A systematic review and meta-analysis conducted to evaluate the combined effect of distraction intervention for needle-related pain in order to provide the basis for developing an effective nursing intervention for children. We searched three electronic databases, PubMed, Embase, and CINAHL, for original articles published in the period from 1 January 2011 to 31 July 2019. In addition, a manual search was performed on the basis of references in the literature and the references of the articles in pursuit of comprehensive data until 10 December 2019. Meta-analysis was performed by the synthesis of the effect size, homogeneity, heterogeneity, and trim-and-fill method using MIX 2.0 Pro. Well-planned RCTs, single-center studies, high-quality studies, participants older than 10 years of age, and visual and clown distraction interventions were effective for needle-related pain and distress management among children. The results showed evidence supporting the effect of distraction interventions for children’s needle-related pain and distress. Through this review, strategies were identified to design better interventions to improve the outcomes. Several international pain-related expert groups, including the World Health Organization (WHO), contend that optimally effective pain management is a fundamental human right and good and ethical practice ,2. ThereBoth healthy and medically ill children may have difficulty with needle-related procedures . VaccinaBecause it is very important and difficult to evaluate and manage children’s pain, many hospitals regard pain as the fifth vital sign ,15,16,17With the report that children’s pain and fear associated with needle insertion can adversely affect the process of treatment, various interventions have recently been introduced to relieve them. Albeit it is necessary to apply interventions that can effectively reduce pain and distress in children, it is difficult to apply them in clinical practice when special preparation and training and complicated procedures are required. As distraction techniques are often applied by nurses and parents and can relieve pain in children during treatment, they have recently attracted attention as practical nursing interventions . Distraction intervention is defined as a cognitive or behavioral strategy to relieve pain, stress, and anxiety by distracting children from a harmful stimulus to what they do or something attractive through a non-pharmacological method of pain management . LiteratPain management needs to be provided on a scientific ground, not based on personal opinions or beliefs; every healthcare provider needs to provide optimal pain management . Nurses This study aimed to estimate the overall effect size of distraction interventions on needle-related pain and distress in children and provide a ground for developing a nursing intervention that would effectively relieve needle-related pain and distress in children.We performed a systematic and comprehensive review and a meta-analysis to determine the effects of distraction interventions on needle-related pain and distress in children. The study was performed according to the systematic consideration handbook presented by Cochrane Collaboration  and the Articles were first searched based on the criteria of population, intervention, comparison, outcome, and study design (PICO-SD). The population was limited to children, intervention to distraction intervention for relieving needle-related pain and distress, comparison to patients given usual care, outcome to needle-related pain and distress, and study design to randomized controlled trials (RCTs) and studies with a quasi-experimental design. An electronic database search was performed for national and international studies according to the inclusion and exclusion criteria to choose articles published in English that showed specific statistics of the intervention effects, including the mean and standard deviation and the sample number.Three electronic databases—PubMed, Embase, and CINAHL —were useOf the total 686 screened articles , 27 articles were finally included based on the exclusion criteria for overlapping, population, study design, intervention, and variables. Of these, 13 articles with two experimental groups were included in the analysis, with the interventions in each group separated from each other. As a result, a total of 45 studies were included in this analysis .The Checklist for Randomized Controlled Trials and the Checklist for Quasi-Experimental Studies in the Joanna Briggs Institute of Critical Appraisal Tools  were useThroughout the course of data screening and collection, two researchers independently reviewed each study included in the analysis. The EXCEL program was used to exclude overlapping articles. Next, titles and abstracts were reviewed to identify articles that met the inclusion criteria; if it was difficult to determine if they met the criteria on the basis of titles or abstracts alone, the original text was referenced to determine inclusion. The bibliographical information of every article was coded in the EXCEL program and managed in the identical way, with the excluded articles recorded by stages. For the final articles, authors, publication year, country, number of centers, population size, participants’ age, Institutional Review Board (IRB) approval status, funding status, research design, intervention type and characteristics, intervention in the control group, outcome variables, and quality evaluation scores were collected and recorded in the coding table.2 for the actual variance of the observed total variance or the interobserver variance rate was estimated [2 > 50% regarded as indicator of heterogeneity [The characteristics of the studies were presented as frequencies or the mean and standard deviation. MIX 2.0 Pro  was used for statistical analysis of the method of combining the effect size. For the effect size, standardized mean difference and 95% confidence intervals (CIs) were used for the same outcome variable and the weight of each effect size was estimated using the inverse number of variances . The ranstimated , with I2ogeneity . The funogeneity .There were 14 studies published before 2015 and 31 after 2015; six in East Asian countries, such as India and Taiwan, 12 in American countries, such as the United States, Canada, and Brazil, and 27 in other countries. There were 40 single-center studies and 36 had a population of 50 to less than 300 persons. In 41studies, the mean age of the population was <10 years and four studies  had participants aged ≥10 years. Forty-one studies had IRB approval and 15 were funded. There were 41 RCTs, including two crossover RCTs, and four quasi-experimental studies. Regarding distraction intervention types, visual distraction was used in 19 studies, audial distraction in seven, clowns in two, cognitive behavioral therapy in two, multiple methods, including touch and acupressure, in 13, and local anesthesia in two studies. Thirty-eight studies involved no intervention or usual care given by parents in the control group. Characteristics of the included studies are presented in For the quality evaluation, two RCTs and two quasi-experimental studies among the final 45 studies were included in the pilot test for scores. There was 90.5% consistency, and it was agreed that inconsistent items would be scored 0 if the homogeneity was “not tabulated in the results of the text though described in the abstract”. In the methodological quality evaluation, 41 RCTs scored 9.05 (range = 7–12) and four quasi-experimental studies scored 7.00 (range = 5–9). As for the qualitative level of the studies, the conclusion had no possibility of being changed.d tends to overestimate the population variance, especially for small samples (n < 20) [In the 41 studies, the mean of the differences between the pre-test and the post-test in both groups, the standard deviation of the differences, and the sample size were used to estimate standardized mean differences, which were presented in a synthesis forest plot . Since t(n < 20) . Second,(n < 20) .p = 0.002). The effect size was highly heterogeneous: I2 = 92.1% [For the children, the overall effects of needle-related pain were at the medium level of −0.50 (95% CI = −0.82 to −0.18) and the needle-related pain decreased significantly after distraction intervention . For the 38 single-center studies, the overall effects were at a medium level of −0.51 (95% CI = −0.85 to −0.17) and were statistically significant . For the 37 studies without IRB approval, the overall effects were at a medium level of –0.64 (95% CI = −0.89 to −0.39) and the needle-related pain decreased significantly after distraction intervention . For the 15 studies with funding, the overall effects were at a high level of –0.83 (95% CI = −1.20 to −0.46) and the needle-related pain decreased significantly after distraction intervention .For the 26 studies with participants aged ≥10 years, the overall effects were at a high level of –1.07 (95% CI = −1.60 to −0.53) and the needle-related pain decreased significantly after distraction intervention . While the overall effects of multiple distraction methods, including audial, cognitive, and touch and acupressure, were statistically insignificant, those of the visual distraction method was at a high level of −0.76 (95% CI = −1.15 to −0.37), which was statistically significant . The overall effects of clowns were at a high level of −3.64 (95% CI = −4.76 to −2.52), which was statistically significant . For the total 37 RCTs, including the two crossover RCTs, the overall effects were at a medium level of −0.61 (95% CI = −0.92 to −0.30) and the needle-related pain decreased significantly after distraction intervention .For the 17 studies with a score ≥10 in the quality evaluation, the overall effects were at a medium level of −0.65 (95% CI = −0.98 to −0.32) and the needle-related pain decreased significantly after distraction intervention . For the 14 studies related to observer anxiety (nurses), the overall effects were at a high level of −1.03 (95% CI = −1.67 to −0.40) and observer anxiety (nurses) decreased significantly after distraction intervention .In the 45 studies, besides needle-related pain in children as a principal variable, observer pain was measured in parents and nurses, anxiety in children, parents, and nurses, and blood cortisol in children . Twenty-In the publication bias analysis for validation, funnel plot analysis was first performed, as usually recommended, to identify publication biases . As seenA total of 45 studies published from 2011 to 2019 were included in the meta-analysis for the effect size of distraction intervention on needle-related pain and distress in children. The results can be discussed as follows. Of the 45 studies, 32 (69.6%) were published after 2015 and the majority of them were published in the United States, Canada, and Brazil . Twenty-six articles on distraction and 13 on hypnosis for needle-related pain and distress in children and adolescents  indicateOf the 45 studies, 41 (89.1%) were conducted in participants aged <10 years on average and 17 (37.0%) had participants aged ≥10 years. This implies that for the study design, consideration was given to the fact that young children might be vulnerable to fear of needle insertion. However, it is necessary to pay attention to the decrease of the overall effects in children aged ≥10 years in the subgroup analysis for needle-related pain. Since children aged ≥10 years may experience needle-related pain and distress in various settings, it is necessary to conduct an RCT on distraction intervention in this population.The meta-analysis found that the overall effects of needle-related pain were at a medium level and that the needle-related pain and distress decreased significantly after distraction intervention. Regarding the type of distraction interventions, visual distraction and clown programs were effective in relieving needle-related pain and distress; therefore, it is necessary to actively develop methods of relieving needle-related pain and distress taking these intervention types into account. There are diverse settings and methods of using distraction intervention . RecentlThe RCTs that were conducted at a single center and scored ≥10 in the quality evaluation showed medium to high levels of effects, which were statistically significant. Journal editors have recently tried to apply diverse methods for securing the quality and transparency of studies. One of the methods is to ensure that researchers comply with the guidelines for reporting results; the items in the guidelines are consistent with those in the quality evaluation . EvidencIn the 45 studies besides needle-related pain directly measured in children, observer pain and anxiety were measured in parents and nurses. After distraction intervention, the overall effects on needle-related pain and observer pain were statistically insignificant. Similarly, Uman et al.  failed tThis study has the limitations of a meta-analysis; it is difficult to include unpublished articles and those not retrieved in the analysis. Because some of the included studies were narrow in scope, there were limitations in generalizing the results. It was a necessary process for planning new interventions in the future by analyzing various interventions, but the low statistical power of the meta-analysis results obtained for some variables of the interventions analyzed was. Furthermore, articles not written in English were excluded, which limits the interpretation. Other limitations are that few studies were conducted in older children or adolescents and that limited information about the distraction intervention procedure was presented for other researchers to conduct repeated research and was insufficient to solve any problems with the usability of distraction intervention in clinical practice. In addition, no studies have been conducted to determine whether applying distraction interventions was effective in terms of time and costs.This study aimed to determine the effect size of distraction intervention on needle-related pain and distress in children, analyze the contents of the intervention, and present a direction for its practical application and further research through a meta-analysis of 45 studies published from 2011 to 2019. Despite several limitations of the previous studies, distraction intervention was significantly effective in relieving needle-related pain and distress in children. Well-planned RCTs conducted at a single-center, high-quality study, participants older than 10 years of age, and visual and clown distraction interventions were effective for needle-related pain and distress management among children. Based on these results, the following suggestions can be made:First, it is necessary to examine the effects of distraction intervention on needle-related pain and distress more scientifically and increase intervention research to expand it into the area of nursing.Second, it is necessary to apply it to various pediatric nursing settings with various types of longer intervention based on the theoretical framework; randomized experimental study, which is a study design effective in applying the results, is required. Methodological strictness is required in terms of study design, implementation, and reporting.Third, it is necessary to provide education and training to parents and healthcare professionals, including nurses, to narrow the gap between theories and practice concerning distraction intervention.


We investigated the predictors of mortality within 28 days among preterm infants at a tertiary hospital in Lusaka, Zambia.st January 2018 to 30th September 2019. Information was retrieved with a follow-up period of 28 days post-delivery to discharge/mortality. We used the Weibull hazards regression to establish the best predictor model for mortality among the neonates.we reviewed admission records linked to birth, mortality, and hospital discharge from 1a total of 3237 case records of women with a median age of 27 years  were included in the study, of which 971 (30%) delivered term infants and 2267 (70%) preterm infants. The overall median survival time of the infants was 98 hours . Preterm birth was not associated with increased hazards of mortality compared to term birth (p=0.078). Being in the Kangaroo Mother Care compared to Neonatal Intensive Care Unit (NICU), and a unit increase in birth weight were independently associated with reduced hazards of mortality. On the other hand, having hypoxic-ischemic encephalopathy, experiencing difficulty in feeding and vaginal delivery compared to caesarean section independently increased the hazards of mortality.having hypoxic-ischemic encephalopathy, vaginal delivery, and experiencing difficulty in feeding increases the risk of mortality among neonates. Interventions to reduce neonatal mortality should be directed on these factors in this setting. Preterm birth (PTB) is the birth of a baby before 37 completed weeks of gestation and is a global burden with associated complications which remain high , 2. GlobIn developing countries, neonatal mortality average around 26 per 1000 live births in contrast, just 3 per 1000 live births in developed countries , 8. For In Zambia, a number of interventions have been adopted to improve survival of preterm infants such as administration of antenatal corticosteroids like dexamethasone in women presenting with preterm labour, neonatal resuscitation, and KMC which involves the mother and neonate in skin to skin contact and adequate breastfeeding . AdditioStudy design: this was a retrospective cohort study. The study used admission records from 1st January 2018 to 30th September 2019 with linked birth, mortality, and hospital discharge records. The interest was to identify preterm infants from admission to determine their survival rates past 28 days from admission to NICU ward. Preterm infants who survived past 28 days or discharged before 28 days were right-censored [censored  while alStudy setting: the study was conducted in NICU and Kangaroo Mother Care (KMC) admission ward at the Women and Newborn Hospital in Lusaka, Zambia. This is the largest referral hospital in Zambia for both obstetric and gynaecological conditions [nditions . On avernditions . The hosStudy population and sampling procedure: the study population comprised neonates who were admitted to the NICU and those sent to KMC ward, with complete follow-up time from birth to either discharge or mortality. We defined a neonate as a newborn infant less than 28 days of life [ of life . These wSample size and power analysis: a preliminary study conducted in Zambia reported 37.2% mortality among neonates attributed to preterm births and 60% to other causes, and this corresponded to 1.5% (16/1754) and 9.1% (27/1754) respectively from the total mortality in the study population. Using the freedman method [n method  on the aData extraction: data was collected from Neonatal Case Record (NCR) and admission files using an Excel-based predesigned data collection form by trained assistants. Completeness of information on all variables as recorded in the files was audited at the end of each day to ensure accuracy. Relevant demographic and medical data were extracted from the medical records. Demographic data included maternal age, sex and age of baby (in hours), on admission. For medical data, we recorded birth weight, gestational age, Apgar score, feeding status, care of preterm infants, diagnosis of sepsis, kangaroo mother care, diagnosis of hypoxic-ischaemic encephalopathy, mode of delivery and HIV exposure status. The extracted data was then entered into Microsoft excel operating system. Data coding, cleaning and validation were conducted until the database corresponded with data collected on the forms. After that data was exported to Stata (version 16) in readiness for analysisMortality: interest was to model predictors of neonatal mortality with time to the event . Information on RDS, sepsis, KMC, feeding status, HIE, mother's HIV status, gestational age, NEC and birth weight were used to control for confounding.Statistical methods: continuous variables such as birth weight of the baby and maternal age were tested for normality using Shapiro-Wilk test and Quantile-Quantile plots therefore median, and interquartile range (IQR) were reported for descriptive statistics because the variables were skewed, while for categorical variables, frequencies and percentages were reported. For the comparison of baseline characteristics, Wilcoxon rank-sum test (Mann-Whitney test) was used for maternal age and birth weight. We used Pearson chi-square test of independence for categorical variables after checking the assumption of a chi-square test (expected cell frequency should not be less than 5). The effect of preterm birth and other predictors on mortality was estimated using adjusted Weibull model. This model was used given that the assumptions of constant hazard overtime for a Cox model was not satisfied. In order to find a Weibull regression model, firstly backward elimination with a liberal P-value for exclusion of P=0.20 was carried out in order to identify clinical and socio-demographic factors to include in the final model. The main primary exposure (preterm birth) was then fixed in the model with the identified clinical and socio-demographic factors. The model was then subjected to a backward elimination selection with a stricter P-value for exclusion of P=0.10. Appropriate model fitting parameters and assumptions were checked after fitting the final model. The Kaplan-Meier survival curve was used to illustrate the difference in survival between preterm and term neonates. Inflation of type-I error rate was avoided, loss of power and classification of individuals who are close to the chosen cut point as having very different levels of risk, by not categorising continuous predictor variables (such as birth weight) [ weight) . All staEthical considerations: the University of Zambia Biomedical Research Ethics Committee UNZABREC approved this study (ref: UNZA-221/2019). Additional permission was obtained from Women and Newborn Hospital