A cross-over study was conducted in 16 healthy adult volunteers to describe the urinary excretion of polyphenols from date seeds and investigate the antioxidant effect after consumption of different doses of date seeds powder (DSP), bread (DSB) and extract (DSE). After 12 h of fasting, one of the six treatments  was provided along with breakfast, with a two weeks wash-out period between 2 consecutive treatments. Blood was drawn at baseline, 1, 2, 8 and 24 h post intake. Urine was collected at baseline, 3, 8, and 24 h post intake. An abundant release of polyphenols was detected in urine within the 0–3 h post intake, reached a peak at 8 h, then decreased with polyphenols still being detected up to 24 h post intake. The antioxidant defence system, as measured by reduced glutathione (GSH), was strengthened as soon as 1 h and up to 8 h post intake. Markers of protein and lipid oxidative damages were reduced from 1 h and up to 8 and 24 h post intake, respectively. This supports an antioxidant effect of date seeds products in humans, most probably due to their polyphenols. Due to a continuous and worrying increase, chronic diseases including cardiovascular diseases, diabetes and cancer constitute a substantial public health concern worldwide. Oxidative stress and free radicals are playing a vital role in the development of these diseases by inducing damages on cells and macromolecules. The human body has integrated defence systems, including glutathione. They are usually effective in protecting against oxidative damages. However, overwhelming them with an excess of free radicals can cause diseases. Due to their antioxidant properties, some natural compounds can provide a second protective barrier . Among tPhoenix dactylifera L.) is a fruit which is primarily produced in the Middle East region. It is not only consumed locally but in other parts of the world as well. Date seeds constitute 6%–15% of the total weight of the ripe date depending on variety and grade quality. They are being wasted in large quantities or used mainly for animal  feed. Interestingly, date seeds possess excellent nutritional quality. The determination of the macro- and micro-nutrient profiles of various varieties of date seeds revealed a high amount of fibre (67.6–74.2 g/100 g) and considerable amounts of some minerals, vitamins, lipids, and protein [Khalas variety [Date , no metabolic or intestinal disorder, no history of gastrointestinal surgery (except appendectomy), under no prescription medication, no alcohol consumption, non-smoking, not taken antibiotics during the 6 months preceding inclusion in the study, and no blood donation during the month preceding inclusion in the study. The whole study was conducted in the Ain Al Khaleej Hospital, Al Ain, United Arab Emirates.A cross-over design, with six arms, was conducted in 16 healthy adults, including eight women and eight men. They were included after an initial screening visit during which exclusion and inclusion criteria were checked. Inclusion criteria for the study were: age between 18 and 55 years, normal weight status , date seed bread (DSB) and date seed extract (DSE), were considered. Two different doses of each product were tested, either a total of six treatments, with each subject receiving a single dose of each treatment . Each suPhoenix dactylifera L.) seeds of the Khalas variety were used in this trial. They were provided by the Al Foah Company-Emirates Dates factory, Al-Ain, United Arab Emirates. Dates were collected randomly from tamr (fully ripe dates) batches at the end of the season with no preference to size, colour, appearance, or firmness. Date seed powder (DSP) was prepared by milling cleaned and dried date seeds. The powder was sieved by a BZS 200 sieve machine and particles of less than 300 microns were used in the study as treatments: DSP1 and DSP2  tubes by phlebotomist at the hospital, then promptly centrifuged. Plasma and serum were stored at −80 °C. The points which are of interest for this study are baseline , 1, 2, 8 and 24 h after ingestion. Urine was collected at baseline and 24 h. In-between, cumulative urine was kept in a hermetic and labelled container in the fridge, over the post-ingestion periods 0–3 h, 3–8 h and 8–24 h. All samples were stored at −80 °C before analysis.Glucose, total cholesterol, Low Density Lipoprotein (LDL)-cholesterol, High Density Lipoprotein (HDL)-cholesterol, triglycerides, creatinine, albumin, urea, creatine kinase, lactate dehydrogenase, gamma-glutamyltransferase (GGT), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were measured in serum using enzymatic colorimetric methods on Roche/Hitachi Cobas C systems . NCEP guidelines were used as a reference for the lipid profile . For the other biochemical parameters, normal ranges as provided by the manufacturer were considered. Total protein content was measured following the method of Lowry et al. .An ultra-performance liquid chromatography-electrospray ionization/quadrupole-time-of-flight (UPLC-ESI-QTOF) mass spectrometry (MS) was employed to analyse the polyphenolic metabolites in urine using a method described earlier . Brieflyg for 10 min. The 100 µL of 0.2 M tris buffer  solution in the ratio of 1 EDTA:10 Tris) was added to the supernatant followed by 5µL of 0.01 M DTNB reagent (wt/vol in methanol). The absorbance of the samples was read against blank at 412 nm and the results were calculated using the formula below:Measurements were done at baseline, 1, 2, 8 and 24 h after ingestion. Glutathione reduced form (GSH) was measured spectrophotometrically by using the method described earlier [2 PO4 buffer, pH 6.8  containing 0.2% (v/v) triethanolamine. Xterra MS C18 reverse phase column of 5 μm pore size was used for the analysis. The column temperature was 35 °C and the flow rate was 1 mL/min with an injection volume of 20 μL. The fluorescence detection wavelength was set at 532 nm (excitation) and 553 nm (emission). All samples were analysed in duplicate. Protein-bound carbonyls (PC) was used to assess the extent of protein oxidation. It was determined spectrophotometrically at 370 nm by the 2,4-dinitrophenylhydrazine method described by Castegna et al. [Malondialdehyde (MDA), which is a lipid peroxidation product, was measured using the modified thiobarbituric acid reactive substances (TBARs) procedure . Brieflya et al. .http://www.phenol-explorer.eu.A food frequency questionnaire was administered at screening, mainly to estimate the polyphenol intake of each subject. It was adapted from the questionnaire developed for Iranian adults by Mirmiran et al. . The aveSPSS (v24) was used to perform statistical analysis. Means ± standard deviation (SD) were calculated. ANOVA was used for gender comparisons. When no gender difference was detected, results for the whole sample will be presented. Results for biochemical parameters at baseline and 24 h were compared by using paired t-tests. An ANOVA model with repeated measures was performed to compare the values of GSH, MDA and PC at baseline, 1, 2, 8 and 24 h. When the assumption of sphericity was violated, the greenhouse-Geisser correction was considered. Post hoc Bonferroni tests were used to determine which specific means differed. Gender and average daily polyphenols consumption in tertiles were introduced as between-subject factors. Data from urinary excretion of metabolites of date seeds were analysed using the same parameters. The post hoc Bonferroni test was used to compare data at baseline (0 h), 0–3 h, 3–8 h and 8–24 h. Comparisons were also made between the two doses of DSP, DSB and DSE. GraphPad Prism version 8.1.2 was used to build figures for the manuscript.Sixteen subjects, eight women and eight men were initially included. One subject decided to drop out after the first two experiments and was immediately replaced by a subject from the same gender. After blood samples analysis, abnormally high levels of fasting glucose and dyslipidemia were detected for two subjects. Even though fasting status was orally checked by the research team and the nurse before baseline blood collection, it cannot be excluded that subjects were not fasting. Consequently, they were excluded from the analysis. Also, they were advised to visit their regular physician to follow-up with their glucose level and lipid profile. Finally, 14 subjects, eight women and six men, were included in the statistical analysis. They were between the ages of 25.43 ± 5.11 years on average and all had a healthy weight status. Their average consumption of polyphenols was 3.02 ± 1.93 g/d .Before consumption of any date seeds products at DSP1 baseline, all subjects had a normal fasting glucose and lipid profile. Only the HDL-Cholesterol level was below the NCEP recommended level for both genders . Twenty-Twenty predominant metabolites were detected in the urine samples following ingestion of all date seed treatments . ExtractA significant increase in the level of aromatic acids such as hydroxybenzoic acid, protocatechuic acid, vanillic acid and vanillic acid sulphate was observed in three hours in urine . HydroxyThe predominant metabolites of proanthocyanidins, such as methyl-epicatechin sulphate and valerolactone compounds, were found the urine samples from all subjects . There wAll three hydroxyphenyl acids, 3-hydroxyphenyl acetic acid, 3-hydroxyphenyl propionic acid, and 3-hydroxyphenyl valeric acid, released in the gut were predictably increased from 3 h to 24 h in urine following consumption of date seed treatments . Dose diRegarding the impact of the treatments on the antioxidant defence system, GSH level increased significantly compared to the baseline, 1 h after ingestion in all six treatments. This change in GSH ranged from 36.44% with DSE1 to 57.11% with DSP1  and was Malondialdehyde content was modified with DSP1, DSP2, DSE1 and DSE2 but not with DSB1 and DSB2 (both date seeds bread) . BrieflyThe prevalence of chronic diseases is alarming worldwide, and recent scientific and therapeutic progress has failed in curbing its growth. The use of natural and functional ingredients is a possible alternative that could contribute to protecting the populations against such diseases. Knowing the crucial role of oxidative stress in the development of chronic diseases, ingredients with antioxidant properties represent potent candidates for the development of functional food products. However, the bioavailability of the bioactive compounds from these ingredients will determine their real health potential in humans. Indeed, digestive, absorptive and metabolic processes are likely to affect the chemical structure of these compounds and consequently, their biological activity. Therefore, it is not enough to confirm the health properties in humans, a description of their bioavailability is also critical.Date seeds, a local natural resource, are an excellent source of polyphenols . AntioxiBesides, the corresponding amounts of date seeds products  were quite easily consumed by the subject. The total amount of polyphenols in each dose was much below the average estimated daily intake of polyphenols of the study sample, which is supporting the fact that doses were all realistic.Similar to previous