Factors influencing Frey syndrome after parotidectomy with acellular dermal matrix.

BACKGROUND: Frey syndrome, also known as ototemporal nerve syndrome or gustatory sweating syndrome, is one of the most common complications of parotid gland surgery. This condition is characterized by abnormal sensations in the facial skin accompanied by episodes of flushing and sweating triggered by cognitive processes, visual stimuli, or eating. AIM: To investigate the preventive effect of acellular dermal matrix (ADM) on Frey syndrome after parotid tumor resection and analyzed the effects of Frey syndrome across various surgical methods and other factors involved in parotid tumor resection. METHODS: Retrospective data from 82 patients were analyzed to assess the correlation between sex, age, resection sample size, operation time, operation mode, ADM usage, and occurrence of postoperative Frey syndrome. RESULTS: Among the 82 patients, the incidence of Frey syndrome was 56.1%. There were no significant differences in sex, age, or operation time between the two groups (P > 0.05). However, there was a significant difference between ADM implantation and occurrence of Frey syndrome (P < 0.05). ADM application could reduce the variation in the incidence of Frey syndrome across different operation modes. CONCLUSION: ADM can effectively prevent Frey syndrome and delay its onset.

Oral VV116 versus placebo in patients with mild-to-moderate COVID-19 in China: a multicentre, double-blind, phase 3, randomised controlled study.

BACKGROUND: Spread of SARS-CoV-2 led to a global pandemic, and there remains unmet medical needs in the treatment of Omicron infections. VV116, an oral antiviral agent that has potent activity against SARS-CoV-2, was compared with a placebo in this phase 3 study to investigate its efficacy and safety in patients with mild-to-moderate COVID-19. METHODS: This multicentre, double-blind, phase 3, randomised controlled study enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomisation to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2-5) or oral placebo (on the same schedule as VV116) for 5 days. Randomisation stratification factors included SARS-CoV-2 vaccination status and the presence of high-risk factors for progression to severe COVID-19. Inclusion criteria were a positive SARS-CoV-2 test, an initial onset of COVID-19 symptoms 3 days or less before the first study dose, and a score of 2 or more for any target COVID-19-related symptoms in the 24 h before the first dose. Patients who had severe or critical COVID-19 or who had taken any antiviral drugs were excluded from the study. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. Efficacy analyses were performed on a modified intention-to-treat population, comprising all patients who received at least one dose of VV116 or placebo, tested positive for SARS-CoV-2 nucleic acid, and did not test positive for influenza virus before the first dose. Safety analyses were done on all participants who received at least one dose of VV116 or placebo. This study was registered with ClinicalTrials.gov, NCT05582629, and has been completed. FINDINGS: A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04-1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04-1·33; p=0·0009), consistent with the interim analysis. The incidence of adverse events was similar between groups (242 [35·9%] of 674 patients vs 283 [42·1%] of 673 patients). INTERPRETATION: Among patients with mild-to-moderate COVID-19, VV116 significantly reduced the time to sustained clinical symptom resolution compared with placebo, with no observed safety concerns. FUNDING: Shanghai Vinnerna Biosciences, Shanghai Science and Technology Commission, and the National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Intravoxel incoherent motion diffusion-weighted MRI for predicting the efficacy of high-intensity focused ultrasound ablation for uterine fibroids.