management to extract data and conduct the study at the hospital. Data were de-identified to protect the participant's confidentiality.Clinical and demographic characteristics of study participants: the study reviewed 3237 medical records of neonates with case records of the mother's delivery notes. Majority 1854 (55.7%) of the neonates were males. About 2366 (71.2%) were delivered vaginally, 953 (38.8%) through caesarean section. From the total, 584 (18%) were exposed to HIV infection, 926 (27.9%) developed Hypoxic Ischaemic Encephalopathy (HIE), 1528 (46.5%) had RDS. Furthermore, 1501 (45.1%) developed sepsis, 329 (10%) had difficulty in feeding, 1162 (35%) were in KMC and 167 (5%) developed NEC. The median maternal age was 27 years . From a total of 3237, 1963 died for whom there was information on time in hours until the event of death. Assuming hazard function to be constant, the incident rate of mortality from a total person-time follow up of 392340 hours was estimated as 0.0049 per hour or 4.9 per 1000 person-hours, which would correspond to 0.0048976*24=0.12 per day or 120 per 1000 persons per day. The median survival time of the neonates was 98 hours . There was a significant difference in birth weight in kilograms  between the infants who did not die and those who died respectively. Additionally, there was evidence of a difference in mortality and mode of delivery (p<0.0001), HIE (p<0.0001), KMC (p<0.0001), NEC (p<0.0001), Gestational age (p<0.0001). On the other hand, exposure to HIV infection (p=0.795), RDS (p=0.484) sepsis (p=0.836), difficult feeding (p=0.316) were not significantly associated with mortality . In the following section, we compare two competing models . The Cox-proportional hazards model is based on the assumption that the hazards  are constant over time . The Weibull model assumes that the hazards are not constant but can increase or decrease monotonically [onically .The cox-proportional hazards model: the results of the Cox-proportional hazards model are presented =: In(p)=0 for which the test statistics is-0.31 and reports that we rejected  the null hypothesis and state that the hazard is not constant. The value parameter P<1 (0.74) indicates that the baseline hazard is monotone decreasing. Therefore, the Weibull model is suitable for modelling this data that is exhibiting monotone hazard rate. From the results of the Weibull model, Being in KMC , having sepsis , and a unit increase in birth weight  were significantly associated with reduced hazards of mortality controlling for all covariates. On the other hand, having HIE , experiencing difficulty in feeding  and vaginal delivery compared to caesarean section  independently increased the hazards of mortality in this population.This study was aimed at assessing predictors of mortality among preterm infants at Women and Newborn Hospital in Lusaka, Zambia. The overall median survival of neonates was 98 hours IQR;34-360). We found that preterm infants were at increased risk of mortality compared to term infants, although we could not rule out random chance finding. Additionally, we found evidence of a difference in risk of mortality between preterm and term neonates and mode of delivery, HIE, KMC, NEC and gestational age. From the Weibull model, we noted that the best predictors of mortality were KMC, difficulty in feeding, sepsis, birth weight, HIE and vaginal delivery. Our results are similar to current evidence on neonatal mortality , 33 thou-360. We The response of the neonates organ systems to the demands of the extrauterine environment, including NICU have an important impact on the neonates' risk of mortality , 36. Accet al. [et al. [We found a significant difference in birth weight between infants who died and those who did not. Birth weight independently decreased the risk of mortality in the first 28 days of post-natal life. Low-birth-weight of neonates has been linked to early infant mortality previously -44. The et al.  found a  [et al.  found th [et al. . This co [et al. , 50. Anoet al. [The findings on HIE in our study support the current evidence in the medical literature that it is a very serious neonatal condition responsible for increased neonatal hospitalisation and mortality -54. Thiset al.  who obseSurprisingly, we found that sepsis was associated with reduced hazards of mortality among neonates in our study. However, it is well documented in the extant literature that sepsis is responsible for increased mortality among neonates in the first 28 days -64. AccoThis study has limitations worth noting. Firstly, we were unable to verify the consistency of case definitions used for the diagnosis of major conditions known to be associated with neonatal mortality, which may have affected the accuracy of the data recorded. For instance, in the study setting due to shortages of blood culture bottles, the diagnosis of sepsis is mainly presumed and may depend on the level of competence of the attending medical personnel. This may have led to misclassification of neonates in our model and may have had affected the overall results on sepsis. Secondly, we could not control for some maternal variables like prophylaxis with steroids during pregnancy, type of pregnancies (multiple or singleton gestation), diseases during pregnancy, place of delivery, prolonged rupture of membranes, maternal fever, meconium-stained amniotic fluid and premature rupture of membranes as these were not recorded in the files. However, our study has some strength. First, the study used a large data set, giving us adequate power to detect differences in mortality between preterm and term neonates compared to similar studies. Second, we conducted this study in a setting with a very high rate of preterm births and associated complications. This enabled us to assess adequately for various known risk factors of mortality. Additionally, most previous studies have not justified the use of a Cox proportional regression model which is strict on assumptions of constant hazards of mortality over time. Our study was able to demonstrate that the hazards of mortality may actually not be constant over time and regression modelling that takes this aspect into account, like the Weibull model may explain the data well.From our findings, the factors associated with risk of mortality among neonates were difficulty in feeding, HIE and vaginal delivery. These findings are suggestive of the need for NICU staff to closely monitor neonates presenting with HIE and manage them promptly to reduce their risk of mortality. Mortality in these neonates is best modelled in the Weibull model that takes into account varying baseline hazards over a follow-up period.The neonatal mortality rate is quite high in sub-Saharan Africa;The risk of mortality is higher for preterm infants than the term infants;Sub-Saharan Africa shares this burden disproportionately when compared to other developed countries.The neonatal mortality rate at a tertiary public health institution in Zambia which is the largest referral hospital for obstetric and neonatology conditions in the country;Kangaroo mother care reduces the hazards of mortality within 28 days in the study population;The best model that explains neonatal mortality data well is the Weibull regression model.


In China, green food refers to a wide array of certified agricultural and processed edible commodities that are produced strictly following defined standard protocols and labelled with a specified “Green Food” logo. The demand for green labelled rice is rapidly growing due to its higher quality and adherence to safety standards compared to conventional rice. Therefore, the physicochemical and nutritional quality of green rice needs to be further investigated for consumers’ benefits. Using Daohuaxiang 2, one of the most famous types of green rice, we found that green rice was significantly superior to conventional rice in terms of thousand kernel weight, chalkiness, amylose content, and rheological properties. Green rice contained lower levels of heavy metals than conventional rice due to a dramatic reduction in chemical inputs during its cultivation. The concentrations of Cr, As, Cd, Pb in green rice decreased, respectively, from 98.7 to 180.1 μg/kg, 49.8 to 62.3 μg/kg, 7.8 to 9.1 μg/kg, and 29.0 to 42.8 μg/kg on average. Gas chromatography coupled with mass spectrometry (GC–MS)-based metabolomics, in combination with multivariate analysis, revealed that 15 metabolites differentially accumulated when comparing green and conventional rice. Among these, 12 metabolites showed a high accumulation in green rice, including seven amino acids, two sugars, and three fatty acids. Overall, our results suggest the superior quality of a type of green rice that is popular in China, which may boost green rice consumption and facilitate the further expansion of green rice production in China. Rapid economic growth in China has been accompanied by the increasing concern of consumers with respect to food quality and safety. In China, there are three levels of certification systems for food, which is indicative of the stringency of the associated standards, namely safe food, green food, and organic food . Green fRice is one of the most important staple cereal foods for half of the world’s population. In order to ensure food security, many countries frequently apply greater amounts of chemical fertilizers than required. The average rate of applied nitrogen (N) fertilizer was 180 kg N/ha for rice in China, which is 75% higher than the world average ,7,8. NitRice comprises the largest proportion of green food products and accounts for 14.9%. According to statistics, the yearly output yield of green-certified rice is 15.6 million tons, which was 7.4% of the total output of the nation in 2019 (CGFDC). The most important at-attitudinal factors relating to consumers’ choice of green food include health concerns, environmental concerns, and taste preferences . To dateOryza sativa ssp. japonica cv. Daohuaxiang 2) is predominantly grown in Wuchang city, Heilongjiang Province. Thus, Daohuaxiang 2 was selected for this study. The aim of the present study was to investigate and compare the nutritional quality of green labelled (hereafter referred to as “green rice”) and conventional rice. To the best of our knowledge, no papers comparing the quality of green and conventional rice have been published. This paper reports the first study investigating the effects of green versus conventional agricultural practices on rice quality. It is expected that the information obtained in the present study could provide insights into green food in China and help consumers be better informed about green food, thus, promoting consumer confidence.Wuchang is a city located in the northeast of China, and it is an important rice growing area with natural conditions that are excellent for this purpose. Wuchang rice has be-come extremely popular and well-known and is associated with high quality rice in China . The braTwenty commercially available Daohuaxiang 2 rice samples, including ten green-certified and ten conventional