animal studies ,17,28, tOverall, the kinetics of urine excretion of polyphenols is in agreement with previous results for other polyphenol sources such as cocoa  and red Vanillic acid is significantly increased at 0–3 h in comparison to baseline, which could be attributed to its formation in the liver by methylation . A similOther important proanthocyanidin metabolites that were identified are valerolactone compounds and other aromatic acids, such as 3-hydroxyphenyl acetic, propionic, and valeric acid along with 3–4 dihydroxyphenyl valeric acid and its sulphate, and hippuric and hydroxy hippuric acid. All of these metabolites are well documented with the consumption of other proanthocyanin sources such as grapeseed and cocoa ,32. The The antioxidant effects that are reported in this study are most probably involving date seeds polyphenols and metabolites. First, such effects are typical of polyphenols. Then, an up-regulation of the body enzymatic defence system, like GSH, through the activation of transcription factors and the scavenging of free radicals through either a direct interaction with the radicals or the inhibition of enzymes involved in the free radicals’ production were described as some of the primary mechanisms by which polyphenols exert their antioxidant properties . FinallyInterestingly, up to 8 h, the urine polyphenols are similar to those identified after in vitro intestinal absorption  and are Noticeably, the consumption of date seeds bread did decrease the level of protein carbonyl but not the level of MDA, suggesting that polyphenols from date seeds bread would bind more proteins than lipids to protect against oxidative damages. It is well known that the release of glucose in the blood is inducing an increased production of free radicals. These later were shown to increase the level of advanced glycation end products, which in turn would raise the level of protein carbonyls . The carPolyphenols are preventing the development of chronic diseases in different other ways. This includes a lipid-lowering effect and a modulation of the blood glucose level ,46,47. HIt should be noticed that the analysis here included only 14 subjects. However, this sample size is within the range of several subjects being included in similar clinical trials. In this study, a qualitative approach was used to study the urine excretion of the polyphenol metabolites. Urine analysis was not performed against metabolites standards. Therefore, the results are reflecting the total excretion of polyphenols metabolites and the presence of specific compounds but without further quantification. This is preventing us from highlighting the probable differences between the date seeds products. However, this allows us to conclude about the implication of date seeds polyphenols in the expression of the antioxidant effects after a single dose of date seeds powder, bread, or extract and, in this way, to satisfy the purpose of the study. Finally, doses were tested only one time in each subject. Although the experimental conditions were carefully controlled for all subjects and for each treatment, it is hard to conclude about a good level of reliability of our results.The interaction of undigested polyphenols with microbiota was not considered here. This should be studied to provide a complete overview of the bioavailability of date seeds polyphenols. Indeed, an interaction between gut microorganisms and polyphenols is recognized, with polyphenols influencing the growth of the microorganisms and the gut microbiota print and gut microorganisms metabolizing the “undigestible” polyphenolic compounds with the release of metabolites likely to be absorbed and to exert biological effects in the human body.This work highlighted the antioxidant effect of a single dose of date seeds products  in humans. This is in favour of a high potential of date seeds products as functional ingredients, knowing that further studies testing a longer-term consumption of date seeds products should be conducted to confirm our results.


Among the surgical methods for lumbar disc herniation, open lumbar microdiscectomy is considered the gold standard. Recently, percutaneous endoscopic lumbar discectomy is also commonly performed for lumbar disc herniation for its various strong points. The present study aims to examine whether percutaneous endoscopic lumbar discectomy and open lumbar microdiscectomy show better results as surgical treatments for lumbar disc herniation in the Korean population. In the present meta-analysis, papers on Korean patients who underwent open lumbar microdiscectomy and percutaneous endoscopic lumbar discectomy were searched, both of which are surgical methods to treat lumbar disc herniation. The papers from 1973, when percutaneous endoscopic lumbar discectomy was first introduced, to March 2018 were searched at the databases of MEDLINE, EMBASE, PubMed, and Cochrane Library. Seven papers with 1254 patients were selected. A comparison study revealed that percutaneous endoscopic lumbar discectomy had significantly better results than open lumbar microdiscectomy in the visual analogue pain scale at the final follow-up , Oswestry Disability Index , operation time , and hospital stay . There were no statistical differences in the MacNab classification , complication rate , recurrence rate , and reoperation rate . All 7 papers used for the meta-analysis were non-RCTs. Some differences , treatment options before the operation, follow-up period, etc.) existed depending on the selected paper, and the sample size was small as well. While percutaneous endoscopic lumbar discectomy showed better results than open lumbar microdiscectomy in some items, open lumbar microdiscectomy still showed good clinical results, and it is therefore reckoned that a randomized controlled trial with a large sample size would be required in the future to compare these two surgical methods. Among the surgical methods for lumbar disc herniation, open lumbar microdiscectomy (OLD) is considered the gold standard . Lumbar Recently, percutaneous endoscopic lumbar discectomy (PELD) is also commonly performed for lumbar disc herniation for its various strong points compared to OLD such as surgery under local anesthesia, less damage to surrounding muscles and bone structures, and fast patient recovery –12. IndiNevertheless, it has not been clearly confirmed whether PELD, which had good results recently, is better than OLD, the gold standard, in Korean patients.The purpose of this study is to determine through a meta-analysis whether PELD or OLD has better results as a surgical treatment for lumbar disc herniation in the Korean population.Relevant studies were searched in MEDLINE, EMBASE, PubMed, and Cochrane Library. Retrieval time was from 1973, when PELD was first introduced, to March 2018. The papers were extracted using search keywords such as “lumbar disc herniation,” “microdiscectomy,” “percutaneous endoscopic lumbar discectomy,” “intervertebral disc displacement,” “transforaminal lumbar discectomy,” “minimally invasive discectomy,” and “interlaminar discectomy”; the researcher extracted only those studies conducted on humans, which were written in English.Two authors (M Kim and S Lee) identified the titles and abstracts or both and summarized the data from the selected articles. The searched papers were selected based on the following criteria: (1) those which were either randomized or nonrandomized controlled trials, (2) those that had at least one significant result on Korean patients, and (3) those on patients who underwent PELD or OLD for lumbar disc herniation. The papers on those who had a combined surgery and lesions in more than one area and case reports, letters, and comments were excluded.The following data were extracted from the papers collected by two of the authors (M Kim and S Lee): (a) basic information such as the type of trial, follow-up period, type of surgery, sample size, and patient age and sex and (b) clinical results such as the visual analogue pain scale (VAS) score (leg and back), complication rate, recurrence rate, reoperation rate, hospital stay, operation time, MacNab classification, and Oswestry Disability Index (ODI).All 7 collected papers were nonrandomized clinical trials, and the Newcastle-Ottawa Quality Assessment Scale (NOQAS) was used for quality assessment. Out of a possible 9 items, 3 of selection, comparability, and exposure or outcome account for 4, 2, and 3 points, respectively. Five points or more indicated a low risk of bias, while 4 or less indicated having a high risk of bias .The continuous variables  were weighted with the number of patients, and the weighted average results were calculated. They were analyzed using standard deviations at a 95% confidence interval (CI). Meanwhile, the binary variables  were analyzed using the odds ratio (OR) at a 95% CI. I2 statistics were used to determine heterogeneity, and more than 50% was regarded as heterogeneous. The Review Manager software  was used as a statistical program for analysis.A total of 433 papers were searched, and 426 of them, which did not meet the selection criteria, were excluded. The basic characteristics of the selected papers are presented in 2=0%, p=0.91).Among the 7 papers, 5 presented the results of the VAS (leg), and 293 subjects were included in the analysis: 134 in the PELD group and 159 in the OLD group. The PELD group's average VAS was 2.04, while that of the OLD group was 2.47. The PELD group showed a significantly lower average VAS (leg) at the final follow-up than the OLD group  . No hete2=85%, p=0.0001).Among the 7 papers, 4 presented the results of the Visual VAS (back), and 246 subjects were included in the analysis: 112 in the PELD group and 134 in the OLD group. The PELD group's average VAS (back) was 2.40, while that of the OLD group was 3.14. The PELD group showed a significantly lower average VAS (back) at the final follow-up than the OLD group  . Heterog2=0%, p=0.72).Among the 7 papers, 3 presented the results of the MacNab score (success rate), and 1,009 subjects were included in the analysis: 347 in the PELD group and 662 in the OLD group. Those who answered with excellent or good were defined as successful, and 298 among the 347 subjects in the PELD group answered with successful in the MacNab criteria. Among the 662 subjects in the OLD group, 564 answered with successful. There were no significant differences in the average MacNab score (success rate) between the PELD and OLD groups  . There w2=67%, p=0.03).Among the 7 papers, 4 presented the results of the ODI, and 246 subjects were included in the analysis: 112 in the PELD group and 134 in the OLD group. The PELD group's average ODI was 14.54%, while that of the OLD group was 16.52%. The PELD group showed a significantly lower average ODI at the final follow-up than the OLD group  . Heterog2=57%, p=0.07).Among the 7 papers, 4 presented the results of the complication rate, and 1,105 subjects were included in the analysis: 387 in the PELD group and 718 in the OLD group. Fourteen subjects in the PELD group and 26 subjects in the OLD group had complications. There were no significant differences in the complication rate