Evaluating the Demand for Nucleic Acid Testing in Different Scenarios of COVID-19 Transmission: A Simulation Study.

INTRODUCTION: The 2019 novel coronavirus (COVID-19) has been recognized as the most severe human infectious disease pandemic in the past century. To enhance our ability to control potential infectious diseases in the future, this study simulated the influence of nucleic acid testing on the transmission of COVID-19 across varied scenarios. Additionally, it assessed the demand for nucleic acid testing under different circumstances, aiming to furnish a decision-making foundation for the implementation of nucleic acid screening measures, the provision of emergency materials, and the allocation of human resources. METHODS: Considering the transmission dynamics of COVID-19 and the preventive measures implemented by countries, we explored three distinct levels of epidemic intensity: community transmission, outbreak, and sporadic cases. Integrating the theory of scenario analysis, we formulated six hypothetical epidemic scenarios, each corresponding to possible occurrences during different phases of the pandemic. We developed an improved SEIR model, validated its accuracy using real-world data, and conducted a comprehensive analysis and prediction of COVID-19 infections under these six scenarios. Simultaneously, we assessed the testing resource requirements associated with each scenario. RESULTS: We compared the predicted number of infections simulated by the modified SEIR model with the actual reported cases in Israel to validate the model. The root mean square error (RMSE) was 350.09, and the R-squared (R2) was 0.99, indicating a well-fitted model. Scenario 4 demonstrated the most effective prevention and control outcomes. Strengthening non-pharmaceutical interventions and increasing nucleic acid testing frequency, even under low testing capacity, resulted in a delayed epidemic peak by 78 days. The proportion of undetected cases decreased from 77.83% to 31.21%, and the overall testing demand significantly decreased, meeting maximum demand even with low testing capacity. The initiation of testing influenced case detection probability. Under high testing capacity, increasing testing frequency elevated the detection rate from 36.40% to 77.83%. Nucleic acid screening proved effective in reducing the demand for testing resources under diverse epidemic prevention and control strategies. While effective interventions and nucleic acid screening measures substantially diminished the demand for testing-related resources, varying degrees of insufficient testing capacity may still persist. CONCLUSIONS: The nucleic acid detection strategy proves effective in promptly identifying and isolating infected individuals, thereby mitigating the infection peak and extending the time to peak. In situations with constrained testing capacity, implementing more stringent measures can notably decrease the number of infections and alleviate resource demands. The improved SEIR model demonstrates proficiency in predicting both reported and unreported cases, offering valuable insights for future infection risk assessments. Rapid evaluations of testing requirements across diverse scenarios can aptly address resource limitations in specific regions, offering substantial evidence for the formulation of future infectious disease testing strategies.

Optimal resource allocation model for COVID-19: a systematic review and meta-analysis.

BACKGROUND: A lack of health resources is a common problem after the outbreak of infectious diseases, and resource optimization is an important means to solve the lack of prevention and control capacity caused by resource constraints. This study systematically evaluated the similarities and differences in the application of coronavirus disease (COVID-19) resource allocation models and analyzed the effects of different optimal resource allocations on epidemic control. METHODS: A systematic literature search was conducted of CNKI, WanFang, VIP, CBD, PubMed, Web of Science, Scopus and Embase for articles published from January 1, 2019, through November 23, 2023. Two reviewers independently evaluated the quality of the included studies, extracted and cross-checked the data. Moreover, publication bias and sensitivity analysis were evaluated. RESULTS: A total of 22 articles were included for systematic review; in the application of optimal allocation models, 59.09% of the studies used propagation dynamics models to simulate the allocation of various resources, and some scholars also used mathematical optimization functions (36.36%) and machine learning algorithms (31.82%) to solve the problem of resource allocation; the results of the systematic review show that differential equation modeling was more considered when testing resources optimization, the optimization function or machine learning algorithm were mostly used to optimize the bed resources; the meta-analysis results showed that the epidemic trend was obviously effectively controlled through the optimal allocation of resources, and the average control efficiency was 0.38(95%CI 0.25-0.51); Subgroup analysis revealed that the average control efficiency from high to low was health specialists 0.48(95%CI 0.37-0.59), vaccines 0.47(95%CI 0.11-0.82), testing 0.38(95%CI 0.19-0.57), personal protective equipment (PPE) 0.38(95%CI 0.06-0.70), beds 0.34(95%CI 0.14-0.53), medicines and equipment for treatment 0.32(95%CI 0.12-0.51); Funnel plots and Egger's test showed no publication bias, and sensitivity analysis suggested robust results. CONCLUSION: When the data are insufficient and the simulation time is short, the researchers mostly use the constructor for research; When the data are relatively sufficient and the simulation time is long, researchers choose differential equations or machine learning algorithms for research. In addition, our study showed that control efficiency is an important indicator to evaluate the effectiveness of epidemic prevention and control. Through the optimization of medical staff and vaccine allocation, greater prevention and control effects can be achieved.