rice samples, were purchased from a local Beijing supermarket. According to the selection criteria, the same variety (Daohuaxiang 2) and representative brands available at the time of sampling were selected as the experimental materials . All of High-performance liquid chromatography (HPLC)-grade methanol, acetonitrile, dichloromethane, and water were obtained from Fisher Scientific . Formic acid of HPLC grade was purchased from TIC . Bis (trimethylsilyl) trifluoroacetamide (BSTFA), trimethylchlorosilane (TMCS), adonitol, nitric acid, acetic acid, and perchloric acid were obtained from Sigma Aldrich .The thousand kernel weight (TKW) of green and conventional rice was determined in triplicate based on randomly selected kernels that were weighed using an electrical balance. The bulk density was calculated as the ratio of milled rice grains to their volume and is reported as g/mL. The chalkiness degree was assessed according to the method of the China National Standard NY/T 593–2013. The moisture, protein, and fat content were analyzed by near-infrared (NIR) spectroscopy . The determination of amylose was carried out calorimetrically using the amylose–iodine reaction. The amylose content was calculated using mixed standards of amylose and amylopectin . The peaThe elements in rice were determined using the method described in a previous report . In brieg. Next, 0.7 mL of the upper layer solution was transferred to a 1.5 mL Eppendorf tube and vacuum-dried in a CentriVap centrifugal vacuum concentrator . Sixty microliters of methoxyamine hydrochloride (20 mg/mL in pyridine) was added to each vial and incubated for 30 min at 80 °C. Subsequently, 80 μL BSTFA reagent  was added, followed by a reaction time of 1.5 h at 70 °C. GC-MS analysis was conducted using an Agilent 7890 gas chromatograph  system equipped with a Shimadzu GC–MS QP2010 Plus . The instrumental settings followed previous protocols [Metabolomic analysis using gas chromatography coupled with mass spectrometry (GC-MS) was performed according to a previous report, with slight modifications . First, rotocols .t-test was performed to analyze significance of cross-group difference, and p values lower than 0.05 indicated statistical significance.Tentative identification of metabolites was achieved using National Institute of Standards and Technology (NIST) 15 standard mass spectral databases  with a similarity of more than 80%, verified by available reference compounds. Peak areas were normalized to the internal standard and exported to MS Office Excel . Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) was conducted using SIMCA-P + software . Statistical analysis was conducted using the SPSS statistical software . The Student’s The physical properties, including the thousand kernel weight, bulk density, chalkiness, and percentage of chalky kernels, of the green and conventional rice are reported in Most inspection guides for rice use chalkiness and the percentage of chalky kernels for grading. The chalky grain rate of first-grade high-quality rice is lower than 10%, while that of inferior rice is higher than 30% in China . ChalkinThe main chemical components of green and conventional rice are shown in Previous studies have reported that the protein content is negatively correlated to the palatability of rice ,30,31. MLow-amylose rice is generally soft and sticky after cooking, whereas high-amylose rice is harder and less sticky. This result, in accordance with previous results, indicate that organic rice shows a higher amylose content than conventional rice ,38. A hip < 0.05). Peak viscosity is an indicator of water-binding capacity. The peak viscosity of green rice ranged from 3625 to 4463 centipoise (cP), with a mean value of 4250 cP, while for conventional rice, this ranged from 3417 to 4325 cP, with a mean value of 4055 cP. The final viscosity indicates the ability of the starch to obtain a gel structure after cooking and cooling. The final mean viscosity value of 4353 cP for green rice was high compared to that of conventional rice. Breakdown viscosity is associated with the ease of cooking rice starch, and this value for green rice (1526 cP) was higher than that of conventional rice (1478 cP), but this difference was statistically insignificant (p = 0.5231). Setback viscosity indicates the rate of starch retrogradation, and green rice was found to have lower rates of starch retrogradation compared with conventional rice.The pasting properties, as determined by RVA, are widely accepted indicators for the critical and rapid assessment of the eating and cooking quality of rice . The peaCooking quality is an important attribute with respect to consumers’ acceptance, and has been found to vary significantly for rice depending on the cultivation system. Overuse of N fertilizers leads to poor eating and cooking quality of the grain . The pasFour toxic elements of the rice samples were analyzed . ChromiuArsenic (As) is a ubiquitous metalloid that can cause cancer in humans and enter the food chain mainly from contaminated drinking water . Rice haRice grains around the world are frequently contaminated with cadmium (Cd), which poses a serious threat to human health and has attracted widespread concern . The conLead (Pb) is one of the more frequently studied elements in rice ,49. It hp values < 0.05). P and K were the most abundant essential elements in both types of rice, and the P contents of the green rice and conventional rice ranged from 657.3 to 772.0 mg/kg and 671.3 to 995.2 mg/kg, respectively. For K, the content found in green rice ranged from 453.8 to 667.4 mg/kg, which is lower than that in the conventional rice, which ranged from 535.1 to 739.5 mg/kg. Both elements were significantly higher in conventional rice, which may be due to the fact that P and K are contained in synthetic fertilizer and are largely used in conventional rice farming.The levels of eight essential elements  were determined in the rice samples. These micronutrients are important for human health, and a deficiency of these microelements can result in serious diseases. The ANOVA results of each element for the green and conventional rice showed that the P, K, Mg, Fe, and Zn levels were significantly different  concentrations in green rice ranged from 11.6 to 15.2 mg/kg, while the concentration in conventional rice ranged from 13.7 to 17.1 mg/kg. The mean zinc content in green rice was 13.3 mg/kg, and the mean value in conventional rice was 15.3 mg/kg. Zn is one of the most essential elements required for the growth of human beings. The relatively low Zn concentrations found in both types of rice cannot meet the daily dietary requirement .The results of the present study indicate the importance of management practice in contributing to rice element accumulation. Concentrations of all examined toxic  and essential elements  in green rice were lower compared to those of conventional rice. Chemical fertilizers promote the absorption of more elements from the soil by the rice. There were no significant differences found in Ca, Cu, and Na between the green and conventional rice. The synthetic N, P, and K compound fertilizers are applied at high concentrations in conventional rice, so the associated elements are accumulated at higher levels. With strict regulations and regular inspection, green rice contained significantly lower levels of toxic elements than conventional rice. These results are useful as scientific evidence of the greater safety of green rice in comparison with conventional rice in terms of toxic metal levels. In a study by Xiao et al. in China, the range of Cr, As, Cd, and Pb contents in rice increased from 0 to 200 μg/kg, 100 to 200 μg/kg, 0 to 150 μg/kg, and 0 to 100 μg/kg, respectively . When cop < 0.05  and PC2 (12.2%) . A similp < 0.05 . These sThe 15 differential metabolites included seven amino acids, five sugars, and three fatty acids. The heatmap shows the abundance of metabolites in different clusters from each sample . In greeThe results of untargeted metabolomics in this study revealed that the metabolic variations between green and conventional rice were significantly different. Amino acids are essential nutritional components in rice. The difference in amino acid contents between green and conventional rice may be due to their different production systems. The green rice was produced with a limited amount of chemical fertilizers in combination with organic fertilizers. In a previous study, the combined application of organic and chemical fertilizers significantly increased the nitrogen use efficiency, soil matter, microbial activity in the soil, and rice yield ,16,60. Sp-values of less than 0.001. It was reported that nitrogen overfertilization significantly inhibited sugar biosynthesis and lower its accumulation with the application of K [We noted that the contents of sucrose and lactose were significantly higher in green rice than in conventional rice, with ion of K . Howeverion of K . All of ion of K . It has ion of K .In our study, most metabolites were highly accumulated in green rice. Most probably, the production systems of green rice involved chemical fertilizers combined with organic fertilizers, which can improve the utilization rate of fertilizers and the microbial activities in soil and alter metabolic pathways to certain extent within the plant, thus, enhancing the accumulation of beneficial metabolites in rice.Currently, the growing concern of consumers as regards food safety and the environment is gaining strength. The current agricultural system in China heavily depends on the use of chemical N, which negatively affects N use efficiency and soil health, the environment, and food safety. This paper investigated and compared the quality and metabolomics of rice grown in green-certified versus conventional production systems. The physicochemical and rheological properties were higher for rice grown under the green-certified system than under the conventional farming system. The toxic elements in both types of rice were very low, indicating that the investigated rice sold in Beijing markets can be regarded as very safe, although the green rice was found to be safer than the conventional rice, as it had a lower toxicity. However, the essential elements  were present at lower levels in green rice compared with conventional rice. Through untargeted metabolomics analysis using GC–MS, we found that 15 of the 64 detected metabolites were more highly expressed in green rice, and three metabolites were more highly expressed in the conventional rice. The differences between the two types of rice in terms of metabolites may be mainly due to the reductions in the use of synthetic fertilizers and the combined use of organic and chemical fertilizers. Thus, the green rice production system is a potential alternative to the conventional system, which allows for a reduction in chemical fertilizer use, producing safer rice of a higher quality and, thus, is financially attractive to farmers. The results of this study could be useful in the further development of green rice production in China.