between the PELD and OLD groups  . Heterog2=0%, p=0.62).Among the 7 papers, 4 presented the results of the recurrence rate, and 1,105 subjects were included in the analysis: 387 in the PELD group and 718 in the OLD group. Twenty-three subjects in the PELD group and 52 in the OLD group had recurrence. There were no statistically significant differences in the recurrence rate between the PELD and OLD groups  . There w2=0%, p=0.49).Among the 7 papers, 4 presented the results of the reoperation rate, and 1,065 subjects were included in the analysis: 372 in the PELD group and 693 in the OLD group. Thirty-one subjects in the PELD group and 43 subjects in the OLD group had reoperation. There were no significant differences in the reoperation rate between the PELD and OLD groups  . There w2=91%, p<0.00001).Among the 7 papers, 6 presented the results of operation time, and 1,172 subjects were included in the analysis: 424 in the PELD group and 748 in the OLD group. The PELD group's average operation time was 55.84 min, and that of the OLD group was 83.99 min. The PELD group's average operation time was significantly shorter than that of the OLD group  . Heterog2=92%, p<0.00001).Among the 7 papers, 5 presented the results of hospital stay, and 270 subjects were included in the analysis: 129 in the PELD group and 141 in the OLD group. The PELD group's average hospital stay was 2.69 days, and that of the OLD group was 7.47 days. The PELD group's average hospital stay was significantly shorter than that of the OLD group  . HeterogIn general, OLD has been mostly performed as a surgical treatment for lumbar disc herniation. This technique could possibly lead to lumbar instability and iatrogenic injury as it requires the removal of some posterior structures such as lamina, ligament flavum, and facet joints, dissection of muscles near the spine, and pulling of nerve branches , 23. In Recently, a meta-analysis, which compared OLD and PELD as surgical treatments for lumbar disc herniation, reported two cases in 2016 , 30. EacIn the present study, PELD showed statistically significantly better results than OLD in the VAS score (of both leg and back) at the final follow-up, ODI, operation time, and hospital stay. We believe it is especially meaningful that contrary to previous meta-analysis studies , 30 PELDThe MacNab classification was recorded in only 3 among the 7 papers, and there were no significant differences between the two surgical methods. At the final follow-up, both surgical methods showed successful results. So, we have determined that both methods are effective.In this study, there were no significant differences in reoperation and recurrence rate. There were two previous reports stating that there were no differences between the two surgical methods , 33 and Complications included infection, spinal cord injury, cerebrospinal fluid leak, damage to nerve roots, and postoperative sensory abnormalities , 19, 20.This study has some limitations. All 7 papers used for the meta-analysis were nonrandomized trials, and there was selection bias as a result. The quality of these trials was also fairly high. In addition, clinical heterogeneity existed in this study. Type of surgery , surgical indications, treatment options before the operation, and follow-up period during the symptom period varied depending on the selected paper, and the sample size was small as well. Particularly revision surgery may demand different approach-related surgical technique and more operation time. They may be subject to more complications that do not exist during the initial surgery. Finally, a physician's proficiency makes a huge difference in PELD, and it is believed that the difference in physicians in each paper would have worked as a bias.This meta-analysis found that PELD had significantly better results than OLD in the VAS score, ODI, operation time, and hospital stay as a surgical treatment for lumbar disc herniation in the Korean population. Nevertheless, OLD still showed good clinical results, and therefore a randomized controlled study with a large sample size would be required in the future to compare these two surgical methods.


The association of body mass index (BMI) with risks of ischemic stroke subtypes have not been established.Cumulative average BMI was calculated using self-reported body weight and height obtained from baseline  and 5- and 10-year questionnaire surveys of Japan Public Health Center-based prospective (JPHC) study. A total of 42,343 men and 46,413 women aged 40–69 years were followed-up for the incidence of lacunar, large-artery occlusive, and cardioembolic strokes. A sub-distribution hazard model was used to estimate sub-distribution hazard ratios (SHRs) and the 95% confidence intervals (CIs).P = 0.007), large-artery occlusive (trend P = 0.002), and cardioembolic (trend P < 0.001) strokes in men, and with lacunar (trend P < 0.001) and large-artery occlusive (trend P = 0.003) strokes in women. There were approximately two-fold excess risk of cardioembolic stroke in both sexes and of lacunar and large-artery occlusive strokes in women for cumulative average BMI ≥30 kg/m2 compared to BMI 23–<25 kg/m2.During a median of 20.0 years of follow-up, we documented 809 and 481 lacunar, 395 and 218 large-artery occlusive, and 568 and 298 cardioembolic strokes in men and women, respectively. After adjustment for baseline age, updated smoking, alcohol consumption, leisure-time physical activity, and histories of hypertension, dyslipidemia, and diabetes mellitus, cumulative average BMI was positively linearly associated with lacunar (trend Cumulative average BMI showed a positive linear effect on sub-distribution hazards of lacunar, large-artery occlusive, and cardioembolic strokes in both sexes, except for cardioembolic stroke in women. One study in American communities 5 reported linear and positive associations of BMI with all ischemic stroke subtypes, which was totally explained by known risk factors . Another study in Japan  did not find any associations except for a positive association between BMI and lacunar stroke in women, which was independent of known risk factors, including systolic blood pressure.6 One explanation for the discrepancies might be that the mean BMIs and the compositions of ischemic stroke subtypes differ considerably between the two populations.7–9 However, it might also be due to differences in the way BMI was modeled: baseline only in the former5 versus updated as time-dependent covariate in the latter.6 BMI used in the latter study would mainly reflect a short-term effect of the exposure since BMI obtained in the nearest examinations before the events of cerebral infarction was related to the outcome. This might be appropriate for an exposure like blood pressure, which would elevate generally with advancing age, but might not be for an exposure like BMI, which would change in different directions with aging. Instead, we defined cumulative index of BMI as a kind of time-dependent exposure in the present study since potential effect of BMI on the outcome would require longer time. Nevertheless, we carried out baseline BMI only or updated BMI analyses to facilitate comparisons among studies. Since cumulative average BMI was regarded to capture the average level of exposure over longer-term than a single measurement, such as baseline (long latent period) or update (short latent period), yielding useful information for prevention, the analysis using cumulative average BMI was considered as the main one.Ischemic stroke is one of the leading causes of long-term disability and mortality worldwide.10,11 It would be more relevant to examine the association in a more contemporary cohort. In the present study, we examined the associations of BMI with ischemic stroke subtypes in a Japanese representative and more recent cohort. Since hypertension is the most significant risk factor for ischemic stroke, the stratified analysis by hypertension was also conducted to examine the possible effect modification.Furthermore, we could not readily assume that similar observation would be made even if another study was conducted in Japan employing similar methodological approaches, since the mean BMI increased from 21.7 to 23.3 from 1960 to 1990 in men aged 50–59 in Japan.12,13 Of 140,420 individuals enrolled , two public health-center areas without data on cardiovascular disease incidence , individuals not in the target age range , non-Japanese, and those who moved out before baseline survey (n = 552) were excluded from the present analysis. A self-administered questionnaire regarding height, body weight, lifestyles, and medical histories was distributed to all participants at baseline and returned from 43,130 subjects in Cohort I and 51,948 in Cohort II. Subjects with missing information on height or body weight ; smoking, alcohol consumption, leisure-time physical activity, histories of hypertension, dyslipidemia, or diabetes mellitus ; as well as those who reported histories of cardiovascular disease or cancer  at baseline were further excluded, leaving 42,343 men and 46,413 women  for the analysis. The study protocol of the JPHC study, was approved by the Human Ethics Review Committees of the National Cancer Center (13-021), Osaka University (14285-4), and Fujita Health University (HM15-255).The Japan Public Health Center-based prospective (JPHC) study was established in 1990 (Cohort I) and 1993–1994 (Cohort II) based on resident registry of 29 districts under 11 public health-center areas throughout Japan.2). The validity of self-report was examined in the JPHC Study participants (Cohort I) for whom health check-up data were available.14 Namely, the self-reported BMIs (mean: 23.45 in men and 23.57 in women) were slightly lower than measured BMIs (mean: 23.54 in men and 23.78 in women), and the Spearman correlation coefficients were 0.89 in men and 0.91 in women in the self-reported BMI range from 14 to 40 kg/m2. Smoking was categorized into never-smoker, ex-smoker, current smoker of <20 cigarettes/day, and current smoker of ≥20 cigarettes/day. Alcohol consumption habit was evaluated as the weekly consumption by multiplying weekly frequency and the amount of five specific alcoholic beverages taken on each occasion, which was grouped into never-drinker, former-drinker, and current drinker of <150 g/week, current drinker of 150–<300 g/week, and current drinker of ≥300 g/week. The frequency of leisure-time physical activity was assessed as none, 1–3 times/month, 1–2 times/week, 3–4 times/week, and almost everyday. Histories of hypertension, dyslipidemia, or diabetes mellitus were defined using the self-report of previous diagnoses or current use of medications, as well as by physical and laboratory data for those with blood pressure, total cholesterol, and casual glucose measurements at baseline  using the following criteria: systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg; total cholesterol ≥240 mg/dL; and blood glucose ≥126 mg/dL for those fasting more than 8 hours (otherwise ≥200 mg/dL).Follow-up questionnaire surveys were conducted at 5 and 10 years to update height, body weight, lifestyles, and medical histories. BMI was calculated