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BackgroundWind-cold (WC) and Wind-heat (WH) are common syndromes of upper respiratory tract infections (URTIs) in traditional Chinese medicine (TCM), presenting different clinical features, but the transcriptomic changes associated with these syndromes remained unclear.Materials and MethodsPatients with WC and WH syndromes were recruited from outpatient unit, pharyngeal swabs were collected for pathogen detection. Peripheral blood samples were obtained on day 1 and day 6, with healthy volunteers as controls. Transcriptome sequencing was performed to identify differentially expressed genes and pathways associated with the two syndromes. Marker genes for each syndrome were identified, and a machine learning classifier was developed.ResultsA total of 124 samples from 34 WC, 30 WH patients, and 16 health controls were included in this study. No significant differences in etiological spectrum were observed between the syndromes. Both syndromes showed distinct gene expression profiles compared to health control. Gene enrichment analysis indicated that TGF-β and Wnt/β -catenin pathways were downregulated in the WH. The oxidative phosphorylation pathways were downregulated in WC cohort compared to the WH cohort. As the URTIs improved from day 1 to day 6, oxidative phosphorylation pathway activity returned to normal levels. The marker genes for WC and WH syndromes were identified and a random forest classifier was built, achieving an accuracy of 0.88.ConclusionWC and WH syndromes demonstrated distinct gene expression profiles, supporting more precise TCM diagnosis. WC syndrome is marked by mitochondrial dysfunction, while WH syndrome is characterized by downregulated TGF-β and Wnt/β-catenin pathways.

Citri Grandis Exocarpium (Huajuhong, CGE) is the peel of the unripe fruits of Citrus grandis ‘Tomentosa’ and Citrus grandis (L.) Osbeck, which is commonly used in the clinic for the treatment of cough and indigestion. The pharmacological mechanism of CGE is unclear. In this study, the pharmacological effect of CGE was predicted by System Traditional Chinese Medicine (SYSTCM), which integrated the pharmacological effect prediction approach by artificial intelligence into the systemic traditional Chinese medicine (TCM) platform. The main pharmacological effect of CGE was antiallergy, promoting bile, blood lipid regulation, cardiotonics, diuresis, and antiarrhythmia by prediction of SYSTCM. In vitro cell experiments were carried out to identify the antiallergic effect of CGE. Extracts of Citri Grandis Exocarpium (ECGE) inhibited lipopolysaccharide-induced cell injury and nitric oxide release in RAW264.7 cells. ECGE and naringin-inhibited immunoglobulin E-induced cell degranulation in RBL-2H3 cells. Target profiling, protein interaction network, and molecular docking of compounds from CGE indicated that mitogen-activated protein kinase 14 (MAPK14) and matrix metalloprotease 9 (MMP9) were key potential targets of CGE with antiallergic activity. This study identified and validated the antiallergic effect of CGE by combining SYSTCM, cell experiments, and virtual screening, which provided a new paradigm and approach for studying the pharmacological effect and mechanism of TCM.

Background:Cordyceps sinensis is a traditional Chinese medicine that has shown promise for the management of chronic bronchitis (CB). We aim to assess the efficacy and safety of a preparation of C sinensis named Bailing capsule (Hirsutella sinensis, Cs-C-Q80) compared with a placebo in patients with CB.Methods: This randomized, double-blind, placebo-controlled, parallel-group clinical trial (Chinese Clinical Trial Registry; registration number: ChiCTR1900025707) recruited patients with CB from eight hospitals in China between May 2019 and December 2020. Patients were randomized 2:1 to receive Bailing capsule or a placebo orally for 48 weeks (2.0 g, three times a day).Results: Among 240 patients who were randomized, 238 (Bailing capsule: 159, placebo: 79) were included in the primary analysis. Bailing capsule significantly reduced the frequency of acute exacerbation of CB (AECB) compared with the placebo during treatment (0.43 ± 0.82 vs. 1.56 ± 1.34; P < 0.001) and follow-up (0.21 ± 0.64 vs. 0.45 ± 0.93; P = 0.026). Bailing capsule improved the severity of expectoration (P = 0.046) and wheezing (P = 0.010) in AECB during follow-up. The severity of CB after treatment was significantly improved in the Bailing capsule group compared with the placebo group (P = 0.035), particularly in terms of expectoration (P = 0.012) and wheezing (P = 0.003). The risk of adverse events, mainly including infectious and invasive diseases and gastrointestinal symptoms, did not significantly differ between the two groups (29.6% vs. 30.4%).Conclusion: In patients with CB, Bailing capsule significantly reduces the frequency of AECB and ameliorates the severity of AECB and CB symptoms.Clinical Trail Registration:https://www.chictr.org.cn, identifer ChiCTR1900025707.

