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Objective To examine the current prevalence and cost of paediatric off-label drug prescriptions in Gansu, China, and the potential influencing factors.Design The prevalence of off-label prescriptions in paediatrics was evaluated according to the National Medical Products Administration drug instructions in the China Pharmaceutical Reference (China Pharmaceutical Reference, MCDEX) database. The evidence of the prescription was determined by existing clinical practice guidelines and the Thomson Grade in the Micromedex 2021 compendium. We used logistic regression to investigate the characteristics that influence paediatric off-label drug use after single-factor regression analysis.Setting A multicentre cross-sectional study of outpatient paediatric prescriptions in 196 secondary and tertiary hospitals in Gansu Province, China, in March and September 2020.Results We retrieved 104 029 paediatric prescriptions, of which 39 480 (38.0%) contained off-label use. The most common diseases treated by off-label drugs were respiratory system diseases (n=15 831, 40.1%). A quarter of off-label prescriptions had adequate evidence basis (n=10 130, 25.6%). Unapproved indications were the most common type of off-label drug use (n=25 891, 65.6%). A total of 1177 different drugs were prescribed off-label, with multienzyme tablets being the most common drug (n=1790, 3.5%). The total cost of the prescribed off-label drugs was ¥106 116/day. Off-label prescriptions were less frequent in tertiary than in secondary hospitals. Topical preparations were more commonly prescribed off-label than other types of drugs. Senior-level clinicians prescribed drugs off-label more often than intermediate and junior clinicians.Conclusion Off-label drug use is widespread in paediatric practice in China. Three-quarters of the prescriptions may potentially include inappropriate medication use, resulting in a daily economic burden of about ¥81 000 in 2020 in Gansu Province with 25 million inhabitants. The management of off-label drug use in paediatrics in China needs improvement.

Abstract Introduction Thoracic paravertebral block (TPVB) and subcostal transverse abdominis plane block (TAP) have been considered to provide an effective analgesic effect for laparoscopic and thoracoscopic surgery, respectively. The purpose of this randomized, controlled, and prospective study was to evaluate the analgesic effect of TPVB combined with TAP in patients undergoing total minimally invasive Mckeown esophagectomy. Methods Between February 2020 and December 2021, a total of 168 esophageal cancer patients undergoing McKeown esophagectomy at the Cancer Center of Sun Yat-Sen University, China, were randomly assigned to receive patient-controlled epidural analgesia alone (group PCEA, n = 56), patient-controlled intravenous analgesia alone (group PCIA, n = 56), and TPVB combined with TAP and patient-controlled intravenous analgesia (group PVB, n = 56). The primary outcome was a visual analogue scale (VAS) pain score on movement 48 h postoperatively. Secondary endpoints were pain scores at other points, intervention-related side effects, surgical complications, and length of intensive care unit and hospital stay. For the VAS pain score, the Kruskal–Wallis method was conducted for comparison of 3 treatment groups and further pairwise comparison with Bonferroni correction. Results On movement, the VAS in the PVB group was higher than that in the PCEA group at 48 h, 72 h, 96 h, and 120 h postoperatively (p

In order to objectively evaluate the operation effect of the Sustainable Supply Chain (SSC) collaborative governance of Water Diversion Projects (WDPs), this paper, from the perspectives of SSC and collaborative governance, and according to the existing modes of SSC collaborative governance of WDPs, constructs the collaborative management mechanism of related subjects of WDPs, and then constructs the evaluation model of the collaborative governance capacity of WDPs by using the DEMATEL (Decision-Making Trial and Evaluation Laboratory)-ANP (Analytic Network Process) method. Specifically, in this paper, the indexes at various levels are selected through literature mining and text analysis, and the mutual influence degrees among index are determined with the help of DEMATEL, so that the causality diagram can be drawn. On this basis, we obtain the global weight and the mixed weight of each index by using the ANP method and SD (Super Decisions) software, thus determining the relative importance of each index. The study finds that with regard to the SSC collaborative governance capability of WDPs, the highest requirement is made on Information Collaboration Capability (ICC) which also provides the foundational guarantee. The proportion carried by Subject Participation and Collaboration Capability (SPCC) is the lowest, however, its mixed weight is 1.9077, second only to ICC. Both Water Quantity Collaboration Capability (WQCC) and Water Quality Assurance Coordination Capacity (WQACC) account for a high percentage, which is consistent with the actual situation. The study provides a capability evaluation index system for the SSC collaborative governance of WDPs, enriches the theory of SSC collaborative governance of WDPs, and provides decision-making support for the operation and management of WDPs. HIGHLIGHTS The evaluation model of large-scale project collaborative governance is provided.; It provides a solution to judge the relationship between model indicators, which makes up for the shortcomings of indicator independence.; It provides an idea for the evaluation of collaborative governance capacity of water transfer projects.;

The South-to-North Water Diversion project, as one of China's strategic projects, plays an important role in China's development. Sixty-two years after the project was conceived, the central route project began to supply water in 2014. Users along the route are both beneficiaries and project influencers. Their behavior characteristics in the project operation have become a topic worthy of study. In this paper, based on a questionnaire conducted among government departments, enterprises and residents and on stakeholder theory, under the theory model of Sustainable Supply Chain (SSC) around the Triple Bottom Line (TBL) including society, economy and environment, the ecological compensation, sewage treatment and reservoir operation management in Xichuan County were investigated and studied. A total of 289 answers were recovered. Through the survey, it is found that: stakeholders include 15 township governments in Xichuan County, water conservancy project supporting facilities construction companies, ecological industry companies, water supply companies and other enterprises, as well as agricultural growers, rural farmers and non-agricultural residents in Xichuan County. Government stakeholders pursue the development of the overall operation of the project, while enterprises and residents pursue the development of individual economy. Finally, this paper lists the relevant indexes, which provide the opportunity for behavior evolution analysis and sustainable research of the project. HIGHLIGHTS Research into a public welfare water diversion project.; The stakeholders of water diversion project are identified.; Combines water diversion project with sustainable supply chain.; The behavior characteristics of stakeholders are analyzed.; It lays the foundation for later behavior analysis.;

