Fabrication of Heterostructural FeNi3-Loaded Perovskite Catalysts by Rapid Plasma for Highly Efficient Photothermal Reverse Water Gas Shift Reaction.

Metal-semiconductor heterostructured catalysts have attracted great attention because of their unique interfacial characteristics and superior catalytic performance. Exsolution of nanoparticles is one of the effective and simple ways for in-situ growth of metal nanoparticles embedded in oxide surfaces and their favorable dispersion and stability. However, both high-temperature and a reducing atmosphere are required simultaneously in conventional exsolution, which is time-consuming and costly, and particles often agglomerate during the process. In this work, Ca0.9Ti0.8Ni0.1Fe0.1O3-δ (CTNF) is exposed to dielectric blocking discharge (DBD) plasma at room temperature to fabricate alloying FeNi3 nanoparticles from CTNF perovskite. FeNi3-CTNF has outstanding catalytic activity for photothermal reverse water gas shift reaction (RWGS). At 350 °C under full-spectrum irradiation, the carbon monoxide (CO) yield of FeNi3-CTNF (10.78 mmol g-1 h-1) is 11 times that of pure CaTiO3(CTO), and the CO selectivity is 98.9%. This superior catalytic activity is attributed to the narrow band gap, photogenerated electron migration to alloy particles, and abundant surface oxygen vacancies. The carbene pathway reaction is also investigated through in-situ Raman spectroscopy. The present work presents a straightforward method for the exsolution of nanoalloys in metal-semiconductor heterostructures for photothermal CO2 reduction.

Landsat-derived impervious surface area expansion in the Arctic from 1985 to 2021.

Accurate and timely impervious surface mapping is essential for assessing land cover change, urban heat island, and monitoring human activity intensity and ecological change. While various global impervious surface datasets become available, these datasets exhibit significant omissions in Arctic regions. Hence, in this study, we present a 30-m impervious surface area (ISA) dataset of Arctic from 1985 to 2021 (GISA_Arcitc). To this aim, we proposed to combine visually interpreted ISA samples and automatically generated NonISA samples for Arctic ISA mapping. Then, adaptive random forest (RF) classifiers were used for long time-series ISA mapping and the result was post-processed to improve the spatial-temporal consistency. Finally, the accuracy of GISA_Arcitc was assessed using the 37,800 independent test samples. GISA_Arctic possessed an overall accuracy of 93.59 % and a F-score of 0.934. It is found that the Arctic ISA increased from 857.83 km2 to 2115.49 km2 during the past 37 years. More than 84 % of the Arctic ISA increment is embraced by three countries: Russia, Finland, and Norway. Courtesy of the long time-series GISA_Arctic, the sources of Arctic ISA expansion were further analyzed. It was found that the top three land covers transformed to ISA are tundra, forest and grassland. The GISA_Arctic could contribute to further understanding of human activities and Arctic ecological changes, which can be accessed from http://irsip.whu.edu.cn/resources/resources_v2.php.

Long-Term Impact of N, P, K Fertilizers in Different Rates on Yield and Quality of Anisodus tanguticus (Maxinowicz) Pascher.

Anisodus tanguticus (Maxinowicz) Pascher (Solanaceae) is a traditional Chinese herb that is widely used in folklore and clinical practice. In recent years, wild populations have been severely impacted to the point of extinction due to over-harvesting and reclamation. Therefore, artificial cultivation is important to relieve the pressure of market demand and protect wild plant resources. Using a "3414" fertilization design, i.e., 3 factors (N, P, and K), 4 levels, and 14 fertilization treatments, with 3 replicates and a total of 42 experimental plots, A. tanguticus was harvested in October 2020, June 2021, August 2021, and October 2021, and the yield and alkaloid content were determined. The study aimed to provide a theoretical basis and technical reference for the standardization of A. tanguticus cultivation. Biomass accumulation and alkaloid content showed a trend of increasing and then decreasing with the application of nitrogen, phosphorus, and potassium, and the biomass accumulation was the highest at the application levels of nitrogen and phosphorus in T6 and T9 and at the application levels of medium and low potassium. The alkaloid content showed an increasing trend between October of the first year and June of the second year and a decreasing trend in the second year with the increase in the harvesting period. Yield and alkaloid yield showed a decreasing trend between October of the first year and June of the second year and an increasing trend in the second year with the increase in the harvesting period. The recommended application rates are 225-300 kg/ha2 for nitrogen, 850-960 kg/ha2 for phosphorus, and 65-85 kg/ha2 for potassium.

Development of a novel MR-conditional microwave needle for MR-guided interventional microwave ablation at 1.5T.