Improving the business environment (BE) is crucial for sustainable regional development. Innovative city design characterized by innovation driven and knowledge intensive is an important way to shape and optimize urban BE. This study constructs a quasi-natural experiment based on China’s Innovative city pilot (ICP) policy. The beneficial contribution of the ICP policy to the improvement of urban BE is empirically examined using asymptotic double-difference models and prefecture-level city panel data from 2004 to 2019. The results find that innovative urban design can effectively improve urban BE, and this policy effect still holds after a multidimensional robustness test. The mechanism test shows that optimizing the allocation of innovation factors is the influence mechanism of ICP policy to optimize urban BE. This mechanism includes four paths: technological innovation effect, government efficiency improvement effect, policy-leading effect, and human capital aggregation effect. Further analysis reveals that this policy effect is more pronounced in central and western regions and regions with higher administrative levels but does not differ significantly depending on the market potential. Furthermore, the ICP policy has a spatial spillover effect, which can improve BE levels in neighboring cities. The findings provide strong evidence for optimizing urban BE and promoting economic transformation and development through regional innovation policies.

Objective: The aim of this study was to evaluate the efficacy and safety of the Chinese herbal formula San-Huang Gu-Ben Zhi-Ke (SHGBZK) as a treatment for patients with stable chronic obstructive pulmonary disease (COPD) diagnosed with lung-spleen Qi deficiency.Method: A randomized, double-blind, placebo-controlled trial was designed. 98 adults aged between 40 and 80 years with stable COPD diagnosed with lung-spleen Qi deficiency were included. All participants received basic treatment for COPD. Patients in the experimental group took SHGBZK, while the control group took placebo. The primary outcome was the frequency of acute exacerbation. The secondary outcomes were lung function, symptom score, exercise capacity and quality of life.Results: Of 98 patients who underwent randomization, 50 patients in the SHGBZK group and 48 in the placebo group were included in the full analysis set. After 24-week therapy and 28-week follow-up, patients in treatment group had significant improvements in symptom, exercise capacity and quality of life. After Subgroup analysis, the frequency of acute exacerbation in patients with a COPD Assessment Test (CAT) score of at least 10 or a modified Medical Research Council (mMRC) score of at least 2 was significantly lower in the SHGBZK group than in the placebo group. Lung function in patients with frequent exacerbation was significantly higher in the SHGBZK group than in the placebo group. The incidence of adverse events was generally similar in the two groups.Conclusion: SHGBZK had beneficial effects on symptom, exercise capacity and quality of life in stable COPD patients. SHGBZK also had the potential to reduce the frequency of exacerbation and improve lung function in specific groups of COPD patients.Clinical Trial Registration:https://www.chictr.org.cn/showproj.html?proj=26933, identifier ChiCTR1800016349

