A Population Pharmacokinetic Assessment of the Effect of Food on Selumetinib in Patients with Neurofibromatosis Type 1-Related Plexiform Neurofibromas and Healthy Volunteers.

Selumetinib is clinically used for pediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas. Until recently, selumetinib had to be taken twice daily, after 2 hours of fasting and followed by 1 hour of fasting, which could be inconvenient. This population analysis evaluated the effect of low- and high-fat meals on the pharmacokinetic (PK) parameters of selumetinib and its active metabolite N-desmethyl selumetinib. The dataset comprised 511 subjects from 15 clinical trials who received ≥1 dose of selumetinib and provided ≥1 measurable postdose concentration of selumetinib and N-desmethyl selumetinib. A 2-compartment model with sequential 0- and 1st-order delayed absorption and 1st-order elimination adequately described selumetinib PK characteristics. A 1-compartment model reasonably described N-desmethyl selumetinib PK characteristics over time simultaneously with selumetinib. Selumetinib geometric mean area under the concentration-time curve ratio (1-sided 90% confidence interval [CI] lower bound) was 76.9% (73.3%) with a low-fat meal and 79.3% (76.3%) with a high-fat meal versus fasting. The lower bound of the 1-sided 90% CI demonstrated a difference of <30% between fed and fasted states. Considering the flat exposure-response relationship within the dose range (20-30 mg/m2), the observed range of exposure, and the variability in the SPRINT trial, this was not considered clinically relevant.

Acute Toxicity Assessment and Prediction Models of Four Heavy Metals.

Water quality criteria (WQC) are developed to protect aquatic organisms. Toxicity data of local fish are essential to improve the applicability of WQC derivatives. However, the paucity of local cold-water fish toxicity data limits the development of WQC in China. Brachymystax lenok is a representative Chinese-endemic cold-water fish, which plays an important role in the characterization of metal toxicity in the water environment. Whereas, the ecotoxicological effects of copper, zinc, lead and cadmium, as well as its potential as a test species for the metal WQC, remain to be investigated. In our study, acute toxicity tests of copper, zinc, lead and cadmium were performed on this fish according to the OECD method and 96 h-LC50 values were calculated. The results showed that the 96 h-LC50 values of Cu2+, Zn2+, Pb2+ and Cd2+ for B. lenok were 134, 222, 514 and 734 µg/L, respectively. Toxicity data for freshwater species and Chinese-native species were collected and screened, and the mean acute values of each metal for each species were ranked. The results showed that the accumulation probability of zinc by B. lenok was the lowest and less than 15%. Thus, B. lenok was sensitive to Zn and can be considered as the test cold-water fish for derivation of Zn WQC. In addition, B. lenok in comparison with warm-water fish, we found that cold-water fish are not always more sensitive to heavy metals than warm-water fish. Finally, the models for toxic effects prediction of different heavy metals on the same species were constructed and evaluated the reliability of the model. We suggest that the alternative toxicity data provided by the simulations can be used to derive WQC for metals.

Wild soybean salt tolerance metabolic model: Assessment of storage protein mobilization in cotyledons and C/N balance in the hypocotyl/root axis.

Salt stress has become one of the main factors limiting crop yield in recent years. The post-germinative growth is most sensitive to salt stress in soybean. In this study, cultivated and wild soybeans were used for an integrated metabonomics and transcriptomics analysis to determine whether wild soybean can resist salt stress by maintaining the mobilization of stored substances in cotyledons and the balance of carbon and nitrogen in the hypocotyl/root axis (HRA). Compared with wild soybean, the growth of cultivated soybean was significantly inhibited during the post-germinative growth period under salt stress. Integrating analysis found that the breakdown products of proteins, such as glutamate, glutamic acid, aspartic acid, and asparagine, increased significantly in wild soybean cotyledons. Asparagine synthase and fumarate hydratase genes and genes encoding HSP20 family proteins were specifically upregulated. In wild soybean HRA, levels of glutamic acid, aspartic acid, asparagine, citric acid, and succinic acid increased significantly, and the glutamate decarboxylase gene and the gene encoding carbonic anhydrase in nitrogen metabolism were significantly upregulated. The metabolic model indicated that wild soybean enhanced the decomposition of stored proteins and the transport of amino acids to the HRA in cotyledons and the GABA shunt to maintain carbon and nitrogen balance in the HRA to resist salt stress. This study provided a theoretical basis for cultivating salt-tolerant soybean varieties and opened opportunities for the development of sustainable agricultural practices.