PURPOSE: To develop an MR-conditional microwave needle that generates a spherical ablation zone and clear MRI visibility for MR-guided microwave ablation. METHODS: An MR-conditional microwave needle consisting of zirconia tip and TA18 titanium alloy tube was investigated. The numerical model was created to optimize the needle's geometry and analyze its performance. A geometrically optimized needle was produced using non-magnetic materials based on the electromagnetics simulation results. The needle's mechanical properties were tested per the Chinese pharmaceutical industry standard YY0899-2013. The MRI visibility performance and ablation characteristics of the needle was tested both in vitro (phantom) and in vivo (rabbit) at 1.5T. The RF-induced heating was evaluated in ex vivo porcine liver. RESULTS: The needle's mechanical properties met the specified requirements. The needle susceptibility artifact was clearly visible both in vitro and in vivo. The needle artifact diameter (A) was small in in vivo (Ashaft: 4.96 ± 0.18 mm for T1W-FLASH, 3.13 ± 0.05 mm for T2-weighted fast spin-echo (T2W-FSE); Atip: 2.31 ± 0.09 mm for T1W-FLASH, 2.29 ± 0.08 mm for T2W-FSE; tip location error [TLE]: -0.94 ± 0.07 mm for T1W-FLASH, -1.10 ± 0.09 mm for T2W-FSE). Ablation zones generated by the needle were nearly spherical with an elliptical aspect ratio ranging from 0.79 to 0.90 at 30 W, 50 W for 3, 5, 10 min duration ex vivo ablations and 0.86 at 30 W for 10 min duration in vivo ablations. CONCLUSION: The designed MR-conditional microwave needle offers excellent mechanical properties, reliable MRI visibility, insignificant RF-induced heating, and a sufficiently spherical ablation zone. Further clinical development of MR-guided microwave ablation appears warranted.

A novel method to detect the early warning signal of COVID-19 transmission.

BACKGROUND: Infectious illness outbreaks, particularly the corona-virus disease 2019 (COVID-19) pandemics in recent years, have wreaked havoc on human society, and the growing number of infected patients has put a strain on medical facilities. It's necessary to forecast early warning signals of potential outbreaks of COVID-19, which would facilitate the health ministry to take some suitable control measures timely to prevent or slow the spread of COVID-19. However, since the intricacy of COVID-19 transmission, which connects biological and social systems, it is a difficult task to predict outbreaks of COVID-19 epidemics timely. RESULTS: In this work, we developed a new model-free approach, called, the landscape network entropy based on Auto-Reservoir Neural Network (ARNN-LNE), for quantitative analysis of COVID-19 propagation, by mining dynamic information from regional networks and short-term high-dimensional time-series data. Through this approach, we successfully identified the early warning signals in six nations or areas based on historical data of COVID-19 infections. CONCLUSION: Based on the newly published data on new COVID-19 disease, the ARNN-LNE method can give early warning signals for the outbreak of COVID-19. It's worth noting that ARNN-LNE only relies on small samples data. Thus, it has great application potential for monitoring outbreaks of infectious diseases.

Modifiable risk factors associated with cardiovascular disease and mortality in China: a PURE substudy.

AIMS: To examine the incidence of cardiovascular disease (CVD) and mortality in China and in key subpopulations, and to estimate the population-level risks attributable to 12 common modifiable risk factors for each outcome. METHODS AND RESULTS: In this prospective cohort of 47 262 middle-aged participants from 115 urban and rural communities in 12 provinces of China, it was examined how CVD incidence and mortality rates varied by sex, by urban-rural area, and by region. In participants without prior CVD, population-attributable fractions (PAFs) for CVD and for death related to 12 common modifiable risk factors were assessed: four metabolic risk factors (hypertension, diabetes, abdominal obesity, and lipids), four behavioural risk factors (tobacco, alcohol, diet quality, and physical activity), education, depression, grip strength, and household air pollution. The mean age of the cohort was 51.1 years. 58.2% were female, 49.2% were from urban areas, and 59.6% were from the eastern region of China. The median follow-up duration was 11.9 years. The CVD was the leading cause of death in China (36%). The rates of CVD and death were 8.35 and 5.33 per 1000 person-years, respectively, with higher rates in men compared with women and in rural compared with urban areas. Death rates were higher in the central and western regions of China compared with the eastern region. The modifiable risk factors studied collectively contributed to 59% of the PAF for CVD and 56% of the PAF for death in China. Metabolic risk factors accounted for the largest proportion of CVD (PAF of 41.7%), and hypertension was the most important risk factor (25.0%), followed by low education (10.2%), high non-high-density lipoprotein cholesterol (7.8%), and abdominal obesity (6.9%). The largest risk factors for death were hypertension (10.8%), low education (10.5%), poor diet (8.3%), tobacco use (7.5%), and household air pollution (6.1%). CONCLUSION: Both CVD and mortality are higher in men compared with women, and in rural compared with urban areas. Large reductions in CVD could potentially be achieved by controlling metabolic risk factors and improving education. Lowering mortality rates will require strategies addressing a broader range of risk factors.