Purpose: To evaluate the significance of magnetic resonance (MR) intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) quantitative parameters in predicting early efficacy of high-intensity focused ultrasound (HIFU) ablation of uterine fibroids before treatment. Method: 64 patients with 89 uterine fibroids undergoing HIFU ablation (51 sufficient ablations and 38 insufficient ablations) were enrolled in the study and completed MR imaging and IVIM-DWI before treatment. The IVIM-DWI parameters, including D (diffusion coefficient), D* (pseudo-diffusion coefficient), f (perfusion fraction) and relative blood flow (rBF) were calculated. The logistic regression (LR) model was constructed to analyze the predictors of efficacy. The receiver operating characteristic (ROC) curve was drawn to assess the model's performance. A nomograph was constructed to visualize the model. Results: The D value of the sufficient ablation group (931.0(851.5-987.4) × 10-6 mm2/s) was significantly lower than that of the insufficient ablation group (1052.7(1019.6-1158.7) × 10-6 mm2/s) (p<0.001). However, differences in D*, f, and rBF values between the groups were not significant (p>0.05). The LR model was constructed with D value, fibroid position, ventral skin distance, T2WI signal intensity, and contrast enhanced degree. The area under the ROC curve, specificity, and sensitivity of the model were 0.858 (95% confidence interval: 0.781, 0.935), 0.686, and 0.947. The nomogram and calibration curves confirmed that the model had excellent performance. Conclusion: The IVIM-DWI quantitative parameters can be used to predict early effects of HIFU ablation on uterine fibroids. A high D value before treatment may indicate that the treatment will be less effective in the early stages.

Lipid metabolism for predicting the recurrence of hypertriglyceridemic acute pancreatitis.

Rationale and objectives: To investigate the predictive value of lipid metabolism in predicting the recurrence of hypertriglyceridemic acute pancreatitis (HTG-AP). Materials and methods: A total of 892 patients were admitted to our hospital for acute pancreatitis (AP) from January 2017 to December 2020, of whom 198 diagnosed with HTG-AP were enrolled in this retrospective study. Demographic information, length of stay, smoking index, alcohol abuse, necrosis, severity, baseline lipid metabolism and other blood biochemical indicators were recorded. The risk factors of recurrence were evaluated using univariate and multivariate Cox proportional risk analyses, and the cumulative recurrence-free survival rate of patients were calculated using Kaplan Meier method and the differences between groups were compared using the log-rank test. Results: Univariate and multivariate analysis showed that triglyceride (hazard ratio, 2.421; 95% CI, 1.152-5.076; P = 0.020), non high-density lipoprotein (hazard ratio, 4.630; 95% CI, 1.692-12.658; P = 0.003) and apolipoprotein A1 (hazard ratio, 1.735; 95% CI, 1.093-2.754; P = 0.019) were important predictors for recurrence of HTG-AP. Subsequently, patients were divided into four groups according to the cut off values of triglyceride, non high-density lipoprotein and apolipoprotein A1. It was found that the cumulative recurrence-free survival rate of patients in highest-risk group or high-risk group was significantly lower than that of medium-risk group (P < 0.001, P = 0.003) or low risk group (P < 0.001). Conclusion: Serum triglycerides, non high-density lipoprotein and apolipoprotein A1 are independent predictors of recurrence in HTG-AP patients, which can provide reference for individualized treatment and prevention of recurrence in HTG-AP patients.

Case Report: Parvovirus B19 infection complicated by hemophagocytic lymphohistiocytosis in a heart-lung transplant patient.

Immunosuppressed patients can contract parvovirus B19, and some may experience hemophagocytic lymphohistiocytosis (HLH). Herein, we describe the first report of hemophagocytic lymphohistiocytosis in a heart-lung transplant patient with concomitant parvovirus B19 infection. The patient was treated with intravenous immune globulin (IVIG) and the features of HLH were remission. This instance emphasizes the significance of parvovirus B19 monitoring in transplant patients with anemia; if HLH complicates the situation, IVIG may be an adequate remedy. Finally, a summary of the development in diagnosing and managing parvovirus B19 infection complicated by HLH is provided.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Anti-C5a Antibody BDB-001 for Severe COVID-19: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Clinical Trial in Healthy Chinese Adults.

