Executable Network Models of Integrated Multiomics Data.

Multiomics profiling provides a holistic picture of a condition being examined and captures the complexity of signaling events, beginning from the original cause (environmental or genetic), to downstream functional changes at multiple molecular layers. Pathway enrichment analysis has been used with multiomics data sets to characterize signaling mechanisms. However, technical and biological variability between these layered data limit an integrative computational analyses. We present a Boolean network-based method, multiomics Boolean Omics Network Invariant-Time Analysis (mBONITA), to integrate omics data sets that quantify multiple molecular layers. mBONITA utilizes prior knowledge networks to perform topology-based pathway analysis. In addition, mBONITA identifies genes that are consistently modulated across molecular measurements by combining observed fold-changes and variance, with a measure of node (i.e., gene or protein) influence over signaling, and a measure of the strength of evidence for that gene across data sets. We used mBONITA to integrate multiomics data sets from RAMOS B cells treated with the immunosuppressant drug cyclosporine A under varying O2 tensions to identify pathways involved in hypoxia-mediated chemotaxis. We compare mBONITA's performance with 6 other pathway analysis methods designed for multiomics data and show that mBONITA identifies a set of pathways with evidence of modulation across all omics layers. mBONITA is freely available at https://github.com/Thakar-Lab/mBONITA.

Efficacy of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in treatment of COVID-19: A randomized controlled trial.

BACKGROUND: With the global epidemic of coronavirus disease (COVID-19), China has made progress in the prevention and control of the epidemic, and traditional Chinese medicine (TCM) has played a key role in dealing with the disease's effects on the respiratory system. This randomized controlled clinical trial evaluated the clinical efficacy and prognosis of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in patients with COVID-19. METHODS: A total of 283 patients participated in this clinical trial, and participants were randomly assigned to receive either 1) Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules or 2) Linahua granules, both combined with western medicine, or 3) western medicine alone for 14 days. At the end of the trial, the improvement and resolution rates of clinical symptoms and the rate of patients who progressed to severe disease status were evaluated. RESULTS: After 14 days of treatment, there was no significant difference in the improvement rate of clinical symptoms among the three groups (P > 0.05). Huoxiang Zhengqi dropping pills combined with Lianhua Qingwen granules has advantages in the treatment of nausea, vomiting and limb soreness. During treatment, all participants were treated with western medicine, and there was a significant difference in the use of macrolides among the three groups (P < 0.05). Specifically, the utilization rate of antibiotics in the western medicine group was significantly greater than that of the other two groups. Among the 182 diagnosed patients who completed this clinical trial, 13 patients progressed to severe disease, including one case in the Huoxiang + Lianhua group (1.6 %), five cases in the Lianhua group (8.6 %), and seven cases in the western medicine group (11.1 %). There was no statistical differences in this rate among the three groups (P > 0.05). However, the proportion of patients who progressed to severe disease in the Huoxiang + Lianhua group was the lowest, suggesting that the combination of TCM with western medicine has a potential advantage in improving the prognosis of patients with COVID-19. CONCLUSION: The use of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules combined with western medicine may have clinical advantages for COVID-19 patients in improving clinical symptoms, reducing utilization rate of anti-infective drugs, and improving patient prognosis, which could pave the way for the use of complementary medicine in treating this infection.

[Effectiveness of Extracorporeal Shockwave Therapy in Treating Superior Lateral Brachial Cutaneous Nerve Compression Syndrome].

Objective To evaluate the effectiveness of radial extracorporeal shockwave therapy(rESWT) for the treatment of superior lateral brachial cutaneous nerve(SLBCN) compression syndrome.Methods A total of 40 patients with SLBCN compression syndrome who were treated in our department from March 2013 to October 2015 were equally randomized into two groups according to random number table:rESWT group(treated with rESWT for 1 cycle) and control group(treated with local hormone injection for 1 cycle). Visual analogue scale(VAS) and Constant-Murley scale(CMS) were applied to evaluate the shoulder joint function before treatment and 1 month and 1 year after treatment. Results The average CMS scores were(66.7±0.9) and(65.7±1.1)scores in rESWT group and control group,respectively,before treatment(t=0.67,P=0.510) and were(86.9±1.0) and(86.4±1.1)scores one month after treatment(t=0.35,P=0.730);it increased to(89.7±0.7) scores in rESWT group one year later,which was significantly higher than that in control group[(85.3±0.8)scores](t=3.56,P=0.002). The improvement rate was 95% in rESWT group and only 75% in control group. Before treatment,the median VAS score in rESWT group and control group were 5.00(5.00,6.00) and 5.00(4.00,5.75)scores(u=1.13,P=0.29);one month after treatment,the median VAS score in these two groups were 2(1.00,2.75) and 2.00(1.00,2.00)scores(u=0.04,P=0.85);one year later,it was 1.00(0.00,1.00) scores in rESWT group,significantly lower than that in [2.00(1.00,2.00)scores] control group(u=5.09,P=0.02). Conclusion Compared with local hormone injection,rESWT can remarkably alleviate pain and restore shoulder joint function in patients with SLBCN compression syndrome after one year of treatment.