Advances in Pathogenesis, Progression, Potential Targets and Targeted Therapeutic Strategies in SARS-CoV-2-Induced COVID-19.

As the new year of 2020 approaches, an acute respiratory disease quietly caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. Subsequently, COVID-19 broke out on a global scale and formed a global public health emergency. To date, the destruction that has lasted for more than two years has not stopped and has caused the virus to continuously evolve new mutant strains. SARS-CoV-2 infection has been shown to cause multiple complications and lead to severe disability and death, which has dealt a heavy blow to global development, not only in the medical field but also in social security, economic development, global cooperation and communication. To date, studies on the epidemiology, pathogenic mechanism and pathological characteristics of SARS-CoV-2-induced COVID-19, as well as target confirmation, drug screening, and clinical intervention have achieved remarkable effects. With the continuous efforts of the WHO, governments of various countries, and scientific research and medical personnel, the public's awareness of COVID-19 is gradually deepening, a variety of prevention methods and detection methods have been implemented, and multiple vaccines and drugs have been developed and urgently marketed. However, these do not appear to have completely stopped the pandemic and ravages of this virus. Meanwhile, research on SARS-CoV-2-induced COVID-19 has also seen some twists and controversies, such as potential drugs and the role of vaccines. In view of the fact that research on SARS-CoV-2 and COVID-19 has been extensive and in depth, this review will systematically update the current understanding of the epidemiology, transmission mechanism, pathological features, potential targets, promising drugs and ongoing clinical trials, which will provide important references and new directions for SARS-CoV-2 and COVID-19 research.

Methylparaben as a preservative in the development of a multi-dose HPV-2 vaccine.

The human papillomavirus (HPV) vaccine is the simplest, most economical, convenient, and effective method of preventing cervical cancer. However, the current HPV vaccine is supplied as a single-dose vial with a relatively high cost per dose, which hinders its supply to low- and middle-income countries (LMICs), where the demand for HPV vaccine is highest. Therefore, it is necessary to develop a multi-dose HPV vaccine to promote large-scale affordable vaccination in LMICs. Moreover, the addition of preservatives is required to reduce the risk of microbial contamination in multi-dose vaccines within a single vial. In this study, we investigated the effects of six preservatives on HPV 16L1 and 18L1 virus-like particles in solution, as well as the aluminum adsorption status, under normal and high-temperature conditions. Multiple methods were employed, including dynamic light scattering, differential scanning calorimetry, an in vitro relative potency assay, and an in vivo potency assay in mice. Based on the above results, four types of selected preservatives were further studied, and an antimicrobial effectiveness test was performed on the HPV-2 vaccine, which was employed as a model HPV vaccine. Finally, three preservatives were selected based on their performance to evaluate the long-term stability of the HPV-2 vaccine. The results indicated that 0.12% methylparaben is the most suitable preservative for the multi-dose HPV-2 vaccine, guaranteeing the shelf life for at least three years and meeting "B" standards for antimicrobial effectiveness. The formula developed in this study can contribute toward combating cervical cancer in LMICs.

Does Industrial Agglomeration or Foreign Direct Investment Matter for Environment Pollution of Public Health? Evidence From China.