INTRODUCTION: Severe Coronavirus Disease 2019 (COVID-19) progresses with inflammation and coagulation, due to an overactive complement system. Complement component 5a (C5a) plays a key role in the complement system to trigger a powerful "cytokine and chemokine storm" in viral infection. BDB-001, a recombinant human immunoglobulin G4 (IgG4) that specially binds to C5a, has the potential to inhibit the C5a-triggered cytokine storm in treating COVID-19 patients and other inflammation diseases. Here, we have explored its safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy adults. This trial is registered with http://www.chinadrugtrials.org.cn/(CTR20200429 ). METHODS: Thirty-two enrolled participants were randomized into three single-dose cohorts (2, 4, and 8 mg/kg) and 1 multi-dose cohort (4 mg/kg), and received either BDB-001 or placebo (3:1) double-blindly. The safety and tolerability after administration were evaluated for 21 days for single-dose cohorts and 28 days for the multi-dose cohort. The pharmacokinetics of BDB-001 in plasma and pharmacodynamics as free C5a in plasma were analyzed. RESULTS: The incidence of drug-related adverse events (AEs) was low, and all AEs were mild or moderate: neither AEs ≥ 3 (NCI-Common Terminology Criteria For Adverse Events, CTCAE 5.0) nor serious adverse events (SAEs) were found. The area under the concentration-time curve from time zero to 480 h (AUC0-480h), that from time zero to infinity (AUCinf), and peak plasma concentration ©max) increased dose-dependently from 2 to 8 mg/kg in the single-dose cohorts and were characterized by a nonlinear pharmacokinetics of target-mediated drug disposal (TMDD). The accumulation index by AUC0-tau after five administrations (4 mg/kg) from the multi-dose cohort was 6.42, suggesting an accumulation effect. Furthermore, inhibition of C5a at the plasma level was observed. CONCLUSION: The results of this phase I study supported that BDB-001 is a potent anti-C5a inhibitor with safety, tolerability, and no immunogenicity. TRIAL REGISTRATION NUMBER: CTR20200429.

Development and validation of a combined model based on dual-sequence MRI radiomics for predicting the efficacy of high-intensity focused ultrasound ablation for hysteromyoma.

OBJECTIVES: To determine the value of dual-sequence magnetic resonance imaging (MRI)-based radiomics in predicting the efficacy of high-intensity focused ultrasound (HIFU) ablation for hysteromyoma. METHODS: A total of 142 patients with 172 hysteromyomas (95 hysteromyomas from the sufficient ablation group, and 77 hysteromyomas from the insufficient ablation group) were enrolled in the study. The clinical-radiological model was constructed with independent clinical-radiological risk factors, the radiomics model was constructed based on the optimal radiomics features of hysteromyoma from dual sequences, and the two groups of features were incorporated to construct the combined model. A fivefold cross validation procedure was adopted to validate these models. A nomogram was constructed, applying the combined model in the training cohort. The models were assessed with receiver operating characteristic (ROC) curves and integrated discrimination improvement (IDI). An independent test cohort comprising 40 patients was used to evaluate the performance of the optimal model. RESULTS: Among the three models, the average areas under the ROC curves (AUC) of the radiomics model and combined model were 0.803 (95% confidence interval (CI): 0.726-0.881) and 0.841 (95% CI: 0.772-0.909), which were better than the clinical-radiological model in the training cohort. The IDI showed that the combined model had the best prediction accuracy. The combined model also showed good discrimination in both the validation cohort (AUC = 0.834) and the independent test cohort (AUC = 0.801). CONCLUSION: The combined model based on the dual-sequence MRI radiomics is the most promising tool from our study to assist clinicians in predicting HIFU ablation efficacy.

Viral reactivation in the lungs of patients with severe pneumonia is associated with increased mortality, a multicenter, retrospective study.