Objective: Our aim was to systematically investigate the efficacy of Tanreqing (TRQ) injection on in-hospital outcomes among inpatients with frequent or infrequent AECOPD.Methods: In this ongoing, nationwide multicenter registry designed to investigate clinical characteristics, management, and prognoses of Chinese patients admitted for AECOPD in real-world settings, we collected characteristics, comorbidities, in-hospital prognoses, and information on the COPD assessment test (CAT) questionnaire, PEACE questionnaire, and modified British Medical Research Council (mMRC) questionnaire from each enrolled patient. Frequent AECOPD was determined as being admitted to the hospital ≥1 time or visiting the emergency room (ER) ≥ 2 times due to AECOPD within a year. A propensity match method and univariable and multivariable regression models were performed to analyze the efficacy of TRQ on clinical outcomes for inpatients with frequent AECOPD.Results: A total of 4135 inpatients were involved in the analysis, including 868 administered with TRQ and 3267 not administered with TRQ. After propensity score match, among those administered with TRQ, 493 had frequent AECOPD and 358 had infrequent AECOPD. A significant reduction of CAT score at discharge (TRQ median 12, IQR 8.0–16.0; non-TRQ median 13, IQR 9.0–18.0, p = 0.0297), a lower rate of ICU admission (TRQ 0.8% vs. non-TRQ 2.6%, p = 0.0191), and a shorter length of stay (LOS) (TRQ median 11, IQR 9.0–14.0; non-TRQ median 11, IQR 8.0–14.0, p = 0.004) were observed in the TRQ group, compared with the non-TRQ group among frequent AECOPD patients. In the subgroup analysis, for those with a PEACE score >7 on admission, TRQ contributed to a significantly lower CAT score at discharge (p = 0.0084) and a numerically lower ICU admission rate with a marginal statistical significance. Among those with phlegm-heat symptom complex on admission ≥2, a lower CAT score at discharge and a lower ICU admission were also observed in the TRQ group.Conclusion: TRQ injection had better efficacy in patients with frequent AECOPD in reducing ICU admission and alleviating respiratory symptoms, especially for those with higher severity on admission or more phlegm-heat symptoms.

Background: Guben Zhike decoction (GBZKD) is derived from the experience of Professor Enxiang Chao, an esteemed master of Chinese medicine, while treating chronic obstructive pulmonary disease (COPD). GBZKD reinforces the healthy qi and consolidates defensive qi. This study explored the efficacy and potential mechanism of action of GBZKD in a COPD mouse model using proteomics. Methods: A COPD mouse model was established through cigarette smoke exposure and intranasal lipopolysaccharide administration. The model was verified through lung function test and lung histopathological observation. Label-free quantitative proteomics was used to detect the lung tissue proteins of mice from the GBZKD, COPD, and control groups. Results: GBZKD markedly improved the lung function and associated pathological conditions in the COPD mouse model. Proteomic analysis identified 4316 proteins, of which 3696 were quantitative proteins. We highlighted 287 and 184 proteins with significant regulatory roles in the lung tissues of COPD mice and GBZKD-treated mice, respectively. These proteins participated in multiple functions, including complement/coagulation cascade, immune response, and metabolic pathways. Conclusion: GBZKD exhibits multitarget and multipathway therapeutic effects in a COPD mouse model.

Abstract Background Due to the large number of patients, high mortality rate as well as high social costs and economic burden, chronic obstructive pulmonary disease (COPD) has become one of the most important health problems around the world, which has attracted people’s attention. Currently, Chinese herbs have been widely used as alternative medicine (CAM) for COPD patients. The Chinese herbal formula San-Huang Gu-Ben Zhi-Ke (SHGBZK) has shown good clinical efficacy in COPD in preclinical studies. Animal experiments have shown that it has mucosal immune barrier function and can maintain airway wall integrity, reduce inflammatory cell infiltration, promote inflammatory damage repair, and relieve narrow airway conditions. Methods/design This study is a randomized, double-blind, placebo-controlled trial. A total of 100 patients with stable COPD diagnosed with deficiency of lung qi and spleen qi will be recruited and randomly assigned to one of two treatment groups: SHGBZK treatment, N = 50; placebo treatment, N = 50. The two groups will receive basic treatment for COPD according to the 2017 GOLD Guidelines for Chronic Obstructive Pulmonary Disease. Patients will stick to the treatment they used to take as much as possible, and will be given present general treatment when acute exacerbation of COPD occurs during the study. Both groups will receive a 24-week intervention and patient status will be assessed at 24 weeks and then 28 weeks after treatment. After the 24-week treatment, patients will be followed up for another 28 weeks. Outcome measures, including the frequency and duration of acute exacerbation, lung function, traditional Chinese medicine symptom score, exercise capacity, and quality of life will be assessed. Discussion It is hypothesized that SHGBZK will have beneficial effects in reducing the frequency and duration of acute exacerbations, improving the exercise capacity function of patients with stable COPD diagnosed with a deficiencies in lung qi and spleen qi. This study may establish a new treatment method for COPD patients, differentiating it from other drugs in clinical use used for similar clinical indications. Trial registration Chinese Clinical Trial Registry, ChiCTR1800016349. Registered on 26 May 2018.

