The Overlap Subgroup of Functional Dyspepsia Exhibits More Severely Impaired Gastric and Autonomic Functions.

GOALS: A combination of multiple tests was introduced to noninvasively investigate the differences in pathophysiologies among functional dyspepsia (FD) subgroups, including postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and overlap. BACKGROUND: It has not been extensively evaluated whether different pathophysiologies are involved in FD subgroups. STUDY: This multicenter study included 364 FD patients fulfilling Rome IV criteria and 47 healthy controls. A combined noninvasive gastric and autonomic function test was performed: The electrogastrogram and electrocardiogram were recorded simultaneously in the fasting state and after a drink test. Symptoms after drinking were recorded using visual analog scale. RESULTS: (1) Compared with HC, FD patients showed a decreased maximum tolerable volume (MTV) ( P <0.01) and percentage of normal gastric slow waves [normal gastric slow waves (%NSW)] ( P <0.01), and increased postdrinking symptoms, anxiety ( P <0.01), and depression ( P <0.01). The drink reduced %NSW in both FD patients and HC; however, the effect was more potent in patients. (2) The PDS and overlap groups displayed a reduced MTV ( P <0.05). The overlap group exhibited a higher symptom score at 30 minutes after drinking, and higher anxiety and depression scores, and a higher sympathovagal ratio than the EPS ( P <0.05 for all) and PDS ( P <0.01 for all). (3) In the PDS subgroup, the MTV, postprandial sympathovagal ratio, and depression were associated with the overall dyspepsia symptom scale (DSS, P =0.034, 0.021, 0.043, respectively). No significant associations were found in the other 2 subgroups. CONCLUSIONS: The combination of multiple tests can detect pathophysiological abnormities in FD patients. Overall, patients with overlap symptoms display more severe pathophysiologies.

The Short-Term Efficacy of Bifidobacterium Quadruple Viable Tablet in Patients With Diarrhea-Predominant Irritable Bowel Syndrome: Potentially Mediated by Metabolism Rather Than Diversity Regulation.

INTRODUCTION: The therapeutic effect of probiotics for irritable bowel syndrome (IBS) was controversial. This study aims to evaluate the short-term efficacy of Bifidobacterium quadruple viable tablet in patients with diarrhea-predominant IBS and explore factors associated with response to probiotics. METHODS: A randomized, double-blind, placebo-controlled, multicenter trial was performed in 15 hospitals. A total of 290 patients who fulfilled the eligibility criteria were assigned to the probiotics or placebo group randomly with a ratio of 1:1 for a 4-week treatment and a 2-week follow-up. The primary outcome was the response rate. It was regarded as the proportion of patients with composite responses of improvement in both abdominal pain and diarrhea simultaneously. RESULTS: After 4-week continuous administration, the response rates of the probiotics and the placebo were 67.59% and 36.55%, respectively ( P < 0.001). In the probiotics, those with higher abdominal pain scores (2.674 [1.139-6.279]) were more likely to respond, but responders in placebo had lower Hamilton Depression Scale score (0.162 [0.060-0.439]), lower Hamilton Anxiety Scale score (0.335 [0.148-0.755]), and higher degree of bloating (2.718 [1.217-6.074]). Although the diversity of the microbiota was not significantly changed by probiotics, the abundance of bacteria producing short-chain fatty acids (SCFAs), including Butyricimonas ( P = 0.048), Pseudobutyrivibrio ( P = 0.005), Barnesiella ( P = 0.020), and Sutterella ( P = 0.020), and the concentration of SCFAs including butyric acid ( P = 0.010), valeric acid ( P = 0.019), and caproic acid ( P = 0.046) in feces increased. DISCUSSION: A Bifidobacterium quadruple viable tablet had a significant short-term efficacy for the treatment of diarrhea-predominant IBS and was more effective in patients with higher abdominal pain scores. This kind of probiotics could improve the abundance of several bacteria producing SCFAs and the concentration of fecal SCFAs compared with placebos.

An iron oxide nanoworm hybrid on an interdigitated microelectrode silica surface to detect abdominal aortic aneurysms.