Background: Transcriptional regulators are seminal players in the onset and progression of prostate cancer. However, clarification of their underlying regulatory circuits and mechanisms demands considerable effort. Methods: Integrated analyses were performed on genomic, transcriptomic, and clinicopathological profiles of primary prostate cancer and transcription factor-binding profiles, which included estimating transcription factor activity, identifying transcription factors of prognostic values, and discovering cis- and trans-regulations by long noncoding RNAs. Interactions between transcription factors and long noncoding RNAs were validated by RNA immunoprecipitation quantitative PCR. RNA interference assays were performed to explore roles of the selected transcription regulators. Findings: Sixteen transcription factors, namely, ETS1, ARID4B, KLF12, GMEB1, HBP1, MXI1, MYC, MAX, PGR, BCL11A, AR, KLF4, SRF, HIF1A, EHF, and ATOH1, were jointly identified as a prognostic signature. Candidate long noncoding RNAs interplaying with the prognostic signature constituent transcription factors were further discovered. Their interactions were randomly checked, and many of them were experimentally proved. Transcription regulation by MYC and its long noncoding RNA partner AL590617.2 was further validated on their candidate targets. Moreover, the regulatory network governed by the transcription factors and their interacting long noncoding RNA partners is illustrated and stored in our LNCTRN database (https://navy.shinyapps.io/lnctrn). Interpretation: The prognostic signature constituent transcription factors and their interacting long noncoding RNAs may represent promising biomarkers and/or therapeutic targets for prostate cancer. Furthermore, the computational framework proposed in the present study can be utilized to explore critical transcriptional regulators in other types of cancer. Funding: This work was supported by National Natural Science Foundation of China and Fudan University.

The androgen receptor (AR) and its related signaling pathways play an important role in the development of prostate cancer (PCa). Long non-coding RNAs (lncRNAs) are involved in the regulation of tumorigenesis and development, but their specific mechanism of action remains unclear. This study examines the function and mechanisms of action of lncRNA AC016745.3 in the development of PCa. It shows that dihydrotestosterone (DHT) results in the AR-dependent suppression of AC016745.3 expression in the LNCaP androgen-sensitive human prostate adenocarcinoma cell line. In addition, overexpression of AC016745.3 inhibits the proliferation and migration of PCa cells, and suppresses the expression of AR target genes. This research also demonstrates that the protein NONO interacts with AR and functions as an AR co-activator, promoting AR transcriptional activity. Furthermore, using RNA immunoprecipitation (RIP)-PCR experiments, the study demonstrates that both NONO and AR can bind AC016745.3. Moreover, cell phenotypic experiments reveal that NONO can promote cellular proliferation and migration, and that AC016745.3 can partially antagonize the pro-oncogenic functions of NONO in PCa cells. In summary, the results indicate that AC016745.3 can bind NONO, suppressing its ability to promote AR-dependent transcriptional activity. Furthermore, DHT-dependent suppression of AC016745.3 expression can enhance NONO’s promotion effect on AR.

The androgen receptor (AR) signaling pathway plays an important role in the initiation and progression of prostate cancer. Circular RNAs (circRNAs), the novel noncoding RNAs without 5′ to 3′ polarity or 3′ poly (A), play an important role in multiple diseases. However, the potential roles of androgen-responsive circRNAs in prostate cancer remain unclear. In this study, we identified 3237 androgen-responsive circRNAs and 1954 androgen-responsive mRNAs after dihydrotestosterone (DHT) stimulation using microarray. Among them, the expression of 1296 androgen-responsive circRNAs was consistent with that of their parent genes, and we thought AR might regulate the expression of these circRNAs at the transcriptional level. In addition, 1941 circRNAs expression was not consistent with their parent genes, and we speculated that AR may regulate the expression of those circRNAs at the posttranscriptional level through affecting alternative splicing. Analyzing the androgen-responsive circRNAs regulated at the posttranscriptional level, we identified two key RNA binding proteins (RBPs), WTAP and TNRC6, using the circInteractome database, which may play important role in the biogenesis of androgen-responsive circRNAs. Furthermore, we explored the potential biological functions and predicted the molecular mechanisms of two dysregulated circRNAs (circNFIA and circZNF561) in prostate cancer. In this study, we revealed that circNFIA was upregulated in prostate cancer tissues and plasma samples from patients with prostate cancer; circNFIA may play an oncogenic role in prostate cancer. In contrast, circZNF561 was downregulated and may act as a tumor suppressor in prostate cancer. Our results suggest that androgen-responsive circRNAs might regulate the progression of prostate cancer and could be novel diagnostic biomarkers.