This article focuses on the interaction between China's industrial agglomeration, foreign direct investment (FDI) and environmental pollution of public health in the past 15 years. By conducting theoretical and empirical research, we try to reveal the relationship and mechanism between the economic growth and public health from the perspective of environmental pollution. By constructing an embedded theoretical model of industrial agglomeration and FDI, this article combines other environmental pollution influencing factors, expounds the impact mechanism of industrial agglomeration on environmental pollution. Based on the provincial-level panel data of China on environmental pollution and industrial agglomeration, the empirical test is carried out through the threshold panel regression model. According to the results, industrial agglomeration can significantly rectify the regional environmental pollution, thereby benefiting public health. FDI has a phased impact on the relationship between industrial agglomeration and environmental pollution. Specifically, when the level of FDI is low, the positive improvement effect of industrial agglomeration on environmental pollution is relatively strong. This is mainly because industrial agglomeration can promote economic growth, technological progress, and enhance environmental awareness. When the level of FDI exceeds the first threshold and continues to rise, the positive improvement effect of industrial agglomeration is maximized. Before the level of FDI exceeds the second threshold, this effect gradually weakens. The population concentration and excessive expansion of city scale brought about by industrial agglomeration will lead to the increase of regional resource and energy consumption, thus aggravating environmental pollution. The policy implication is that while the government and enterprises are vigorously increasing the level of foreign investment, they must pay equal attention to economic growth and public health, and the level of industrial agglomeration should match the level of foreign investment so as to give full play to the positive improvement effect of industrial agglomeration on environmental pollution, and realize the coordinated development of the regional economy, environment and population health.

Active Enhancer Assessment by H3K27ac ChIP-seq Reveals Claudin-1 as a Biomarker for Radiation Resistance in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) represents the third most common malignant tumor in the worldwide. Radiotherapy is the common therapeutic treatment for CRC, but radiation resistance is often encountered. ChIP-seq of Histone H3K27 acetylation (H3K27ac) has revealed enhancers that play an important role in CRC. This study examined the relationship between an active CRC enhancer and claudin-1 (CLDN1), and its effect on CRC radiation resistance. METHODS: The target CRC genes of active enhancers were obtained from public H3K27ac ChIP-seq, and the genes highly expressed in radio-resistant CRC were screened and intersected with enhancer-driven genes. The clinical roles of CLDN1 in radiation resistance were examined using the t-test, standard mean deviation (SMD), summary receiver operating characteristic curve and Kaplan-Meier curves. The co-expressed genes of CLDN1 were calculated using Pearson Correlation analysis, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and Gene Set Variation Analysis (GSVA) analyses were used to examine the molecular mechanisms of CLDN1. RESULTS: Total 13 703 CRC genes were regulated by enhancers using 58 H3K27ac ChIP-seq. Claudin-1 (CLDN1) was enhancer-driven and notably up-regulated in CRC tissues compared to non-CRC controls, with a SMD of 3.45 (95 CI % = .56-4.35). CLDN1 expression was increased in radiation-resistant CRC with a SMD of .42 (95% CI = .16-.68) and an area under the curve of .74 (95% CI = .70-.77). The cell cycle and immune macrophage levels were the most significant pathways associated with CLDN1. CONCLUSION: CLDN1 as an enhancer-regulated gene that can boost radiation resistance in patients with CRC.

Ambient and personnel occupational dose assessment in a Hospital's PET/CT center.

This study used thermoluminescent dosimeters (TLDs) to measure cumulative radiation doses in a PET/CT center. It covered 18 areas and four personnel groups. Because the isolated lead shielding separated the patients from the nurses, wearing protective clothing when injecting radiopharmaceuticals was unnecessary. Fingertip doses of the dispensing and nurse groups were below the occupational limit. Current radiopharmaceutical transportation and injection operations in this PET/CT center provide considerable radiation protection to medical personnel.

[Distribution Characteristics and Pollution Assessment of Nutrients in Hengshui Lake Sediments].