In light of the COVID-19 pandemic and the Sino–US trade war, this study proposes a grey sharing decision-making evaluation model for production base movement and the sustainable operation of enterprises in the footwear industry. First, a focus group technique was employed; personnel from the footwear industry, corresponding government agencies, and the academic community were invited to jointly identify the most important criteria when considering a production base movement. The group listed seven criteria: labor cost, materials, exchange rate fluctuation, tariff, supply chain, transfer cost, and the government. The grey situation decision-making algorithm based on group knowledge and entropy were used to identify the most suitable country for production base movement. The footwear industry is labor-intensive, and is affected by various factors such as land resources, labor costs, material supply, environmental protection, and sales markets. Consequently, in pursuit of profit maximization, major consumer markets, footwear manufacturers, wholesalers, and retailers worldwide are shifting their focus to lower-cost countries, leading to constant movement of global shoemaking bases (Kong Cheong Shoes Group Taiwan's footwear industry has gone through five phases: (1) Early phase (1949–1960): Under the business strategy adopted during this period, the store and factory were located in the same place, with the main service being shoe customization. Each shoemaker could therefore make only one or two pairs of shoes per day  to analyze the movement of the production bases of original equipment manufacturers (OEMs), for the sustainable operation and development of footwear enterprises. For this purpose, first, the focus group method was used; personnel from the footwear industry, government, and academic community were invited to jointly identify the criteria for evaluating production base movement. Thereafter, the grey situation decision-making (GSDM) algorithm and entropy were used to construct the model. The results of this study can serve as a useful reference for the sustainable operation of shoemaking OEMs.The shoe supply chain includes the sourcing of raw materials, transforming them into semi-finished goods , and branding   = Nij, where Ni is the evaluation value of the mapping.If The entropy weight Step 1 Normalize the assessment production base movement index.Step 2 Calculate the relative amount of the production base movement information of the assessment index.Sj is between 0 and 1; and Step 3 Calculate the weight of the criterion index.Step 4 Calculate mapping data M.M satisfies M (Sij) = Nij R, M can be referred to as the mapping effectiveness measurement. The properties of M are as follows:If mapping data For benefit effectiveness-measuring target of M.For the cost effectiveness-measuring target of M.i is the index of the measurable production base movement factor, and j is the index of the participation in the evaluation needs of decision makers.For the moderate effectiveness-measuring target of M.Eij have i measuring targets. If the mapping of Sij is M (Sij) = Nij, then the synthetic measured effectiveness value, Eij, for one of the events is as follows:Let the production base movement scenario The associated mapping synthetic effectiveness measuring vectors xi, and If Founded in 1977, Zong Da Company experienced the most prosperous period in Taiwan's footwear export sales. During this period, the Taiwanese footwear industry began to produce upstream raw materials for other industries, including textile, rubber, and plastics. All materials accounted for 60% of the overall cost of sneakers. Different shoe parts require different materials. Upstream materials had a complete supply chain . In 1991, Zong Da Company moved its production base to China mainly for two reasons: (1) rising wages and a drastic exchange rate increase resulted in a sharp decline in profits, and (2) a high growth rate was estimated in the global sneakers market in the future. However, owing to the 2018 Sino–US trade war, and in the wake of both wage increases as well as the COVID-19 pandemic in 2020, changes occurred in consumption patterns and there were sharp fluctuations in exchange rates, causing the Zong Da Company to actively start considering moving its production base.This study used a focus group method  exchange rate fluctuations—$1 was equivalent to NT$26.8 and CNY5.34, respectively  Low-end shoes, using the same production pattern as in Solution A, are produced in China; however, profitability will be worse than before. (2) The production and R&D of high-end shoes are moved to Taiwan. Taiwan has well-educated R&D personnel. Automated production helps increase product value. Initial investments are high, but profitability will also be high in the long run. (3) The Taiwanese government has proposed a southward investment plan, in which the company can establish strategic alliances in Southeast Asian countries to enjoy local government subsidies.Disadvantages:(1) Insufficient basic electric power in Taiwan is a concern for the production division. (2) Business tax in Taiwan is slightly higher than that in neighboring countries, but the exchange rate risk is lower in Taiwan.Solution C:Move the production base to Vietnam.Advantages:Vietnam has a complete supply chain for the footwear industry, which can maintain its existing production and ordering models.Disadvantages:Most shoes produced in Vietnam are exported to Europe, and comply with European environmental specifications and requirements. However, the shoes produced by Zong Da Company are exported to the United States rather than Europe, and there will be uncertainties in managing distributors.Solution D:Move the production base to Myanmar.Advantages:Myanmar has a complete supply chain for the footwear industry, which can maintain its existing production and ordering models.Disadvantages:The political environment is unstable, and there are high uncertainty risks associated with exchange rates and domestic tax rates.Solution E:Evaluate the export and domestic markets and move the production base to the Philippines.Advantages:(1) The economic growth rate of the Philippines is above 6.9%, and consumption is strong. (2) Labor costs in the Philippines are lower than those in other countries. (3) The population is growing rapidly to over 100 million, providing a large domestic market. (4) The government is willing to set up industrial zones that provide tax incentives. (5) Shoes are exported to the U.S. market with a relatively stable exchange rate and tariff preferences.Disadvantages:In the Philippines, there is no complete supply chain for the footwear industry, and the wage advantage is not obvious.Step 6 Formulate the criteria and decision-making plans to evaluate the production base movement.Topic 2: Selecting a research method for evaluating production base movementThe participating scholars proposed a combination of GSDEM and entropy to evaluate solutions. Combining these two research methods has the following advantages: (1) GSDEM is mainly used for dealing with an event and coping with multiple decisions in the event, and can effectively optimize the method of ranking dual-situation solutions. Its advantages include objective evaluation, simple computation, clear principles, and reliable effects. (2) Entropy can be used to calculate the weights of the evaluation criteria based on data randomness. The weights of the evaluation criteria are not affected by the preferences of decision makers, thus achieving objective decision-making for the company’s sustainable operation in the future. The decision-making process for evaluating the production base movement is as follows:Step 6.1: Calculate the GSDEM data of the evaluation criteria for the five alternative solutions.The seven evaluation criteria include: labor costs, materials, exchange rate fluctuations, tariffs, supply chain, transfer costs, and government policies. These criteria were submitted to 20 participants based on historical data and professional judgment. Data 0–1) were analyzed using Eq.  and and3) antep 6.3: Calculate the GSDEM evaluation data after adjustment.SEquation  was usedStep 6.4: Standardize the data.Among the seven evaluation criteria, the polarity of the values of two criteria, supply chain and government policies, should be as large as possible, and that of the other five criteria should be as small as possible. Therefore, the data were normalized using Eqs.  and 7)..7). The Step 6.5: Calculate the comprehensive GSDEM measure data of the solutions.The comprehensive GSDEM values were calculated using Eqs. , 10) an an10) anThe footwear industry is labor-intensive. It cannot last long in any one place, regardless of location. Almost every 20 years, the shoe industry needs to move to a place where labor is cheaper. All construction begins from scratch. This is also a problem faced by Taiwanese shoe companies, including world-renowned Taiwanese OEMs who have made overseas investments. For example, the Pou Chen Group has factories in Vietnam, Indonesia, Bangladesh, Cambodia, and Myanmar; the Feng Tay Group has production bases in Vietnam, Indonesia, and India; the Ching Luh Group has factories in Vietnam and Indonesia; and the Fulgent Sun Group has investments in Vietnam and Cambodia.Therefore, the focus group concluded that Solution B can enable the company to develop sustainably. Low-end shoes should be outsourced to Chinese or other international partner manufacturers. In Taiwan, product upgrades should be conducted, and production bases should not be moved.After moving its shoemaking base to China in 1991, Zong Da Company again achieved record-breaking revenue. However, in the wake of the Sino–US trade war, wage increases, and exchange rate fluctuations in 2018, achieving a smooth transition between the old and new business models will be a major challenge for the traditional footwear industry. The conclusions of this study are as follows:Experts from the footwear industry, government, and academic community were invited to jointly construct an objective decision-making model of production base movement for sustainable operations in the footwear industry. The evaluation process is easy and can also solve the problem of production base movement in the footwear industry and enable the sustainable development of enterprises.In the context of globalization, although the number of manufacturers whose main shoemaking base is located in Taiwan has decreased drastically, the supply chain is not as complete as before 1991. However, Taiwanese manufacturers still have a pivotal position in the global footwear industry. For example, global manufacturers that have established long-term cooperation with Zong Da Company are still the leading footwear manufacturers worldwide and are important partners of international sports brands such as Nike and Adidas.Zong Da Company adopted Solution B as its operational plan. In accordance with this solution, automated production was used suggested to reduce manpower. An operational R&D center should be set up in Taiwan to develop and design new shoe materials and models and to produce high value-added and differentiated products to reduce the risks of the Sino–US trade war and tariff uncertainties. This center should also serve as a raw material management and procurement center that supports production bases in other countries to cope with the dilemma resulting from the reduction of overall scale.Solutions C, D, and E suggest moving the production base to Southeast Asian countries. With increasing investment in various countries, the entry of industries, and various issues  arising from economic development, the business environment is also deteriorating. Since 2014, issues such as anti-Chinese movements, strikes, and riots have frequently occurred in these countries. Regardless of where the shoemaking base is moved to, the same problems persist in the business environment. Only by carrying out technology R&D, product innovation, and industrial upgrade in Taiwan can enterprises survive sustainably and avoid continuous evaluation of the production base movement issue.Following the COVID-19, decision B, to outsource the production of low-end shoes to China or other international partners, was optimal, allowing Taiwan to upgrade its products, thereby creating an international division of labor strategy of “receiving orders in Taiwan and producing shoes outside Taiwan.” The company's revenue can reach a new peak.After the COVID-19 pandemic and the Sino-US trade war, at headquarters in Taiwan, the development and upgrade of high-end sports shoes and functional shoes, quotations, material procurement, financial management and control, and so on. The mass production part is outsourced to factories in China or other partner countries for assembly. The verifies the following results: (1) the global sneaker market grew by 9.4%, from US$58.53 billion in 2016 to US$63.223 billion in 2017. The U.S. market grew by 4.1%, from US$23.269 billion to US$22.355 billion (Sporting Goods Intelligence The main limitation of this research is that it analyzes the international situation and economic conditions from the beginning of the Sino–US trade war from 2018 to 2020 before the COVID-19 pandemic. Future research directions include the following:


Despite the adherence to the Mediterranean dietary pattern (MD) being associated with a reduced risk of several cancers, there is no report about the highly prevalent diet-disease associations in Afghanistan, particularly about gastric cancer (GC).The aim of this study was to investigate the association between MD and GC in Afghanistan.This hospital-based case-control study was carried out on a total number of 270 subjects (90 cases and 180 controls) aged between 20 and 75 years. Using the convenience-sampling method, cases and controls were selected. Cases were patients with GC whose condition was pathologically confirmed. The controls were apparently healthy people who were matched with cases in terms of age (±5 years) and sex. Assessment of dietary intake was done using a pre-tested food frequency questionnaire, designed specifically for Afghanistan. Adherence to the MD pattern was done based on the scores suggested in earlier studies.P-trend = 0.05) compared with those in the lowest tertile. After considering potential environmental factors, age, and sex, the observed association disappeared . After further adjustment for BMI in the last model, we found that participants with the highest MD score were 83% less likely to have GC than those in the lowest tertile .Out of 270 studied subjects, 73% were men. We found that subjects in the highest tertile of MD score had 52% decreased odds of GC (OR: 0.48; 95% CI: 0.24–0.98, We found that greater adherence to MD might be associated with a lower odds of GC. Gastric cancer (GC) is one of the most common malignancies in the world; however, its prevalence has steadily declined over the past 50 years . DespiteSeveral lifestyle-related factors have been known to affect the risk of GC , 5. AmonMost studies on the link between dietary factors and GC are limited to developed nations as limited information is available in developing countries, especially in Afghanistan. Given the particular nature of dietary intakes in Afghanistan along with the high prevalence of GC in this country , 11, it This hospital-based case-control study was carried out on a total number of 270 subjects aged between 20 and 75 years in Kabul, Afghanistan, in 2019. The sample size was calculated based on the formula for case–control studies . We hypoParticipants’ usual dietary intakes during the past year were examined by a pre-tested Willett-format food frequency questionnaire (FFQ), that was designed specifically for the Afghan population. The questionnaire included 103 food items, with standard portion sizes according to Afghan common dietary intakes. The FFQ was completed through face-to-face interviews by a trained interviewer in the presence of individuals who were involved in the preparation and cooking of foods. All reported consumption frequencies were converted to grams per day by using household measures. Daily intakes of energy and nutrients were calculated for each person by using the USDA food consumption database. Almost all foods included in the questionnaire were available in the database, whereas for those foods not available in the database, similar ones were considered. Similar foods were chosen based on similarities in macronutrients . For example, we put the information for meat for Pacha (leg meat).We calculated MD score based on nine components  as mentioned in earlier studies , 17. ParThe diagnosis of GC was confirmed based on the pathological test using the third edition of the International Classification of Diseases for Oncology (ICDO-3) and morphology codes 8490/3 , 19. We 2).A pre-tested questionnaire was used to collect data on demographic characteristics including age, BMI, physical activity, sex, marital status, education level, occupation, smoking status, alcohol consumption, tooth brushing (times per week), and kebab food consumption. By using an International Physical Activity Questionnaire (IPAQ), we assessed the physical activity of participants through the face-to-face interviews. The results of the IPAQ were expressed as Metabolic Equivalents per week (METs/week). A trained dietitian completed all measurements. Weight was measured to the nearest 0.1 kg using a digital scale  with minimal clothes and without shoes. By the use of a tape measure, we measured the height of participants in a standing position without wearing shoes to the nearest 0.1 cm. BMI was calculated as weight (kg) divided by height in  which was adjusted for age, sex, and total energy intake. To examine the association between Mediterranean diet scores and GC, we used binary logistic regression in three different models. First, we adjusted for age (continuous), and sex. Further adjustments were done for physical activity (continuous), marital status (married/not married), Kebab food consumption (yes/no), smoking (yes/no), tooth brushing , job status , education , and alcohol use (yes/no) in the second model. To reach the obesity–independent relationships, further controlling was made for BMI in the final model. In all statistical analyses, the first tertile of Mediterranean diet score was used as the reference category. To obtain the overall trend of odds ratios across increasing tertiles of Mediterranean diet score, we considered tertiles as an ordinal variable in the logistic regression models. All statistical analyses were conducted using SPSS software version 25 . P ≤ 0.001) and more likely to be farmer and worker , be current smokers , and consume kebab food . Also, cases had a lower mean of BMI , less likely to be university post-graduated , and do tooth brushing . There were no other significant differences in other variables between cases and controls.Compared to controls, cases were more physically active (METs) , meat products , total energy , protein , MUFA , and vitamins B1 , B3  and the had lower intakes of fruit , vegetables , nuts , legumes , dairy products , PUFA , dietary fiber , vitamin B2 (0.993 ± .04 vs. 1.301 ± 0.028 P ≤ 0.001), B6 , B9 , B12 , calcium , and magnesium . Food and nutrients intakes of study participants across tertiles of MD score are presented in Compared to controls, patients with GC had higher consumption of fish  compared with those in the lowest tertile. After adjustment for age and sex in the first model, this protective association became slightly attenuated . After further adjustment for potential environmental confounders, there was no significant association between adherence to MD score and GC . When we included BMI in the last model, we found that participants with the highest MD score were 83% less likely to have GC than those in the lowest tertile .Furthermore, four levels of multivariable-adjusted ORs for GC across tertiles of MD score are shown in In this case–control study, we found that individuals with the greatest adherence to the Mediterranean diet had lower odds of GC than those with the lowest adherence. To the best of our knowledge, this is the First study in Afghanistan that examined the association between MD patterns and GC.Gastric cancer is the third leading cause of cancer-related death globally. According to the World Cancer Research Fund, the incidence of stomach cancer was 6.1% worldwide in 2018 . In the Helicobacter pylori and its consequent damages , increasing the chemo-protective effects , and inhibiting tumor development , anti-oxidative and anti-inflammatory effects   might be damages . Red mea damages .The strengths of our study are being the first study in Afghan adults as well as considering a wide range of confounders. Some potential limitations should also be taken into account while interpreting our findings. Given the case–control design of the study, having recall bias and selection bias is unavoidable. In addition, causality cannot be inferred based on our findings due to the case-control design of the study. Because of the use of FFQ to assess dietary intakes, misclassification of study participants might have occurred. We tried our best to consider lots of confounders in the study; however, residual confounding cannot be ignored. Although we determined the sample size based on the suggested formula for case–control studies, larger studies seem to be required to confirm our findings. Finally, we did not consider sodium intake as a confounding factor, even though previous studies showed that the Mediterranean diet patterns have a limited effect on restricting sodium intake .In conclusion, in this hospital-based case-control study we found that higher adherence to MD might be associated with a lower odds of GC. Further studies are needed to confirm this association.The raw data supporting the conclusions of this article will be made available by the authors, on reasonable request to the corresponding author.This study was ethically approved by medical bioethics committee of TUMS (Code: IR.TUMS.MEDICINE.REC. 1399.184). The patients/participants provided their written informed consent to participate in this study.AE and SM were involved in the study’s conception, design, statistical analysis, and interpretation of the data. FA and AB were involved in data collection, data cleaning, statistical analysis, and manuscript drafting. AE supervised the study. All authors approved the final manuscript for submission.