Abstract Soil microbes play important roles in plant growth and health. Little is known about the differences of soil microbes between healthy and bacterial wilt infected soils with Ralstonia solanacearum. By Illumina-MiSeq sequencing of 16S rRNA and 18S rRNA gene amplicons, we found the soil microbial composition and diversity were distinct between healthy and bacterial wilt infected soils. Soil microbial community varied at different plant growth stages due to changes of root exudates composition and soil pH. Healthy soils exhibited higher microbial diversity than the bacterial wilt infected soils. More abundant beneficial microbes including Bacillus, Agromyces, Micromonospora, Pseudonocardia, Acremonium, Lysobacter, Mesorhizobium, Microvirga, Bradyrhizobium, Acremonium and Chaetomium were found in the healthy soils rather than the bacterial wilt infected soils. Compared to bacterial wilt infected soils, the activities of catalase, invertase and urease, as well as soil pH, available phosphorous and potassium content, were all significantly increased in the healthy soils. In a conclusion, the higher abundance of beneficial microbes are positively related the higher soil quality, including better plant growth, lower disease incidence, and higher nutrient contents, soil enzyme activities and soil pH.

Background: Depression is reported to occur 5–10 years early than the onset of motor symptoms in Parkinson (PD) patients. However, markers for early diagnosis of PD in individuals with sub-clinical depression still remain to be identified.Purpose: This study utilized Regional Homogeneity (ReHo) to investigate the alterations in resting state brain activities in Parkinson (PD) patients with different degrees of depression.Methods: Twenty non-depressed PD patients, twenty mild to moderately depressed PD patients, and thirteen severely depressed PD patients were recruited. Hamilton Depression Scale (HDS) and the Beck Depression Inventory (BDI) were assessed depression. Resting-state functional magnetic resonance imaging (rs-MRI) was analyzed with ReHo.Results: PD patients with mild to moderate depression had decreased ReHo in the left dorsal anterior cingulate cortex when compared with PD patients without depression. PD patients with severe depression exhibited increased ReHo in the left inferior prefrontal gyrus and right orbitofrontal area when compared with PD patients with mild to moderate depression. ReHo values in the bilateral supplementary motor area (SMA) in PD patients with severe depression was also increased when compared with PD patients without depression.Conclusions: This study suggests that rs-MRI with ReHo analysis can detect early changes in brain function that associate with depression in PD patients, which could be biomarkers for early diagnosis and treatment of PD related depression.

Introduction Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) brings a serious impact on patients’ quality of life, and has extremely high morbidity and mortality worldwide. Although there are many therapies being developed to alleviate symptoms and reduce mortality, a few studies have supported which treatment method is the best. Traditional Chinese medicine (TCM) has shown good potential in the prevention and treatment of AECOPD, especially in terms of supplementation and reduction of dosage and adverse effect of Western medicine. The purpose of this study is to compare the effectiveness of combination of TCM and Western medicine with conventional therapy alone for AECOPD, and to ensure whether the combined therapy may reduce the use of systemic glucocorticoid in AECOPD without influencing efficacy.Methods and analysis A multicentre, randomised, double-blind, placebo-controlled study was conducted to enrol a total of 360 eligible patients who will be randomised into integrated Chinese and Western medicine group A, B and Western standard Medicine group C. After 5 days of intervention and 1 month of follow-up, the efficacy and safety of Xin Jia Xuan Bai Cheng Qi Decoction in patients with AECOPD will be observed. The results of evaluation indicators include: clinical symptoms, biochemical indicators such as blood gas analysis, inflammatory markers, hospitalisation time, TCM syndrome evaluation, biological indicators such as airway, intestinal flora sequencing.Ethics and dissemination This trail has been approved by the Ethics Committee of China-Japan Friendship Hospital. The results will be disseminated in international peer-reviewed journals and be presented in academic conferences. The results will also be disseminated to patients by telephone, inquiring on patient’s poststudy health status during the follow-up.Trial registration number ChiCTR1800016915