An abdominal aortic aneurysm (AAA) is abnormal swelling in the abdominal aorta and a prevalent life-threatening disease. This research introduces a new interdigitated microelectrode (IDME)-sensing surface modified by iron oxide nanoworms (IONWs) for detecting the AAA biomarker insulin-like growth factor-1 (IGF1). A sandwich pattern was formulated with the IGF1 aptamer and IGFBP1 (IGF binding protein-1) on the IONW-constructed IDME hybrid to identify IGF1. The surface morphology of the IONWs revealed a uniform distribution of worm-like structures (80-100 nm) as confirmed by FESEM and FETEM analyses. Further, the presence of the major elements, Fe and O, was confirmed by EDX and XPS studies. The crystal planes that appeared in the IONW reflect cubic magnetite. IONW-modified IDME attained a limit of detection for IGF1 of 1 fM (3σ) with an aptamer-IGF1-IGFBP1 sandwich. This sandwich with IGFBP1 enhanced the current level at all concentrations of IGF1 and displayed linearity in the range 1 fM to 100 pM with a determination coefficient of R2 = 0.9373 [y = 3.38221x - 4.79]. Control experiments with complementary aptamer sequences, IGF2 and IGFBP3 did not show notable signal changes, indicating the specific detection of IGF1. This IONW constructed electrode helps to achieve the detection of low amounts of IGF1 and diagnose AAA at the stage prior to rupture.

Risk factors for the critical illness in SARS-CoV-2 infection: a multicenter retrospective cohort study.

BACKGROUND: Prior studies reported that 5 ~ 32% COVID-19 patients were critically ill, a situation that poses great challenge for the management of the patients and ICU resources. We aim to identify independent risk factors to serve as prediction markers for critical illness of SARS-CoV-2 infection. METHODS: Fifty-two critical and 200 non-critical SARS-CoV-2 nucleic acid positive patients hospitalized in 15 hospitals outside Wuhan from January 19 to March 6, 2020 were enrolled in this study. Multivariable logistic regression and LASSO logistic regression were performed to identify independent risk factors for critical illness. RESULTS: Age older than 60 years, dyspnea, respiratory rate > 24 breaths per min, leukocytosis > 9.5 × 109/L, neutrophilia > 6.3 × 109/L, lymphopenia < 1.1 × 109/L, neutrophil-to-lymphocyte ratio > 3.53, fibrinogen > 4 g/L, d-dimer > 0.55 µg/mL, blood urea nitrogen > 7.1 mM, elevated aspartate transaminase, elevated alanine aminotransferase, total bilirubin > 21 µM, and Sequential Organ Failure Assessment (SOFA) score ≥ 2 were identified as risk factors for critical illness. LASSO logistic regression identified the best combination of risk factors as SOFA score, age, dyspnea, and leukocytosis. The Area Under the Receiver-Operator Curve values for the risk factors in predicting critical illness were 0.921 for SOFA score, 0.776 for age, 0.764 for dyspnea, 0.658 for leukocytosis, and 0.960 for the combination of the four risk factors. CONCLUSIONS: Our findings advocate the use of risk factors SOFA score ≥ 2, age > 60, dyspnea and leukocytosis > 9.5 × 109/L on admission, alone or in combination, to determine the optimal management of the patients and health care resources.

