonary nodules including under different ASIR blending levels (0%, 60%, and 80%) and high-definition (HD) or non-HD modes were assessed. The true positive (TP) rate, false positive (FP) rate and the sensitivity were recorded. RESULTS: The stand-alone sensitivity of CAD system was 78.03% (515/660) in SDCT images and 70.15% (456/650) on LDCT images (p < 0.05). The sensitivity of CAD system to pulmonary nodules under non-HD mode was higher than that under HD mode. The detectability of nodules in images reconstructed with 60% and 80% ASIR was found significantly superior to that with 0% ASIR (p < 0.001). The overall sensitivity of CAD system on LDCT images reconstructed with 60% ASIR under HD mode was greater than that with 0% ASIR (p < 0.05), but lower than that with 80% ASIR. However, under non-HD mode, CAD demonstrated a comparable performance on LDCT images reconstructed with 60% ASIR to those reconstructed with 80% ASIR. CONCLUSION: Using the CAD system to detect pulmonary nodules on LDCT images with appropriate levels of ASIR could maintain high diagnostic sensitivity while reducing the radiation dose, which is useful to optimize the radiology workflow.

Engineering single-atom catalysts toward biomedical applications.

Due to inherent structural defects, common nanocatalysts always display limited catalytic activity and selectivity, making it practically difficult for them to replace natural enzymes in a broad scope of biologically important applications. By decreasing the size of the nanocatalysts, their catalytic activity and selectivity will be substantially improved. Guided by this concept, the advances of nanocatalysts now enter an era of atomic-level precise control. Single-atom catalysts (denoted as SACs), characterized by atomically dispersed active sites, strikingly show utmost atomic utilization, precisely located metal centers, unique metal-support interactions and identical coordination environments. Such advantages of SACs drastically boost the specific activity per metal atom, and thus provide great potential for achieving superior catalytic activity and selectivity to functionally mimic or even outperform natural enzymes of interest. Although the size of the catalysts does matter, it is not clear whether the guideline of "the smaller, the better" is still correct for developing catalysts at the single-atom scale. Thus, it is clearly a new, urgent issue to address before further extending SACs into biomedical applications, representing an important branch of nanomedicine. This review begins by providing an overview of recent advances of synthesis strategies of SACs, which serve as a basis for the discussion of emerging achievements in improving the enzyme-like catalytic properties at an atomic level. Then, we carefully compare the structures and functions of catalysts at various scales from nanoparticles, nanoclusters, and few-atom clusters to single atoms. Contrary to conventional wisdom, SACs are not the most catalytically active catalysts in specific reactions, especially those requiring multi-site auxiliary activities. After that, we highlight the unique roles of SACs toward biomedical applications. To appreciate these advances, the challenges and prospects in rapidly growing studies of SACs-related catalytic nanomedicine are also discussed in this review.

Reversible Bronchiectasis in COVID-19 Survivors With Acute Respiratory Distress Syndrome: Pseudobronchiectasis.

To retrospectively analyze whether traction bronchiectasis was reversible in coronavirus disease 2019 (COVID-19) survivors with acute respiratory distress syndrome (ARDS), and whether computed tomography (CT) findings were associated with the reversibility, 41 COVID-19 survivors with ARDS were followed-up for more than 4 months. Demographics, clinical data, and all chest CT images were collected. The follow-up CT images were compared with the previous CT scans. There were 28 (68%) patients with traction bronchiectasis (Group I) and 13 (32%) patients without traction bronchiectasis (Group II) on CT images. Traction bronchiectasis disappeared completely in 21 of the 28 (75%) patients (Group IA), but did not completely disappear in seven of the 28 (25%) patients (Group IB). In the second week after onset, the evaluation score on CT images in Group I was significantly higher than that in Group II (p = 0.001). The proportion of reticulation on the last CT images in Group IB was found higher than that in Group IA (p < 0.05). COVID-19 survivors with ARDS might develop traction bronchiectasis, which can be absorbed completely in most patients. Traction bronchiectasis in a few patients did not disappear completely, but bronchiectasis was significantly relieved. The long-term follow-up is necessary to further assess whether traction bronchiectasis represents irreversible fibrosis.