Background: Recently, immune checkpoint inhibitors (ICIs) have been proved one of the most promising anti-cancer therapy, series clinical trials have confirmed their efficacy. But they are also associated with distinctive set of toxic effects, which are recognized as immune-related adverse events. Among those immune-related adverse events, pneumonitis is rare, but it is often clinically serious and potentially life-threatening. Although many clinical trial results of PD-1/PD-L1 inhibitors had been reported incidence of pneumonitis, the knowledge based on the individual cohort data from each clinical trial is limited. So we conducted a meta-analysis of trials of PD-1/PD-L1 inhibitors in patients with advanced cancer and compared relative risk and incidence among different tumor types and therapeutic regimens. Such an analysis may provide important knowledge of this rare but clinically significant and potentially serious immune-related adverse event.Methods: Electronic databases were used to search eligible literatures, include randomized controlled trials (RCTs) comparing immune checkpoint inhibitors vs. standard therapies. All-grade (1–4) or high-grade (3–4) pneumonitis events were extracted. The summary relative risk, summary incidence, and 95% confidence intervals were calculated.Results: The incidence of all-grade and high-grade pneumonitis in non-small cell lung cancer (NSCLC) was significantly higher compared with other tumor types, such as Melanoma, urothelial carcinoma (UC), head and neck squamous cell carcinoma (HNSCC) (3.1% vs. 2.0%; p = 0.02, 1.4% vs. 0.6%; p = 0.03). The risk of all-grade pneumonitis was obtained from all patients in both experimental arm and control arm. Treatment with immune checkpoint inhibitors targeting PD-1/PD-L1 did significantly increase the risk of all-grade and high-grade pneumonitis compared with controls (fixed effects, RR: 4.70; 95% CI: 2.81–7.85; p < 0.00001, RR: 3.33; 95% CI: 1.68–6.59; p = 0.0006).Conclusion: The incidence of immune checkpoint inhibitors related pneumonitis was higher in NSCLC than other tumor types. Patients treated with immune checkpoint inhibitor in experiment arms are more likely to experience any grade pneumonitis than control arms. These findings suggest that clinician need to draw more attention on this rare but serious adverse event.

Angelica sinensis, a traditional Chinese herbal medicine and food, which has a long history of clinical application, is used to improve health conditions and treat various diseases. Angelica sinensis polysaccharides (ASP), the main active component of this traditional Chinese medicine, have multicomponent, multitarget characteristics and very broad pharmacological activities. They play important roles in the treatment of several diseases. In addition, the effect is significant, which may provide a more comprehensive database and theoretical support for applying ASP in the treatment of disease and could be considered a promising candidate for preventing disease. This review summarizes the research progress on the extraction, chemical structure, pharmacological effects, and mechanisms of ASP and its derivatives by reviewing relevant national and international literature and provides comprehensive information and a reliable basis for the exploration of new treatment strategies involving botanical drugs for disease therapy. Literature information was obtained from scientific ethnobotany and ethnomedicine databases (up to September 2024), mainly from the PubMed, Web of Science, and CNKI databases. The literature has explored the extraction, purification, structure, and pharmacological effects of Angelica sinensis polysaccharides. The search keywords for such work included “Angelica sinensis” or “Angelica sinensis polysaccharides,” and “pharmacological effects,” “extraction” and “structure.” Multiple studies have shown that ASP has important pharmacological effects, such as antitumor, anemia-improving, anti-inflammatory, antioxidative, immunomodulatory, hepatoprotective, antifibrotic, hypoglycemic, antiradiation, and antiviral effects, the mechanisms of which appear to involve the regulation of inflammation, oxidative stress, and profibrotic signaling pathways. As a natural polysaccharide, ASP has potential applications as a drug. However, further research should be undertaken to clarify the unconfirmed regulatory mechanisms, conduct standard clinical trials, and evaluate the possible side effects. This review establishes a theoretical foundation for future studies on the structure, mechanism, and clinical use of ASP.

Soil organic matter (SOM) is critical for soil fertility, crop growth, and plays an important role in the global carbon cycle and climate change. Therefore, spatial prediction of SOM is important to rational soil resource utilization, agricultural production, and ecological environment management. However, large-area SOM mapping research heavily relies on legacy soil data, and large-scale recent SOM mapping may not be possible or have lower accuracy due to limited or less recent data availability. In this study, we aimed to improve SOM prediction and mapping accuracy by combining legacy data with limited recent data. Three models, namely, partial least squares regression (PLSR), random forest (RF), and one-dimensional convolutional neural network (1D-CNN), were applied and compared. The results showed that combining legacy and recent data effectively improved SOM prediction accuracy compared to using only recent data. Among the three modeling methods, 1D-CNN exhibited superior performance, with an averaged determination coefficient of the prediction (R2) of 0.58, a root mean square error (RMSE) of 4.56 g/kg, and a ratio of performance to interquartile distance (RPIQ) of 2.05. The predicted SOM content for both legacy (1980 s) and recent (2010 s) periods showed similar spatial distribution patterns throughout the Huanghuaihai Plain. Generally, there was a noticeable trend of increasing SOM content from northwest to southeast, with higher values observed in Jiangsu and lower values concentrated in Henan, Hebei, and Shandong regions within the study area. Over time, SOM contents in the Huanghuaihai Plain showed an increasing trend, with an average increase of 5.90 g/kg from legacy to recent period. This study provides a promising approach for improving SOM prediction and mapping accuracy at large scales, particularly when recent data availability is limited.