Nocturnal stomatal behaviour and its impact on water use strategies of desert herbs in the Gurbantunggut Desert, Northwest China.

Nocturnal stomatal behaviour has the potential to exert a profound influence on plant-water relations, especially water use efficiency. However, we know very less about plant functional type differences in nocturnal stomatal conductance and their roles in plant stress adaptation, especially drought adaptation. To address this critical knowledge gap, we assessed diel leaf gas exchanges in eight ephemeral and perennial herbs growing on the southern edge of the Gurbantunggut Desert, Northwest China. For both ephemeral and perennial herbs, the nocturnal stomatal conductance (gs) exceeded 30 % of daytime gs, except for an ephemeral herb (Malcolmia scorpioides). The nocturnal gs in the studied perennial herbs were significantly higher than it in the ephemeral herbs. The results suggest that circadian-driven stomatal priming plays a pivotal role in accelerating the attainment of steady-state gs during the morning for perennial herbs, thereby enhancing their capacity for carbon capture. Moreover, the nocturnal stomatal behaviour of the ephemeral herbs favored water retention in the morning, consequently enhanced intrinsic water use efficiency and long-term water use efficiency. In summary, plant functional type differences in the magnitude of nocturnal stomatal opening were related to differences in water acquisition and utilization and highlighted diverse water use strategies in the desert plants.

Efficacy of Jinhua Qinggan Granules Combined With Western Medicine in the Treatment of Confirmed and Suspected COVID-19: A Randomized Controlled Trial.

Objective: To conduct a randomized controlled clinical trial to evaluate the clinical efficacy and prognostic value of Jinhua Qinggan granules in patients with confirmed and suspected coronavirus disease 2019 (COVID-19). Methods: A total of 123 suspected and confirmed COVID-19 patients participated in this clinical trial and were randomly divided into Jinhua and Western medicine groups. For 14 days, the Jinhua group was treated with Jinhua Qinggan granules and antiviral drugs, and the Western medicine group was treated with antiviral drugs alone. We collected information on clinical symptoms, disease aggravation rates, and negative conversion rates of nucleic acids in patients, and observed the effects of anti-infective drugs. Results: There was no significant difference in symptom improvement rates between the two groups, both confirmed and suspected patients (P > 0.05). Both treatments relieved symptoms such as fever, fatigue, and diarrhea. However, the Jinhua treatment was superior in relieving fever and poor appetite. Anti-infective drug use rates were significantly lower in the Jinhua group than in the control group. Conclusion: Jinhua Qinggan granules combined with Western medicine could relieve the clinical symptoms of fever and poor appetite in COVID-19 patients, reduce the use of antibiotics to a certain extent. Clinical Trial Registration: The registration number at China Clinical Trial Registry is ChiCTR2000029601.

Add-On Chinese Medicine for Coronavirus Disease 2019 (ACCORD): A Retrospective Cohort Study of Hospital Registries.