[Effect of moxibustion on skin lesions and immune inflammatory response in psoriasis mice].

OBJECTIVE: To observe the effect of moxibustion on skin lesions and immune inflammatory response in psoriasis mice, and to explore the possible mechanism of moxibustion for psoriasis. METHODS: A total of 32 male BALB/c mice were randomly divided into a normal group, a model group, a moxibustion group and a medication group, 8 mice in each group. Psoriasis model was induced by applying 5% imiquimod cream on the back for 7 days in the model group, the moxibustion group and the medication group. At the same time of model establishment, the moxibustion group was treated with suspension moxibustion on skin lesions on the back, 20 min each time, once a day; the medication group was treated with 1 mg/kg methotrexate tablet solution by gavage, once a day. Both groups were intervened for 7 days. The daily changes of skin lesions were observed, and the psoriasis area and severity index (PASI) score was evaluated; the histopathological changes of skin lesions were observed by HE staining; the positive expression of proliferating cell nuclear antigen (PCNA) and T lymphocyte surface marker CD3 were detected by immunohistochemistry; the expression level of serum interleukin (IL) -17A was detected by ELISA, and the relative expressions of tumor necrosis factor-α (TNF-α), IL-1ß and IL-6 mRNA in skin lesions were detected by real-time PCR. RESULTS: The increased and hypertrophy scale, dry skin, red and swollen epidermis and obvious infiltration were observed in the model group, and each score and total score of PASI were higher than those in the normal group (P<0.01). The scale score, infiltration score, and total score of PASI in the moxibustion group were lower than those in the model group (P<0.01); the infiltration score and total score of PASI in the medication group were lower than those in the model group (P<0.01, P<0.05). The inflammatory cell infiltration in the model group was obvious, and the thickness of epidermal layer was increased compared with that in the normal group (P<0.01); the inflammatory cell infiltration and Munro micro abscess were decreased in the moxibustion group and the medication group, and the thickness of epidermal layer was decreased compared with that in the model group (P<0.01). Compared with the normal group, the positive cell number of PCNA and T was increased (P<0.01), and the body mass was decreased, and the spleen index was increased (P<0.01), and the expression of serum IL-17A and the relative expression of TNF-α, IL-1ß and IL-6 mRNA in the skin lesions was increased in the model group (P<0.01). Compared with the model group, the positive cell number of PCNA and T was reduced (P<0.01), and the spleen index and the relative expression of TNF-α, IL-1ß and IL-6 mRNA were reduced (P<0.01) in the moxibustion group and the medication group; the body mass of mice in the moxibustion group was higher than that in the model group (P<0.01); the content of serum IL-17A in the medication group was lower than that in the model group (P<0.01); the relative expression of TNF-α, IL-1ß mRNA in the moxibustion group was higher than that in the medication group (P<0.01). CONCLUSION: Moxibustion could effectively improve the scale and infiltration of skin lesions in psoriasis mice. Its mechanism may be related to inhibiting inflammatory response and regulating immunity.

LAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is now the second leading cause of cancer death worldwide and lacks effectual therapy due to its high rate of tumor recurrence and metastasis. The aim of this study was to investigate the effects of L antigen family member 3 (LAGE3, a member of the LAGE gene family involved in positive transcription) on the progression of HCC. METHODS: The expression of LAGE3 was detected by quantitative real-time polymerase chain reaction. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation assay, EdU, and cell cycle analysis assay were employed to evaluate the proliferation of HCC cells. Annexin V-FITC/PI and TUNEL assay were used to assess the apoptosis rate of HCC cells. Wound healing and transwell assay were used to investigate the migration and invasion of HCC cells. A xenograft model of HCC was established with 2 × 106 Hep3B or SK-HEP1 cells to investigate the in vivo effects of LAGE3. Then, the protein levels of LAGE3, p-p38, p-38, c-Jun N-terminal kinase (JNK),p-JNK, extracellular signal-regulated kinase (ERK), and p-ERK were detected by western blot. RESULTS: We found that LAGE3 was upregulated in HCC tissues compared to adjacent tissues, and its high expression was correlated with poor overall survival by bioinformatics analysis. Next, we manually regulated the expression of LAGE3 in HCC cells. The knockdown of LAGE3 inhibited the proliferation of HCC cells by arresting the cell cycle in G1 phase. Also the downregulation of LAGE3 inhibited cell migration and invasion and induced apoptosis of HCC cells, while overexpression of LAGE3 promoted the malignant phenotypes of HCC. These results were further confirmed by the in vivo growth of HCC xenografts and the inhibition of apoptosis of HCC tumor cells. Furthermore, we found that LAGE3 exerted cancer-promoting effects by potentiating the JNK and ERK signaling pathway. An ERK inhibitor (10 µM SCH772984) or JNK inhibitor (25 µM SP600125) repressed the upregulated LAGE3-induced proliferation, migration, and invasion of HCC cells. CONCLUSIONS: LAGE3 enhanced the malignant phenotypes of HCC by promoting the JNK and ERK signaling pathway.