BackgroundChina had achieved impressive success in improving maternal health, while the progress of reducing maternal mortality ratio (MMR) varied across regions. Some studies had reported maternal mortality from national or provincial perspective, but researches of the MMR on long-term period at the city or county level rare been reported. Shenzhen has experienced significant socioeconomic and health changes, reflecting the typical development of China's coastal city. This study mainly introduced the levels and trends of maternal death in Baoan district, Shenzhen from 1999 to 2022.MethodsMaternal mortality data were extracted from registration forms and the Shenzhen Maternal and Child Health Management System. Linear-by-Linear Association tests were used to evaluate the trends of MMR among different groups. The study periods were divided into three stages by 8-year interval and χ2 test or Fisher's test was used to test the difference in maternal deaths of different periods.ResultsDuring 1999–2022, a total of 137 maternal deaths occurred in Baoan, the overall MMR was 15.91 per 100,000 live births, declined by 89.31% with an annualized rate of 9.26%. The MMR declined by 68.15% in migrant population, with an annualized rate of 5.07%, faster than that in permanent population (48.73%, 2.86%). The MMR due to direct and indirect obstetric causes shown a downward trend (P

Tumor cell migration is affected by the aryl hydrocarbon receptor (AhR). However, the systematic molecular mechanisms underlying AhR-mediated migration of human neuroblastoma cells are not fully understood. To address this issue, we performed an integrative analysis of mRNA and microRNA (miR) expression profiles in human neuroblastoma SK-N-SH cells treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent agonist of AhR. The cell migration was increased in a time- and concentration- dependent manner, and was blocked by AhR antagonist (CH223191). A total of 4,377 genes were differentially expressed after 24-hour-treatment with 10-10 M TCDD, of which the upregulated genes were significantly enriched in cell migration-related biological pathways. Thirty-four upregulated genes, of which 25 were targeted by 78 differentially expressed miRs, in the axon guidance pathway were experimentally confirmed, and the putative dioxin-responsive elements were present in the promoter regions of most genes (79 %) and miRs (82 %) in this pathway. Furthermore, two promigratory genes (CFL2 and NRP1) induced by TCDD was reversed by blockade of AhR. In conclusion, AhR-mediated mRNA-miR networks in the axon guidance pathway may represent a potential molecular mechanism of dioxin-induced directional migration of human neuroblastoma cells.

Climatological characteristics of pre-summer (April-to-June) rainfall over South China (SC) are examined using 1980-2017 hourly rainfall observations at the national-level weather stations and the ERA-Interim reanalysis data.The short-(1-6 h), moderate-(7-12 h), and long-duration (>12 h) rainfall events are defined at individual stations. The rainfall amount, occurrence frequency, and intensity of the three rainfall types are compared between the two periods of the pre-summer rainy season, i.e., pre-and post-monsoon-onset periods, as well as among three designated subregions, namely, the west inland, east inland, and coastal regions. The major findings are as follows. (1) After the onset of South China Sea (SCS) monsoon, the average rainfall amount and hourly rainfall intensity increase over the entire SC irrespective of the rainfall-events'duration.The occurrence frequency increases for both the short-(1-6 h) and long-duration (> 12 h) rainfall types, but decreases for the moderate-duration (7-12 h) rainfall type. (2) The rainfall amount, frequency and intensity show pronounced regional variations and substantial sub-seasonal variations over SC. Owing to more favorable thermodynamic conditions after the monsoon onset, rainfall intensifies over entire SC, with larger increases of the longer-duration (> 6 h) events over the west-inland region. Moreover, the rainfall events occur more frequently over the west-inland and coastal regions, but less over the east-inland region. As a result, the total rainfall amounts increase over the west-inland and coastal regions after the onset of monsoon, while changing little over the east-inland region. (3) The rainfall events over the west-inland region mainly occur in nocturnal hours during both periods, with the longer-duration events beginning earlier and the beginning and peaking hours of each rainfall type delaying gradually from west to east. The short-duration rainfall events dominantly initiate in the afternoon (about 14:00 BT) over the east-inland, which is more prominent after the SCS monsoon onset, while the beginning and peaking hours of the longer-duration events over the east-inland lack a regional coherence. The short-duration rainfall events over the coastal region mainly initiate during 05:00-08:00 BT in the pre-monsoon-onset period. After the onset of monsoon, this feature remains within 50 km from the coastal line, but changes to around 14:00 BT farther away from the coastal line in the coastal region. The long-duration events over the coastal region tend to initiate in nighttime and peak in daytime during both periods.

Effective drugs for the treatment of myocardial fibrosis (MF) are lacking. Traditional Chinese medicine (TCM) has garnered increasing attention in recent years for the prevention and treatment of myocardial fibrosis. This Article describes the pathogenesis of myocardial fibrosis from the modern medicine, along with the research progress. Reports suggest that Chinese medicine may play a role in ameliorating myocardial fibrosis through different regulatory mechanisms such as reduction of inflammatory reaction and oxidative stress, inhibition of cardiac fibroblast activation, reduction in extracellular matrix, renin-angiotensin-aldosterone system regulation, transforming growth Factor-β1 (TGF-β1) expression downregulation, TGF-β1/Smad signalling pathway regulation, and microRNA expression regulation. Therefore, traditional Chinese medicine serves as a valuable source of candidate drugs for exploration of the mechanism of occurrence and development, along with clinical prevention and treatment of MF.

Abstract Objectives This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1–3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH). Methods The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects’ clinical manifestations and laboratory tests were analyzed retrospectively. Results Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3+, CD4+, CD8+, NK, and CD3-CD19+ cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 μg/L, the sensitivity and specificity of D-Dimer was 88.90 and 90.20%, respectively. Conclusion The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV.

Based on the hourly precipitation data from 67 national-level weather stations over Yunnan Province from 1982 to 2016, three hourly-precipitation types with varying intensities, namely, the extreme (above the 95th percentile), heavy (between the 80th and 95th percentile), and moderate-to-weak (below the 80th percentile) hourly precipitation types, are defined using the percentile method, and their 35 year climatological means and long-term changes are investigated. Results are as follows. (1) The high-value center of mean precipitation intensity is located in southern Yunnan and the high-value center of occurrence frequency is in the northwest, which correspond to the areas with the highest and second highest annual precipitation amount, respectively. Precipitation in Yunnan Province is produced mainly in summer and autumn. Meanwhile, there is a spring rainy season in northwest Yunnan that is characterized by high occurrence frequency, strong intensity, and large precipitation amount during February to April. (2) The thresholds of both the extreme and the heavy hourly precipitation types decrease progressively from south to north and from west to east. (3) In the past 35 year, the annual amount and occurrence frequency of each precipitation type in most areas of the province show a decreasing trend, being most evident in autumn, which weakens with the precipitation intensity. In contrast, the hourly precipitation intensity presents an upward trend that is statistically significant in the extreme precipitation type during summer and autumn.