A network meta-analysis of risk factors of infection among close contacts of COVID-19.

Objective: We aimed to use network meta-analysis to compare the impact of infection risk factors of close contacts with COVID-19, identify the most influential factors and rank their subgroups. It can provide a theoretical basis for the rapid and accurate tracking and management of close contacts. Methods: We searched nine databases from December 1, 2019 to August 2, 2023, which only took Chinese and English studies into consideration. Odd ratios (ORs) were calculated from traditional meta-estimated secondary attack rates (SARs) for different risk factors, and risk ranking of these risk factors was calculated by the surface under the cumulative ranking curve (SUCRA). Results: 25 studies with 152647 participants identified. Among all risk factors, the SUCRA of type of contact was 69.6 % and ranked first. Among six types of contact, compared with transportation contact, medical contact, social contact and other, daily contact increased risk of infection by 12.11 (OR: 12.11, 95 % confidence interval (CI): 6.51-22.55), 7.76 (OR: 7.76, 95 % CI: 4.09-14.73), 4.65 (OR: 4.65, 95 % CI: 2.66-8.51) and 8.23 OR: 8.23, 95 % CI: 4.23-16.01) times, respectively. Overall, SUCRA ranks from highest to lowest as daily contact (94.7 %), contact with pollution subjects (78.4 %), social contact (60.8 %), medical contact (31.8 %), other (27.9 %), transportation contact (6.4 %). Conclusion: The type of contact had the greatest impact on COVID-19 close contacts infection among the risk factors we included. Daily contact carried the greatest risk of infection among six types of contact, followed by contact with pollution subjects, social contact, other, medical contact and transportation contact. The results can provide scientific basis for rapid assess the risk of infection among close contacts based on fewer risk factors and pay attention to high-risk close contacts during management, thereby reducing tracking and management costs.

Estimating an EQ-5D-Y-3L Value Set for China.

INTRODUCTION: The standard EQ-5D-Y-3L valuation protocol applies DCE data as the primary preference source to model the relative importance of dimensions while cTTO data served to anchor the DCE coefficients onto the QALY scale. This study aims to estimate an EQ-5D-Y-3L value set for China following this protocol, but with a larger cTTO design to better understand the role of cTTO data in estimating EQ-5D-Y-3L value sets. METHODS: In total, 150 choice sets and 28 EQ-5D-Y-3L health states were valued using DCE and cTTO methods with two independent samples, respectively. General public from 14 different regions were recruited using quota sampling method to achieve representativeness. We compared two modelling strategies: (1) fit the DCE data with mixed logit model with correlated coefficients and a subsequent mapping procedure for anchoring; (2) fit the DCE and TTO data jointly in a hybrid model. Two evaluation criteria (1) coefficient significance and monotonicity; (2) prediction accuracy of the observed cTTO values were used to select the value set. RESULTS: In total, 1476 individuals participated in the study, with 1058 participated the DCE interview and 418 participated the cTTO interview. The highest mean TTO value was 0.924 for state 11112 and the lowest mean TTO value was - 0.088 for state 33333. The hybrid model with an A3 term performed the best and was selected as the value set. DISCUSSION: Following the international protocol and using a larger cTTO design, this study established the EQ-5D-Y-3L value set using a hybrid model for China. Future EQ-5D-Y-3L valuation study could consider using a larger cTTO design for estimating the value set.

Effect of Nucleic Acid Screening Measures on COVID-19 Transmission in Cities of Different Scales and Assessment of Related Testing Resource Demands-Evidence from China.