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Cardiovascular and cerebrovascular diseases are frequently interconnected due to underlying pathology involving atherosclerosis and thromboembolism. The aim of this study was to investigate the impact of clinical interactions among cardiovascular and cerebrovascular diseases on patient outcomes using a large-scale nationwide claims-based dataset. Cardiovascular diseases were defined as myocardial infarction, heart failure, atrial fibrillation, and aortic dissection. Cerebrovascular diseases were defined as cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage. This retrospective study included 2,736,986 inpatient records  at 911 hospitals from 2015 to 2016 from Japanese registry of all cardiac and vascular disease-diagnostic procedure combination dataset. Interactions among comorbidities and complications, rehospitalization, and clinical outcomes including in-hospital mortality were investigated. Among hospitalization records that involved cardiovascular disease, 5.9%  had cerebrovascular disease as a comorbidity and 2.1%  included an incident cerebrovascular complication after hospitalization. Cerebrovascular disease as a comorbidity or complication was associated with higher in-hospital mortality than no cerebrovascular disease (adjusted odds ratio (OR) [95% confidence interval]: 1.10 [1.06–1.14], 2.02 [1.91–2.13], respectively). Among 367,904 hospitalization records that involved cerebrovascular disease, 17.7%  had cardiovascular disease listed as comorbidity and 3.3%  as a complication. Only cardiovascular disease as a complication was associated with higher in-hospital mortality . In addition, in-hospital mortality during rehospitalization due to the other disease was significantly higher than mortality during the hospitalization due to the first disease. In conclusion, substantial associations were observed between cardiovascular and cerebrovascular disease in a large-scale nationwide claims-based dataset; these associations had a significant impact on clinical outcomes. More intensive prevention and management of cardiovascular and cerebrovascular disease might be crucial. According to the World Health Organization, cardiovascular and cerebrovascular diseases are the most frequent causes of death worldwide, accounting for 31% of all deaths in 2016 globally . SeveralEven though most previous studies have recognized the interaction among these diseases, they typically analyzed a dataset from a registry or cohort, which limits the sample size and the number of participating institutions , 7. A coThe Diagnosis Procedure Combination (DPC), which is maintained by the Ministry of Health, Labour and Welfare of Japan, is a patient classification method for inpatients in the acute phase of illness. It has been developed as an assessment tool intended to make acute inpatient care transparent and to standardize, evaluate, and improve the quality of Japanese medical care. In the DPC dataset, all procedures and prescriptions during hospitalization are recorded according to the Japanese fee schedule for reimbursement , 9. The Cardiovascular diseases were defined as MI, heart failure (HF), AF, and aortic dissection (AD). The International Classification of Diseases (ICD)-10 diagnosis codes were I21, I22, I24 for MI, I50 for HF, I48 for AF, and I71.0 for AD. Cerebrovascular diseases were defined as cerebral infarction (CI), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). ICD-10 codes were I63 for CI, I61 for ICH, and I60 for SAH.Identification of patients hospitalized with cardiovascular or cerebrovascular disease was based on the index ICD-10 code in any of the following four data fields: main diagnosis, admission-precipitating diagnosis, most resource-consuming diagnosis, and second most resource-consuming diagnosis. Comorbidity was defined as the presence of the index ICD-10 code in the diagnostic category of comorbidity. Complication was defined as the presence of the index ICD-10 code in the field for main diagnosis, admission-precipitating diagnosis, most resource-consuming diagnosis, second most resource-consuming diagnosis, or diagnostic category of complication.Data in the JROAD-DPC dataset from April 1, 2015 to March 31, 2017 were analyzed in this study. Records for scheduled hospitalizations and multiple admission on the same date were excluded. In addition, records with a disease listed as both a comorbidity and a complication were excluded from the final analysis .When a patient is first hospitalized due to cardiovascular disease and rehospitalized due to cerebrovascular disease, two scenarios can be considered:The cardiovascular disease can be a comorbidity and hospitalization due to cerebrovascular disease appeared in the first recordHospitalization due to cardiovascular disease can occur without prior cardiovascular disease as a comorbidity in the first record and rehospitalization due to cerebrovascular disease appeared in the second record.A similar pattern can be adapted for the first hospitalization due to cerebrovascular disease and rehospitalization due to cardiovascular disease . In the The study was conducted according to the 1964 Declaration of Helsinki and its later amendments. It was approved by the National Cerebral and Cardiovascular Center ethics committee .Data are expressed as medians (inter-quartile range) for continuous variables. Categorical data are expressed as numbers (%). Two-sample tests of proportions were conducted. There were missing data for age in 10,065 (0.37%) records and for in-hospital costs for 15,357 (0.56%) records. The median value for these variables was calculated with the complete dataset. Univariate and multivariable multilevel mixed effects logistic regression models with institution as a random intercept were performed to estimate odds ratios (ORs) and 95% confidence intervals for in-hospital mortality. In order to improve the efficiency of the analysis, basic demographic variables were included in Model I and comorbidities that are strongly related to cardiovascular and cerebrovascular diseases were further included in Model II. Multivariable analysis was conducted with two models. Model I adjusted for age and sex. Model II adjusted for age, sex, and comorbidities . In addition, all hospital costs and charges were converted into US dollars according to the current exchange rate (1 US dollar = 106.00 yen). All statistical analyses were conducted using SAS 9.4  and STATA 16.1 .Among 2,736,986 records of 1,800,255 patients at 911 hospitals, 541,481 records were extracted as hospitalization due to cardiovascular disease and 364,625 records were extracted as hospitalization due to cerebrovascular disease . Among aRegarding the detailed diagnoses in the comorbidity and complication analysis , CI was In the rehospitalization analysis, patients with a first hospitalization and rehospitalization were compared . In TablFor all cardiovascular diseases, in-hospital mortality rate during rehospitalization was significantly higher than that during first hospitalization . In the We analyzed the frequency and clinical characteristics of cardiovascular and cerebrovascular diseases as comorbidities and complications in order to clarify associations between these two types of diseases. We also investigated mortality rate during rehospitalization for each diagnosis and compared it to mortality rate during the first hospitalization. To the best of our knowledge, our study was the first to comprehensively analyze linkages between cardiovascular and cerebrovascular diseases using a large-scale DPC dataset.In the present study, the proportion of patients hospitalized due to cerebrovascular disease who had a cardiovascular disease as a comorbidity or complication was higher than the proportion of patients hospitalized due to cardiovascular disease who had a cerebrovascular disease as a comorbidity or complication. This finding might suggest that cerebrovascular disease often develops as a result of cardiovascular disease and that the acute phase of cerebrovascular disease is more unstable and prone to the development of cardiovascular disease . In bothThe etiology of CI is classified as atherothrombotic, cardioembolic, or lacunar based on the mechanism. There is a strong link between CI and cardiovascular diseases based on atherosclerosis and thromboembolism . Thus, CMortality during rehospitalization was significantly higher than mortality during first hospitalization for both cardiovascular and cerebrovascular disease, regardless of etiology. However, for cerebrovascular disease, there were small differences in mortality between the first hospitalization and rehospitalization, especially for ICH. Although the precise reasons for the differences are unknown, ICH might not be strongly associated with cardiovascular diseases in general, but ICH might be associated with some specific cardiovascular diseases. Regarding incidence and the number of patients, prevention of incident HF is important in patients with cerebrovascular disease. It is important to prevent incident CI in patients with cardiovascular disease. In the present analysis, in-hospital mortality rate from MI and AF was substantially higher for rehospitalization than for first hospitalization. In contrast, in-hospital mortality for CI was substantially higher for rehospitalization than for the first hospitalization. Based these differences in mortality rate, prevention of incident MI and AF is important in patients with cerebrovascular disease. Similarly, it is important to prevent incident CI in patients with cardiovascular disease.The current guidelines regarding secondary prevention of cardiovascular or cerebrovascular disease recommend strict control and intensive management of cardiovascular risk factors in “very high-risk” patients , 21. AllThis study had several limitations. First, since the present analysis was based on the DPC dataset, there are no data about laboratory results and imaging examinations, detailed etiology, and cause of death. Thus, more details about factors associated with mortality or rehospitalization could not be determined. Second, each institution was required to provide their DPC information annually and JROAD-DPC did not necessarily include consecutive DPC datasets. Therefore, these results might underestimate the probability of rehospitalization across the 2 years. Third, since the DPC dataset was a limited annual dataset in 2016 and 2017, the first hospitalization in this study does not necessarily mean the patient’s first-ever episode of disease during their lifetime. Instead, it reflects first-ever episode of disease during the year of interest. Finally, even though mortality and incidence of cerebrovascular disease in Japan are similar to those in Western countries, the mortality and incidence rates of cardiovascular disease in Japan are still lower than those in Western countries . Thus, tSubstantial associations were observed between cardiovascular and cerebrovascular disease in a Japanese nationwide claims-based dataset. Of note, patients hospitalized with cerebrovascular disease frequently had cardiovascular disease as a comorbidity or complication. These associations had a significant impact on clinical outcomes such as in-hospital mortality, LOS, and total medical costs during rehospitalization. In patients with cardiovascular or cerebrovascular disease, more intensive prevention and management of the other disease are crucial. Therefore, the significant association between cardiovascular and cerebrovascular disease might be an important theme for future research.S1 TableValues are expressed as odds ratios . AD, aortic dissection; AF, atrial fibrillation; CI, cerebral infarction; HF, heart failure; ICH, intracerebral hemorrhage; MI, myocardial infarction; SAH, subarachnoid hemorrhage. Model I adjusted for age and sex. Model II adjusted for age, sex, and comorbidities .(DOCX)Click here for additional data file.S2 TableValues are expressed as odds ratios . AD, aortic dissection; AF, atrial fibrillation; CI, cerebral infarction; HF, heart failure; ICH, intracerebral hemorrhage; MI, myocardial infarction; SAH, subarachnoid hemorrhage. Model I adjusted for age and sex. Model II adjusted for age, sex, and comorbidities .(DOCX)Click here for additional data file.