ITIH5, a p53-responsive gene, inhibits the growth and metastasis of melanoma cells by downregulating the transcriptional activity of KLF4.

ITIH5, a member of the inter-α-trypsin inhibitory (ITI) gene family, acts as a putative tumour-suppressor gene in many cancers. However, its role and the regulatory mechanism in melanoma are still unclear. Here, we found that the expression of ITIH5 was decreased in melanoma tissues compared with normal skin tissues. Decreased expression of ITIH5 was correlated with clinicopathological features and predicted poor prognosis in patients with melanoma. Forced expression of ITIH5 significantly inhibited melanoma cell proliferation and metastasis in vitro and ex vivo while knockdown of ITIH5 expression enhanced the malignant behaviour of melanoma cells. In further mechanistic studies, we showed that p53 can directly bind to the promoter of ITIH5 and thus promotes transcription of ITIH5 in melanoma cells. Additionally, we found that ITIH5 interacted with Krüppel-like factor 4 (KLF4) and inhibited its transcriptional activity. Collectively, our data not only identified a tumour-suppressive role of ITIH5 in melanoma but also revealed that upregulation of ITIH5 by p53 suppressed melanoma cell growth and migration likely by downmodulating the transcriptional activity of KLF4.

Effect of Shuangdan Mingmu capsule, a Chinese herbal formula, on oxidative stress-induced apoptosis of pericytes through PARP/GAPDH pathway.

BACKGROUND: Diabetic retinopathy (DR) has become a worldwide concern because of the rising prevalence rate of diabetes mellitus (DM). Despite much energy has been committed to DR research, it remains a difficulty for diabetic patients all over the world. Since apoptosis of retinal microvascular pericytes (RMPs) is the early characteristic of DR, this study aimed to reveal the mechanism of Shuangdan Mingmu (SDMM) capsule, a Chinese patent medicine, on oxidative stress-induced apoptosis of pericytes implicated with poly (ADP-ribose) polymerase (PARP) / glyceraldehyde 3-phosphate dehydrogenase (GAPDH) pathway. METHODS: Network pharmacology approach was performed to predict biofunction of components of SDMM capsule dissolved in plasma on DR. Both PARP1 and GAPDH were found involved in the hub network of protein-protein interaction (PPI) of potential targets and were found to take part in many bioprocesses, including responding to the regulation of reactive oxygen species (ROS) metabolic process, apoptotic signaling pathway, and response to oxygen levels through enrichment analysis. Therefore, in vitro research was carried out to validate the prediction. Human RMPs cultured with media containing 0.5 mM hydrogen oxide (H2O2) for 4 h was performed as an oxidative-damage model. Different concentrations of SDMM capsule, PARP1 inhibitor, PARP1 activation, and GAPDH inhibitor were used to intervene the oxidative-damage model with N-Acetyl-L-cysteine (NAC) as a contrast. Flow cytometry was performed to determine the apoptosis rate of cells and the expression of ROS. Cell counting kit 8 (CCK8) was used to determine the activity of pericytes. Moreover, nitric oxide (NO) concentration of cells supernatant and expression of endothelial nitric oxide synthase (eNOS), superoxide dismutase (SOD), B cell lymphoma 2 (BCL2), vascular endothelial growth factor (VEGF), endothelin 1 (ET1), PARP1, and GAPDH were tested through RT-qPCR, western blot (WB), or immunocytochemistry (ICC). RESULTS: Overproduction of ROS, high apoptotic rate, and attenuated activity of pericytes were observed after cells were incubated with media containing 0.5 mM H2O2. Moreover, downregulation of SOD, NO, BCL2, and GAPDH, and upregulation of VEGFA, ET1, and PARP1 were discovered after cells were exposed to 0.5 mM H2O2 in this study, which could be improved by PARP1 inhibitor and SDMM capsule in a dose-dependent way, whereas worsened by PARP1 activation and GAPDH inhibitor. CONCLUSIONS: SDMM capsule may attenuate oxidative stress-induced apoptosis of pericytes through downregulating PARP expression and upregulating GAPDH expression.