BACKGROUND: COVID-19 is in its epidemic period, and China is still facing the dual risks of import and domestic rebound. To better control the COVID-19 pandemic under the existing conditions, the focus of this study is to simulate the nucleic acid testing for different population size cities in China to influence the spread of COVID-19, assess the situation under different scenarios, the demand for the laboratory testing personnel, material resources, for the implementation of the nucleic acid screening measures, emergency supplies, and the configuration of human resources to provide decision-making basis. METHODS: According to the transmission characteristics of COVID-19 and the current prevention and control strategies in China, four epidemic scenarios were assumed. Based on the constructed SVEAIiQHR model, the number of people infected with COVID-19 in cities with populations of 10 million, 5 million, and 500,000 was analyzed and predicted under the four scenarios, and the demand for laboratory testing resources was evaluated, respectively. RESULTS: For large, medium, and small cities, whether full or regional nucleic acid screening can significantly reduce the epidemic prevention and control strategy of different scenarios laboratory testing resource demand difference is bigger, implement effective non-pharmaceutical interventions and regional nucleic acid screening measures to significantly reduce laboratory testing related resources demand, but will cause varying degrees of inspection staff shortages. CONCLUSION: There is still an urgent need for laboratory testing manpower in China to implement effective nucleic acid screening measures in the event of an outbreak. Cities or regions with different population sizes and levels of medical resources should flexibly implement prevention and control measures according to specific conditions after the outbreak, assess laboratory testing and human resource need as soon as possible, and prepare and allocate materials and personnel.

Responsiveness and minimal clinically important difference of the EQ-5D-5L in cervical intraepithelial neoplasia: a longitudinal study.

BACKGROUND: With the widespread clinical application of the five-level version of the EuroQol five-dimensional questionnaire (EQ-5D-5L), whether the questionnaire scores are responsive to changes in patients' health and how much changes in questionnaire scores represent patients' real health changes require consideration. Consequently, we assessed responsiveness and estimated the minimal clinically important difference (MCID) of the EQ-5D-5L in surgically treated patients with cervical intraepithelial neoplasia (CIN) to determine the relationship between MCID and minimal detectable change (MDC). METHODS: We conducted a longitudinal, observational study. Participants were patients with CIN from the gynecology inpatient department of a grade-A tertiary hospital in Shihezi, Xinjiang, China. Participants completed the EQ-5D-5L and the Global Rating of Change Questionnaire (GRCQ) at baseline and one month post-surgery. The Wilcoxon signed-rank test was used to compare EQ-5D-5L scores pre- and post-treatment. We calculated the effect size (ES) and the standardized response mean (SRM) to quantitatively assess responsiveness. Distribution-based, anchor-based, and instrument-defined methods were used to estimate MCID. MCID to MDC ratios at individual- and group-levels were also calculated. RESULTS: Fifty patients with CIN completed the follow-up investigation (mean age 44.76 ± 8.72 years; mean follow-up time 32.28 ± 1.43 days). The index value and EQ visual analogue scale (EQ VAS) of the EQ-5D-5L improved by 0.025 and 6.92 (all p < 0.05) at follow-up as compared to baseline respectively. The ES and the SRM of the index value were 0.47 and 0.42 respectively, indicating small responsiveness; while the ES and the SRM of EQ VAS were 0.50 and 0.49 respectively, indicating small to moderate responsiveness. The average (range) of MCIDs for index value and EQ VAS were 0.039 (0.023-0.064) and 5.35 (3.12-6.99) respectively. These values can only be used to determine whether patients have experienced clinically meaningful health improvements at the group level. CONCLUSIONS: The EQ-5D-5L has only small to moderate responsiveness in post-surgical patients with CIN, and the MCIDs developed in this study can be used for group-level health assessment. However, further study is needed concerning health changes at the individual level.

Effect of an outpatient copayment scheme on health outcomes of hypertensive adults in a community-managed population in Xinjiang, China.