Viral reactivation is widespread in patients with severe pneumonia, yet the landscape of viral reactivation in the lungs is not well-known. This study aims to assess the landscape and clinical features of viral reactivation in the early onset of severe pneumonia in ICU patients. The clinical data from 97 patients were collected retrospectively from the intensive care units of five teaching hospitals between June 2018 and July 2021. Metagenomic next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid (BALF) was performed at the onset of severe pneumonia. Cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), and Epstein-Barr virus (EBV) were the most common reactivated viruses in the lower respiratory tract of patients with severe pneumonia. After adjusting for the risk of confounding and competition of age, sex, sequential organ failure assessment, acute physiology chronic health assessment II and immunosuppression status, viral reactivation resulted in an overall 2.052-fold increase in 28-day all-cause mortality (95% CI: 1.004-4.194). This study showed that CMV, HSV-1, and EBV were the most common reactivated viruses in the lungs of patients with severe pneumonia. The existence of viral reactivations was associated with an increased risk of mortality. The simultaneous reactivation of multiple viruses needs to be considered in the design of clinical trials.

BMAL1/FOXA2-induced rhythmic fluctuations in IL-6 contribute to nocturnal asthma attacks.

The circadian clock is closely associated with inflammatory reactions. Increased inflammatory cytokine levels have been detected in the airways of nocturnal asthma. However, the mechanisms that contribute to the nocturnal increase in inflammatory responses and the relationship with circadian clock remain unknown. Methods: Inflammatory cytokine levels were measured in asthma patients with and without nocturnal symptoms. Allergic airway disease was induced in mice by ovalbumin (OVA), and different periods of light/dark cycles were used to induce circadian rhythm disorders. Serum shock was used to stimulate the rhythmic expression in human bronchial epidermal cells (16HBE). The expression and oscillation of circadian clock genes and inflammatory cytokines in 16HBE cells subjected to brain and muscle ARNT-like protein-1 (BMAL1) and Forkhead Box A2 (FOXA2) knockdown and treatment with a FOXA2 overexpression plasmid were assessed. Results: Serum IL-6 was found to be significantly higher in asthmatic patients with nocturnal symptoms than those without nocturnal symptoms. The OVA-induced asthma model with a circadian rhythm disorder and 16HBE cells treated with serum shock showed an increase in IL-6 levels and a negative correlation with BMAL1 and FOXA2. The knockdown of BMAL1 resulted in a lower correlation between IL-6 and other rhythm clock genes. Furthermore, knockdown of the BMAL1 and FOXA2 in 16HBE cells reduced the expression and rhythmic fluctuations of IL-6. Conclusions: Our findings suggest that there are increased IL-6 levels in nocturnal asthma resulting from inhibition of the BMAL1/FOXA2 signalling pathway in airway epithelial cells.

Short- and Long-Term Effects of Different Antibiotics on the Gut Microbiota and Cytokines Level in Mice.

Background: Antibiotics are the first line of treatment for infectious diseases. However, their overuse can increase the spread of drug-resistant bacteria. The present study analyzed the impact of different types of antibiotics on the gut microbiome and cytokines level of mice. Methods: A total of five groups of 8-week-old male BALB/c mice (n = 35) were treated with piperacillin-tazobactam (TZP), ceftriaxone (CRO), tigecycline (TGC), levofloxacin (LEV) or normal saline (Ctrl), respectively, for up to 4 weeks. Fecal samples were analyzed by bacterial 16S rRNA gene sequencing for bacterial identification. Blood samples were used for the determination of 23 serum cytokines using multiplex immunoassay. Results: Exposure to antibiotics was shown to affect the normal weight gain of mice. Significant changes in gut composition caused by TZP, CRO and TGC treatment included the decreased abundance of Bacteroidetes (p < 0.01), Muribaculaceae (p < 0.01) and Lachnospiraceae (p < 0.01), and the increased abundance of Proteobacteria (p < 0.05), Enterobacteriaceae (including Klebsiella and Enterobacter) (p < 0.01) and Enterococcaceae (including Enterococcus) (p < 0.01). After 4-week treatment, the TZP, CRO and LEV groups had significantly lower concentrations of several serum cytokines. Correlation analysis of the top 30 bacterial genera and cytokines showed that Enterococcus and Klebsiella were strongly positively correlated with tumor necrosis factor-α (TNF-α), interleukins (IL) IL-12p70 and IL-1ß. Desulfovibrio, Candidatus Saccharimonas, norank_f__norank_o__Clostridia_UCG-014, Lactobacillus, and Roseburia were strongly negatively correlated with these cytokines. Conclusion: This study demonstrates the effects of various antibiotics on the intestinal microflora and immune status of mice. Compared with TZP, CRO and TGC, LEV had minimal impact on the gut microbiota. In addition to TGC, long-term TZP, CRO and LEV intervention can lead to a decrease in serum cytokine levels, which may depend on the intestinal microflora, antibiotic used and the duration of treatment.