Preparing for future waves and pandemics: a global hospital survey on infection control measures and infection rates in COVID-19.

A survey of hospitals on three continents was performed to assess their infection control preparedness and measures, and their infection rate in hospital health care workers during the COVID-19 pandemic. All surveyed hospitals used similar PPE but differences in preparedness, PPE shortages, and infection rates were reported.

Prospective Study of Low- and Standard-dose Chest CT for Pulmonary Nodule Detection: A Comparison of Image Quality, Size Measurements and Radiation Exposure.

OBJECTIVE: To comprehensively and accurately analyze the out-performance of low-dose chest CT (LDCT) vs. standard-dose CT (SDCT). METHODS: The image quality, size measurements and radiation exposure for LDCT and SDCT protocols were evaluated. A total of 117 patients with extra-thoracic malignancies were prospectively enrolled for non-enhanced CT scanning using LDCT and SDCT protocols. Three experienced radiologists evaluated subjective image quality independently using a 5-point score system. Nodule detection efficiency was compared between LDCT and SDCT based on nodule characteristics (size and volume). Radiation metrics and organ doses were analyzed using Radimetrics. RESULTS: The images acquired with the LDCT protocol yielded comparable quality to those acquired with the SDCT protocol. The sensitivity of LDCT for the detection of pulmonary nodules (n=650) was lower than that of SDCT (n=660). There was no significant difference in the diameter and volume of pulmonary nodules between LDCT and SDCT (for BMI <22 kg/m2, 4.37 vs. 4.46 mm, and 43.66 vs. 46.36 mm3; for BMI ≥22 kg/m2, 4.3 vs. 4.41 mm, and 41.66 vs. 44.86 mm3) (P>0.05). The individualized volume CT dose index (CTDIvol), the size specific dose estimate and effective dose were significantly reduced in the LDCT group compared with the SDCT group (all P<0.0001). This was especially true for dose-sensitive organs such as the lung (for BMI <22 kg/m2, 2.62 vs. 12.54 mSV, and for BMI ≥22 kg/m2, 1.62 vs. 9.79 mSV) and the breast (for BMI <22 kg/m2, 2.52 vs. 10.93 mSV, and for BMI ≥22 kg/m2, 1.53 vs. 9.01 mSV) (P<0.0001). CONCLUSION: These results suggest that with the increases in image noise, LDCT and SDCT exhibited a comparable image quality and sensitivity. The LDCT protocol for chest scans may reduce radiation exposure by about 80% compared to the SDCT protocol.

MR Virtual Endoscopy of the Fetal Limb Anomalies Using Three-Dimensional Fast Imaging Employing Steady-State Acquisition Sequence.

OBJECTIVE: To retrospectively investigate the feasibility of magnetic resonance virtual endoscopy (MRVE) to visualize the normal limbs and limb deformities Methods: MR sequences included two-dimensional (2D) single fast spin-echo sequence and 2D and 3D steady-state procession fast imaging sequences. MRVE reconstruction was retrospectively performed by 2 radiologists in 32 fetuses in 30 pregnant women. The correlation between the radiologists for the virtual endoscopy threshold of MRVE was determined. Image quality and limb segment visibility were independently rated. Area under the receiver operating characteristics curve (AUC) of 2D MRI and MRVE was calculated. RESULTS: The mean virtual endoscopy threshold required for the visualization of the limb was 991.93 ± 12.13 and 991.83 ± 12.26 for 2 radiologists, respectively. The correlation between the radiologists for virtual endoscopy threshold was excellent (r = 0.933). The weighted kappa statistic was 0.96 for the evaluation of image quality of limb segments, indicating excellent interobserver agreement. Compared to that of 2D MRI alone, a higher AUC of 2D MRI with MRVE was achieved in detection of both upper and lower limb deformities (0.91 vs. 0.69 and 0.83 vs. 0.71, respectively). CONCLUSION: MRVE may display normal and abnormal fetal limb orientation and structures from multiple perspectives and provide incremental information for obstetrics.

Pectic polysaccharides from Radix Sophorae Tonkinensis exhibit significant antioxidant effects.