Hypertension remains the leading risk factor for death and disability in China, and the ability of hypertensive patients to pay for outpatient care and medication has become a critical issue. To report the effect of an outpatient copayment scheme on health outcomes of hypertensive adults in a community-managed population in Xinjiang, we compared changes in outcomes between insured and uninsured groups from baseline to the first follow-up appointment in a community-managed hypertensive population and evaluated these changes based on propensity score matching and the difference-in-difference method. A total of 1,095 individuals in a community-managed hypertension population were selected for investigation at baseline, among which 805 (73.5%) had follow-up data and 749 (68.4%) were included in our analysis. After accounting for the self-reported severity of hypertension and individual characteristics, there were statistically significant improvements in drug treatment of hypertension and self-reported health. We also found increases in drug treatment for hypertension between groups, after correcting for confounding variables (Odds Ratio, OR 8.05, 95% Confidence interval, CI, 1.31-49.35), and in self-reported health between groups after correcting confounders (OR 1.96, 95% CI, 1.12 to 3.42). Adjusted estimates (confounding variables) were corrected for age, sex, income, marital status, education level, employment, family size, self-reported severity of hypertension, course of hypertension, and number of medications. As a result, decreased outpatient copayment was associated with an increase in antihypertensive treatment coverage, and an improvement in self-reported health among community-managed hypertensive populations in Xinjiang, China.

Prevalence of human papillomavirus infection and type distribution among Uyghur females in Xinjiang, northwest China.

Human papillomavirus (HPV) infection has a key role in the development of cervical cancer. The present study aimed to determine the HPV type distribution among females of Uyghur ethnicity in Xinjiang province, northwest China. A total of 12,165 individuals aged 30-79 years from 12 villages in Zepu County, Kashgar Prefecture, Xinjiang province were recruited for screening. Cervical and vaginal swabs from each subject were collected by gynecologists and tested for HPV DNA using Luminex xMAP technology. The results indicated that the overall HPV prevalence was 9.34% (1,136/12,165) in the present cohort; 7.41% (901/12,165) of the individuals were positive for high-risk type HPV (HR-HPV) and 1.64% (200/12,165) were positive for multiple types. Among the individuals who tested positive for HR-HPV types, the three most prevalent types were HPV16 (2.83%), HPV31 (0.99%) and HPV68 (0.88%). Subgroup analysis by age indicated that the highest frequency of HPV infections occurred in subjects aged >60 years. The most common genotype combinations in subjects with multiple types were HPV16 + HPV54, HPV16 + HPV31 and HPV16 + HPV68. The present study provided data on the prevalence and type distribution of HPV infections among Uyghur females in Xinjiang province, northwestern China, which will assist in the assessment of the potential cost-effectiveness of HPV screening and vaccination in this population. The data will also facilitate the determination of HPV68 and 54 strains that should be included in the multi-type vaccine and the establishment of a vaccination program that caters for the different age groups of the Uyghur population.

Decomposing the effect of drug benefit program on antihypertensive medication adherence among the elderly in urban China.

PURPOSE: Hypertension is a rapidly growing epidemic in People's Republic of China, yet it remains inadequately controlled. This study aimed to identify the relative contributions of program effects and patients' characteristics to the differences in antihypertensive medication nonadherence between drug benefit program enrollees and non-enrollees. PATIENTS AND METHODS: Data were from a cross-sectional survey of 1,969 community-dwelling elderly adults with hypertension. Self-reported adherence was measured following previous studies in People's Republic of China. The Blinder-Oaxaca nonlinear decomposition method was used to identify the relative contributions of program effects and patients' individual characteristics. RESULTS: Eleven percent of the drug benefit program enrollees were nonadherent to their medication, while 17% of non-enrollees were. Blinder-Oaxaca decomposition identified that over 60% of the gap between the two groups was due to the program effects (P=0.024). The rest could be explained by differences in observable characteristics (P<0.001), such as diabetic status, duration of hypertension, and blood pressure control. CONCLUSION: The study confirmed that drug benefit program enrollees were more likely to be adherent to their antihypertensive medication than non-enrollees in the context of People's Republic of China.

Effects of Digital Device Ownership on Cognitive Decline in a Middle-Aged and Elderly Population: Longitudinal Observational Study.