Abstract A double‐moment version of the SBU‐YLIN cloud microphysical scheme in WRF is introduced. It predicts the mass and number mixing ratios of cloud droplet, rain, cloud ice, and precipitating ice. In addition, a number of physical processes, like rain evaporation, collection between rain and snow are also optimized in the new scheme. The scheme is evaluated and compared with the original one‐moment scheme for a squall line case. We found that the double‐moment approach gives a better representation of rain evaporation, which is critical for the development, morphology, and evolution of the simulated squall line, especially for the enhanced trailing stratiform cloud and leading convective line. The relationship between key microphysical processes and squall line dynamics is investigated to identify the driving mechanisms of the descending rear inflow, cold pool, and slantwise updraft. Furthermore, formation of the transition zone in the simulated squall line strongly depends on the flexible description of ice particle properties, such as size, degree of riming and fall speed.

Based on high-resolution surface observation and reanalysis data, this paper analyzes the extreme heat events (EHEs) over two densely populated urban agglomerations in southeast China, namely the Yangtze River Delta (YRD) and the Pearl River Delta (PRD), including the spatial–temporal distribution of heatwaves and warm nights and the synoptic backgrounds for regional heatwaves. The results show that the occurrence frequency of EHEs is modulated significantly by local underlying features (i.e., land–sea contrast, terrain), and the strong nocturnal urban heat island effects make warm nights much more likely to occur in cities than rural areas during heatwaves. About 80% of the YRD regional heatwaves occur from 15 July to 15 August, while a lower fraction (53%) of the PRD heatwaves is found during this mid-summer period, which partially explains the warm-season average intensity of the former being 2–3 times the latter. A persistent, profound subtropical high is the dominant synoptic system responsible for the mid-summer YRD heatwaves, which forces significant descending motion leading to long-duration sunny weather. The mid-summer PRD heatwaves involve both high-pressure systems and tropical cyclones (TCs). A TC is present to the east of the PRD region on most (about 72%) PRD heatwave days. The organized northerly winds in the planetary boundary layer in the outer circulation of the TC transport the inland warm air, which is heated by the foehn effect at the lee side of the Nanling Mountains and possibly also the surface sensible heat flux, towards the PRD region, leading to the occurrence of the extremely high temperatures.

Abstract Objectives Mycoplasma pneumoniae is a leading cause of community-acquired pneumonia in children. However, its mechanism of pathogenesis is not fully understood, and microRNAs might play a role. This study aimed to explore the microRNA-222-3p (miR-222-3p) expression and its possible role in children with M.pneumoniae pneumonia (MPP). Methods Thirty-six children with MPP and twenty-seven age-matched controls from Children’s Hospital of Soochow University were enrolled in this study. MiR-222-3p and cluster of differentiation 4 (CD4) mRNA were detected using real-time PCR in children’s peripheral blood plasma samples. THP-1 cells and mice were stimulated with M.pneumoniae lipid-associated membrane proteins(LAMPs). Results Children with MPP had significantly higher levels of miR-222-3p and lower levels of CD4 in peripheral blood plasma (P

This paper summarizes the research progress on extreme hourly precipitation (EXHP) over China in the past decade. The main results are as follows. (1) Thresholds of EXHP are usually defined using the percentile method or the empirical distribution function method. The thresholds of EXHP in China show substantial regional variations, with the most intense centers over the coastal South China, Hainan and Taiwan islands, and North China Plain, and two secondary ones in the Sichuan Basin and the middle-lower-reaches of the Yangtze River. (2) The EXHP records are classified into four types according to the synoptic situations under which they occur, i.e., the tropical cyclone, surface front, low-level vortex/shear line, and weak-synoptic forcing types. Each type presents distinctive characteristics in regional distribution and seasonal or diurnal variations. (3) An extreme hourly rainfall event (EXRE) is defined as a continuous time period with hourly rainfall rates at a station ≥ 0.1 mm·h-1, with at least one EXHP record and at most 1 h intermittence. The average duration of EXREs exceeds 12 h in the southeast coastal regions and the Yangtze River valley, but is relatively short (< 6 h) in northern China. The rainfall evolution of EXREs is asymmetric, i.e., rainfall rates increase rapidly from the beginning of an event to the extreme value, but more slowly afterwards to the end of the event, especially over the complex terrains in western China. (4) Over the past 50 years, the positive trends of EXHP in China are scattered. Significant increasing trends of EXHP are observed in Shanghai megacity and the urban cluster over the Pearl River Delta during the rapid urbanization period, which differ from their surrounding areas. Both the observation and modeling studies suggest that the strong urban heat island effect in Beijing is conductive to intensification of hourly precipitation.

Abstract Objective We studied the short-term effects of air pollutant concentrations in Suzhou City on respiratory infections in children of different age groups. Methods We employed clinical data from children hospitalized with respiratory infections at the Children’s Hospital of Soochow University during 2014–2016, and air quality for Suzhou City covering the same period.We investigated the relationships between the air pollutant concentrations and respiratory tract infections in children by causative pathogen using time series models with lagged effects. Results The results of single-pollutant models showed that PM2.5, PM10, NO2, SO2 and CO had statistically significant associations with respiratory tract infections in children under 3 years, with the largest effect sizes at a lag of 3 weeks. Notably, the multi-pollutant model found PM2.5 was significantly associated with viral respiratory in children under 7 months, and bacterial respiratory infections in other age groups, while PM10 concentrations were associated with viral infections in preschool children. Conclusion PM2.5, PM10 and NO2 are the main atmospheric pollutants in Suzhou. The associations between pollutant concentrations and viral and bacterial respiratory infections were stronger among children under 3 years than for older age group.s PM2.5 had the strongest influence on viral and Mycoplasma pneumoniae respiratory infections when multiple pollutants were tested together.