as body weight (kg) divided by squared height  of the infarct. Definition of large-artery occlusive stroke was defined as infarct involving cortical areas. Cardioembolic stroke depended on clinical diagnosis with the presence of an embolus in the brain or medical record evidence of a possible source of embolus such as moderate or more severe valvular heart disease, atrial fibrillation, or intracardiac thrombus. Undetermined ischemic stroke included all ischemic strokes that could not be classified into lacunar, large-artery occlusive, or cardioembolic stroke (n = 82 in men and n = 127 in women). They were censored at the time of onset and were not analyzed in relation to BMI in the present study. However, we conducted sensitivity analyses that regarded these undetermined events as lacunar, large-artery occlusive, or cardioembolic stroke. A focal neurological deficit lasting <24 hours  and asymptomatic lacunar stroke were not systemically ascertained and, thus, were not included. The reliability of the same coding system was evaluated in a different study.16All the major hospitals capable of managing acute stroke care located in the sampling areas of the study were registered. The medical records were reviewed regularly by physicians in registered hospital or public health center blinded to the risk factor statuses, using the standard format of registry. To complete surveillance for incidence of fatal stroke, a systematic review of death certificate was conducted. The stroke diagnosis and the incidence date was assigned according to criteria adopted from the National Survey of Stroke criteria, which require a constellation of neurological deficits of sudden or rapid onset lasting at least 24 hours or until death.Subjects were followed-up from the date of the baseline survey  until first incidence of stroke regardless of the subtypes, death, moving out of study area, or the end of 2012, whichever came first. Residence and survival were ascertained annually using residential registries maintained by each municipality. In Japan, residency and death registration are required by law, and these registries are believed to be complete. Participants who moved out from their original residential areas were identified in each area and treated as censored at that time. Information on the cause of death was obtained through the death certificate provided by the Ministry of Health, Labor, and Welfare after the Ministry of Internal Affairs and Communications granted permission.Men and women were analyzed separately. The exposure variable (BMI) was treated in the analyses in three different ways. First, baseline BMI and covariates were used. Second, BMI was updated at 5- and 10-year follow-up. The covariates were also updated as time-dependent variables in the statistical models. Third, as the main analysis, cumulative average BMI was calculated for each subject using values in each 5-year interval questionnaire survey. Namely, it was defined as the values at baseline for those followed up for less than 5 years, as the mean of baseline and 5-year survey for those followed-up for 5 years or more but less than 10 years, and as the mean of baseline, 5-, and 10-year surveys for those followed for more than 10 years. Cumulative averages of numerical covariates were created in the same fashion. Categorical variables were simply updated to newer values. For those who were followed up for 5 years or more or 10 years or more but without 5-year or 10-year questionnaire data on those variables, the missing values were imputed using the last-observation carried forward method.2, with 23–<25 kg/m2 as the reference (a category which contains the mean BMI for men [23.5 kg/m2] and women [23.6 kg/m2]).For all the BMI variables, they were divided into seven categories, <19, 19–<21, 21–<23, 23–<25, 25–<27, 27–<30, ≥30 kg/m17,18 Three statistical models were performed stratified by 9 public health centers. Multivariable model 1 adjusted for baseline age (5-year categories from 40–44 to 65–69 years). Multivariable model 2 adjusted further for smoking, alcohol consumption, and leisure-time physical activity. Multivariable model 3 adjusted further for histories of hypertension, dyslipidemia, and diabetes mellitus. The SHR from Fine and Gray’s model denotes the magnitude of the relative change in the sub-distribution hazard function associated with one unit change in the given covariate.17 Positive SHR denoted as X can be interpreted as evidence that one unit increase in a coefficient is associated with a (X − 1) * 100% increase in the rate of an event of the interest in subjects who are either event-free or who have experienced a competing event. We described SHRs greater and smaller than unity (1) as increased and decreased SHR, respectively, in this study.Since subjects who died would have no probability of experiencing incidence in the future, treating them as non-informative censoring would inflate the estimate of cumulative incidence. The magnitude of inflation in the incidence would be greater in categories with higher mortality rates , resulting in overestimation of relative risks. Thus, deaths from causes other than ischemic stroke, as well as those from undetermined subtype of ischemic stroke, were considered as competing events in the present study. Fine and Gray’s sub-distribution hazard model was used to estimate sub-distribution hazard ratios (SHRs) and 95% confidence intervals (CIs).The stratified analysis by the history of hypertension, either at baseline, 5 years, or 10 years was done in multivariable model 3. Interaction of hypertension with BMI categories was tested.19 stratified by 9 public health centers was used to estimate hazard ratios (HRs) and 95% CIs for incidence occurred between each 5-year questionnaire cycle, after adjusting for time-dependent covariates.For the updated BMI analyses, a time-dependent Cox proportional hazard modelTest of linear trend was performed by assigning median BMI values for all subjects in each BMI category and by treating it as a continuous variable. Test of quadratic trend was done by assigning squared values of median BMI.All analyses were conducted using SAS for Windows, version 9.4 (SAS/STAT 13.1) .Higher cumulative average BMI was associated with younger age in men but older age in women Table . CurrentP < 0.05), except for cardioembolic stroke in women (trend P = 0.14) . We observed the significantly increased SHR of cardioembolic stroke in men whose cumulative average BMI was ≥30 kg/m2 , and that of lacunar stroke in women whose cumulative average BMI were 27–<30 and ≥30 kg/m2 . Similarly, women with cumulative average BMI of ≥30 kg/m2 had increased SHRs of large-artery occlusive and cardioembolic strokes .During a median of 20.0 years of follow-up, 809 and 481 lacunar, 395 and 218 large-artery occlusive, and 568 and 298 cardioembolic strokes were documented in men and women, respectively. Even in the fully-adjusted model that included known mediators, categories of cumulative average BMI were linearly positively associated with all the ischemic stroke subtypes in both sexes  .The stratified analysis by hypertension indicated similar associations of cumulative average BMI with risk of lacunar and cardioembolic stroke regardless of hypertension status in both men and women (n) Table . However2 as well as of lower BMI categories for cardioembolic stroke in women were significant .The analyses that used baseline BMI yielded generally similar but slightly attenuated results, except for its association with cardioembolic stroke in women . The SHRP > 0.05) but not in women where a positive linear association with lacunar (trend P < 0.001) and large-artery occlusive strokes (trend P = 0.03), and a reverse J-shaped association with cardioembolic stroke (quadratic P = 0.002) were found. The associations of BMI ≥30 kg/m2 for lacunar and large-artery occlusive strokes  as well as that of BMI <19.0 kg/m2 for cardioembolic stroke  were more evident compared to the findings obtained by cumulative average or baseline BMI analyses .2, men with BMI ≥30 kg/m2 had 2.1-times higher risk of cardioembolic stroke, and women with BMI ≥30 kg/m2 had 1.8- to 1.9-times higher risks of lacunar, large-artery occlusive, and cardioembolic strokes. Women with BMI of 27–<30 kg/m2 had also 1.4-times higher risk of lacunar stroke. These associations were independent of known confounders or mediators, including age, smoking, alcohol consumption, leisure-time physical activity, and histories of hypertension, dyslipidemia, and diabetes mellitus. Linear associations of cumulative average BMI with all ischemic stroke subtypes in men would indicate the existence of no specific cut-points, which implies the importance of preventing a rise in weight in the population for the prevention of ischemic stroke.In the present prospective study, cumulative average BMI showed a linear and a positive effect on sub-distribution hazard of ischemic stroke across all the subtypes in both sexes except for cardioembolic stroke in women. Compared to persons with BMI of 23–<25 kg/m20 In the present study of extended follow-up with a median of 20.0 years, which focused on ischemic stroke subtypes, we found significant relations of cumulative average BMI with all ischemic stroke subtypes in men. This may be due to increased statistical power, with more cases included in the present study .We have previously reported a linear positive relation of BMI with the incidence of ischemic stroke only in women in the JPHC Study, with a median follow-up of 7.9 years.5,6 Our results derived from a relatively lean population (mean baseline BMI: 23.5 kg/m2) is primarily consistent with that from a previous study of an American population (mean BMI: 27.8 kg/m2), which found BMI quintiles were linearly positively associated with risks of lacunar, non-lacunar, and cardioembolic strokes.5 However, the associations in that study were explained by possible mediators, such as measured systolic blood pressure. Another prospective study of Japanese that updated BMI up to five times with those obtained during follow-up examinations reported that the only significant finding was for lacunar stroke incidence in women.6 That finding might be consistent with the present analysis that simply updated BMI: the significant associations related to BMI ≥30 kg/m2 were found only in women for lacunar and large-artery occlusive strokes. Direct comparison with the ARIC Study regarding possible mediation would be hard since mediators, such as measured systolic blood pressure, total cholesterol, or glucose intolerance, were used in the former, while the majority of the present participants only had self-reported histories of hypertension, dyslipidemia, and diabetes mellitus. Nevertheless, we should consider that residual confounding (mediation) would be likely in the analyses where only self-reported histories were adjusted. However, if the association existed between BMI and ischemic stroke subtypes, independent of known mediators, possible explanations would include insulin resistance, endothelial dysfunction, or a low-grade chronic inflammation state.21,22 In any case, the present study suggests the importance