BACKGROUND: Cognitive decline is a major risk factor for disability and death and may serve as a precursor of dementia. Digital devices can provide a platform of cognitively stimulating activities which might help to slow cognitive decline during the process of normal aging. OBJECTIVE: This longitudinal study aimed to examine the independent protective factors of desktop and cellphone ownership against cognitive decline in mid-life and older adulthood and to examine the combined effect of desktop and cellphone ownership on the same outcome. METHODS: Data was obtained from a China Health and Retirement Longitudinal Studies (CHARLS) cohort made up of 13,457 community-dwelling adults aged 45 years or above in 2011-2012. They were followed for 4 years, with baseline measurements taken as well as 2 two-year follow-up visits. Cognitive function was tested during the baseline test and follow-up visits. A global cognition z-score was calculated based on two domains: word recall and mental intactness. The key independent variables were defined as: whether one had desktops with internet connection at home and whether one had a cellphone. An additional categorical variable of three values was constructed as: 0 (no desktop or cellphone), 1 (desktop or cellphone alone), and 2 (desktop and cellphone both). Mixed-effects regression was adjusted for demographic and health behavior as well as health condition risk factors. RESULTS: Adjusted for demographic and health behavior as well as health condition risk factors, desktop and cellphone ownership were independently associated with subsequent decreased cognitive decline over the four-year period. Participants without a desktop at home had an adjusted cognitive decline of -0.16 standard deviations (95% CI -0.18 to -0.15), while participants with a desktop at home had an adjusted cognitive decline of -0.10 standard deviations (95% CI -0.14 to -0.07; difference of -0.06 standard deviations; P=.003). A similar pattern of significantly protective association of 0.06 standard deviations (95% CI 0.03-0.10; P<.001) between cellphone ownership and cognitive function was observed over the four-year period. Additionally, a larger longitudinal protective association on cognitive decline was observed among those with both of the digital devices, although the 95% CIs for the coefficients overlapped with those with a single digital device alone. CONCLUSIONS: Findings from this study underscored the importance of digital devices as platforms for cognitively stimulating activities to delay cognitive decline. Future studies focusing on use of digital devices are warranted to investigate their longitudinal protective factors against cognitive decline at mid- and later life.

Internet Access and Hypertension Management Among the Elderly Population: A Nationally Representative Cross-Sectional Survey in China.

BACKGROUND: Hypertension is a rapidly growing epidemic in China. Yet, it remains inadequately controlled, especially in rural areas. The internet has shown potential for better health management in different settings; however, few studies have investigated its role in hypertension management in China. OBJECTIVE: This study aims to examine the association between internet access and hypertension awareness, treatment, and control among elderly Chinese adults and to investigate whether the association between internet access and hypertension management differed between those living in urban and rural areas. METHODS: We obtained data from the nationally representative survey of the China Health and Retirement Longitudinal Study in 2011. Hypertension was defined as (1) average systolic blood pressure of ≥140 mm Hg or average diastolic blood pressure of ≥90 mm Hg or (2) currently taking antihypertensive medications. The outcome assessed included hypertension awareness, treatment, and control. The key independent variable was defined as whether one had internet access at home. We performed multivariate logistic regressions for each of the 3 outcomes. RESULTS: Among 5135 hypertensive respondents (age 62.4 [SD 9.9] years; 2351/5135, 45.78% men), 12.89% (662/5135) had internet access at home. Compared with those who had no internet access, internet access was positively associated with hypertension awareness (odds ratio [OR] 1.36, 95% CI 1.07-1.73) and treatment (OR 1.38, 95% CI 1.09-1.75), but not with control (OR 1.19, 95% CI 0.90-1.58). Internet access reduced urban-rural disparity in hypertension awareness by 9.6% (P=.02), treatment by 8.3% (P=.05), but not in control. In addition, the moderating effect of internet access on urban-rural disparities in hypertension management was larger among females. The decreased urban-rural disparities were primarily driven by that internet access improved the management level in rural areas. CONCLUSIONS: Despite the low rate of internet access among the elderly population, the internet shows its potential as a platform for achieving better hypertension management in China. Strategies for reducing the disparities in hypertension management and overall disease burden of hypertension among the elderly population might consider the internet as a platform.

Factors affecting medication adherence in community-managed patients with hypertension based on the principal component analysis: evidence from Xinjiang, China.