[Comparison of shaping ability of 4 nickel-titanium rotary instruments in preparation of curved root canals].

PRUPOSE: To compare the shaping ability of 4 nickel-titanium rotary instruments in preparation of curved root canals. METHODS: Forty extracted human maxillary first or second molars with mesiobuccal root canal curvature ranging from 20°-40° were selected. The teeth were randomly equally divided into 4 groups(n=10). Mesial root canals were separately prepared using Protaper Universal, Protaper Next, TF, and S3 nickel-titanium instruments. A series of preoperative and postoperative images were taken by Micro-CT． Mimics 17.0 software was used to analyze the following parameters: canal transportation, centering ratio values, root canal volume, volume of removed dentin, and canal/root width ratio. Data analysis was performed by using SPSS 20.0 software package. RESULTS: In terms of canal transportation after preparation at 1, 3 and 5 mm from the apex, Protaper Universal was more than the other three groups(P＜0.05). The centering ratio value of Protaper Universal was significantly smaller than that of the other three groups at 1 mm from the apex(P＜0.05). The amount of dentin removal was significantly different after instrumentation with the four test systems(P＜0.05). Protaper Universal had the highest mean volume of removed dentin. After preparation, all root canals had a diameter that was not larger than 39% of the root diameter at the coronal and middle segments. CONCLUSIONS: Under the conditions of this study, Protaper Next, TF, S3 systems seem to be better choices than Protaper Universal system in preparing curved root canals.

Interleukin-6 and granulocyte colony-stimulating factor as predictors of the prognosis of influenza-associated pneumonia.

BACKGROUND: Pneumonia is a common complication of influenza and closely related to mortality in influenza patients. The present study examines cytokines as predictors of the prognosis of influenza-associated pneumonia. METHODS: This study included 101 inpatients with influenza (64 pneumonia and 37 non-pneumonia patients). 48 cytokines were detected in the serum samples of the patients and the clinical characteristics were analyzed. The correlation between them was analyzed to identify predictive biomarkers for the prognosis of influenza-associated pneumonia. RESULTS: Seventeen patients had poor prognosis and developed pneumonia. Among patients with influenza-associated pneumonia, the levels of 8 cytokines were significantly higher in those who had a poor prognosis: interleukin-6 (IL-6), interferon-γ (IFN-γ), granulocyte colony-stimulating factor (G-CSF), monocyte colony-stimulating factor (M-CSF), monocyte chemoattractant protein-1 (MCP-1), monocyte chemoattractant protein-3, Interleukin-2 receptor subunit alpha and Hepatocyte growth factor. Correlation analysis showed that the IL-6, G-CSF, M-CSF, IFN-γ, and MCP-1 levels had positive correlations with the severity of pneumonia. IL-6 and G-CSF showed a strong and positive correlation with poor prognosis in influenza-associated pneumonia patients. The combined effect of the two cytokines resulted in the largest area (0.926) under the receiver-operating characteristic curve. CONCLUSION: The results indicate that the probability of poor prognosis in influenza patients with pneumonia is significantly increased. IL-6, G-CSF, M-CSF, IFN-γ, and MCP-1 levels had a positive correlation with the severity of pneumonia. Importantly, IL-6 and G-CSF were identified as significant predictors of the severity of influenza-associated pneumonia.