of weight control for the prevention of all ischemic stroke subtypes.Few studies have addressed the association between the degree of obesity and risks of ischemic stroke subtypes.2 category compared to the reference category (23–<25 kg/m2) seemed more evident in women than in men. This might be due to some unmeasured stroke risk factors that are reportedly more strongly related to obesity in women than in men, such as low-grade systematic inflammation23,24 and prothrombotic factors.25 In any case, the present results imply that avoidance of obesity offers the potential of reducing lacunar and large-artery occlusive strokes in women.The excess risks of lacunar and large-artery occlusive strokes for BMI ≥30 kg/m26 the most important risk factor for cardioembolic stroke.27,28 Furthermore, low body weight was reportedly a significant risk factor for stroke incidence in male and female Japanese patients with atrial fibrillation.29 Further studies that obtained atrial fibrillation as well as use of antiplatelet medication, which may modify the association of atrial fibrillation with risk of cardioembolic stroke30 are warranted.The updated BMI analysis showed that the risk of cardioembolic stroke for the lowest BMI category with cardioembolic stroke was significantly elevated in women. This finding might correspond to a U-shaped association reported between BMI and atrial fibrillation,31,32 This tendency might have contributed to the prevention of large-artery occlusive stroke because dyslipidemia and diabetes, as well as hypertension, are major risk factors for this stroke subtype.33,34 Another reason for the lack of that association might be related to the fact that hypertension is the single strongest risk factor for large-artery occlusive infarction, the impact of BMI could be masked and not be properly evaluated in men with hypertension. In women without hypertension, the lack of the association between cumulative average BMI and risk of large-artery occlusive stroke might merely be by chance, probably because the number of large-artery occlusive stroke cases was small.The stratified analyses by hypertension yielded somewhat puzzling results: the lack of association between cumulative average BMI and risk of large-artery occlusive stroke in men with hypertension and in women without hypertension. The lack of the association in men with hypertension may be due to the higher probability of treatment for dyslipidemia and diabetes in the higher categories of BMI by local physicians.2 as well as for those with 19–<21 kg/m2 were more apparent in the baseline BMI analysis compared to the cumulative average BMI analysis. In addition, the associations of BMI ≥30 kg/m2 with risks of lacunar and large-artery occlusive strokes, as well as the association of BMI <19 kg/m2 with risk of cardioembolic stroke, were more evident in the updated BMI analysis compared to the cumulative average BMI analysis. Women might be more susceptible to a short-term effect of BMI, which is indicated by the fact that women gain weight with aging on average.35Simply speaking, the analyses that only used baseline or updated BMI produced attenuated results, which implies that cumulative average BMI captured important and relevant aspect of long-term effect of BMI on the sub-distribution hazard of ischemic stroke subtypes better than single-point measures. However, this was not true for women. The increased risk of cardioembolic stroke observed for women with BMI ≥30 kg/mThe strengths of the present study include valid identification of sufficient numbers of incident ischemic stroke subtypes that enabled us to conduct sex-specific analyses or stratified analyses by hypertension. Moreover, we examined three BMI variables in relation to ischemic stroke subtype risks, somewhat different results of which would aid better comparisons among studies. Also, we took competing risk of death into account to obtain more accurate estimates of the associations.36,37 overweight or obese subjects underestimated their body weight and underweight subjects overestimated their body weight,38 which would be related to attenuation of the observed associations. Second, the information about atrial fibrillation was not available. Although inconsistencies exist in the literature,39–41 low as well as high BMI were reportedly associated with high risk of atrial fibrillation.41,42 The present reverse J-shaped association of BMI with cardioembolic stroke risk might have been partly explained via atrial fibrillation. However, the adjustment for self-reported arrhythmia or the exclusion of those with self-reported arrhythmia did not materially change the reverse J-shaped association. Third, we were unable to evaluate to what extent the observed association was mediated through measured blood pressure or blood levels of glucose and lipids, since less than 25% subjects had complete data. Previous studies in Western populations have reported that these mediators alone or together entirely explained the effect of BMI on incident lacunar, nonlacunar, and cardioembolic stroke.5 Further studies in East Asian population are needed to clarify whether the significant association found in the present study would be explained via those measured potential mediators.The present study has potential limitations. First, BMI was calculated from self-reported body weight and height. Although the validity of self-reported height and body weight has been reported,2 compared to BMI 23–<25 kg/m2.In conclusion, cumulative average BMI showed a positive linear effect on sub-distribution hazards of lacunar, large-artery occlusive, and cardioembolic strokes in both sexes, except for cardioembolic stroke in women. There were approximately two-fold excess risk of cardioembolic stroke in both sexes and of lacunar and large-artery occlusive strokes in women for BMI ≥30 kg/m


Hemodialysis patients, especially from Asia, with shared hemodialysis devices, hemodialysis units > 2, blood transfusion, kidney transplantation, and drug addiction were at increased risk of HCV infection. The HCV infection rate increased with the duration of hemodialysis. High-risk hemodialysis patients should be monitored and receive timely screening.Hemodialysis is an effective replacement therapy for chronic renal failure patients. In recent decades, the number of hemodialysis patients has grown rapidly and some measures for preventing blood-borne diseases have been implemented, but hepatitis C virus (HCV) infection remains a significant problem. The meta-analysis published in 2009 on HCV infection-related factors was based on localized study objects, and some additional studies have been published since 2009; however, the contribution of these factors remains under dispute. Our study pooled the odds ratios (ORs) or mean standard deviations (MDs) with 95% confidence intervals (CIs) and analyzed sensitivity using Review Manager 5.1 software  by searching data in the PubMed, Elsevier, Springer, Wiley, and EBSCO databases. Spearman correlation analysis was performed using the SPSS package. In our meta-analysis, 1715 HCV-infected hemodialysis patients and 7093 non-HCV-infected hemodialysis patients from 44 studies were analyzed. The pooled ORs with 95% CIs were: histories of blood transfusion, 4.30 ; weekly hemodialysis times > 2, 6.00 ; kidney transplantation, 5.80 ; hemodialysis units > 2, 6.90 ; shared hemodialysis devices, 5.00 ; and drug addiction, 4.73 . The pooled MDs with 95% CIs were duration of hemodialysis (months) 27.48 . There was a positive correlation between duration of hemodialysis and the HCV infection rate ( Hemodialysis is an effective replacement therapy for chronic renal failure patients that can increase survival times . In receHemodialysis patients are at high risk of blood-borne diseases, especially infectious hepatitis C virus (HCV) and hepatitis B virus (HBV) ,4,5. TheHowever, the rate and number of HBV infections have declined greatly since the World Health Organization recommended that HBV vaccination be included in national immunization programs in 1992, and subsequently mass vaccination for hepatitis B has been implemented on a population-wide scale ,11,12.By contrast, an effective vaccine is lacking for HCV, and hemodialysis patients who require regular invasive treatment and are at high risk of HCV infection . A studyOver the past 10 years, most countries have published standard operating procedures for blood purification including measures such as using a dialyzer only once , dialyziHowever, although the rate of HCV infection among patients has declined, HCV infection among hemodialysis patients remains a significant problem ,20,22.Previous studies have shown that many factors influence the development of HCV infection, such as blood transfusion, duration on hemodialysis, weekly hemodialysis times, and a history of kidney transplantation ,38,39,40In this study, we used hemodialysis patients as research objects and extended the analysis of risk factors for HCV infection by performing a meta-analysis.Searches were performed for each of the specified databases on the Bo Ku data service platform. We used the search terms “Hepatitis C”, “HCV”, and “Hemodialysis” in the search field “Title/Abstract”, and the electronic databases searched included the following six international databases: PubMed, Elsevier, Springer, Wiley, OVID, and EBSCO. We also used the search terms “Hepatitis C”, “HCV”, and “Hemodialysis” in the search field “Abstract” and searched two Chinese electronic databases: Chinese Medical Journal Database and Chinese National Knowledge Infrastructure. The searches were completed in the first week of September, 2018. We also searched the references listed at the end of the included articles.In this study, the eligibility criteria for the inclusion of literature in the meta-analysis were as follows: (1) the literature is the original research; (2) the literature was an observational study with specific temporal and geographic characteristics; (3) the literature was published with the full text available; (4) all cases and controls were hemodialysis patents and the source of samples was clearly stated; (5) hepatitis C was diagnosed according to the national diagnostic criteria that existed at that time  and possLiterature was excluded from the meta-analysis when (1) the data reported could not be used to calculate the odds ratio (OR) or mean standard deviation (MD) with 95% confidence interval (CI) for the main variable; (2) the literature duplicated the same research; (3) the literature used the same research objects; and (4) the literature was deemed to be of poor quality literature  ,66.We used a pre-made form for data extraction, and then two trained reviewers assessed the literature one by one and completed the form. The following data were extracted from the qualified studies: first author, year of the study, location, the number of hemodialysis patients in the HCV-infected group and the non-HCV-infected group, sample size, male to female ratio, and age distribution for HCV infection development among hemodialysis patents.Discrepancies between the assessment results obtained by the two reviewers were resolved by