PURPOSE: The analysis of factors affecting the nonadherence to antihypertensive medications is important in the control of blood pressure among patients with hypertension. The purpose of this study was to assess the relationship between factors and medication adherence in Xinjiang community-managed patients with hypertension based on the principal component analysis. PATIENTS AND METHODS: A total of 1,916 community-managed patients with hypertension, selected randomly through a multi-stage sampling, participated in the survey. Self-designed questionnaires were used to classify the participants as either adherent or nonadherent to their medication regimen. A principal component analysis was used in order to eliminate the correlation between factors. Factors related to nonadherence were analyzed by using a χ2-test and a binary logistic regression model. RESULTS: This study extracted nine common factors, with a cumulative variance contribution rate of 63.6%. Further analysis revealed that the following variables were significantly related to nonadherence: severity of disease, community management, diabetes, and taking traditional medications. CONCLUSION: Community management plays an important role in improving the patients' medication-taking behavior. Regular medication regimen instruction and better community management services through community-level have the potential to reduce nonadherence. Mild hypertensive patients should be monitored by community health care providers.

A systematic review and meta-analysis of bidirectional effect of arsenic on ERK signaling pathway.

Arsenic is a toxic metal, which ultimately leads to cell apoptosis. ERK is considered a key transcriptional regulator of arsenic­induced apoptosis. Due to a few controversial issues about arsenic­mediated extracellular signal­regulated MAP kinases (ERK) signaling, a meta­analysis was performed. Subgroup analyses demonstrated that high doses (≥2 µmol/l) of arsenic increased the expression of Ras, ERK, ERK1, ERK2, phosphorylated (p)­ERK, p­ERK1, and p­ERK2, while low doses (<2 µmol/l) decreased the expression of Ras, ERK1, p­ERK, and p­ERK2 when compared to control groups. Long term exposure (>24 h) to arsenic led to inhibition of expression of ERK1, p­ERK1, and p­ERK2, whereas short­term exposure (≤24 h) triggered the expression of ERK1, ERK2, p­ERK, p­ERK1, and p­ERK2. Furthermore, normal cells exposed to arsenic exhibited higher production levels of Ras and p­ERK. Conversely, exposure of cancer cells to arsenic showed a lower level of production of Ras and p­ERK as well as higher level of p­ERK1 and p­ERK2 as compared to control group. Short­term exposure of normal cells to high doses of arsenic may promote ERK signaling pathway. In contrast, long­term exposure of cancer cells to low doses of arsenic may inhibit ERK signaling pathway. This study may be helpful in providing a theoretical basis for the diverging result of arsenic adverse effects on one hand and therapeutic mechanisms on the other concerning arsenic­induced apoptosis.

Comparison of effectiveness and adverse effects of gefitinib, erlotinib and icotinib among patients with non-small cell lung cancer: A network meta-analysis.

The present network meta-analysis aimed to compare the effectiveness and adverse effects of gefitinib, erlotinib and icotinib in the treatment of patients with non-small cell lung cancer (NSCLC). Two reviewers searched the Cochrane, PubMed, Embase, ScienceDirect, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals and Wanfang databases for relevant studies. Studies were then screened and evaluated, and data was extracted. End-points evaluated for NSCLC included complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), median survival time (MST) and adverse effects, including rash, diarrhea, nausea and vomiting, fatigue and abnormal liver function. For the analysis of incorporated studies, RevMan, SPSS, R and Stata software were used. A total of 43 studies with 7,168 patients were included in the network meta-analysis. No significant differences were observed in CR, PR, SD, PD, ORR or DCR between gefitinib, erlotinib and icotinib by using network meta analysis. Compared with gefitinib, erlotinib resulted in a higher rate of nausea and vomiting [adjusted odds ratio (OR)=2.0; 95% credible interval, 1.1-3.7]. However, no significant differences were observed in the rates of rash, diarrhea, fatigue or abnormal liver function using network meta-analysis. Compared with erlotinib, gefitinib resulted in a lower SD rate [OR=0.86; 95% confidence interval (CI): 0.75-0.99; P=0.04], and lower rates of rash (OR=0.45; 95% CI, 0.36-0.55; P<0.00001), diarrhea (OR=0.75; 95% CI, 0.61-0.92; P=0.005), nausea and vomiting (OR=0.47; 95% CI, 0.27-0.84; P=0.01) and fatigue (OR=0.43; 95% CI, 0.24-0.76; P=0.004) through meta-analysis of two congruent drugs. However, gefitinib resulted in a higher rate of rash compared with icotinib (OR=1.57; 95% CI, 1.18-2.09; P=0.002). Otherwise, no significant differences were observed in CR, PR, PD, ORR, DCR and abnormal liver function between gefitinib, erlotinib and icotinib through meta-analysis of two congruent drugs. The PFS rate for gefitinib, erlotinib and icotinib was 5.48, 5.15 and 5.81 months, respectively. The MST was 13.26, 13.52, 12.58 months for gefitinib, erlotinib and icotinib, respectively. Gefitinib and icotinib resulted in significantly higher PFS rates compared with erlotinib (P<0.05). Erlotinib resulted in a significantly longer MST compared with gefitinib and icotinib (P<0.05). In conclusion, gefitinib, erlotinib and icotinib had similar effectiveness for the treatment of patients with advanced NSCLC. However, gefitinib resulted in a lower frequency of fatigue, and nausea and vomiting, compared with the other two drugs. Icotinib resulted in a lower frequency of rash. Erlotinib resulted in a longer MST, but was also associated with a higher frequency of rash, and nausea and vomiting.