Considering Hengshui Lake as the research object, the representative surface sediments at eleven points were collected in March 2019, and the morphological distribution characteristics of carbon, nitrogen, and phosphorus nutrients in the lake sediments were analyzed. The results showed that the total organic carbon (TOC) content in Hengshui Lake sediments was 93.226 mg·g-1, which might lead to a higher risk of potential nitrogen source release. The total nitrogen (TN) content was 1.850 mg·g-1, which was a moderate pollution load; the contents of various nitrogen forms and the proportions in TN were Res-N (0.973 mg·g-1, 52.57%) > WAEF-N (0.531 mg·g-1, 28.69%) > SOEF-N (0.208 mg·g-1, 11.23%) > IEF-N 0.088 (mg·g-1, 4.77%) > SAEF-N (0.051 mg·g-1, 2.75%). These results further indicated that the risk of nitrogen release from sediments in Hengshui Lake was relatively high. The content of total phosphorus (TP) was 1.020 mg·g-1 and that of inorganic phosphorus (IP) was 0.839 mg·g-1, accounting for 82.27% of the TP content, which was a moderate pollution load; the average content of various phosphorus forms and the proportions in IP were Ca-P (0.440 mg·g-1, 52.44%) > Res-P (0.200 mg·g-1, 23.84%) > Fe-P and Al-P (0.169 mg·g-1, 20.14%) > NH4Cl-P (0.030 mg·g-1, 3.58%). In general, the risk of phosphorus release from sediments in Hengshui Lake was relatively low. The analysis of C/N, C/P, and N/P characteristics showed that the organic matter in Hengshui Lake sediments mainly originated from terrestrial grasses and sedge plants, and the phosphorus in the sediments was mainly affected by terrestrial input. Correlation analysis showed that the correlation between carbon, nitrogen, and phosphorus in Hengshui Lake sediment was weak, and the sources of the three nutrients might be different; the correlation between each form of phosphorus was stronger than that of each form of nitrogen, and each form of phosphorus had very good homology. The sources of various forms of nitrogen were diverse and complex. The pollution status of the lake area was evaluated by organic index and organic nitrogen. The results showed that the nutrient pollution in Hengshui Lake sediments was serious, reaching the Grade Ⅳ standard. The potential risk of nitrogen in sediments should be taken seriously and effectively controlled.

[Occurrence and Ecological Risk Assessment of Typical Persistent Organic Pollutants in Hengshui Lake].

Sediment samples were collected from 11 typical sites in Hengshui Lake separately in August 2018 and March 2019. Characteristics and ecological risk assessment of typical persistent organic pollutants (POPs), including polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs), in these sediments were analyzed. The results showed that the average content of ΣPAHs in sediments of Hengshui Lake was 875.49 ng·g-1 and 1010.17 ng·g-1 in August 2018 and March 2019, respectively. Compared with other regions in China and abroad, ΣPAHs in sediments from Hengshui Lake were at moderate pollution level. Distribution of ΣPAHs varied between different sites, but the values changed within a narrow range in different seasons. Sources of PAHs in sediments from Hengshui Lake were complex, but combustion of wood and coal was the main source, followed by oil pollution. Generally, the ecological risk of PAHs was at a low level. However, fluorene pollution control should be strengthened. For ΣOCPs, the average values in sediments were 35.57 ng·g-1 and 38.39 ng·g-1 in August and March, respectively. Compared with other regions, the pollution of ΣOCPs was at a moderate level. In addition, the distribution of ΣOCPs varied a small amount between different sites. There were significant differences between the two seasons. The contents of DDTs in sediments were mainly related to the residual DDTs after long-term soil weathering and the input of recent DDTs sources. Contents of HCHs in sediments were influenced by the use of HCHs in industrial history and inputs of agricultural lindane. Generally, the ecological risk of OCPs was at a medium level, but the DDTs pollution control should be strengthened. For ΣPBDEs, the average values were 1.77 ng·g-1 and 1.45 ng·g-1 in the sediments in August 2018 and March 2019, respectively. Compared with other regions, they were at a lower pollution level. The distribution of ΣPBDEs showed small differences between different sites, and did not obviously vary between spring and summer. The PBDEs in sediments were mainly low-bromine PBDEs, which might be contaminated with penta-BDEs from textiles and foams. Additionally, PBDEs were also probably input by distant settlement and migration from the atmosphere, and soil flushing into the lake. PBDEs posed no immediate ecological risk.

Assessment of Coronavirus Disease 2019 Community Containment Strategies in Shenzhen, China.