Analysis of Spatial Distribution of CVD and Multiple Environmental Factors in Urban Residents.

Cardiovascular disease (CVD) poses a serious threat to urban health with the development of urbanization. There are multifaceted and comprehensive influencing factors for CVD, so clarifying the spatial distribution characteristics of CVD and multiple environmental influencing factors is conducive to improving the active health intervention of urban environment and promoting the sustainable development of cities The spatial distribution characteristics of CVD deaths in a certain district, Bengbu City, Huaihe River Basin, China, in 2019 were explored, and the correlation between multiple environmental factors and CVD mortality was investigated in this study, to reveal the action mechanism of multiple environmental factors affecting the risk of mortality. Relevant studies have shown that (1) CVD deaths are characterized as follows: male deaths are more than females; the mortality is higher in those of higher age; most of them are unemployed; cardiocerebral infarction is the main cause of death; and the deaths are mainly distributed in the central city and near the old urban area. (2) The increased CVD mortality can be attributed to the increased density of restaurants and cigarette and wine shops around the residential area, the increased traffic volume, the dense residential and spatial forms, the low green space coverage, and the distance from rivers. Therefore, appropriate urban planning and policies can improve the active health interventions in cities and reduce CVD mortality.

Application of vascularized mucosal flap for early-medium-term tongue cancer and floor of mouth cancer defect repair: a preliminary study.

OBJECTIVES: This study aimed to assess the efficacy and safety of facial artery musculomucosal (FAMM) flap for small-medium tongue or floor of mouth defects caused by surgical resection of early-medium stage tongue or floor of mouth cancer. METHODS: A retrospective cohort study was conducted and included patients with early-medium stage tongue or floor of mouth cancer and reconstructed by FAMM flap or traditional free or axial flaps. Demographic data and surgery-related data were collected. Patients were followed up for 6 months and evaluated with satisfaction, maximal mouth opening, satisfactory contour and speech, and oral intake function at months 3 and 6. RESULTS: Forty-five patients were included, with 15 in the FAMM group and 30 in the flap group. All patients finished 3 months follow-up, and 1 in each group was lost to follow-up at month 6. All followed-up patients had no recurrence or metastasis. The FAMM group had a significantly shorter surgical time than the flap group (P<0.05). The flap group had significantly more donor sites that were uncomfortable compared with the FAMM group (P<0.05). There was no statistical significance on satisfaction, but the FAMM group had better outcomes on contour, speech, and oral intake function at month 6 than the flap group (P<0.05). The FAMM group had smaller maximal mouth opening than the flap group (P<0.05) at month 3 but equivalent maximal mouth opening at month 6 (P>0.05). CONCLUSIONS: FAMM flap has some advantages for small-medium tongue or floor of mouth defects caused by surgical resection of early-medium stage tongue or floor of mouth cancer, and it could be an ideal choice for clinical application.

Investigation of the Active Ingredients and Mechanism of Polygonum cuspidatum in Asthma Based on Network Pharmacology and Experimental Verification.