Isoliquiritigenin (ILQ) has a number of biological activities such as antitumor and anti-inflammatory effects. However, biomedical applications of ILQ are impeded by its poor aqueous solubility. Therefore, in this research, we prepared a novel ILQ-loaded nanoemulsion, i.e., ILQ-NE, which consisted of Labrafil® M 1944 CS (oil), Cremophor® EL (surfactant), ILQ, and phosphate-buffered saline, by employing a combined sonication (high-energy) and phase-inversion composition (low-energy) method (denoted as the SPIC method). The ILQ-NE increased the ILQ solubility ~1000 times more than its intrinsic solubility. It contained spherical droplets with a mean diameter of 44.10 ± 0.28 nm and a narrow size distribution. The ILQ loading capacity was 4%. The droplet size of ILQ-NE remained unchanged during storage at 4 °C for 56 days. Nanoemulsion encapsulation effectively prevented ILQ from degradation under ultraviolet light irradiation, and enhanced the ILQ in vitro release rate. In addition, ILQ-NE showed higher cellular uptake and superior cytotoxicity to 4T1 cancer cells compared with free ILQ formulations. In conclusion, ILQ-NE may facilitate the biomedical application of ILQ, and the SPIC method presents an attractive avenue for bridging the merits and eliminating the shortcomings of traditional high-energy methods and low-energy methods.

Based on hourly high-density precipitation data in Guangdong Province, China, 134 warm-sector heavy rainfall (WSHR) events were selected from 2016 to 2018. The synoptic weather patterns of these WSHR events were objectively classified using T-mode principal component analysis. Six WSHR weather patterns were identified, as follows: Type 1-southwest (T1-SW), Type 2-southeast (T2-SE), Type 3-coastal jets I (T3-CJI), Type 4-coastal jets II (T4-CJ II), Type 5-western low vortex (T5-WL), and Type 6-high-pressure (T6-HP). Three high-occurrence WSHR centers were finally extracted: the areas of Yangjiang and Shanwei, and the urban agglomeration of Guangdong–Hong Kong–Macao Greater Bay Area (GBA). Compared with the other five patterns, T6-HP is a newly identified WSHR weather pattern, which is related to a local/small-scale weather system in the context of anomalous northward movement of the western Pacific subtropical high. Notably, the precipitation area of the T6-HP type of WSHR event is smaller, which can only be captured by high-density observations. In addition, the occurrence locations of six large-scale extreme precipitation events were closely associated with the urban agglomerations in GBA, implying that urbanization plays an important role in extreme magnitudes of large-scale WSHR events and their occurrence centers.

Cholangiocarcinoma is one of the most aggressive types of malignancy, and is associated with poor patient prognosis. Recent findings suggest that a decrease in pleckstrin homology-like domain family A, member 1 (PHLDA1) expression is significant in the induction of cell migration and tumor invasion. The clinicopathological significance of the expression of PHLDA1, and its potential correlation with the expression of CD133 in cholangiocarcinoma have remained to be elucidated. In the present study, PHLDA1 protein expression was investigated by immunohistochemical analysis of 218 cholangiocarcinoma tissue samples, as well as 30 para-neoplastic and 20 normal bile ducts. The expression status of PHLDA1 and CD133 was determined, and these results were analyzed against the age, gender, tumor location and size, histological grade, clinical stage and overall mean survival time of the patients. The expression of PHLDA1 protein was markedly decreased in 35.3% of cholangiocarcinomas, compared with that of the para-neoplastic and normal cholangiocytes. Carcinomas with loss of expression of PHLDA1 were signifi- cantly correlated with the tumor site (P=0.001), histological grade (P=0.020) and clinical stage (P=0.0001), but not with age (P=0.085), gender (P=0.456 ) or size (P=0.413), respectively. Kaplan-Meier survival analysis indicated that the loss of expression of PHLDA1 was significantly correlated with the overall survival time (Log rank=193.861; P=0.0001). Furthermore, the expression of PHLDA1 was found to be inversely correlated with the expression of CD133 (γ=-0.142; P=0.036). These findings suggested that the decreased expression of PHLDA1 may be significant in the carcinogenesis and progression of cholangiocarcinoma, and may represent a novel adjunct marker of disease prognosis. [ABSTRACT FROM AUTHOR]

On 22 June 2017, an extreme warm-sector rainfall event hit the western coastal area of South China, with maximum hourly and 12-h rainfall accumulations of 189.4 and 464.8 mm, respectively, which broke local historical records. Multisource observations were used to reveal multiscale processes contributing to the extreme rainfall. The results showed that a marine boundary layer jet (BLJ) coupled with a synoptic low-level jet (LLJ) inland played an important role in the formation of an extremely humid environment with a very low lifting condensation level of near-surface air. Under the favorable pre-convective conditions, convection was initialized at a mesoscale convergence line, aided by topographic lifting in the evening. During the nocturnal hours, the rainstorm developed and was maintained by a quasi-stationary mesoscale outflow boundary, which continuously lifted warm, moist air transported by the enhanced BLJ. When producing the extreme rainfall rates, the storm possessed relatively weak convection, with the 40 dBZ echo top hardly reaching 6 km. The extreme rainfall was produced mainly by the warm rain microphysical processes, mainly because the humid environment and the deep warm cloud layer facilitated the clouds’ condensational growth and collision–coalescence, and also reduced rain evaporation. As the storm evolved, the raindrop concentration increased rapidly from its initial stage and remained high until its weakening stage, but the mean raindrop size changed little. The extreme rain was characterized by the highest concentration of raindrops during the storm’s lifetime with a mean size of raindrops slightly larger than the maritime regime.