Importance: A new outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 in Wuhan, China, is spreading rapidly around the globe. Limited information on control in community settings is available. Objective: To detail measures enacted within a community to prevent the spread of coronavirus disease 2019 (COVID-19) and to evaluate the spread of COVID-19 associated with implementation of the program. Design, Setting, and Participants: This case series study details the implementation of prevention measures in a specific community setting among community-dwelling individuals exposed to or at risk of COVID-19 in Haiyu, Shenzhen, China, from January 23 to April 10, 2020. Exposures: Community containment strategies for tracking, quarantine, and management were strictly, cooperatively, and effectively implemented by a team that included a general practitioner, a community manager, and public safety bureau officials. Main Outcomes and Measures: Number of locally acquired cases with indirect links to confirmed COVID-19 cases. Diagnosis with COVID-19 was confirmed when throat swab samples tested positive for severe acute respiratory syndrome coronavirus 2 on reverse transcription-polymerase chain reaction. Results: Approximately 34 686 individuals live in Haiyu, including 2382 residents aged 65 years or older. Seven individuals with COVID-19 acquired outside the community (age, 20-70 years; 3 [42%] women) were moved from quarantine to a hospital for standard isolation treatment. A total of 20 people who were asymptomatic and who had had direct contact with these individuals were closely observed by health care workers at a nearby hotel. Additionally, 800 individuals considered to be at higher risk were moved from quarantine to home isolation for 14 days. There were no locally acquired cases of COVID-19 with indirect links reported in the Haiyu community from the time that the study began on January 23, 2020, to April 10, 2020. Conclusions and Relevance: These findings suggest that cooperation among the authorities of multiple sectors allowed for the implementation of preventive measures that were associated with limited community transmission.

Dental expenditure, progressivity and horizontal inequality in Chinese adults: based on the 4th National Oral Health Epidemiology Survey.

BACKGROUND: The financial burden of oral diseases is a growing concern as the medical expenses rise worldwide. The aim of this study was to investigate the dental expenditure, analyze its progressivity and horizontal inequality under the general health finance and insurance system, and identify the key social determinants of the inequality for Chinese adults. METHODS: A secondary analysis used the data of 13,464 adults from the 4th National Oral Health Epidemiological Survey (NOHES) in China was undertaken. The dental expenditure was collected and divided into out-of-pocket and health insurance payments. Horizontal inequality index and Kakwani index were used to analyze the horizontal inequality and progressivity, respectively. The decomposition model of the concentration index was set up to explore the associated socioeconomic determinants. RESULTS: The results showed that a mean dental expenditure per capita of Chinese adults was $20.55 (95% Confidence Interval-CI: 18.83,22.26). Among those who actually used dental service, the cost was $100.95 (95%CI: 93.22,108.68). Over 90% of dental spending was due to out-of-pocket expenses. For self-reported oral health, the horizontal inequality index was - 0.1391 and for the decayed tooth (DT), it was - 0.2252. For out-of-pocket payment, the Kakwani index was - 0.3154 and for health insurance payment it was - 0.1598. Income, residential location, educational attainment, oral hygiene practice, self-reported oral health, age difference were the main contributors to the inequality of dental expenditure. CONCLUSION: Dental expenditure for Chinese adults was at a lower level due to underutilization. The ratio of payments of dental expenditure and utilization was disproportional, whether it was out-of-pocket or insurance payment. Individuals who were more in need of oral care showed less demand for service or not required service in time. For future policy making on oral health, it is worth the effort to further promote the awareness of the importance of oral health and utilization of dental service.

Cryopreserved biopsy tissues of rectal cancer liver metastasis for assessment of anticancer drug response in vitro and in vivo.