Risk factors for post-hepatectomy liver failure in 80 patients.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a serious complication and a leading cause of death after hepatectomy, an accurate prediction of PHLF is important for improvement of prognosis after hepatectomy. AIM: To retrospectively analyze the risk factors for postoperative liver failure in patients undergoing hepatectomy for liver tumors. METHODS: The clinical data of 80 patients undergoing hepatectomy in our hospital from June 2018 to January 2020 were collected. With laboratory examination as well as pre- and post-operative abdominal three-dimensional reconstructive computed tomography, the demographic data, surgical data, biochemical indicators, coagulation index, routine blood tests, spleen and liver volumes, relative remnant liver volume, and other related indicators were obtained and compared between patients with PHLF and those without PHLF. RESULTS: PHLF occurred in 19 (23.75%) patients. Univariate logistic regression analysis showed that gender, history of hepatitis/cirrhosis, and preoperative bilirubin, albumin, coagulation function, albumin-bilirubin ratio, aspartate amino-transferase-to-platelet ratio index (APRI), Model for End-Stage Liver Disease score, spleen volume (SV), spleen volume/liver volume ratio (SV/LV), and relative remnant liver volume were statistically associated with the occurrence of PHLF (all P < 0.05). Multivariate regression analysis showed that preoperative total bilirubin, platelets (PLT), APRI, and SV/LV were independent risk factors for PHLF (all P < 0.05). The area under the curve and cut-off values were 0.787 and 18.6 mmol/L for total bilirubin, 0.893 and 146 × 1012/L for PLT, 0.907 and 0.416 for APRI, and 0.752 and 20.84% for SV/LV, respectively. CONCLUSION: For patients undergoing liver resection, preoperative total bilirubin, PLT, APRI, and SV/LV are independent risk factors for PHLF. These findings may provide guidance to safely perform liver surgery in such patients.

Identifying pre-outbreak signals of hand, foot and mouth disease based on landscape dynamic network marker.

BACKGROUND: The high incidence, seasonal pattern and frequent outbreaks of hand, foot and mouth disease (HFMD) represent a threat for billions of children around the world. Detecting pre-outbreak signals of HFMD facilitates the timely implementation of appropriate control measures. However, real-time prediction of HFMD outbreaks is usually challenging because of its complexity intertwining both biological systems and social systems. RESULTS: By mining the dynamical information from city networks and horizontal high-dimensional data, we developed the landscape dynamic network marker (L-DNM) method to detect pre-outbreak signals prior to the catastrophic transition into HFMD outbreaks. In addition, we set up multi-level early warnings to achieve the purpose of distinguishing the outbreak scale. Specifically, we collected the historical information of clinic visits caused by HFMD infection between years 2009 and 2018 respectively from public records of Tokyo, Hokkaido, and Osaka, Japan. When applied to the city networks we modelled, our method successfully identified pre-outbreak signals in an average 5 weeks ahead of the HFMD outbreak. Moreover, from the performance comparisons with other methods, it is seen that the L-DNM based system performs better when given only the records of clinic visits. CONCLUSIONS: The study on the dynamical changes of clinic visits in local district networks reveals the dynamic or landscapes of HFMD spread at the network level. Moreover, the results of this study can be used as quantitative references for disease control during the HFMD outbreak seasons.

[Mental health status and its influencing factors among general population and medical personnel in Guangdong Province during COVID-19 pandemic].

OBJECTIVE: To investigate the mental health status and its influencing factors among general population and healthcare professionals in Guangdong Province during COVID-19 pandemic. METHODS: A online questionnaire-based survey was conducted from March 11st to March 15th, 2020.The questionnaire consisted of 4 parts to survey the participants'basic information, understanding of COVID-19 outbreak-associated information, cognition of COVID-19 pandemic and status of anxiety and depression.A total of 1433 valid responses were collected, including 706 from the general population and 727 from healthcare professionals.Cronbach's α coefficient and exploratory factor analysis were used for reliability and validity assessment.Chi-square, Wilcoxon and Kruskal-Wallis test were used for univariate analysis and ordinal or nominal logistic regression was used for multivariate analysis of the data. RESULTS: There was no significant difference between the general population and the healthcare professionals in terms of anxiety, depression and cognition of COVID-19 outbreak after adjustment for demographic variables, but the levels of anxiety and depression of these participants were both higher than those before the pandemic.In the participants from the general population, multivariate logistic regressions showed an OR for anxiety of 1.93(1.18, 3.17) among those who spent 1-2 h a day in reading COVID-19-related news, while those who spent over 3 h had an OR value for anxiety of 1.88(1.14, 3.11);the unmarried individuals had a depression OR of 2.19(1.51, 3.18). Inaccurate cognition of COVID-19 outbreak was positive correlated with the occurrence of anxiety and depression.Unmarried individuals and those with higher educational levels had better cognition of COVID-19 outbreak.Among the healthcare professionals, multivariate logistic regressions suggested that insufficient rest time and worries about contracting the virus contributed to the occurrence of anxiety and depression.Among the nursing staff, the OR of obvious depression was 2.99(1.45, 6.18).Compared to healthcare professionals not working in designated hospital for COVID-19, those who work in the designated hospitals had ORs for obvious and severe depression of 0.48(0.25, 0.93) and 0.39(0.17, 0.89), respectively.Concerns over contracting the virus increased the possibility of incorrect cognition of COVID-19. CONCLUSIONS: Psychological interventions are essential for both the general population and healthcare professionals, especially for unmarried individuals in the general population and the nursing staff.An excessive exposure to COVID-19-related information may have detrimental effects on the mental health.For healthcare professionals, sufficient rest needs to be ensured, and education programs on COVID-19 should be implemented among both residents and healthcare professionals to improve their mental health.