Background: The dose–response association between serum albumin and atrial fibrillation is not well known. This study aims to assess the relationship between albumin and atrial fibrillation and the potential dose–response effect.Methods: Studies reported that the serum albumin and AF were identified by searching the EMBASE, PubMed, and Cochrane Library databases. The potential dose–response effect was performed by using a stage robust error meta-regression.Results: Nine studies were included with a total of 32,130 individuals. Patients with high albumin level were associated with a decreased risk of atrial fibrillation compared with patients with low serum albumin . In the dose–response analysis, for each 10 g/L increase in serum albumin level, the risk of atrial fibrillation decreased by 36% . Furthermore, a significant negative linear relationship between serum albumin and the risk of atrial fibrillation (Pnonlinearity = 0.33) was found.Conclusion: Our dose–response meta-analysis suggests that low serum albumin level is associated with an increased risk of atrial fibrillation. Further studies are needed to explore the effect of induction of elevated serum albumin levels on the prevention of atrial fibrillation. Atrial fibrillation (AF) is the most common arrhythmia in the clinical setting, with a substantially increased morbidity, mortality and bring tremendous economic. Although multiple risk factors, including cardiovascular and noncardiovascular risk factors, have been identified , the potAlbumin is a predominant protein in human plasma . HypoalbWe performed this meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement  12)..12).Database search, selection, data extraction, and statistical analysis were independently conducted by two authors (YL and XL). For all relevant studies, three databases  were searched up to May 27, 2021. No language restrictions were applied. The following search terms were used for all of the databases:  AND . Report data on adults ≥18 years of age that helped assess the association between serum albumin and risk of AF were included. In addition, the conference abstracts and bibliographies of related works of literature were scanned. The detail of the search strategy was listed in Following studies that satisfied the inclusion criteria were selected: (1) studies that reported the serum albumin level and risk of AF; (2) those designed as randomized controlled trials or observational studies; (3) those that made available a quantitative measure of serum albumin level and the corresponding estimate effect and 95% CI in each albumin category for the dose–response analysis. Accordingly, reviews, meta-analyses, congress abstracts, practice guidelines, patents, cases, editorials, replies, or comments studies were excluded. Any inconsistency was resolved through discussions (YL and XL) until consensus was reached.https://jbi.global/critical-appraisal-tools) composed eight items, which score each study for the following items: participant selection, exposure definition, statistical analysis, and outcome data. Studies with a NOS or JBI of ≥6 stars were considered moderate- to high-quality articles , adjustments for confounders, categories of serum albumin, and adjusted odds ratios (ORs) with its 95% confidence intervals (CIs) for each serum albumin category. We included the articles with the longest follow-up or the largest numbers of participants for multiple publications and reports by using the same data. The Newcastle–Ottawa quality scale (NOS) or the Joanna Briggs Institute (JBI) critical appraisal checklist  was applied for quality assessment . The JBIarticles .I2 (95% CI) statistic was calculated with the following interpretation: low heterogeneity, defined as I2 < 50%; moderate heterogeneity, defined as I2 50%−75%; and high heterogeneity, defined as I2 > 75%  (highest vs. lowest) with significant heterogeneity.Three studies , 21, 22 I2 = 87%, P < 0.001) . In the nonlinear model, there was a significant negative linear association between serum albumin and risk AF (Plinearity = 0.33)  . Heterog = 0.33) .I2 = 0%, P < 0.001), however, it was not significant in the group of general population . The association between serum albumin and the risk of AF persisted in other subgroups, including age, regions, publication years, sample size or adjusted for age, sex, cardiovascular diseases, and C-reactive protein (N <10).We conducted subgroup analyses stratified by age, region, confounding factors, and potential intermediate factors. As shown in  protein . The res protein , excludi protein . AccordiThis study showed a significant negative linear association between serum albumin and risk of AF, where 10-g/L serum albumin decreased the risk of AF by 36%. The results were stable in most of the subgroup and sensitive analysis, suggesting the robustness of our findings. To the best of our knowledge, this is the first meta-analysis to assess serum albumin and AF association.2+ release via enhanced ryanodine receptor activity, shortening of the atrial action potential duration, and producing delayed afterdepolarizations . There might be several potential expansions. First, most of the studies based on hospitalized patients with comorbidities were retrospective and might introduce a larger bias. The residue confounding might enlarge the association of albumin and AF. Second, recent studies also have shown that albumin was a potential connection with cardiovascular diseases and diabetes. Therefore, we propose that the association between low serum albumin and AF may be amplified in patients with comorbidities or at high risk of developing comorbidities. However, considering the limited sample size, the role of serum albumin in patients with comorbidities or at high comorbidities risk needs to be further investigated. Further studies with prospective design and a larger sample size are required.Previous findings showed discrepant effects of albumin among men and women. Among women of the Copenhagen City Heart Study, a protective effect was noted with a significant linear association. All categories of albumin showed no benefit of AF compared with lowest ablumin level among men. In contrast, findings from the Atherosclerosis Risk in Communities cohort showed a significant protective effect of albumin, regardless of sex. The contrasting results regarding sex might derive from different baseline characteristics, such as region, race, age, and follow-up time. For example, the incidence of AF in the Copenhagen City Heart Study and Atherosclerosis Risk in Communities cohort differ significantly, with 3.2%  for the Copenhagen City Heart Study and 17.6%  for the Atherosclerosis Risk in Communities cohort. The protective effect of albumin among men might appear as the prolonged time of follow-up in the Copenhagen City Heart Study. Therefore, it is still unclear whether there is a gender difference in the association between albumin and AF and should be further studied.The measurement of serum albumin is simple, cheap, and routinely available. Given the potential link between low serum albumin level and AF, albumin supplement  for patients with hypoalbuminemia might be a therapeutic target for reducing the risk of AF. Decreased serum albumin levels imply an undernourished state, which usually leads to poor clinical outcomes. For example, AF post cardiac operation was one of the most common complications, low albumin levels have been reported to be a significant predictor for AF after coronary artery bypass graft surgery . Howeverhttps://www.crd.york.ac.uk/prospero/). Finally, there was substantial heterogeneity in the primary analysis, which may derive from the baseline characteristics of patients. However, there was no evidence of heterogeneity when Liao et al. was excluded, with results remaining positive.This is the first meta-analysis that reported the association between albumin and AF risk and the robustness of the findings in multiple subgroup analyses. However, several limitations also should be recognized. First, this is an observation-based study, which cannot deduce the causal relationship. Low serum albumin level is an indicator of undernutrition status. Serum albumin might be an intermediate factor in the association between undernutrition status and risk of AF. Unmeasured and insufficiently measured variables could have resulted in residual confounding. Second, as we know, sex is an independent risk factor for AF. A sex difference might exist in the association between albumin and the risk of AF . HoweverOur dose–response suggested low serum albumin level is significantly associated with an increased risk of AF. Further studies are needed to explore the effect of induction of elevated serum albumin levels on the prevention of AF.The original contributions presented in the study are included in the article/XZ and JT were responsible for the entire project and revised the draft. XL and YW performed the systematic literature review and drafted the first version of the manuscript. All authors took part in the interpretation of the results and prepared the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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