Living tumors are of great scientific value for clinical medicine and basic research, especially for drug testing. An increasing number of drug tests fail due to the use of imperfect models. The aim of the present study was to develop a novel method combining vitrification­based cryopreservation of tumor biopsies and precision­cut slice cultivation for the assessment of anticancer drug responses. Biological characteristics of rectal cancer liver metastasis biopsies could be retained by vitrification­based cryopreservation. The patient­derived xenograft models were successfully established using both fresh and warmed biopsy tissues. Precision­cut slicing provided a similar three­dimensional architecture and heterogeneity to the original tumor. The positive drug responses in the xenograft model were consistent with those in precision­cut slice cultures in vitro. The present study demonstrated that live tumor biopsies could be preserved using vitrification­based cryopreservation. The warmed tissues developed xenograft tumors, which were also useful for either in vivo or in vitro anticancer drug testing. Precision­cut slices derived from the warmed tissues provided an efficient tool to assess anticancer drug response in vitro.

Assessment of the efficacy of passive cellular immunotherapy for glioma patients.

To evaluate the therapeutic efficacy of passive cellular immunotherapy for glioma, a total of 979 patients were assigned to the meta-analysis. PubMed and the Cochrane Central Register of Controlled Trials were searched initially from February 2018 and updated in April 2019. The overall survival (OS) rates and Karnofsky performance status (KPS) values of patients who underwent passive cellular immunotherapy were compared to those of patients who did not undergo immunotherapy. The proportion of survival rates was also evaluated in one group of clinical trials. Pooled analysis was performed with random- or fixed-effects models. Clinical trials of lymphokine-activated killer cells, cytotoxic T lymphocytes, autologous tumor-specific T lymphocytes, chimeric antigen receptor T cells, cytokine-induced killer cells, cytomegalovirus-specific T cells, and natural killer cell therapies were selected. Results showed that treatment of glioma with passive cellular immunotherapy was associated with a significantly improved 0.5-year OS (p = 0.003) as well as improved 1-, 1.5-, and 3-year OS (p ≤ 0.05). A meta-analysis of 206 patients in one group of clinical trials with 12-month follow-up showed that the overall pooled survival rate was 37.9% (p = 0.003). Analysis of KPS values demonstrated favorable results for the immunotherapy arm (p < 0.001). Thus, the present meta-analysis showed that passive cellular immunotherapy prolongs survival and improves quality of life for glioma patients, suggesting that it has some clinical benefits.

Organochlorine pesticides in ambient air from the littoral cities of northern China: Spatial distribution, seasonal variation, source apportionment and cancer risk assessment.

Concentrations, composition and seasonal variations of organochlorine pesticides (OCPs) in the atmosphere (particulate phase and gaseous phase) at coastal cities in northern China were determined. OCP transport from emission source areas and lifetime excess cancer risks by inhalation exposure to specific OCPs were also investigated. The annual average concentration of total OCPs in gaseous phase ranged from 1.0ng/m3 to 6.3ng/m3, with the peak observed in summer at most sites. Particulate phase concentrations ranged from 29.9pg/m3 to 103.3pg/m3, with the maximum found in the local heating period at most locations. The detection rates of gaseous samples were considerably higher than those of particulate ones. The dominant components included endosulfan (I and II), (α- and γ-) chlordane, pentachlorobiphenyl (PeCB), hexachlorobenzene (HCB), heptachlor, (α-, ß- and γ-) hexachlorocyclohexane (HCH), dichloro-diphenyl-trichloroethane (DDT) and their metabolic products. The specific ratios indicated different applications of DDT, technical HCH and endosulfan at most sites. Large differences in compositional profiles occurred in January (typical heating period) and July (representative non-heating period), and diurnal changes in component concentrations may have been influenced by local emission pattern. The potential source contribution function (PSCF) manifested seasonal concentrations of airborne OCPs affected by the input of potential sources in different regions. The emission sources with higher contribution probabilities to the sites were primarily distributed in the surrounding areas. The lifetime excess cancer risks for the local residents by inhalation exposure to specific components were not high, though the potential threat of α-HCH and HCB should be concerned. CAPSULE: Gaseous OCPs reached peak values in summer and dominated relative to particulate (PM10) values; meanwhile, surrounding sources affected air OCP concentrations, and cancer risks of OCPs by inhalation exposure were not high.

Tongue Image Database Construction Based on the Expert Opinions: Assessment for Individual Agreement and Methods for Expert Selection.