Detecting the outbreak of influenza based on the shortest path of dynamic city network.

The influenza pandemic causes a large number of hospitalizations and even deaths. There is an urgent need for an efficient and effective method for detecting the outbreak of influenza so that timely, appropriate interventions can be made to prevent or at least prepare for catastrophic epidemics. In this study, we proposed a computational method, the shortest-path-based dynamical network marker (SP-DNM), to detect the pre-outbreak state of influenza epidemics by monitoring the dynamical change of the shortest path in a city network. Specifically, by mapping the real-time information to a properly constructed city network, our method detects the early-warning signal prior to the influenza outbreak in both Tokyo and Hokkaido for consecutive 9 years, which demonstrate the effectiveness and robustness of the proposed method.

Fire needle acupuncture or moxibustion for chronic plaque psoriasis: study protocol for a randomized controlled trial.

BACKGROUND: Psoriasis is a chronic, immune-mediated disorder with chronic plaque psoriasis being the primary manifestation during the remission stage. Patients often have a slow course and long history of the disease. The refractory type of psoriasis is a stubborn rash that does not subside easily. We designed this randomized controlled trial to compare the effectiveness and relapse rates of plaque psoriasis in patients treated with either acupuncture, moxibustion or calcipotriol ointment. The ultimate aim of the study is to select an effective traditional Chinese medicine therapy for patients with plaque psoriasis. METHODS: The study will be a multicenter, prospective, randomized controlled trial that compares the effectiveness of fire needle therapy, moxibustion and calcipotriol ointment. In total, 160 patients with plaque psoriasis who meet the inclusion criteria will be recruited from three hospitals in Beijing and then randomly assigned to receive either fire needle therapy (group A1), moxibustion (group A2) or calcipotriol ointment (group B). All participants will receive an 8-week treatment and will then be followed up for another 24 weeks, with time points at weeks 12 and 24 after treatment completion. The primary outcomes to be measured are relapse rates and psoriasis area and severity index score of the target lesions. In addition, the target lesion onset time, dermatology life quality index, traditional Chinese medicine syndrome score, and the relapse interval of the target lesion will be measured. Adverse events will be recorded for safety assessment. DISCUSSION: The aim of this study is to determine whether fire needle therapy or moxibustion could improve the clinical effectiveness for psoriasis lesions and reduce the relapse rate. Once completed, it will provide information regarding therapeutic evaluation on fire needle therapy or moxibustion for plaque psoriasis, which will assist clinicians in selecting the most effective treatment options for patients. TRIAL REGISTRATION: International Clinical Trials Registry Platform (ICTRP), ChiCTR1800019588. Registered on 19 November 2018.

The Effect of Ginkgo Biloba Dropping Pills on Hemorheology and Blood Lipid: A Systematic Review of Randomized Trials.

OBJECTIVE: A systematic review of randomized trials was performed to assess the effect of Ginkgo Biloba Dropping Pills (GBDP) on clinical hemorheology and blood lipid indicators. METHODS: The data of the Embase, Cochrane Library, PubMed, Clinical Trials, China National Knowledge Infrastructure, the Wanfang database, the VIP database, and the Sinomed were retrieved by computers from the establishment of the database to March 27, 2018, and screened and extracted by two researchers according to inclusion and exclusion criteria. Cochrane 5.0 recommended bias risk assessment tool was used to evaluate the methodological quality of the included literature, and Revman 5.3 software were used for meta-analysis. RESULTS: 10 literatures were finally selected in accordance with the standard. There were a total of 1201 cases, 608 cases in ginkgo biloba dropping pill group and 593 in routine treatment group. Compared with control group, GBDP significantly improved plasma viscosity [N=383, RR= - 0.45, 95%CI=(-0.86,-0.04), P=0.03], whole blood high shear [N=232, RR= - 0.92,95%CI=(-1.69, -0.16), P =0.02], whole blood low shear [N = 232, RR = - 2.22, 95% CI = (- 3.74, -0.7), P = 0.004], red blood cell specific volume [N =132, RR = - 4.55, 95% CI = (- 6.36, 2.73), P < 0.000 01], fibrinogen [N=243, RR=-0.60,95%CI=(-0.82,-0.39), P<0.00001], triglyceride [N=912, RR=-0.60,95%CI=(-1.12, -0.07), P =0.03], cholesterol [N=912, RR=-0.97,95%CI=(-1.41, -0.52), P <0.0001], low-density cholesterol [N=1100, RR=-0.72,95%CI=(-1.19, -0.25), P =0.003], and sensitivity analysis before and after of high-density cholesterol [N=1020, RR=0.08,95%CI=(-0.17,0.34), P =0.52] and [N=683, RR=0.27,95%CI=(0.13,0.42), P =0.0003]. And seven adverse reactions were reported. CONCLUSION: GBDP can improve hemorheology indexes, which is to reduce the blood viscosity, to improve blood lipid status, and to prevent and treat cardiocerebral and renal vascular diseases to a certain extent, with slight clinical adverse reactions. But our results were based on small amount of clinical studies with poor quality and insufficient evidence, which may lead to low credibility of conclusions. Therefore, more large-sample, multiple-center, randomized controlled clinical trials and related mechanisms researches are needed to obtain better clinical trial evidence in order to verify the further effectiveness and safety of GBDP on hemorheology.

Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis.

BACKGROUND: Roxadustat (FG-4592) is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. In phase 2 studies involving patients with chronic kidney disease, roxadustat increased levels of endogenous erythropoietin to within or near the physiologic range, along with increasing hemoglobin levels and improving iron homeostasis. Additional data are needed regarding the efficacy and safety of roxadustat for the treatment of anemia in patients with chronic kidney disease who are not undergoing dialysis. METHODS: In this phase 3 trial conducted at 29 sites in China, we randomly assigned 154 patients with chronic kidney disease in a 2:1 ratio to receive roxadustat or placebo three times a week for 8 weeks in a double-blind manner. All the patients had a hemoglobin level of 7.0 to 10.0 g per deciliter at baseline. The randomized phase of the trial was followed by an 18-week open-label period in which all the patients received roxadustat; parenteral iron was withheld. The primary end point was the mean change from baseline in the hemoglobin level, averaged over weeks 7 through 9. RESULTS: During the primary-analysis period, the mean (±SD) change from baseline in the hemoglobin level was an increase of 1.9±1.2 g per deciliter in the roxadustat group and a decrease of 0.4±0.8 g per deciliter in the placebo group (P<0.001). The mean reduction from baseline in the hepcidin level (associated with greater iron availability) was 56.14±63.40 ng per milliliter in the roxadustat group and 15.10±48.06 ng per milliliter in the placebo group. The reduction from baseline in the total cholesterol level was 40.6 mg per deciliter in the roxadustat group and 7.7 mg per deciliter in the placebo group. Hyperkalemia and metabolic acidosis occurred more frequently in the roxadustat group than in the placebo group. The efficacy of roxadustat in hemoglobin correction and maintenance was maintained during the 18-week open-label period. CONCLUSIONS: In Chinese patients with chronic kidney disease who were not undergoing dialysis, those in the roxadustat group had a higher mean hemoglobin level than those in the placebo group after 8 weeks. During the 18-week open-label phase of the trial, roxadustat was associated with continued efficacy. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652819.).

Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis.

BACKGROUND: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis. METHODS: In a trial conducted in China, we randomly assigned (in a 2:1 ratio) patients who had been undergoing dialysis and erythropoiesis-stimulating agent therapy with epoetin alfa for at least 6 weeks to receive roxadustat or epoetin alfa three times per week for 26 weeks. Parenteral iron was withheld except as rescue therapy. The primary end point was the mean change in hemoglobin level from baseline to the average level during weeks 23 through 27. Noninferiority of roxadustat would be established if the lower boundary of the two-sided 95% confidence interval for the difference between the values in the roxadustat group and epoetin alfa group was greater than or equal to -1.0 g per deciliter. Patients in each group had doses adjusted to reach a hemoglobin level of 10.0 to 12.0 g per deciliter. Safety was assessed by analysis of adverse events and clinical laboratory values. RESULTS: A total of 305 patients underwent randomization (204 in the roxadustat group and 101 in the epoetin alfa group), and 256 patients (162 and 94, respectively) completed the 26-week treatment period. The mean baseline hemoglobin level was 10.4 g per deciliter. Roxadustat led to a numerically greater mean (±SD) change in hemoglobin level from baseline to weeks 23 through 27 (0.7±1.1 g per deciliter) than epoetin alfa (0.5±1.0 g per deciliter) and was statistically noninferior (difference, 0.2±1.2 g per deciliter; 95% confidence interval [CI], -0.02 to 0.5). As compared with epoetin alfa, roxadustat increased the transferrin level (difference, 0.43 g per liter; 95% CI, 0.32 to 0.53), maintained the serum iron level (difference, 25 µg per deciliter; 95% CI, 17 to 33), and attenuated decreases in the transferrin saturation (difference, 4.2 percentage points; 95% CI, 1.5 to 6.9). At week 27, the decrease in total cholesterol was greater with roxadustat than with epoetin alfa (difference, -22 mg per deciliter; 95% CI, -29 to -16), as was the decrease in low-density lipoprotein cholesterol (difference, -18 mg per deciliter; 95% CI, -23 to -13). Roxadustat was associated with a mean reduction in hepcidin of 30.2 ng per milliliter (95% CI, -64.8 to -13.6), as compared with 2.3 ng per milliliter (95% CI, -51.6 to 6.2) in the epoetin alfa group. Hyperkalemia and upper respiratory infection occurred at a higher frequency in the roxadustat group, and hypertension occurred at a higher frequency in the epoetin alfa group. CONCLUSIONS: Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652806.).