Objectives To investigate time trends of preterm birth and estimate the contributions of risk factors to the changes in preterm birth rates over a decade (2009–2018) of transitional period in Shenzhen, China.Design Retrospective cohort study between 2009 and 2018.Setting All births in Baoan during January 2009 and December 2018 registered in the Shenzhen Birth Registry Database.Participants 478 044 live births were included with sociodemographic and medical records for both women and infants.Outcome measures The incidence rate of preterm birth stratified by different maternal and infant characteristics. Multiple logistic regression was used to identify significant risk factors associated with preterm birth. The population attributable risk fraction of each factor was calculated to estimate its contribution to variations of preterm birth rate over the 10 years.Results A total of 27 829 preterm births from 478 044 (5.8%) live births were recorded and the preterm birth rate increased from 5.5% in 2009 to 6.2% in 2018. Medically induced preterm birth rate increased from 2.0% in 2009 to 3.4% in 2018 while spontaneous preterm labour rate decreased from 3.3% to 2.7% over the decade years. Risk factors including multiple pregnancy (0.28% increase) drove the rise of preterm birth rate, whereas changes in maternal educational attainment (0.22% reduction) and prenatal care utilisation (0.45% reduction) had contributed to the decline in preterm birth rate.Conclusions An uptrend of preterm birth rate was observed in an area under rapid sociodemographic transitions during 2009–2018 and the changes were associated with these sociodemographic transitions. Continued investments in girls’ education and prenatal care have the potential of reducing preterm birth rate.

Toxicity of ZnO nanoparticles (NPs) are often related to the release of Zn2+ ions due to their dissolution. Studies also suggest that the toxicity of ZnO NPs cannot be solely explained by the release of Zn2+ ions; however, there is a lack of direct evidence of ZnO particulate effects. This study compared the acute toxicity of ZnO NPs and ZnSO4 following intranasal exposure using a combination of metallomics and metabolomics approaches. Significant accumulation of Zn in the liver was only found in the ZnO NP treatment, with 29% of the newly accumulated Zn in the form of ZnO as revealed by X-ray fine structure spectroscopy (XAFS). This is the first direct evidence suggesting the persistence of ZnO NPs in liver upon intranasal exposure. Although both ZnO NPs and ZnSO4 altered the metabolite profiles, with some overlaps and considerable specificity, of both liver and plasma samples, more and distinct metabolites in the liver and opposite effects in the plasma were altered by ZnO NPs compared with ZnSO4, consistent with no accumulation of Zn detected in liver from ZnSO4. Specifically, a large number of antioxidant-related compounds and energetic substrates were exclusively elevated in the liver of ZnO NP-treated animals. These findings provided direct evidence that persistence of ZnO NPs induced particle-specific effects on the antioxidant systems and energy metabolism pathways. Keywords: Zinc oxide nanoparticles, Zinc ions, Metabolite profile, Energy metabolism, oxidative stress

Curcumin (CUR), a polyphenolic substance extracted from plants, has extensive pharmacological activities. However, CUR is difficult to be absorbed in the body due to its poor stability and low solubility. Studies have found that cochleates can be used as a new delivery system to encapsulate bioactive agents for the purpose of improving its stability and bioavailability. In this study, thin-film dispersion and trapping methods were used to prepare curcumin-loaded cochleates (CUR-Cochs). Then CUR-Cochs were characterized and the encapsulation efficiency was determined by HPLC. In addition, the freeze-drying process of CUR-Cochs was studied and related characterization was performed. CCK-8 assay was used to detect the cytotoxicity of cochleates carrier. Additionally, H2O2-induced cellular oxidative damage model were used to evaluate its antioxidant capacity. The results showed that the structure of CUR-Cochs was a spiral cylinder with an average particle size of 463.8 nm and zeta potential of −15.47 mV. The encapsulation efficiency was the highest (83.66 ± 0.8)% with 1:50 CUR-to-lipid mass ratio. In vitro results showed that cochleates had negligible cytotoxicity and owned antioxidant capacity, which provided the possibility for their applications in food and medicine. In general, the method herein might be a promising method to encapsulate CUR for further use as a bioactive agent in functional foods.

Autism spectrum disorder (ASD) has emerged as a major public health concern due to its fast-growing prevalence in recent decades. Environmental factors are thought to contribute substantially to the variance in ASD. Interest in environmental toxins as causes of ASD has arisen due to the high sensitivity of the developing human brain to toxic chemicals, particularly to dioxin and certain dioxin-like compounds (dioxins). As a group of typical persistent organic pollutants, dioxins have been found to exert adverse effects on human brain development. In this paper, we review the evidence for association of exposure to dioxins with neurodevelopmental abnormalities related to ASD based on both human epidemiological and animal studies. It has been documented that exposure to dioxins during critical developmental periods increased risk for ASD. This notion has been demonstrated in different populations exposed to high or background level of dioxins. Furthermore, the effects and mechanisms of action of dioxins relevant to the pathophysiology and pathogenesis of ASD are summarized, describing potential underlying mechanisms linking dioxin exposure with ASD onset. Further studies focusing on effects of prenatal/perinatal exposure to individual dioxin congeners or to mixtures of dioxins on ASD-associated behavioral and neurobiological consequences in animal models, and on the mechanisms of actions of dioxins, are needed in order to better understand how dioxin exposure might contribute to increased risk for ASD. Keywords: Autism spectrum disorder, Dioxins, Neurodevelopmental disorder, ASD pathophysiology, ASD pathogenesis