This study aims at introducing a method for individual agreement evaluation to identify the discordant raters from the experts' group. We exclude those experts and decide the best experts selection method, so as to improve the reliability of the constructed tongue image database based on experts' opinions. Fifty experienced experts from the TCM diagnostic field all over China were invited to give ratings for 300 randomly selected tongue images. Gwet's AC1 (first-order agreement coefficient) was used to calculate the interrater and intrarater agreement. The optimization of the interrater agreement and the disagreement score were put forward to evaluate the external consistency for individual expert. The proposed method could successfully optimize the interrater agreement. By comparing three experts' selection methods, the interrater agreement was, respectively, increased from 0.53 [0.32-0.75] for original one to 0.64 [0.39-0.80] using method A (inclusion of experts whose intrarater agreement>0.6), 0.69 [0.63-0.81] using method B (inclusion of experts whose disagreement score="0"), and 0.76 [0.67-0.83] using method C (inclusion of experts whose intrarater agreement>0.6& disagreement score="0"). In this study, we provide an estimate of external consistency for individual expert, and the comprehensive consideration of both the internal consistency and the external consistency for each expert would be superior to either one in the tongue image construction based on expert opinions.

Report of the National Investigation of Resources for Oral Health in China.

OBJECTIVE: To investigate the current status and distribution of resources for oral health in China, by means of analysing national data from the National Investigation of Resources for Oral Health. METHODS: The National Investigation of Resources for Oral Health in China was performed in 2015, in parallel with the 4th National Oral Health Survey of China (2015 to 2016). A structured questionnaire on resources for oral health was used to collect the data of professional institutions and stomatological/dental workforce in each province. For each province, the local Investigation Group was responsible to summarise the status and distribution of institutions with stomatological/dental departments and stomatological/dental workforce. Descriptive analysis of resources for oral health was performed to learn about the number and percentage of each category both for each province and nationally. The ratio of number of stomatological/dental workforce to population was also calculated and compared with the criteria of the World Health Organisation (WHO). RESULTS: There were totally 75,399 stomatological/dental departments nationally in all professional institutions in the mainland of China, most of which were set in institutions of primary health care services. Institutions of private sectors accounted for a higher proportion (69.8%) which was over two-fold compared to that of public ones (30.2%). General hospitals were the major part of hospitals with stomatological/dental departments compared with stomatological/dental specialised hospitals. Stomatological/dental clinics were the majority of institutions of primary health care services, compared to community health care service centres/stations and township health care services. Amongst all professional institutions of public health with stomatological/dental departments, 35.0% were maternal and child health care services and 11.2% were institutions for prevention and control of oral diseases. The total number of stomatological/dental workforce in the country was 314,347, among whom 171,587 (54.6%) were stomatologists/dentists. The ratio of number of stomatologists/dentists to population was 1:7,768 nationally, which was lower than the WHO standard of 1:5,000. CONCLUSION: The National Investigation of Resources for Oral Health in China exhibited the current status and distribution of resources for oral health over the country, whereas insufficiencies of stomatological/dental workforce and institutions and inequalities of their distribution were found nationally. This could provide some policy suggestions for the health authorities in China to promote oral health in the Chinese population in the future.

Utilisation of Oral Health Services and Economic Burden of Oral Diseases in China.

OBJECTIVE: To evaluate the use of oral health services, the economic burden of oral diseases and related influential factors in China. METHOD: Using the multistage, stratified, equal proportion, random sampling method in the 4th National Oral Health Survey of China conducted in 2015 to 2016, residents aged 3 to 5 years, 12 to 15 years, 35 to 44 years, 55 to 64 years, and 65 to 74 years respectively were recruited, clinically examined and answered a questionnaire. Utilisation of oral health services were assessed in all the age groups and the economic burden of oral diseases in the past 12 months were assessed in the 3 to 5 years and 35 to 74 year-old groups. Chi-squared tests, t tests, correlation analysis and a one-way ANOVA were used to determine the relationships of different factors with utilisation of oral health services and the economic burden of oral diseases. RESULTS: In the subject groups - 3 to 5 years, 12 to 15 years and 35 to 74 years - the prevalence of the utilisation of oral health services in the past 12 months was 14.6% (5,876/40,353), 23.6% (27,936/118,592), and 20.1% (2,708/13,461), respectively. In all three groups, receiving dental treatment was the most common reason for subjects' recent dental visit. The average dental cost in the past 12 months was 403.43 CNY (median = 100) for 3 to 5-year-old children and 850.83 CNY (median = 300) for adults aged 35 to 74 years old. Area, education and annual household income per person were the socio-economic influential factors. Oral health status, oral hygiene and attitudes to and knowledge of oral health affected the utilisation of oral health services and the economic burden of oral diseases. CONCLUSION: The percentage of dental service utilisation was relatively low, and the economic burden was high. The related factors for both utilisation of oral health services and the economic burden of oral diseases included living in area, educational attainment, household income, perceived oral health status, and oral hygiene.