Influence of Human Papillomavirus Infection on the Natural History of Cervical Intraepithelial Neoplasia 1: A Meta-Analysis.

OBJECTIVE: To provide a scientific basis for the prevention and treatment of cervical intraepithelial neoplasia grade 1 (CIN1). This study evaluated the impact of human papillomavirus (HPV) infection on the natural history of CIN1. METHODS: Electronic databases of Cochrane Library, EMBASE, PubMed, CNKI, CBM, and Wanfang were searched in April 2016. The eligibility criteria were documented by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We used the Newcastle-Ottawa scale (NOS) to assess study quality. RESULTS: Thirty-eight studies out of 3,246 identified papers were eligible for inclusion. The risk of CIN1 progression (relative risk [RR]: 3.04; 95% confidence interval [CI]: 2.41-3.83; P < 0.00001) and persistence (RR: 1.48; 95% CI: 1.17-1.87; P = 0.001) was higher in the HPV-positive group than HPV-negative group. Specifically, the risk of CIN1 progression (RR: 13.91; 95% CI: 3.46-55.90; P = 0.000) was higher among persistent high-risk HPV-positive patients and the ratio of CIN1 regression (RR: 0.65; 95% CI: 0.59-0.71; P < 0.00001) was lower in the HPV-positive group than HPV-negative group. CONCLUSION: HPV infection resulted in an increased risk of CIN1 progression and decreased disease reversibility. Persistent high-risk HPV infection resulted in a further increased risk of CIN1 progression.

Oxidative Damage Induced by Arsenic in Mice or Rats: A Systematic Review and Meta-Analysis.

In this meta-analysis, studies reporting arsenic-induced oxidative damage in mouse models were systematically evaluated to provide a scientific understanding of oxidative stress mechanisms associated with arsenic poisoning. Fifty-eight relevant peer-reviewed publications were identified through exhaustive database searching. Oxidative stress indexes assessed included superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione-s-transferase (GST), glutathione reductase (GR), oxidized glutathione (GSSG), malondialdehyde (MDA), and reactive oxygen species (ROS). Our meta-analysis showed that arsenic exposure generally suppressed measured levels of the antioxidants, SOD, CAT, GSH, GPx, GST, and GR, but increased levels of the oxidants, GSSG, MDA, and ROS. Arsenic valence was important and GR and MDA levels increased to a significantly (P < 0.05) greater extent upon exposure to As3+ than to As5+. Other factors that contributed to a greater overall oxidative effect from arsenic exposure included intervention time, intervention method, dosage, age of animals, and the sample source from which the indexes were estimated. Our meta-analysis effectively summarized a wide range of studies and detected a positive relationship between arsenic exposure and oxidative damage. These data provide a scientific basis for the prevention and treatment of arsenic poisoning.

Factors Affecting Arsenic Methylation in Arsenic-Exposed Humans: A Systematic Review and Meta-Analysis.