discussion and checking the original documents.CI or pooled ORCI values with 95% CIs were obtained for this study factor, and then this pooled MDCI or pooled ORCI was compared with the total pooled OR or pooled MD before omitting this study factor. The studies with the maximum weight were omitted from the subgroup analysis, and then pooled, and the pooled MDweight or ORweight values with 95% CI for this study factor were obtained and then this pooled MDweight or pooled ORweight was compared with the total pooled MD or pooled OR before omitting this study factor.The studies with the widest 95% CI for the OR or MD were omitted from the subgroup analysis for this factor, and the remaining studies were pooled and pooled MDIn this meta-analysis, subgroup analyses were used to determine the associations between different study factors and HCV infection, a sensitivity analysis was used to examine the reliability of the associations, and a funnel plot was used to examine publication bias. According to the manufacturer’s instructions, the normal ranges of values for serum alanine aminotransferase (ALT) are about 5–40 units per liter of serum. Based on the standard procedure reported in the instructions, HCV infection was confirmed when a serum sample tested positive for HCV antibodies.2 statistics. The OR or MD was not pooled when its number for the study factor was less than 4. In the meta-analysis, I2 statistics, ranging from 0% to 100%, were used to assess the levels of heterogeneity; values of 0%, 25%, 50%, 75%, and 100% were taken as no, low, medium, high, and significant heterogeneity, respectively [2 ≤ 50% was accepted. Correlation analysis was performed using SPSS version 16 software . Spearman correlation was used for ranked data, with α = 0.05 considered to indicate statistical significance.The OR or MD with 95% CI were taken as the main indicators in this meta-analysis. Review Manager 5.1 software  was used to analyze the fixed-effect model without heterogeneity or the random-effect model with heterogeneity, after the heterogeneity test. The heterogeneity among different studies for study factors was evaluated by Cochran’s chi-square test with a significance level α = 0.1 and Iectively . In thisIn this meta-analysis, a total of 44 research articles were included, and a flow chart of the literature selection process is shown in Of the literature selected, 44 studies included 1715 HCV-infected hemodialysis patients and 7093 non-HCV-infected hemodialysis patients. The study characteristics, region, study type, number of HCV-infected hemodialysis patients and non-HCV-infected hemodialysis patients, study factors, sample size, male/female ratio, and mean participant age (years) are shown in The 11 study factors used to pool OR or MD with 95% CI were as follows: gender , age ; a history of blood transfusion ; weekly hemodialysis times > 2 ; a history of kidney transplantation ; hemodialysis units > 2 ; shared hemodialysis devices ; serum alanine aminotransferase (ALT) levels  ; drug addiction ; a history of surgery ; and duration of hemodialysis (months) .In this meta-analysis, the pooled ORs and their 95% CIs for study factors were as follows: histories of blood transfusion, 4.30 ; weekly hemodialysis times > 2, 6.00 ; a history of kidney transplantation, 5.80 ; hemodialysis units > 2, 6.90 ; shared hemodialysis devices, 5.00 ; serum ALT levels , 5.62 ; drug addiction, 4.73 ; a history of surgery, 1.98 ; and gender , 0.98 .In this meta-analysis, the pooled MDs and their 95% CIs for study factors were as follows: duration of hemodialysis (months), 27.48 ; and age (years), −0.3 .The pooled ORs with their 95% CIs for study factors including histories of blood transfusion, weekly hemodialysis times > 2, kidney transplantation, serum ALT levels , drug addiction, a history of surgery, hemodialysis units > 2, and shared hemodialysis devices are detailed in spearman = 0.990, p < 0.01) and between the duration of hemodialysis and the pooled OR .In terms of the duration of hemodialysis, groups of patients that underwent hemodialysis for 1–2 years, 2–3 years, 3–5 years, 5–10 years, and >10 years had HCV infection rates of 8.57%, 17.99%, 23.68%, 56.76%, and 60.47%, respectively, and pooled ORs with 95% CIs of 0.09 , 0.57 , 1.50 , 6.07 , and 5.76 , respectively. There was a positive correlation between the duration of hemodialysis and the HCV infection rate (rp < 0.10). The effects of these factors were then pooled using the random-effect model, whereas weekly hemodialysis times, kidney transplantation, drug addiction, a history of surgery, and gender were pooled using the fixed-effect model (p > 0.10). A heterogeneity test for pooled MDs with 95% CIs showed that the variation among studies for the duration of hemodialysis (months) was statistically significant (p < 0.10). The effects were then pooled using the random-effect model. These results are detailed in A heterogeneity test for pooled ORs with 95% CIs showed that variations among ORs for study factors including histories of blood transfusion, hemodialysis units > 2, shared hemodialysis devices, and serum ALT levels were statistically significant  being to the right of center, as detailed in CI and MDCI values with the 95% CIs, and these pooled values were close to the respective pooled OR and MD values with 95% CIs, as detailed in In view of the reliability of the pooled ORs or MDs using the random-effect model for terms including histories of blood transfusion, shared hemodialysis devices, hemodialysis units > 2, serum ALT levels, and duration of hemodialysis (months), we omitted studies with the widest 95% CIs for the ORs and MD values, respectively, and pooled and acquired ORweight or MDweight values with 95% CIs, and these pooled values were close to the respective pooled OR or MD values with 95% CIs, as detailed in In view of the reliability of pooled ORs using the random-effect model for terms including histories of blood transfusion, shared hemodialysis devices, hemodialysis units > 2, serum ALT levels, and duration of hemodialysis (months), we omitted studies with the highest weights, and pooled and acquired ORThis study showed that, for hemodialysis patients, the rate of HCV infection increased with the duration of hemodialysis treatment. This meta-analysis also found that hemodialysis patients with a duration of hemodialysis treatment >5 years and/or histories of blood transfusion and/or shared hemodialysis devices and/or hemodialysis units >2 and/or weekly hemodialysis times >2 and/or kidney transplantation and/or histories of surgery and/or drug addiction were at increased risk of developing HCV infection, whereas the age and gender of hemodialysis patients did not affect the risk of developing HCV infection.Our study analyzed the rate of HCV infection among groups of patients with a duration of hemodialysis treatment of 1–2 years, 2–3 years, 3–5 years, 5–10 years, and >10 years, and the study found that the longer the duration of hemodialysis treatment, the higher the rate of HCV infection; this result was consistent with the results reported in the meta-analysis by Sun et al. in 2009 .More specifically, our study showed that patients with a duration of hemodialysis treatment >5 years were at increased risk of developing HCV infection, whereas patients with a duration of hemodialysis treatment <5 years did not have an increased risk of developing HCV infection. This result was not consistent with the findings of the 2009 meta-analysis, which reported that patients with a duration of hemodialysis treatment >1 year were at increased risk of developing HCV infection . These dIn our meta-analysis, the result of a quantitative analysis  also shoIn general, exposure to HCV-contaminated medical equipment or goods can increase the risk of HCV infection, and during the process of hemodialysis, patients have many possible opportunities for exposure to HCV-contaminated equipment or goods ,69.The findings of this meta-analysis showed that hemodialysis patients with a history of shared hemodialysis devices and/or hemodialysis units >2 and/or weekly hemodialysis times >2 and/or a duration of hemodialysis >5 years were at increased risk of HCV infection, and this may be related to the fact that these hemodialysis patients had more opportunities to be exposed to HCV- contaminated medical equipment, HCV-contaminated goods, or the HCV-contaminated hands of medical personnel, potentially leading to nosocomial infection.A study by Alfurayh et al. confirmed the existence of nosocomial transmission in hemodialysis centers by sequence analysis . MoreoveThe findings of this meta-analysis also showed that kidney transplantation hemodialysis patients were at increased risk of HCV infection, and this may be related to the fact that these hemodialysis patients had taken immunosuppressants, which may have resulted in low lymphocyte activation following HCV infection . MoreoveIn general, ELISA was the routine method for screening blood donors for HCV infection, but molecular-based tests such as PCR are more sensitive diagnostic assays, and thus it is possible that some blood donors screened by traditional ELISA methods may have been HCV infectors ,73,74. TOur meta-analysis also found that the age and gender of hemodialysis patients did not affect the risk of developing HCV infection, and this result was consistent with the findings of the 2009 meta-analysis .The sensitivity analysis performed as part of our meta-analysis found that, after omitting studies with the widest 95% CIs for OR or MD values and studies with the maximum weight in subgroup analyses for the duration of hemodialysis treatment (months), histories of blood transfusion, shared hemodialysis devices, hemodialysis units >2, and abnormal serum ALT levels, the two overall effects were not reversed and the pooled OR or MD values were similar to those observed before omitting the studies. This revealed that the pooled ORs or MDs for these study factors were reliable and stable.The limitations of this study were that only articles published in English or Chinese were included in the meta-analysis. In addition, even though the ORs or MDs of the six factors were pooled using a random-effect method, study heterogeneity may have influenced the findings to some extent. Furthermore, some study factors, for example, the degree of deterioration and the socioeconomic status of patients, were not available to be pooled. Lastly, studies included were carried out in the following countries: Iran, Australia, Egypt, and China, and this aspect limits the generalizability of conclusions.It can be concluded that, for hemodialysis patients, the rate of HCV infection increases with the duration of hemodialysis treatment, and that hemodialysis patients, especially from Asia, with histories of blood transfusion and/or weekly hemodialysis times >2 and/or shared hemodialysis devices and/or hemodialysis units >2 and/or kidney transplantation and/or drug addiction were at increased risk of developing HCV infection. High-risk hemodialysis patients should be closely monitored and receive timely screening and therapeutic intervention to reduce the risk of HCV nosocomial infection.