Two pectic polysaccharides (WRSP-A2b and WRSP-A3a) have been obtained from Radix Sophorae Tonkinensis and comparatively investigated in terms of their physical properties and antioxidant activities. Monosaccharide composition, FT-IR, NMR and enzymatic analyses indicate that both WRSP-A2b (13.6 kDa) and WRSP-A3a (44.6 kDa) consist of homogalacturonan (HG), rhamnogalacturonan I (RG-I) and rhamnogalacturonan II (RG-II) domains, with mass ratios of 0.9:1.8:1 and 2.3:2.9:1, respectively. The RG-I domains were further purified and characterized. Results show that WRSP-A2b contains a highly branched RG-I domain, primarily substituted with α-(1→5)-linked arabinans, whereas WRSP-A3a contains a small branched RG-I domain mainly composed of ß-(1→4)-linked galactan side chains. WRSP-A3a exhibits stronger antioxidant activity in scavenging different radicals than WRSP-A2b, a finding that may be due to its higher content of GalA residues and HG domains. Our results provide useful information for screening natural polysaccharide-based antioxidants from Radix Sophorae Tonkinensis.

Functional diagnosis of placenta accreta by intravoxel incoherent motion model diffusion-weighted imaging.

OBJECTIVES: To investigate the diagnostic value of intravoxel incoherent motion (IVIM) DWI for placenta accreta by comparing diffusion and perfusion characteristics of placentas with accreta lesions (APs) with those of normal placentas (NPs). METHODS: Twenty-five pregnant women with AP and 24 with NP underwent 3-T magnetic resonance examinations with IVIM-DWI. The perfusion percentage (f), pseudo-diffusion coefficient (D*), and diffusion coefficient (D) values were calculated from different ROIs: the entire-plane of the AP (AP-ROI) and NP (NP-ROI) and the implanted (IR-ROI) and non-implanted region (NIR-ROI) of the AP. The AP-ROIs and NP-ROIs were compared using covariance analysis; the IR-ROIs and NIR-ROIs were compared using the Wilcoxon signed-rank test. ROC curves were produced to evaluate the parameters for predicting placenta accreta. RESULTS: The f and D* values for the AP-ROIs ([45.0 ± 7.63]%, [11.64 ± 2.15]mm2/s) were significantly higher than those for the NP-ROIs ([31.85 ± 5.96]%, [9.04 ± 3.13]mm2/s) (both p < 0.05); the IR-ROIs (54.8%, 14.03 mm2/s) were also significantly higher than the NIR-ROIs (37.4%, 11.4 mm2/s) (both p < 0.05). No significant differences were found between the D values of the AP-ROIs and NP-ROIs (p > 0.05) or of the IR-ROIs and NIR-ROIs (p > 0.05). The areas under the curve for f and D* of the ROC curves were 0.93 and 0.79, respectively. CONCLUSIONS: These results suggest that the IVIM parameters f and D* can be used to quantitatively evaluate the higher perfusion of AP when compared with NP. Furthermore, IVIM may be a useful functional diagnostic technique to predict placenta accreta. KEY POINTS: • Intravoxel incoherent motion (IVIM) may be a useful diagnostic technique to quantitatively estimate the perfusion of the placenta. • The perfusion percentage (f) and pseudo-diffusion coefficient (D*) values differed significantly between placentas with accreta lesions and normal placentas. • ROC curves showed that perfusion percentage (f) and pseudo-diffusion coefficient (D*) values could accurately predict placenta accreta.

A Case of Critically Ill Infant of Coronavirus Disease 2019 With Persistent Reduction of T Lymphocytes.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) is becoming a global threat. However, our understanding of the clinical characteristics and treatment of critically ill pediatric patients and their ability of transmitting the coronavirus that causes COVID-19 still remains inadequate because only a handful pediatric cases of COVID-19 have been reported. METHODS: Epidemiology, clinical characteristics, treatment, laboratory data and follow-up information and the treatment of critically ill infant were recorded. RESULTS: The infant had life-threatening clinical features including high fever, septic shock, recurrent apnea, petechiae and acute kidney injury and persistent declined CD3+, CD4+ and CD8+ T cells. The duration of nasopharyngeal virus shedding lasted for 49 days even with the administration of lopinavir/ritonavir for 8 days. The CD3+, CD4+ and CD8+ T cells was partially recovered 68 days post onset of the disease. Accumulating of effector memory CD4+ T cells (CD4+TEM) was observed among T-cell compartment. The nucleic acid tests and serum antibody for the severe acute respiratory syndrome coronavirus 2 of the infant's mother who kept intimate contact with the infant were negative despite no strict personal protection. CONCLUSIONS: The persistent reduction of CD4+ and CD8+ T cells was the typical feature of critically ill infant with COVID-19. CD4+ and CD8+ T cells might play a key role in aggravating COVID-19 and predicts a more critical course in children. The prolonged nasopharyngeal virus shedding was related with the severity of respiratory injury. The transmission of SARS-CoV-2 from infant (even very critical cases) to adult might be unlikely.