Exploration of the utility of different doses of Qingfei Dayuan granules: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Clinical studies have confirmed that Qingfei Dayuan (QFDY) granules are effective in the treatment of influenza and upper respiratory tract infections (URTIs) caused by pulmonary heat-toxin syndrome (PHTS). Granules of Chinese medicine formulations have become a widely used dosage form in clinical practice. With the continuous optimization of extraction technology, the advantages of Chinese medicine granules have been gradually demonstrated, but the price of Chinese medicine granules is generally higher than that of traditional dosage forms of Chinese medicine, and we support the rational use of the appropriate dosage of QFDY for patients with these conditions. Therefore, we set up half of the conventional dose as the low dose group, and designed the three-arm study to rigorously compare the efficacy difference of low-dose QFDY, QFDY and the placebo group, with the expectation of providing scientific support for the rational selection of the dose and the safe and effective use of the medicine in clinical practice. METHODS: We recruited 108 patients with clinical diagnoses of influenza and URTIs caused by PHTS to receive treatment at six hospitals in Hubei, China. Using a centralized randomization system, patients were randomly assigned at a 1:1:1 ratio to the QFDY, low-dose QFDY, or placebo control groups to receive the corresponding drug, and the study physicians, subjects, outcome assessors, and statisticians were unaware of group assignments. The primary outcome was the time to complete fever relief. Secondary outcomes included the efficacy of Chinese medicine in alleviating signs and symptoms and the disappearance rate of individual symptoms. Adverse events were monitored throughout the trial. RESULTS: A total of 108 patients were recruited. A total of 106 patients were included in the full analysis set (FAS). In the FAS analysis, there was no statistically significant difference in baseline of the three groups before treatment (P > 0.05). 1. Regarding the median time to complete fever relief, the QFDY, low-dose QFDY and placebo groups had median times of 26 h, 40 h and 48 h, respectively. The QFDY group had a shorter time to complete fever relief than the placebo group, and the difference was statistically significant (P < 0.05), while the low-dose QFDY group had a shorter time than the placebo group, but the difference was not statistically significant (P > 0.05). 2. In terms of the total efficacy of Chinese medicine in alleviating symptoms at the end of three full days of treatment, as well as the cure rate of red and sore throat, stuffy and runny nose, and sneezing, QFDY and low-dose QFDY were superior to the placebo, and the differences were statistically significant (P < 0.01). There was no statistical significance in the comparison between the QFDY group and the low-dose QFDY group (P > 0.05). 3. In terms of the headache cure rate after three full days of treatment, QFDY was superior to the placebo, with a statistically significant difference (P < 0.05), and there was no significant efficacy of low-dose QFDY. 4. Safety comparisons showed no serious adverse events and 30 minor adverse events, which were not clinically considered to be related to the drug and were not statistically significant. CONCLUSIONS: In the treatment of patients with influenza and URTIs caused by PHTS, which are mainly characterized by clinical symptoms such as red and sore throat, stuffy and runny nose, and sneezing, when fever is not obvious or low-grade fever is present, the use of low-dose QFDY to simply alleviate the clinical symptoms is recommended and preferred. Moreover, with its good safety profile, QFDY can be used in the treatment of patients with influenza and URTIs caused by PHTS, which can effectively shorten the duration of fever, significantly increase the total efficacy of Chinese medicine in alleviating symptoms after 3 days of treatment, and accelerate the recovery of symptoms such as red and sore throat, stuffy and runny nose, sneezing, and headache, etc. Clinical Trial Registration: http://www.chictr.org.cn. TRIAL NUMBER: ChiCTR2100043449. Registered on 18 February 2021.

Effectiveness and safety of Qingfei Dayuan granules for treating influenza and upper respiratory tract infections manifested by the pulmonary heat-toxin syndrome: A multicenter, randomized, double-blind, placebo-controlled trial.

Background: Patients diagnosed with influenza and upper respiratory tract infections (URTIs) have similar clinical manifestations and biochemical indices and a low detection rate of viral pathogens, mixed infection with diverse respiratory viruses, and targeted antiviral treatment difficulty in the early stage. According to the treatment strategy of "homotherapy for heteropathy" in traditional Chinese medicine (TCM), different diseases with the same clinical symptoms can be treated with the same medicines. Qingfei Dayuan granules (QFDY), a type of Chinese herbal preparation included in the TCM Diagnosis and Treatment Protocol for COVID-19 of Hubei Province issued by the Health Commission of Hubei Province in 2021, are recommended for patients suffering from COVID-19 with symptoms of fever, cough, and fatigue, among others. Additionally, recent studies have shown that QFDY effectively alleviates fever, cough, and other clinical symptoms in patients with influenza and URTIs. Materials and methods: The study was designed as a multicenter, randomized, double-blind, placebo-controlled clinical trial for treatment for influenza and URTIs manifested by pulmonary heat-toxin syndrome (PHTS) with QFDY. A total of 220 eligible patients were enrolled from eight first-class hospitals in five cities of Hubei Province in China and randomly assigned to receive either 15 g of QFDY or a placebo three times a day for 5 days. The primary outcome was the complete fever relief time. Secondary outcomes included efficacy evaluation of TCM syndromes, scores of TCM syndromes, cure rate of each single symptom, incidence of comorbidities and progression to severe conditions, combined medications, and laboratory tests. Safety evaluations mainly involved adverse events (AEs) and changes in vital signs during the study. Results: Compared with the placebo group, the complete fever relief time was shorter in the QFDY group, 24 h (12.0, 48.0) in the full analysis set (FAS) and 24 h (12.0, 49.5) in the per-protocol set (PPS) (p ≤ 0.001). After a 3-day treatment, the clinical recovery rate (22.3% in the FAS and 21.6% in the PPS) and cure rate of cough (38.6% in the FAS and 37.9% in the PPS), a stuffy and running nose, and sneezing (60.0% in the FAS and 59.5% in the PPS) in the QFDY group were higher than those in the placebo group (p < 0.05). The number of patients taking antibiotics for more than 24 h in the placebo group (nine cases) was significantly higher than that in the QFDY group (one case) (p < 0.05). There were no significant differences between the two groups in terms of scores of TCM syndromes, incidence of comorbidities or progression to severe conditions, combined use of acetaminophen tablets or phlegm-resolving medicines, and laboratory tests (p > 0.05). Meanwhile, no significant difference was found in the incidence of AEs and vital signs between the two groups (p > 0.05). Conclusion: The trial showed that QFDY was an effective and safe treatment modality for influenza and URTIs manifested by PHTS because it shortened the complete fever relief time, accelerated clinical recovery, and alleviated symptoms such as cough, a stuffy and running nose, and sneezing during the course of treatment. Clinical trial registration: https://www.chictr.org.cn/showproj.aspx?proj=131702, identifier ChiCTR2100049695.