Chinese medicine (CM) was extensively used to treat COVID-19 in China. We aimed to evaluate the real-world effectiveness of add-on semi-individualized CM during the outbreak. A retrospective cohort of 1788 adult confirmed COVID-19 patients were recruited from 2235 consecutive linked records retrieved from five hospitals in Wuhan during 15 January to 13 March 2020. The mortality of add-on semi-individualized CM users and non-users was compared by inverse probability weighted hazard ratio (HR) and by propensity score matching. Change of biomarkers was compared between groups, and the frequency of CMs used was analyzed. Subgroup analysis was performed to stratify disease severity and dose of CM exposure. The crude mortality was 3.8% in the semi-individualized CM user group and 17.0% among the non-users. Add-on CM was associated with a mortality reduction of 58% (HR = 0.42, 95% CI: 0.23 to 0.77, [Formula: see text] = 0.005) among all COVID-19 cases and 66% (HR = 0.34, 95% CI: 0.15 to 0.76, [Formula: see text] = 0.009) among severe/critical COVID-19 cases demonstrating dose-dependent response, after inversely weighted with propensity score. The result was robust in various stratified, weighted, matched, adjusted and sensitivity analyses. Severe/critical patients that received add-on CM had a trend of stabilized D-dimer level after 3-7 days of admission when compared to baseline. Immunomodulating and anti-asthmatic CMs were most used. Add-on semi-individualized CM was associated with significantly reduced mortality, especially among severe/critical cases. Chinese medicine could be considered as an add-on regimen for trial use.

Extreme drought affects the productivity, but not the composition, of a desert plant community in Central Asia differentially across microtopographies.

Extreme climatic conditions are major drivers of ecosystem function and dynamics and their frequency is increasing under climate change. Climatic conditions interact with local microtopography, which might either buffer or exacerbate the degree of climatic stress. Here we sought to understand how extremely dry growing seasons affected the composition and productivity of desert ephemeral communities growing in sand dunes from the Gurbantunggut desert in Central Asia, and to which extent did microtopography modulate the response. We set up a rainfall manipulation study on four sand dune microtopographies and, during two consecutive years, we measured soil moisture, nutrients and texture, ephemeral layer composition, plant phenology, biomass accumulation and biomass allocation patterns for the dominant species. We observed significant biomass reductions during the extreme drought but plant community richness and composition were not affected, indicating that the composition of the ephemeral layer in this desert ecosystem may resist under extreme conditions. Additionally, extreme drought increased biomass allocation to reproductive organs of the dominant species. There were also significant microtopographic effects as the sensitivity of biomass to drought in western aspects was larger than in eastern aspects. Our results indicate that previously overlooked microtopographical differences may mediate the impact of climate change on plant communities.

Clinical features and the traditional Chinese medicine therapeutic characteristics of 293 COVID-19 inpatient cases.

Coronavirus disease 2019 (COVID-19) is now pandemic worldwide and has heavily overloaded hospitals in Wuhan City, China during the time between late January and February. We reported the clinical features and therapeutic characteristics of moderate COVID-19 cases in Wuhan that were treated via the integration of traditional Chinese medicine (TCM) and Western medicine. We collected electronic medical record (EMR) data, which included the full clinical profiles of patients, from a designated TCM hospital in Wuhan. The structured data of symptoms and drugs from admission notes were obtained through an information extraction process. Other key clinical entities were also confirmed and normalized to obtain information on the diagnosis, clinical treatments, laboratory tests, and outcomes of the patients. A total of 293 COVID-19 inpatient cases, including 207 moderate and 86 (29.3%) severe cases, were included in our research. Among these cases, 238 were discharged, 31 were transferred, and 24 (all severe cases) died in the hospital. Our COVID-19 cases involved elderly patients with advanced ages (57 years on average) and high comorbidity rates (61%). Our results reconfirmed several well-recognized risk factors, such as age, gender (male), and comorbidities, as well as provided novel laboratory indications (e.g., cholesterol) and TCM-specific phenotype markers (e.g., dull tongue) that were relevant to COVID-19 infections and prognosis. In addition to antiviral/antibiotics and standard supportive therapies, TCM herbal prescriptions incorporating 290 distinct herbs were used in 273 (93%) cases. The cases that received TCM treatment had lower death rates than those that did not receive TCM treatment (17/273 = 6.2% vs. 7/20= 35%, P = 0.0004 for all cases; 17/77= 22% vs. 7/9= 77.7%, P = 0.002 for severe cases). The TCM herbal prescriptions used for the treatment of COVID-19 infections mainly consisted of Pericarpium Citri Reticulatae, Radix Scutellariae, Rhizoma Pinellia, and their combinations, which reflected the practical TCM principles (e.g., clearing heat and dampening phlegm). Lastly, 59% of the patients received treatment, including antiviral, antibiotics, and Chinese patent medicine, before admission. This situation might have some effects on symptoms, such as fever and dry cough. By using EMR data, we described the clinical features and therapeutic characteristics of 293 COVID-19 cases treated via the integration of TCM herbal prescriptions and Western medicine. Clinical manifestations and treatments before admission and in the hospital were investigated. Our results preliminarily showed the potential effectiveness of TCM herbal prescriptions and their regularities in COVID-19 treatment.