Network pharmacology-based study of the protective mechanism of conciliatory anti-allergic decoction on asthma.

BACKGROUND: This study aimed to explore the underlying anti-asthma pharmacological mechanisms of conciliatory anti-allergic decoction (CAD) with a network pharmacology approach. METHODS: Traditional Chinese medicine related databases were utilized to screen the active ingredients of CAD. Targets of CAD for asthma treatment were also identified based on related databases. The protein-protein interaction network, biological function and KEGG pathway enrichment analysis, and molecular docking of the targets were performed. Furthermore, an asthma mouse model experiment involving HE staining, AB-PAS staining, and ELISA was also performed to assess the anti-asthma effect of CAD. RESULTS: There were 77 active ingredients in CAD, including quercetin, kaempferol, stigmasterol, luteolin, cryptotanshinone, beta-sitosterol, acacetin, naringenin, baicalin, and 48 related targets for asthma treatment, mainly including TNF, IL4, IL5, IL10, IL13 and IFN-γ, were identified with ideal molecular docking binding scores by network pharmacology analysis. KEGG pathway analysis revealed that these targets were directly involved in the asthma pathway, Th1 and Th2 cell differentiation, and signaling pathways correlated with asthma (NF-κB, IL17, T cell receptor, TNF, JAK-STAT signaling pathways, etc.). Animal experiments also confirmed that CAD could attenuate inflammatory cell invasion, goblet cell hyperplasia and mucus secretion. The levels of the major targets TNF-α, IL4, IL5, and IL13 can also be regulated by CAD in an asthma mouse model. CONCLUSION: The anti-asthma mechanism of CAD possibly stemmed from the active ingredients targeting asthma-related targets, which are involved in the asthma pathway and signaling pathways to exhibit therapeutic effects.

Early CT features and temporal lung changes in COVID-19 pneumonia in Wuhan, China.

PURPOSE: To analyse the high-resolution computed tomography (HRCT) early imaging features and the changing trend of coronavirus disease 2019 (COVID-19) pneumonia. MATERIALS AND METHODS: Forty-six patients with COVID-19 pneumonia who had an isolated lesion on the first positive CT were enrolled in this study. The following parameters were recorded for each lesion: sites, sizes, location (peripheral or central), attenuation (ground-glass opacity or consolidation), and other abnormalities (supply pulmonary artery dilation, air bronchogram, interstitial thickening, etc.). The follow-up CT images were compared with the previous CT scans, and the development of the lesions was evaluated. RESULTS: The lesions tended to be peripheral and subpleural. All the lesions exhibited ground-glass opacity with or without consolidation. A higher proportion of supply pulmonary artery dilation (89.13 % [41/46]) and air bronchogram (69.57 % [32/46]) were found. Other findings included thickening of the intralobular interstitium and a halo sign of ground glass around a solid nodule. Cavitation, calcification or lymphadelopathy were not observed. The reticular patterns were noted from the 14 days after symptoms onset in 7 of 20 patients (45 %). At 22-31 days, the lesions were completely absorbed only in 2 of 7 patients (28.57 %). CONCLUSION: The typical early CT features of COVID-19 pneumonia are ground-glass opacity, and located peripheral or subpleural location, and with supply pulmonary artery dilation. Reticulation was evident after the 2nd week and persisted in half of patients evaluated in 4 weeks after the onset. Long-term follow-up is required to determine whether the reticulation represents irreversible fibrosis.