Adverse Outcomes Associated With Corticosteroid Use in Critical COVID-19: A Retrospective Multicenter Cohort Study.

Corticosteroid is commonly used to reduce damage from inflammatory reactions in coronavirus disease 2019 (COVID-19). We aim to determine the outcomes of corticosteroid use in critically ill COVID-19 patients. Ninety six critically ill patients, hospitalized in 14 hospitals outside Wuhan from January 16 to March 30, 2020 were enrolled in this study. Among 96 critical patients, 68 were treated with corticosteroid (CS group), while 28 were not treated with corticosteroids (non-CS group). Multivariable logistic regression were performed to determine the possible correlation between corticosteroid use and the treatment outcomes. Forty-six (68%) patients in the CS group died compared to six (21%) of the non-CS group. Corticosteroid use was also associated with the development of ARDS, exacerbation of pulmonary fibrosis, longer hospital stay and virus clearance time. On admission, no difference in laboratory findings between the CS and the non-CS group was observed. After corticosteroid treatment, patients treated with corticosteroids were associated with higher counts of white blood cells, neutrophils, neutrophil-to-lymphocyte ratio, alanine aminotransferase level and Sequential Organ Failure Assessment score. In conclusion, corticosteroid use in critically ill COVID-19 patients was associated with a much higher case fatality rate. Frequent incidence of liver injury and multi-organ failure in corticosteroid treated patients may have contributed to the adverse outcomes. The multi-organ failure is likely caused by more persistent SARS-CoV-2 infection and higher viral load, due to the inhibition of immune surveillance by corticosteroid.

LncRNA MACC1-AS1 attenuates microvascular endothelial cell injury and promotes angiogenesis under hypoxic conditions via modulating miR-6867-5p/TWIST1 in human brain microvascular endothelial cells.

BACKGROUND: Hypoxia following ischemic stroke is a common cause of brain insults. Mounting evidence suggests that long non-coding RNAs (lncRNAs) play a vital role in regulating certain physiological and pathological processes including ischemic stroke. For the first time, the present study investigated the effects and mechanism of LncRNA MACC1-AS1 on hypoxia-induced human brain microvascular endothelial cells (HBMECs). METHODS: LncRNA MACC1-AS1 levels in HBMECs were detected via reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay. Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT), were detected using their respective kits. Flow cytometry and clone formation assay were performed to evaluate the effects of lncRNA MACC1-AS1 on cell apoptosis and cell proliferation respectively. Angiogenesis capacity was evaluated via tube formation assay. Transwell migration assay was performed for assessment of cell migration, Western blot assay was performed for measurement of Twist1 and VE-cadherin level, and permeability assay was performed for evaluation of the cell barrier function. The target gene was predicted via bioinformatics online tool and validated through luciferase reporter assay and RNA pull-down assay. RESULTS: LncRNA MACC1-AS1 was downregulated in hypoxia-induced HBMECs. Overexpression of LncRNA MACC1-AS1 reduced cell apoptosis and oxidative stress, while promoting cell proliferation, migration, and angiogenesis. Moreover, LncRNA MACC1-AS1 overexpression reduced cell permeability and elevated VE-cadherin level, which contributed to maintaining cell barrier function. TWIST1 was validated as the target of miR-6867-5p which was further targeted by lncRNA MACC1-AS1. Thus, LncRNA MACC1-AS1 functions in hypoxia-induced HBMECs by regulating miR-6867-5p/TWIST1. CONCLUSIONS: In this study, we found that LncRNA MACC1-AS1 exerted a protective role in hypoxia-induced HBMECs via regulating miR-6867-5p/TWIST1, indicating a new therapeutic strategy for future ischemic stroke therapy.

Investigation of COVID-19-related symptoms based on factor analysis.