Few studies have explored the neurobiological basis of insight level in obsessive-compulsive disorder (OCD), though the salience network (SN) has been implicated in insight deficits in schizophrenia. This study was then designed to investigate whether resting-state (rs) functional connectivity (FC) of SN was associated with insight level in OCD patients. We analyzed rs-functional magnetic resonance imaging (fMRI) data from 21 OCD patients with good insight (OCD-GI), 19 OCD patients with poor insight (OCD-PI), and 24 healthy controls (HCs). Seed-based whole-brain FC and ROI (region of interest)-wise connectivity analyses were performed with seeds/ROIs in the bilateral anterior insula (AI) and dorsal anterior cingulate cortex (dACC). The right AI-right medial orbital frontal cortex (mOFC) connectivity was found to be uniquely decreased in the OCD-PI group, and the value of this aberrant connectivity correlated with insight level in OCD patients. In addition, we found that the OCD-GI group had significantly increased right AI-left dACC connectivity within the SN, relative to HCs (overall trend for groups: OCD-GI>OCD-PI>HC). Our findings suggest that abnormal right AI-right mOFC FC may mediate insight deficits in OCD, perhaps due to impaired encoding and integration of self-evaluative information about OCD-related beliefs and behaviors. Our findings indicate a SN connectivity dissociation between OCD-GI and OCD-PI patients and support the notion of considering OCD-GI and OCD-PI as two distinct disorder subtypes. Keywords: Obsessive-compulsive disorder, Insight, Salience network, Resting-state functional connectivity, Insula

Background: Previous studies have indicated the resting-state default mode network (DMN) related connectivity serving as predictor of sustained attention performance in healthy people. Interestingly, sustained attention deficits as well as DMN-involved functional connectivity (FC) alterations are common in both patients with schizophrenia (SCZ) and with obsessive-compulsive disorder (OCD). Thus, the present study was designed to investigate whether the DMN related resting-state connectivity alterations in these two psychiatric disorders were neural correlates of their sustained attention impairments.Methods: The study included 17 SCZ patients, 35 OCD patients and 36 healthy controls (HCs). Sustained attention to response task was adopted to assess the sustained attention. Resting-state scan was administrated and seed-based whole-brain FC analyses were performed with seeds located in classical DMN regions including bilateral medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC).Results: Both SCZ and OCD patients had poorer sustained attention than HCs. Sustained attention deficits in OCD was negatively correlated with their impaired FC of right mPFC-left superior frontal gyrus (SFG) within DMN, and that in SCZ was significantly correlated with their altered FC of left mPFC-bilateral anterior cingulate cortex (ACC) which indicated interaction between DMN and salience network. In addition, the FC between left mPFC and right parietal lobe indicating the interaction between DMN and frontal-parietal network was correlated with sustained attention in both SCZ and OCD.Conclusion: These findings suggest the importance of DMN-involved connectivity, both within and between networks in underlying sustained attention deficits in OCD and SCZ. Results further support the potential of resting-state FC in complementing information for cognitive deficits in psychiatric disorders.

The Bering Sea is located between the Aleutian Low and Siberian High, with strong seasonal variations in the oceanic circulation and the sea ice coverage. Within such a large-scale system, the physical processes in the Bering Sea carry interannual variability. The special topography in the Bering Sea traps a strong jet along the Bering Slope, whose instability enriches the eddy activity in the region. A Regional Oceanic Modeling System (ROMS), coupled with a sea ice module, is employed to study multiple-scale variability in the sea ice and oceanic circulation in the Bering Sea for interannual, seasonal, and intra-seasonal eddy variations. The model domain covers the whole Bering Sea and a part of the Chukchi Sea and south of Aleutian Islands, with an averaged spatial resolution of 5 km. The external forcings are momentum, heat, and freshwater flux at the surface and adaptive nudging to reanalysis fields at the boundaries. The oceanic model starts in an equilibrium state from a multiple year cyclical climatology run, and then it is integrated from years 1990 through 2004. The 15 year simulation is analyzed and assessed against the observational data. The model accurately reproduces the seasonal and interannual variations in the sea ice coverage compared with the satellite-observed sea ice data from the National Snow and Ice Data Center (NSIDC). Sea surface temperature and eddy kinetic energy patterns from the ROMS agree with satellite remote sensing data. The transportation through the Bering Strait is also comparable with the estimate of mooring data. The mechanism for seasonal and interannual variation in the Bering Sea is connected to the Siberia-Aleutian index. Eddy variation along the Bering Slope is discussed. The model also simulates polynya generation and evolution around the St. Lawrence Island.