Positive RT-PCR Test Results in 420 Patients Recovered From COVID-19 in Wuhan: An Observational Study.

OBJECTIVE: During the follow-up of patients recovered from coronavirus disease 2019 (COVID-19) in the quarantine and observation period, some of the cured patients showed positive results again. The recurrent positive RT-PCR test results drew widespread concern. We observed a certain number of cured COVID-19 patients with positive RT-PCR test results and try to analyze the factors that caused the phenomenon. METHODS: We conducted an observational study in COVID-19 patients discharged from 6 rehabilitation stations in Wuhan, China. All observed subjects met the criteria for hospital discharge and were in quarantine. Data regarding age, sex, body mass index (BMI), course of disease, comorbidity, smoking status and alcohol consumption, symptoms in and out of quarantine, and intervention were collected from the subjects' medical records and descriptively analyzed. The main outcome of this study was the RT-PCR test result of the observed subjects at the end of quarantine (negative or positive). Logistic regression analysis was used to identify the influencing factors related to recurrent positive RT-PCR test results. RESULTS: In this observational study, 420 observed subjects recovered from COVID-19 were included. The median age was 56 years, 63.6% of the subjects were above 50 years old, and 50.7% (213/420) were female. The most common comorbidities were hypertension [26.4% (111/420)], hyperlipidemia [10.7% (45/420)], and diabetes [10.5% (44/420)]. 54.8% (230/420) manifested one or more symptoms at the beginning of the observation period, the most common symptoms were cough [27.6% (116/420)], shortness of breath 23.8% (100/420)], and fatigue [16.2% (68/420)], with fever rare [2.6% (11/420)]. A total of 325 subjects were exposed to comprehensive intervention; 95 subjects were absence of intervention. The recurrence rate of positive RT-PCR test results with comprehensive intervention was 2.8% (9/325), and that with no intervention was 15.8% (15/95). The results of logistic regression analysis showed that after adjusted for factors such as age, sex, and comorbidity and found out that comprehensive intervention was correlated with the recurrent positive RT-PCR test results. There was appreciably less recurrence in the comprehensive intervention group. CONCLUSIONS: The factors related to positive RT-PCR test results in observed subjects recovered from COVID-19 were age, comorbidity, and comprehensive intervention, among which comprehensive intervention might be a protective factor. CLINICAL TRIAL REGISTRATION: Chictr.org.cn, identifier ChiCTR2000030747.

Water use patterns of co-occurring C3 and C4 shrubs in the Gurbantonggut desert in northwestern China.

In water-limited ecosystems, spatial and temporal partitioning of water sources is an important mechanism that facilitates plant survival and lessens the competition intensity of co-existing plants. Insights into species-specific root functional plasticity and differences in the water sources of co-existing plants under changing water conditions can aid in accurate prediction of the response of desert ecosystems to future climate change. We used stable isotopes of soil water, groundwater and xylem water to determine the seasonal and inter- and intraspecific differences variations in the water sources of six C3 and C4 shrubs in the Gurbantonggut desert. We also measured the stem water potentials to determine the water stress levels of each species under varying water conditions. The studied shrubs exhibited similar seasonal water uptake patterns, i.e., all shrubs extracted shallow soil water recharged by snowmelt water during early spring and reverted to deeper water sources during dry summer periods, indicating that all of the studied shrubs have dimorphic root systems that enable them to obtain water sources that differ in space and time. Species in the C4 shrub community exhibited differences in seasonal water absorption and water status due to differences in topography and rooting depth, demonstrating divergent adaptations to water availability and water stress. Haloxylon ammodendron and T. ramosissima in the C3/C4 mixed community were similar in terms of seasonal water extraction but differed with respect to water potential, which indicated that plant water status is controlled by both root functioning and shoot eco-physiological traits. The two Tamarix species in the C3 shrub community were similar in terms of water uptake and water status, which suggests functional convergence of the root system and physiological performance under same soil water conditions. In different communities, Haloxylon ammodendron differed in terms of summer water extraction, which suggests that this species exhibits plasticity with respect to rooting depth under different soil water conditions. Shrubs in the Gurbantonggut desert displayed varying adaptations across species and communities through divergent root functioning and shoot eco-physiological traits.