BACKGROUND: Polygonum cuspidatum is a Chinese medicine commonly used to treat phlegm-heat asthma. However, its anti-asthmatic active ingredients and mechanism are still unknown. The aim of this study was to predict the active ingredients and pathways of Polygonum cuspidatum and to further explore the potential molecular mechanism in asthma by using network pharmacology. METHODS: The active ingredients and their targets related to Polygonum cuspidatum were seeked out with the TCM systematic pharmacology analysis platform (TCMSP), and the ingredient-target network was constructed. The GeneCards, DrugBank and OMIM databases were used to collect and screen asthma targets, and then the drug-target-disease interaction network was constructed with Cytoscape software. A target protein-protein interaction (PPI) network was constructed using the STRING database to screen key targets. Finally, GO and KEGG analyses were used to identify biological processes and signaling pathways. The anti-asthmatic effects of Polygonum cuspidatum and its active ingredients were tested in vitro for regulating airway smooth muscle (ASM) cells proliferation and MUC5AC expression, two main symptoms of asthma, by using Real-time PCR, Western blotting, CCK-8 assays and annexin V-FITC staining. RESULTS: Twelve active ingredients in Polygonum cuspidatum and 479 related target proteins were screened in the relevant databases. Among these target proteins, 191 genes had been found to be differentially expressed in asthma. PPI network analysis and KEGG pathway enrichment analysis predicted that the Polygonum cuspidatum could regulate the AKT, MAPK and apoptosis signaling pathways. Consistently, further in vitro experiments demonstrated that Polygonum cuspidatum and resveratrol (one active ingredient of Polygonum cuspidatum) were shown to inhibit ASM cells proliferation and promoted apoptosis of ASM cells. Furthermore, Polygonum cuspidatum and resveratrol inhibited PDGF-induced AKT/mTOR activation in ASM cells. In addition, Polygonum cuspidatum decreased H2O2 induced MUC5AC overexpression in airway epithelial NCI-H292 cells. CONCLUSION: Polygonum cuspidatum could alleviate the symptoms of asthma including ASM cells proliferation and MUC5AC expression through the mechanisms predicted by network pharmacology, which provides a basis for further understanding of Polygonum cuspidatum in the treatment of asthma.

Evaluation of the safety and efficacy of using human menstrual blood-derived mesenchymal stromal cells in treating severe and critically ill COVID-19 patients: An exploratory clinical trial.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019 and has subsequently spread worldwide. Currently, there is no effective method to cure COVID-19. Mesenchymal stromal cells (MSCs) may be able to effectively treat COVID-19, especially for severe and critical patients. Menstrual blood-derived MSCs have recently received much attention due to their superior proliferation ability and their lack of ethical problems. Forty-four patients were enrolled from January to April 2020 in a multicenter, open-label, nonrandomized, parallel-controlled exploratory trial. Twenty-six patients received allogeneic, menstrual blood-derived MSC therapy, and concomitant medications (experimental group), and 18 patients received only concomitant medications (control group). The experimental group was treated with three infusions totaling 9 × 107 MSCs, one infusion every other day. Primary and secondary endpoints related to safety and efficacy were assessed at various time points during the 1-month period following MSC infusion. Safety was measured using the frequency of treatment-related adverse events (AEs). Patients in the MSC group showed significantly lower mortality (7.69% died in the experimental group vs 33.33% in the control group; P = .048). There was a significant improvement in dyspnea while undergoing MSC infusion on days 1, 3, and 5. Additionally, SpO2 was significantly improved following MSC infusion, and chest imaging results were improved in the experimental group in the first month after MSC infusion. The incidence of most AEs did not differ between the groups. MSC-based therapy may serve as a promising alternative method for treating severe and critical COVID-19.

Risk factors analysis of COVID-19 patients with ARDS and prediction based on machine learning.

COVID-19 is a newly emerging infectious disease, which is generally susceptible to human beings and has caused huge losses to people's health. Acute respiratory distress syndrome (ARDS) is one of the common clinical manifestations of severe COVID-19 and it is also responsible for the current shortage of ventilators worldwide. This study aims to analyze the clinical characteristics of COVID-19 ARDS patients and establish a diagnostic system based on artificial intelligence (AI) method to predict the probability of ARDS in COVID-19 patients. We collected clinical data of 659 COVID-19 patients from 11 regions in China. The clinical characteristics of the ARDS group and no-ARDS group of COVID-19 patients were elaborately compared and both traditional machine learning algorithms and deep learning-based method were used to build the prediction models. Results indicated that the median age of ARDS patients was 56.5 years old, which was significantly older than those with non-ARDS by 7.5 years. Male and patients with BMI > 25 were more likely to develop ARDS. The clinical features of ARDS patients included cough (80.3%), polypnea (59.2%), lung consolidation (53.9%), secondary bacterial infection (30.3%), and comorbidities such as hypertension (48.7%). Abnormal biochemical indicators such as lymphocyte count, CK, NLR, AST, LDH, and CRP were all strongly related to the aggravation of ARDS. Furthermore, through various AI methods for modeling and prediction effect evaluation based on the above risk factors, decision tree achieved the best AUC, accuracy, sensitivity and specificity in identifying the mild patients who were easy to develop ARDS, which undoubtedly helped to deliver proper care and optimize use of limited resources.