Paeonol inhibits the development of 1­chloro­2,4­dinitrobenzene­induced atopic dermatitis via mast and T cells in BALB/c mice.

Our previous studies suggested that paeonol, the active constituent of the traditional Chinese medicine Cortex Moutan, may be an effective treatment for inflammatory disorders. In the present study, the therapeutic potential of paeonol on atopic dermatitis (AD) was investigated using animal and cell experiments. AD­like lesions were induced by repeated application of 1­chloro­2,4­dinitrobenzene (DNCB) to the shaved dorsal skin of BALB/c mice, and P815 cells were used for in vitro assays. The skin lesions, serum and spleens of the mice were analyzed using lesion severity scoring, histological analysis, flow cytometry, reverse transcription­quantitative polymerase chain reaction, western blotting and ELISA, in order to investigate the anti­AD effects of paeonol. In addition, western blotting and ELISA were conducted for in vitro analysis of P815 cells. The results demonstrated that oral administration of paeonol inhibited the development of DNCB­induced AD­like lesions in the BALB/c mice by reducing severity of the lesions, epidermal thickness and mast cell infiltration; this was accompanied by reduced levels of immunoglobulin E and inflammatory cytokines [interleukin (IL)­4, histamine, IL­13, IL­31 and thymic stromal lymphopoietin], along with regulation of the T helper (Th) cell subset (Th1/Th2) ratio. Application of paeonol also reduced the protein expression levels of phosphorylated (p)­p38 and p­extracellular signal­regulated kinase (ERK) in skin lesions. In vitro, paeonol reduced the expression levels of tumor necrosis factor­α and histamine in P815 cells, and inhibited p38/ERK/mitogen­activated protein kinase signaling. The present findings indicated that paeonol may relieve dermatitis by acting on cluster of differentiation 4+ T and mast cells; therefore, paeonol may represent a potential therapeutic strategy for the treatment of allergic inflammatory conditions via immunoregulation.

Hesperidin inhibits keratinocyte proliferation and imiquimod-induced psoriasis-like dermatitis via the IRS-1/ERK1/2 pathway.

AIMS: To evaluate the therapeutic benefits of Hesperidin (Hes) using an imiquimod (IMQ)-induced psoriasis-like mouse model and human immortalized keratinocytes (HaCaT) cells stimulated with lipopolysaccharide (LPS). METHODS: Mice were treated with IMQ and orally administered Hes (125-500 mg/kg/day), methotrexate (MTX) 1 mg/kg/day or distilled water. HaCaT cells were stimulated with LPS (1 µg/mL) and relevant indices were measured after administration with different concentrations of Hes (5-20 µg/mL) for 24 h. Inflammatory skin lesions in IMQ mice were evaluated using the psoriasis area severity index (PASI) and pathological staining. Proteins in the IRS-1/ERK1/2 pathway and inflammatory factors were assessed using western blotting or quantitative real-time PCR. In addition, factors related to IRS-1 secretion levels were assessed by enzyme-linked immunosorbent assays. Extracellular flux (XF) analysis was used to assess cellular metabolic levels. KEY FINDINGS: Hes significantly improved psoriasis-like skin lesions of IMQ-treated mice and inhibited LPS-induced HaCaT cell proliferation. In addition, Hes remarkably decreased PASI scores, reduced epidermal thickness, decreased proliferation and differentiation of epidermal cells, inhibited mRNA expression of inflammatory factors, reduced local skin lesions and serum insulin and glucose levels. Furthermore, Hes modulated the secretion levels of serum Leptin, Adiponectin and Resistin, and inhibited the activation of the IRS-1/ERK1/2 signaling pathway and regulated HaCaT cells metabolism. SIGNIFICANCE: This study demonstrated that Hes administration could have significant therapeutic value for the prevention and clinical treatment of psoriasis.