P ≤ 0.025). These findings will be useful for the planning of eye care services and resource allocation.We evaluated the prevalence of visual impairment (VI) and blindness among Chinese adults in the Singapore Chinese Eye Study , and compared the trends with the Tanjong Pagar Survey, Singapore (TPS), conducted a decade earlier. The SCES comprised of 3,353 Chinese adults aged ≥40 years . Participants underwent standardized examinations, including measurements of presenting, and best-corrected visual acuity (VA). Bilateral VI (VA < 20/40 to ≥20/200) and blindness (VA < 20/200) were defined based on the United States definition (better-seeing eye). Age-standardized prevalence was calculated using the 2010 Singapore Chinese Population Census. Primary causes and factors associated with VI and blindness were evaluated. In SCES, the age-standardized prevalence of presenting bilateral VI and blindness were 17.7% and 0.6%, respectively; the age-standardised prevalence of best-corrected bilateral VI and blindness were 3.4% and 0.2%, respectively. The previous TPS reported similar rates of best-corrected bilateral VI (3.8%) and blindness (0.3%). In SCES, cataract remains the main cause for both best-corrected bilateral VI (76.0%) and blindness (50.0%). Older age, female, lower income, lower educational level, and smaller housing type were associated with presenting bilateral VI or blindness (all  As Chinese account for 20% of the world population, with a global estimate of more than one billion persons2, data on VI and blindness on this ethnic group is important. In this regard, several population-based surveys previously provided considerable information on the trends of VI among Chinese living in both rural and urban parts of China5. Nevertheless, the prevalence and causes of VI among migrant Chinese who live outside of China are lacking6.The estimated number of people visually impaired in the world stands at 285 million, with 39 million diagnosed blind. Asia alone accounts for 63.4% and 57.5% of worldwide visual impairment (VI) and blindness, respectively7. In the 1990s, the Tanjong Pagar Survey (TPS) was conducted to determine the prevalence of blindness and VI in the Singapore Chinese population8. Over the past one decade, socioeconomic conditions and healthcare services in Singapore have improved markedly. Furthermore, the Singapore population is aging rapidly, with a predicted figure of 1 in 5 residents being 65 years old or older by 20307. Hence, the trends of VI and blindness among Singapore Chinese may also change considerably over the years.In Singapore, Chinese make up the largest ethnic group and currently account for 74.3% of the Singapore populationThe Singapore Chinese Eye Study (SCES) was conducted between 2009–2011 with the key objective to obtain contemporary information on the prevalence of VI and blindness, their causes and key risk factors. The purpose of this current report was to evaluate the prevalence rates and causes of VI and blindness among Chinese adults in the SCES, and to compare the trends with the TPS, conducted a decade earlier. This information will help to improve the understanding on the long-term trends of blinding ocular diseases in Chinese adults residing in Singapore, and will be useful for the future planning of health services and preventive programs for VI and blindness.9. The study was conducted in the south-western part of Singapore. Based on age-stratified random 4,605 individuals were identified to be eligible, of which, 3,353 individuals (response rate of 72.8%) were eventually recruited and participated in the study. The study adhered to the Declaration of Helsinki. Ethics approval was obtained from the institutional review board of the Singapore Eye Research Institute, Singapore, and written informed consent was obtained from all participants.The SCES is a population-based, cross-sectional study of 3,353 Chinese adults aged 40 years or older conducted from February 9, 2009, through December 19, 2011. Details of the study design, sampling plan, and methods have been reported previously in detail8. Of the 1,717 persons considered eligible to participate, 1,232 participated in the study (response rate of 71.8%), 1,152 had relevant data on visual acuity. Details of the study design and methods of TPS have been described previously8. The study adhered to the Declaration of Helsinki. Ethics approval was obtained from Singapore National Eye Centre Ethics Committee, and written informed consent was obtained from all participants8.On the other hand, the TPS is a population-based study conducted from 1997 to 1998, on Chinese adults aged 49 to 80 years living in the Tanjong Pagar district 10. When no numbers could be read at 4 m, the participant was moved to 3, 2, or 1 m, consecutively. When no number could be read at even 1 m, VA was then assessed as counting fingers, hand movements, perception of light, or no perception of light.All study participants underwent a detailed ocular examination including slit lamp examination, intraocular pressure measurement, dilated fundus examination, and fundus photography. The presenting VA (PVA) with habitual correction, and best-corrected VA (BCVA) afer subjective refraction were recorded using an Early Treatment of Diabetic Retinopathy Study logarithm of Minimum Angle of Resolution (logMAR) number chart  at a distance of 4 metersBoth the United States (U.S.) and the modified WHO definitions were used to define VI. According to the U.S. definition, VI was defined as VA < 20/40 but ≥20/200 in the better-seeing eye, and blindness was defined as VA < 20/200 in the better-seeing eye. Based on the WHO definition, VI was defined as VA < 20/60 but ≥20/400 in the better-seeing eye, and blindness was defined as VA < 20/400 in the better-seeing eye. We used a modified WHO definition, which classified persons with VA of counting fingers or worse as blind. All subjects were further categorised into 5 mutually exclusive categories: (1) bilateral blindness; (2) bilateral VI (VI in one eye and VI/blindness in the other eye); (3) unilateral blindness; (4) unilateral VI; and (5) bilateral normal vision. Unilateral VI and unilateral blindness cases were defined based on the worse-seeing eye, with the fellow eye having normal vision.11. Age-related macular degeneration (AMD) was graded from retinal photographs using the Wisconsin Age-related Maculopathy grading system12. Diabetic retinopathy (DR) was graded from retinal photographs using a modification of the Arlie House classification system for the Early Treatment Diabetic Retinopathy Study13. If there were more than one condition in the same eye or across both eyes, the main cause of visual impairment was further determined, based on the severity of the underlying eye diseases.Primary causes of VI or blindness were ascertained on the basis of clinical history, examination, disease definition, and clinical judgment. Under-corrected refractive error was defined when BCVA was at least 2 lines (in logMAR chart) better than PVA. Glaucoma was diagnosed according to the International Society of Geographical and Epidemiological Ophthalmology scheme9.Detailed interviewer-administered questionnaires were also performed to collect relevant medical history , socio-economic status information , and lifestyle-related information  as reported previouslySystolic and diastolic blood pressures (BP) were measured using an automated sphygmomanometer . Non fasting blood samples were extracted from participants to determine levels of serum glucose and glycosylated haemoglobin (HbA1C). Body mass index was also measured. Patients with hypertension were defined as having systolic BP ≥ 140 mmHg, diastolic BP ≥ 90 mmHg, use of antihypertensive medications, or self-reported physician diagnosed hypertension. Diabetes was defined as having random glucose level of ≥11.1 mmol/L, HbA1c of ≥6.5 mmol/L, use of diabetic medications, or self-reported physician diagnosed diabetes.All statistical analyses were performed using R version 2.15.3 . Prevalence estimates of VI and blindness were calculated, and standardized to the Singapore Chinese Population 2010 Census. Bootstrapping was further performed to compare the age-standardized prevalence rates between the SCES and TPS. Multiple logistic regression analysis was used to assess the association between demographic, socioeconomic, and systemic factors with presenting and best-corrected bilateral VI or blindness (U.S definition) in SCES.The datasets generated and/or analysed during the current study are not publicly available due to local Institutional Review Board regulation, but are available from the corresponding author on reasonable request.Table In SCES, based on PVA and U.S definition, age-standardised prevalence of bilateral blindness was 0.6% , 17.7%  for bilateral VI, 2.1%  for unilateral blindness, and 21.1%  for unilateral VI  conducted a decade ago. In SCES, 17.7% and 0.6% had presenting bilateral VI and blindness (U.S. definition), respectively; while 3.4% and 0.2% had best-corrected bilateral VI and blindness (U.S definition), respectively. These rates in SCES were slightly lower compared to those in the previous TPS. The principal cause of best-corrected bilateral VI and blindness was cataract. This is a unique study which provided rare formation on the long-term change in prevalence of VI and blindness in an urban Chinese population, over a decade. Collectively, these findings will be useful for the future designing of eye health services, and will help to better guide planning in health resource allocation.14.The slightly lower prevalence of VI and blindness in the current SCES compared to TPS, may be attributed to increased awareness of eye health and eye diseases, and enhanced accessibility to eye care services in Singapore, over the past decade. This explanation is further substantiated with the reported increase in eye care utilisation in Singapore over the years, with an annual growth rate of 8.6% per year since year 200218. This comparison is especially marked when comparing with previous studies of rural areas such as the Yunnan Minority Eye Study and Kailu Study18. Overall, these differences are expected given the differences in accessibility and utilisation of eye care services between Singapore and the above-mentioned areas. Nevertheless, it should also be noted that accurate comparisons across studies is limited by the inherent variations in population characteristics, and time period between studies. Thus, these observed differences should also be interpreted with caution.In addition, when comparing with other population-based studies among Chinese adults in China, Taiwan and Mongolia, the prevalence rates of VI and blindness in SCES are also relatively lower4. This finding indicates that more public education and awareness enhancement are required in this aspect, in a bid to further reduce the rate of avoidable VI due to uncorrected refractive error. On the other hand, cataract was the most common cause for best-corrected bilateral VI in SCES. In TPS and other Asian populations, it was similarly reported that cataract was the most common cause of best-corrected bilateral VI19. These collectively indicate that cataract still remains a major burden for best-corrected VI after a decade, further emphasizing the importance of continually improving accessibility to cataract surgery and optimal cataract surgery outcomes, which will in turn help to further reduce cataract-related VI and blindness. In addition, cataract was also the leading cause for best-corrected bilateral blindness in SCES. In contrast, glaucoma was the most common cause for best-corrected bilateral blindness in TPS, and cataract was the second leading cause instead8. This difference may be explained by the higher proportion of advanced glaucoma cases observed in TPS back in late 1990s20. Approximately 40% of glaucoma cases identified in TPS were of late stage with blindness in at least one eye. Interestingly, a decade later in SCES, no glaucoma case was reported as the primary cause for bilateral