Traditional Chinese medicine pharmacovigilance in signal detection: decision tree-based data classification.

BACKGROUND: Traditional Chinese Medicine (TCM) is a style of traditional medicine informed by modern medicine but built on a foundation of more than 2500 years of Chinese medical practice. According to statistics, TCM accounts for approximately 14% of total adverse drug reaction (ADR) spontaneous reporting data in China. Because of the complexity of the components in TCM formula, which makes it essentially different from Western medicine, it is critical to determine whether ADR reports of TCM should be analyzed independently. METHODS: Reports in the Chinese spontaneous reporting database between 2010 and 2011 were selected. The dataset was processed and divided into the total sample (all data) and the subsample (including TCM data only). Four different ADR signal detection methods-PRR, ROR, MHRA and IC- currently widely used in China, were applied for signal detection on the two samples. By comparison of experimental results, three of them-PRR, MHRA and IC-were chosen to do the experiment. We designed several indicators for performance evaluation such as R (recall ratio), P (precision ratio), and D (discrepancy ratio) based on the reference database and then constructed a decision tree for data classification based on such indicators. RESULTS: For PRR: R1-R2 = 0.72%, P1-P2 = 0.16% and D = 0.92%; For MHRA: R1-R2 = 0.97%, P1-P2 = 0.20% and D = 1.18%; For IC: R1-R2 = 1.44%, P2-P1 = 4.06% and D = 4.72%. The threshold of R,Pand Dis set as 2%, 2% and 3% respectively. Based on the decision tree, the results are "separation" for PRR, MHRA and IC. CONCLUSIONS: In order to improve the efficiency and accuracy of signal detection, we suggest that TCM data should be separated from the total sample when conducting analyses.

Predicting pathway cross-talks in ankylosing spondylitis through investigating the interactions among pathways

Given that the pathogenesis of ankylosing spondylitis (AS) remains unclear, the aim of this study was to detect the potentially functional pathway cross-talk in AS to further reveal the pathogenesis of this disease. Using microarray profile of AS and biological pathways as study objects, Monte Carlo cross-validation method was used to identify the significant pathway cross-talks. In the process of Monte Carlo cross-validation, all steps were iterated 50 times. For each run, detection of differentially expressed genes (DEGs) between two groups was conducted. The extraction of the potential disrupted pathways enriched by DEGs was then implemented. Subsequently, we established a discriminating score (DS) for each pathway pair according to the distribution of gene expression levels. After that, we utilized random forest (RF) classification model to screen out the top 10 paired pathways with the highest area under the curve (AUCs), which was computed using 10-fold cross-validation approach. After 50 bootstrap, the best pairs of pathways were identified. According to their AUC values, the pair of pathways, antigen presentation pathway and fMLP signaling in neutrophils, achieved the best AUC value of 1.000, which indicated that this pathway cross-talk could distinguish AS patients from normal subjects. Moreover, the paired pathways of SAPK/JNK signaling and mitochondrial dysfunction were involved in 5 bootstraps. Two paired pathways (antigen presentation pathway and fMLP signaling in neutrophil, as well as SAPK/JNK signaling and mitochondrial dysfunction) can accurately distinguish AS and control samples. These paired pathways may be helpful to identify patients with AS for early intervention.