Photodynamic therapy (PDT) is a treatment modality that uses light to target tumors and minimize damage to normal tissues. It offers advantages including high spatiotemporal selectivity, low side effects, and maximal preservation of tissue functions. However, the PDT efficiency is severely impeded by the hypoxic feature of tumors. Moreover, hypoxia may promote tumor metastasis and tumor resistance to multiple therapies. Therefore, addressing tumor hypoxia to improve PDT efficacy has been the focus of antitumor treatment, and research on this theme is continuously emerging. In this review, we summarize state-of-the-art advances in strategies for overcoming hypoxia in tumor PDTs, categorizing them into oxygen-independent phototherapy, oxygen-economizing PDT, and oxygen-supplementing PDT. Moreover, we highlight strategies possessing intriguing advantages such as exceedingly high PDT efficiency and high novelty, analyze the strengths and shortcomings of different methods, and envision the opportunities and challenges for future research.

Background: The relationships between the expression of CD133, Ki-67 and prognosis in gastric adenocarcinoma are unknown and needs exploring. Methods: The samples of gastric adenocarcinoma from 336 Chinese patients with follow-up were analyzed for CD133 and Ki-67 protein expressions by immunohistochemical method. Results: CD133 was expressed in up to 57.4% (193/336) of this group of gastric carcinoma. The expression of CD133 was significantly higher in carcinoma than in normal (P = 0.0001) and dysplastic mucosas (P = 0.004). CD133 was positive corresponded with the tumour size, grade, infiltrative depth and clinical stage (all P < 0.05). The overall mean survival time of the patients with CD133 positive expression was shorter than that of patients with negative expression (P = 0.0001). The expression of CD133 has a positive correlation with that of Ki-67 (r = 0.188, P = 0.001) in gastric adenocarcinoma. CD133 was an independent prognostic indicator. (P = 0.0001). Conclusions: It is suggested that CD133 may play an important role in the evolution of gastric adenocarcinoma and should be considered as a potential marker for the prognosis. [ABSTRACT FROM AUTHOR]

Chemical cross-linking combined with proteolytic digestion and mass spectrometry (MS) is a promising approach to provide inter- and intramolecular distance constraints for the structural characterization of protein topologies and functional multiprotein complexes. Despite the relative straightforwardness of these methodologies, the identification and characterization of cross-linked proteins presents a significant analytical challenge, due to the complexity of the resultant peptide mixtures, as well as the array of inter-, intra-, or "dead-end"-cross-linked peptides that may be generated from a single cross-linking experiment. To address these issues, we describe here the synthesis, characterization, and initial evaluation of a novel "fixed charge" sulfonium ion-containing cross-linking reagent, S-methyl 5,5'-thiodipentanoylhydroxysuccinimide. The peptide products obtained by reaction with this reagent are all shown to fragment exclusively via facile cleavage of the C-S bond directly adjacent to the fixed charge during CID-MS/MS, resulting in the formation of characteristic product ions that enable the presence and type (i.e., inter, intra, or dead-end) of the cross-linked products to be readily determined, independently of the "proton mobility" of the precursor ion. Subsequent isolation and dissociation of these products by MS³ provides additional structural information required for identification of the peptide sequences involved in the cross-linking reactions, as well as for characterization of the specific site(s) at which cross-linking has occurred. The specificity of these gas-phase fragmentation reactions, as well as the solubility and stability of the cross-linking reagent under aqueous conditions, suggests that this strategy holds great promise for use in future studies aimed at the structural analysis of large proteins or multiprotein assemblies. [ABSTRACT FROM AUTHOR]

An intercomparison of six cloud-resolving and large-eddy simulation models is presented. This case study is based on observations of a persistent mixed-phase boundary layer cloud gathered on 7 May, 1998 from the Surface Heat Budget of Arctic Ocean (SHEBA) and First ISCCP Regional Experiment - Arctic Cloud Experiment (FIRE-ACE). Ice nucleation is constrained in the simulations in a way that holds the ice crystal concentration approximately fixed, with two sets of sensitivity runs in addition to the baseline simulations utilizing different specified ice nucleus (IN) concentrations. All of the baseline and sensitivity simulations group into two distinct quasi-steady states associated with either persistent mixed-phase clouds or all-ice clouds after the first few hours of integration, implying the existence of multiple equilibria. These two states are associated with distinctly different microphysical, thermodynamic, and radiative characteristics. Most but not all of the models produce a persistent mixed-phase cloud qualitatively similar to observations using the baseline IN/crystal concentration, while small increases in the IN/crystal concentration generally lead to rapid glaciation and conversion to the all-ice state. Budget analysis indicates that larger ice deposition rates associated with increased IN/crystal concentrations have a limited direct impact on dissipation of liquid in these simulations. However, the impact of increased ice deposition is greatly enhanced by several interaction pathways that lead to an increased surface precipitation flux, weaker cloud top radiative cooling and cloud dynamics, and reduced vertical mixing, promoting rapid glaciation of the mixed-phase cloud for deposition rates in the cloud layer greater than about 1-2x10-5 g kg-1 s-1. These results indicate the critical importance of precipitation-radiative-dynamical interactions in simulating cloud phase, which have been neglected in previous fixed-dynamical parcel studies of the cloud phase parameter space. Large sensitivity to the IN/crystal concentration also suggests the need for improved understanding of ice nucleation and its parameterization in models.