Case Report: Hemophagocytic Lymphocytosis in a Patient With Glutaric Aciduria Type IIC.

Hemophagocytic lymphocytosis (HLH) is a rare disease caused by inborn errors of immunity (IEI), secondary to infection, lymphoma or autoimmune disorders, but we often overlook the fact that HLH can be secondary to inborn errors of metabolism (IEM). Here, we describe a patient who was diagnosed with glutaric aciduria type IIC complicated by features suggestive of possible HLH. The diagnosis of glutaric aciduria type IIC, a IEM, was confirmed by whole exome sequencing. The patient was treated with coenzyme Q10 and riboflavin which effectively improved her liver function. During treatment, the patient developed severe anemia and thrombocytopenia. Persistent fever, splenomegaly, cytopenias, increased ferritin, hypertriglyceridemia, hypofibrinogenemia, and hemophagocytosis in the bone marrow pointed to the diagnosis of HLH; however, the patient eventually died of gastrointestinal bleeding. After other potential causes were ruled out, the patient was diagnosed with glutaric aciduria type IIC complicated by features suggestive of possible HLH. When cytopenias occurs in IEM patients, HLH is a possible complication that cannot be ignored. This case suggests a possible relationship between IEM and risk for immune dysregulation.

Qi-Xian Decoction Upregulated E-cadherin Expression in Human Lung Epithelial Cells and Ovalbumin-Challenged Mice by Inhibiting Reactive Oxygen Species-Mediated Extracellular-Signal-Regulated Kinase (ERK) Activation.

BACKGROUND Loss of the epithelial barrier is characterized by a reduction in E-cadherin expression and is a hallmark of asthma. Qi-xian decoction (QXT) is a Chinese medicinal formula that has been used to effectively treat asthma. This study aimed to investigate the effect of QXT on E-cadherin expression in human lung epithelial 16HBE cells and ovalbumin-challenged mice and to explore the underlying molecular mechanism. MATERIAL AND METHODS Ovalbumin (OVA)-induced mice were used as a model of asthma. Real-time PCR and Western blotting were utilized to examine mRNA and protein levels. Lung tissue reactive oxygen species (ROS) levels were evaluated using dichloro-dihydro-fluorescein diacetate (DCFH-DA). Serum superoxide dismutase (SOD) and the total antioxidant capacity (TAOC) were measured via enzyme-linked immunosorbent assay (ELISA)-based analyses. 16HBE cells were utilized to explore the effect of QXT or hydrogen peroxide (H2O2) on the expression of E-cadherin in vitro. RESULTS We found that QXT treatment increased E-cadherin expression and decreased extracellular-signal-regulated kinase (ERK) phosphorylation levels in the lung tissues of OVA-challenged mice. QXT also downregulated ROS levels and increased serum SOD and TAOC levels in OVA-challenged mice. In vitro studies demonstrated that increased ROS generation induced by H2O2 resulted in decreased E-cadherin expression levels in 16HBE cells, which was attenuated by inhibition of ERK signaling. Moreover, the H2O2-induced downregulation of E-cadherin expression, increased ROS generation, and ERK activation in 16HBE cells were restored by treatment with QXT water or ethanol extract. CONCLUSIONS These data demonstrate that one mechanism by which QXT protects against asthma is to restore E-cadherin expression in vivo and in vitro by inhibiting ROS-mediated ERK activation.