blindness (Table With regards to causes of visual loss, under-corrected refractive error was the main cause of presenting bilateral VI in SCES. This is consistent with previous Chinese population studies22. Likewise, Beijing Eye Study also reported that lower educational level was associated with VI5. One possible explanation might be that individuals with lower educational level may have limited awareness and understanding of their own medical conditions, are less likely to go for routine eye health screening, and more likely of having poorer compliance when referred to tertiary eye care for further treatment23. Lastly, lower socioeconomic status such as lower income and smaller housing residence type were found to be associated with presenting bilateral VI or worse. Nevertheless, it should be noted that this association may be bidirectional; while persons with lower economic status may be more likely to suffer from poor vision, it is also likely that VI hinders individual’s earning and career potential.Furthermore, we observed that older age and lower educational level were also associated with both presenting, and best-corrected bilateral VI or worse. Previous studies similarly showed that older age was associated with VI, with some reported marked increase in the rate of VI for those aged 70 years and aboveThe strengths of this study include a large sample of urban Chinese population, and the use of standardized examination protocol which was similar to that of TPS. This allowed for relatively direct comparison between the 2 studies, thus providing unique information on the long-term change in prevalence of VI and blindness in Singapore Chinese population. Nevertheless, our study has a few limitations. First, as automated perimetry was only performed on a subset of study participants identified to be glaucoma suspects, loss of visual fields was not included as part of the definition for blindness. Therefore, the prevalence of blindness due to glaucoma may have been underestimated. Second, as cataract accounted for 76.0% of VI after refractive correction, it was possible that concurrent retinal diseases might had been masked by significant cataract, especially among elderly individuals.In conclusion, the SCES showed relatively low prevalence of VI and blindness among Chinese adults living in Singapore. These estimates are slightly lower compared with previous findings from the TPS conducted a decade earlier. Cataract remains the leading cause of best-corrected bilateral VI and blindness. These findings will further help to improve the understanding on the long-term trends of blinding ocular diseases in Chinese adults residing in Singapore, which are useful for the future planning of health services, resource allocation, and preventive programs for VI and blindness.Supplementary Table 1


This study aims to explore the feasibility of narrow-band imaging (NBI) applied for the diagnostic screening of a high-risk population of nasopharyngeal carcinoma (NPC) and increase the accuracy rate of nasopharyngeal biopsy and the diagnosis rate of early-stage patients.The positive high-risk population of NPC to EB virus antibody was followed up. At the same time, serological screening and pharyngorhinoscopy were carried out. The specific methods were as follows: (1) all subjects received nasopharyngeal examinations through both the HD endoscopic white light mode (WL) and NBI mode, (2) nasopharyngeal biopsy was conducted on positive subjects with microscopic examination, and, finally, (3) a comparative analysis was conducted between the biopsy pathology results and microscopy results. In addition, the following comparative indicators were recorded under different modes: sensitivity, specificity, accuracy, positive likelihood ratio, and negative likelihood ratio. Then, the area under the ROC curve and the kappa coefficient were calculated.A total of 115 subjects were detected to be positive by microscopic examination under the WL mode. Among these subjects, 19 subjects were diagnosed with NPC. In addition, 24 subjects were detected to be positive by microscopic examination under the NBI mode. Among these subjects, 23 subjects were diagnosed with NPC. Under the WL mode, the specific values of the comparative indicators were as follows: sensitivity, 82.61%; specificity, 0%; and area under the ROC curve, 0.413. Furthermore, the WL mode in the diagnosis on the high-risk population of NPC exhibited poor consistency with the biopsy pathology results (kappa coefficient = − 0.069). Under the NBI mode, the specific values of the comparative indicators were as follows: sensitivity, 100%; specificity, 98.96%; and area under the ROC curve, 0.995. Furthermore, the NBI mode in the diagnosis on the high-risk population of NPC exhibited relatively satisfactory consistency with the biopsy pathology results (kappa coefficient = 0.973). Therefore, the NBI mode is significantly superior to the WL mode.NBI endoscopic examinations should be conducted on a routine basis for high-risk populations of NPC. This can decrease the frequency of biopsies and enhance diagnostic effects. Nasopharyngeal carcinoma (NPC) is a common malignant head and neck tumor . It has This was a study, in which a general NPC investigation was carried out by the People’s Hospital of Guangxi Zhuang Autonomous Region in collaboration with the Guangxi Cangwu Nasopharyngeal Carcinoma Prevention Institute, Bobai People’s Hospital and Luchuan People’s Hospital from October 2013 to December 2014. All the eligible subjects were asked to participate in the screening tests. Inclusion criteria were as follows: (1) age between 29 and 60 years, (2) without prevalent NPC, and (3) having a good physical and psychological self-consciousness. Those with history of nasopharyngeal carcinoma were excluded. The high-risk population of NPC was selected by conducting EB virus antibody tests of the peripheral venous blood collected from the subjects. Starting August 2015, the high-risk population of NPC was followed up, and examinations included serological test of EB virus antibody and nasopharyngeal endoscopy. Among the 5960 persons who are at high risk in these three counties, three were with history of nasopharyngeal carcinoma, 39 persons were with EB virus antibody (+) turned negative, and finally 5918 were enrolled into the study. Informed consent was obtained.Examinations under the WL mode: positive symptoms include mass lesion, apophysis and rough superficial mucosa, anabrosis, and local mucosa color abnormity in the nasopharyngeal region. The remaining symptoms were regarded as negative.Examinations under the NBI mode: (1) abnormal and positive symptoms include the increased superficial vessels of the mucosa, increased (expanded) vessel diameter, disordered texture, local circuitry, intensively distributed punctiform vessels, and lumbriciform, or rope-strip-shaped vascular disruptions . (2) NegAn HD electronic nasopharyngolarygnoscope with both WL and NBI modes  was adopted. In this study, all subjects received nasopharyngeal examinations through the HD electronic nasopharyngolarygnoscope. Examination steps: a mixed solution of 1% tetracaine + 1% ephedrine was used for contraction, and the nasal cavity and nasal nasopharyngeal mucosa were sterilized twice. Through the nasal cavity, the HD electronic nasopharyngolarygnoscope was placed in the nasopharyngeal region for the examination. The examinations were first carried out under WL mode, and subsequently under NBI mode; and the examination results were recorded. The result judgment standards were as follows:Biopsy indications: endoscopic examination was conducted regularly for positive subjects under either WL mode or NBI mode, and negative subjects were examined both under WL mode and NBI mode. Nasopharyngeal tissue biopsy pathology results were regarded as the diagnostic criterion of NPC. The pathological diagnosis was conducted with reference to the World Health Organization (WHO) NPC histopathological typing . For patP value < 0.05 was considered statistically significant.Statistical software SPSS 17.0 was adopted, and chi-squared test was used to compare the corresponding rates. A Up to December 30, 2015, a total of 5918 high-risk subjects  were followed up. The mean age of these subjects was 48. Among them, 119 were positive patients, as detected by endoscopic examination, with the rate of 2.01%.P < 0.001, Table Among the 5918 subjects that were followed up, the WL mode microscopic examination revealed 115 positive cases and 5803 negative cases, while the NBI mode microscopic examination revealed 24 positive cases (0.41%) and 5894 negative cases. The difference among these positive rates for both modes was statistically significant  and one case was diagnosed with chronic inflammation of the nasopharyngeal mucosa. Under the WL mode, 115 positive cases received nasopharyngeal biopsy, in which 19 cases were diagnosed with NPC (Table P = 0.143). Furthermore, morphologic abnormality (apophysis or anabrosis) rate was 82.61%, which was obviously higher than that of the chronic inflammation of the nasopharyngeal mucosa (60.42%), and the difference was statistically significant (P = 0.045). Under the NBI mode, the increase rate, expansion rate, and morphologic abnormality rate of blood vessels with NPC were all significantly more than those of the chronic inflammation of the nasopharyngeal mucosa (P < 0.001) , but the difference was not statistically significant (P < 0.05). However, under the NBI mode, the consistency between the diagnosis of the high-risk population of NPC and biopsy pathology results were very satisfactory (kappa coefficient = 0.973), while such consistency under the WL mode was poor (kappa coefficient)  Table .Table 4CA total of 23 cases were diagnosed with NPC, and staging was carried out according to the AJCC (Version 7) NPC staging scheme. The results are as follows: T1, eight cases; T2, 13 cases; and T3, two cases. Moreover, all 23 cases had no lymphatic metastasis. The staging of NPC diagnosed under the NBI mode is shown below: stage I, eight cases; stage II, 13 cases; and stage III, two cases. The diagnosis rate of the early stage (stage I and II) was 91.3%. For the WL mode: stage I, four cases; stage II, 13 cases; and stage III, two cases. The diagnosis rate of the early stage (stage I and II) was 89.5% Table  and 5.TaBeing endemic in South China, the five-year survival rate of early-stage NPC can reach up to 89.7% , while tIn current literature, under the WL mode, 115 cases were diagnosed with abnormities, in which 19 cases were diagnosed with NPC, which was significantly more than that under the NBI mode (24 cases). This indicates that these 115 cases received nasopharyngeal biopsy under the WL mode. This was familiar with that of a previous study, where the nasopharyngeal endoscopy coupled with NBI was able to provide a rapid, convenient, and highly reliable screening for high-risk populations . Few litSome research indicated that , 22 earlSince the nasopharyngeal position is relatively deep, early-stage NPC symptoms were obvious. In particular, it can be easily missed and diagnosis could be delayed for subjects with no lymphatic metastasis. For positive patients with the EB virus antibody, once a lymphatic metastasis is found, the patients can be early diagnosed in a timely manner, in general. At the earlier stage, we have also come to a similar conclusion through tracking and following up other areas . In our These present research results revealed that the sensitivity, specificity, and accuracy of the NBI mode are relatively higher than those of the WL mode for the diagnosis of NPC. Through the authenticity and reliability evaluation of these two modes, it was found that the NBI mode was superior to the WL mode. Therefore, we consider that endoscopic examination under the NBI mode should be applied to the diagnostic protocol of NPC, in order to significantly reduce the biopsy rate of non-NPC patients, relieve the subject’s pain, reduce the general investigation fund expenditure, and early detect NPC in patients.