Chronic arsenic exposure is a critical public health issue in many countries. The metabolism of arsenic in vivo is complicated because it can be influenced by many factors. In the present meta-analysis, two researchers independently searched electronic databases, including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze factors influencing arsenic methylation. The concentrations of the following arsenic metabolites increase (p< 0.000001) following arsenic exposure: inorganic arsenic (iAs), monomethyl arsenic (MMA), dimethyl arsenic (DMA), and total arsenic. Additionally, the percentages of iAs (standard mean difference (SMD): 1.00; 95% confidence interval (CI): 0.60-1.40; p< 0.00001) and MMA (SMD: 0.49; 95% CI: 0.21-0.77; p = 0.0006) also increase, while the percentage of DMA (SMD: -0.57; 95% CI: -0.80--0.31; p< 0.0001), primary methylation index (SMD: -0.57; 95% CI: -0.94--0.20; p = 0.002), and secondary methylation index (SMD: -0.27; 95% CI: -0.46--0.90; p = 0.004) decrease. Smoking, drinking, and older age can reduce arsenic methylation, and arsenic methylation is more efficient in women than in men. The results of this analysis may provide information regarding the role of arsenic oxidative methylation in the arsenic poisoning process.

Lutein has a protective effect on hepatotoxicity induced by arsenic via Nrf2 signaling.

Arsenic produces liver disease through the oxidative stress. While lutein can alleviate cytotoxic and oxidative injury, nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a critical role in defending oxidative species. However, the mechanisms by which lutein protects the liver against the effect of arsenic are not known. Therefore, this study aims to investigate the mechanisms involved in the action of lutein using mice model in which hepatotoxicity was induced by arsenic. We found that mice treatment with lutein could reverse changes in morphological and liver indexes and result in a significant improvement in hepatic function comparing with arsenic trioxide group. Lutein treatment improved the activities of antioxidant enzymes and attenuated increasing of ROS and MDA induced by arsenic trioxide. Lutein could increase the mRNA and protein expression of Nrf2 signaling related genes (Nrf2, Nqo1, Ho-1, and Gst). These findings provide additional evidence that lutein may be useful for reducing reproductive injury associated with oxidative stress by the activation of Nrf2 signaling. Our findings suggest a possible mechanism of antioxidant lutein in preventing the hepatotoxicity, which implicate that a dietary lutein may be a potential treatment for liver diseases, especially for arsenicosis therapy.

Implementing a cervical cancer awareness program in low- income settings in Western China: a community-based locally affordable intervention for risk reduction.

BACKGROUND: Some 60 years after introduction of the Papanicolaou smear worldwide, cervical cancer remains a burden in developing countries where >85% of world new cases and deaths occur, suggesting a failure to establish comprehensive cervical-cancer control programs. Effective interventions are available to control cervical cancer but are not all affordable in low-income settings. Disease awareness saves lives by risk-reduction as witnessed in reducing mortality of HIV/AIDS and smoking-related cancers. SUBJECTS AND METHODS: We initiated a community-based awareness program on cervical cancer in two low-income Muslim Uyghur townships in Kashi (Kashgar) Prefecture, Xinjiang, China in 2008. The education involved more than 5,000 women from two rural townships and awareness was then evaluated in 2010 and 2011, respectively, using a questionnaire with 10 basic knowledge questions on cervical cancer. Demographic information was also collected and included in an EpiData database. A 10-point scoring system was used to score the awareness. RESULTS: The effectiveness and feasibility of the program were evaluated among 4,475 women aged 19-70 years, of whom >92% lived on/ below US$1.00/day. Women without prior education showed a poor average awareness rate of 6.4% (164/2,559). A onetime education intervention, however, sharply raised the awareness rate by 4-fold to 25.5% (493/1,916). Importantly, low income and illiteracy were two reliable factors affecting awareness before or after education intervention. CONCLUSIONS: Education intervention can significantly raise the awareness of cervical cancer in low-income women. Economic development and compulsory education are two important solutions in raising general disease awareness. We propose that implementing community-based awareness programs against cervical cancer is realistic, locally affordable and sustainable in low-income countries, which may save many lives over time and, importantly, will facilitate the integration of comprehensive programs when feasible. In this context, adopting this strategy may provide one good example of how to achieve "good health at low cost".