Over the last couple of years, video service distribution among smart phones and other mobile video devices is becoming increasingly popular in sensor networks. However, the huge energy consumption caused by video encoding and transmitting and the slowly evolving battery technologies become the major bottlenecks that hinder the development of video streaming services. Hence energy efficient video coding and transmitting solutions are required to be investigated. Yet, energy consumption reduction of mobile video devices will be accompanied with Quality of Experience (QoE) degradation of video applications. Such diverse tendency makes it difficult to encode and transmit video streams with less energy as well as better QoE. This paper analyzes the major energy consuming factors in mobile video devices. A specific energy consumption model concerning encoding bitrates and transmitting power level is built. Further, a noninvasive QoE perceptive model is adopted so that the energy efficiency problem becomes a cross-layer optimization problem. Chaos particle swarm optimization is used to solve this cross-layer optimization problem with fast convergence. By this method, energy consumption of mobile video device is minimized with acceptable QoE for video users. At last, Pareto front of energy and QoE is analyzed to certify the performance of our method.

Background Immunotherapy represented by programmed death protein-1 (PD-1) inhibitors has gradually become the standard treatment of advanced non-small cell lung cancer (NSCLC) in recent years, changing the treatment landscape of advanced NSCLC. However, most PD-1-related studies excluded patients with NSCLC more than 70 or 75 years, resulting in relatively limited data about the efficacy and safety of PD-1 inhibitors in elderly patients. Objective This study aims to evaluate the efficacy and safety of PD-1 inhibitors in elderly patients with advanced NSCCL. Methods This study selected elderly patients with advanced NSCLC over 65 years who received PD-1 inhibitors monotherapy in Department of Thoracic Surgery and Oncology of the Fourth Affiliated Hospital of Gansu University of Traditional Chinese Medicine from October 2018 to November 2021. A total of 63 elderly patients with NSCLC were included. The PD-1 inhibitors of the study were approved in Chinese market, including camrelizumab, sintilimab and pembrolizumab. The data about efficacy and safety of PD-1 inhibitors were collected in the hospital electronic medical record system. All patients were followed up regularly to obtain the long-term prognostic data until 2022-03-15. The efficacy data of PD-1 inhibitors, the prognosis of elderly patients with advanced NSCLC and the toxicity and side effects of PD-1 inhibitors were collected. Cox comparative risk model was used to explore the influencing factors of the prognosis of elderly patients with advanced NSCLC. Results The median age of the 63 elderly patients with advanced NSCLC was 71 (65, 89) years. The best response assessment during PD-1 inhibitors therapy showed that no patients had complete response, 14 patients had partial responses, 21 patients had stable status, and 28 patients had progressive status. The objective response rate (ORR) of patients with advanced NSCLC treated with PD-1 inhibitors monotherapy was 22.2% (14/63) , and the disease control rate (DCR) was 66.7% (14/21) . Prognostic data showed that the median progression free survival (PFS) of the 63 patients with advanced NSCLC was 3.3 (2.0, 4.6) months and the median overall survival (OS) was 10.2 (6.1, 14.3) months. Among 63 elderly patients with NSCLC, 46 of them (73.0%) had treatment related adverse reaction during PD-1 inhibitors monotherapy, and the rate of grade 3 or above adverse reactions was 14.3%. The most common adverse reactions were fatigue, diarrhea, rash and abnormal liver function with the rates of 23.8% (15/63) , 19.1% (12/63) , 15.9% (10/63) and 14.3% (9/63) , respectively. Cox comparative risk model analysis suggested that ECOG performance status and number of metastatic lesions might be independent factors of PFS in patients with advanced NSCLC treated with PD-1 inhibittors. Conclusion PD-1 blockades monotherapy demonstrated potential efficacy and acceptable safety for elderly patients with NSCLC. ECOG performance status and number of metastatic lesions might be potential risk factors that predict the PFS of the patients.