BACKGROUND: The application of factor analysis in the study of the clinical symptoms of coronavirus disease 2019 (COVID-19) was investigated, to provide a reference for basic research on COVID-19 and its prevention and control. METHODS: The data of 60 patients with COVID-19 in Jingzhou Hospital of Traditional Chinese Medicine and the Second People's Hospital of Longgang District in Shenzhen were extracted using principal component analysis. Factor analysis was used to investigate the factors related to symptoms of COVID-19. Based on the combination of factors, the clinical types of the factors were defined according to our professional knowledge. Factor loadings were calculated, and pairwise correlation analysis of symptoms was performed. RESULTS: Factor analysis showed that the clinical symptoms of COVID-19 cases could be divided into respiratory-digestive, neurological, cough-wheezing, upper respiratory, and digestive symptoms. Pairwise correlation analysis showed that there were a total of eight pairs of symptoms: fever-palpitation, coughexpectoration, expectoration-wheezing, dry mouth-bitter taste in the mouth, poor appetite-fatigue, fatiguedizziness, diarrhea-palpitation, and dizziness-headache. CONCLUSIONS: The symptoms and syndromes of COVID-19 are complex. Respiratory symptoms dominate, and digestive symptoms are also present. Factor analysis is suitable for studying the characteristics of the clinical symptoms of COVID-19, providing a new idea for the comprehensive analysis of clinical symptoms.

Fabrication of micropatterns on polypropylene films via plasma pretreatment combined with UV-initiated graft polymerization.

In this study, micropatterns on polypropylene films were fabricated via plasma pretreatment and UV-initiated graft polymerization. Firstly, radio-frequency plasma, which does not significantly influence bulk attributes of substrates due to limited penetration depth, was utilized to activate polypropylene films. Then, different sizes of micropatterns of poly(hydroxyethyl methacrylate) (PHEMA) were fabricated on the polypropylene films via UV-initiated graft polymerization of hydroxyethyl methacrylate by using photo-masks. Scanning electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, and contact angle (CA) were employed to characterize changes of pristine polypropylene films and modified ones in surface morphology, roughness, hydrophilicity, free energy and the surface chemical composition. All of these confirmed the successful grafting of different sizes of PHEMA micropatterns on the polypropylene surface. Furthermore, the influence of PHEMA micropatterns on cell proliferation and cytotoxicity was evaluated in vitro. Analysis of cell behaviour indicated that PHEMA micropatterns of the appropriate size can promote cellular adhesion and proliferation, and the PHEMA-micropatterned polypropylene films had good biocompatibility. The approach presented here provides an alternative to synthesize on the surface of polypropylene films' micropatterns with the aim of using them in a diverse array of applications.

Effects of Chinese herbal cataplasm Xiaozhang Tie on cirrhotic ascites.

BACKGROUND: Conventional methods of treating cirrhotic ascites are inadequate. We sought to identify a novel, effective approach to relieve the suffering of patients with cirrhotic ascites. AIM OF THE STUDY: To investigate the efficacy of Xiaozhang Tie, a traditional Chinese herbal cataplasm composed of dahuang (Rheum palmatum L.), laifuzi (Raphanus sativus L.), concocted gansui (Euphorbia kansui T.N. Liou ex T.P. Wang), chenxiang [Aquilaria sinensis (Lour.) Gilg], dingxiang (Eugenia caryophyllata Thunb.), bingpian (Borneolum syntheticum) and shexiang (artificial Moschus), as an adjuvant in treating cirrhotic ascites. MATERIALS AND METHODS: A multicenter, randomized, placebo-controlled trial was conducted. One hundred patients with cirrhotic ascites were divided into two groups of equal size. The test group took an umbilical compress with Xiaozhang Tie for 30 days while the control group was administered an umbilical compress with placebo, in addition to primary therapy. Efficacy was evaluated according to the criteria including ascites volume, urine 24-h volume, abdominal circumference, body weight, abdominal distention, appetite, flatus and defecation. RESULTS: Ninety-two patients completed the study, 7 were withdrawn and 1 was excluded. The effective rate of grades I and II was 63.3% for the test group (n=49) and 38.0% for the control one (n=50). Both groups showed decreased body weight and abdominal circumference, increased urine volume and improved symptoms after treatment. However, the differences between pre-treatment and post-treatment in body weight, abdominal circumference and urine volume were 8.7±5.8 kg, 12.4±8.3 cm and 683±644 ml respectively in the test group, noticeably higher than those in the control group, which were 5.3±4.6 kg, 8.0±6.5 cm and 372±697 ml, respectively. The ranking orders of the symptoms of the test group were significantly lower than those of the control group after treatment. No severe adverse reactions were seen. CONCLUSION: Xiaozhang Tie as an adjuvant to primary therapy of cirrhotic ascites is safe and shows a remarkable efficacy on relieving abdominal distention.