Over the last few years, the development of genome editing has revolutionized research on the human genome. Recent advances in developing programmable nucleases, such as meganucleases, ZFNs, TALENs and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas, has greatly expedited the progress of gene editing from concept to clinical practice. The CRISPR has advantages over other nuclease-based genome editing tools due to its high accuracy, efficiency, and strong specificity. Eight years after CRISPR application for human genome edition by Emmanuelle Charpentier and Jennifer A. Doudna, the 2020 Nobel Prize in Chemistry has been jointly given to them for development of CRISPR-Cas9 gene editing, allows scientists to precisely cut and edit of DNA.

Background: Interstitial lung disease (ILD) is a category of chronic lung diseases with more than 200 subtypes. Idiopathic interstitial pneumonia (IIP), systemic sclerosis (SSc) ILD, and familial interstitial pneumonia (FIP) are three major groups of lung diseases with different causes or with unknown causes. Mucin5B (MUC5B) belongs to the mucin family, which contribute to the lubricating and viscoelastic properties of the whole saliva, normal lung mucus, and cervical mucus. The association between MUC5B rs35705950 and ILDs risks has been widely studied. However, the results were inconclusive and inconsistent.

Methods: In the present meta-analysis, the database PubMed, Embase, Cochrane Central Register of Controlled Trials, CNKI and Chinese Biomedical Literature Database were searched till Aug 20^th, 2018. Overall 16 publications with 28 studies, 76345 cases and 18402 controls were included.

Results: The results indicated a significant increase of overall IIP risk for TT genotype and T allele of the rs35705950 in all genetic models (TT vs GG, OR=9.11; TT vs GT+TT, OR=5.80; GT+TT vs GG, OR=4.34; T vs G, OR=4.03. P<0.0001). Subgroup analysis by subtypes of IIP revealed higher risks of TT genotype and T allele for IPF and iNSIP (P<0.05). A significant increase of FIP risk was also found for the TT genotype and T allele of the rs35705950 (TT vs GG, OR=17.08; GT+TT vs GG, OR=6.02; T vs G, OR=1.64.P<0.05).

Conclusion: No significant relations existed between the rs35705950 and SSc-ILD risks. MUC5B rs35705950 might be a predictor for the susceptibility of IIP and FIP.

Background: To summarize the cases of physicians overwork death between Jan 2007 and Dec 2018, the tragedy merits the attention of the authorities and policy-makers to increase their efforts to reduce death among physicians in China.

Methods: Data were extracted from medical databases, local mass media, official documents and medical Bulletin Board System (BBS), in which only included articles, reports and news listed in the retrieval strategy, and unpublished data were excluded.

Results: Overall, 110 cases (7 females and 103 males) were enrolled in this study. Most incidents have occurred since 2012, especially in 2017. Of these, 86 (78.18%) physicians worked in public tertiary hospitals, four times more than the number of cases taking place in secondary hospitals. Additionally, overwork death was the most common in surgery-related departments that account for up to 65 (59.1%). Notably, these events, taking place in first-tier cities and the southeastern coastal areas of China, included 27 chief physicians, 31 associate of chief physicians, 21 attending physicians, 10 resident physicians and 4 standardized training physicians.

Conclusion: Overwork death among Chinese physicians is not only a contemporary health problem but also a critical social issue. The laws and regulations should be perfected to prevent the events. Meanwhile, the public should be aware of the need for more understanding and trust in physicians in China.

Background: This study aimed to explore effective education method to improve influenza vaccine uptake rate.

Methods: Meta-analysis of Randomized Clinical Trials was conducted in this study including subgroup analysis and publication bias test. Electronic databases comprised PubMed, EBSCO, Elsevier, Springer, Wiley, and Cochrane were searched for studies published up to Oct 8, 2019.

Results: Influenza vaccination was significantly different in massages or letters intervention group (OR=1.30, 95%CI: 1.05-1.61). No heterogeneity and publication bias existed in this meta-analysis (I²=43.60%, P=0.131, P_begg =0.754, P_egger=0.051).

Conclusion: Education by messages and letters was effective according to this study. Education messages could be more efficacy combined with easer vaccine access.

Background: We investigated the efficacy of esomeprazole for the treatment of gastroesophageal reflux disease (GERD) in a meta-analysis of clinical trials results.

Methods: Medline, Embase, PubMed and Web of Science databases were systematically searched for suitable studies, and double-blind, randomized controlled trials (RCTs) were involved. A meta-analysis of RCTs was performed to analyze the efficacy of esomeprazole on clinical outcomes that associated with the severity of GERD.

Results: A total of 8 clinical trials were selected in our meta-analysis (N=4495, patients with GERD). Esomeprazole treatment yielded a significant improvement in clinical signs and symptoms of GERD compared to placebo group. Funnel plot and Egger test showed there was no significant bias in the publication. Cochrane collaboration tool and Jadad scale were used to indicate that all 8 RCTs were of high quality. The results of Galbraith radial plot showed that no study was the major source of heterogeneity. Esomeprazole treatment significantly decreased the relapse rates more than that of placebo group (RR = 0.729; 95% CI: 0.670 to 0.794; P<0.001). It seems to be lower rates of heartburn (RR = 0.747; 95%CI: 0.665-0.839; P <0.001) and epigastric pain (RR = 0.795; 95%CI: 0.679-0.932; P =0.005) in esomeprazole-treated group compared with the placebo group. Moreover, serious adverse events was less likely to happen after esomeprazole therapy (RR = 1.406, 95% CI: 1.030-1.918; P =0.032).

Conclusion: Compared with the control group, esomeprazole is a promising therapeutic agent that improves the management of patients with GERD.

Background: The objectives of this study were to systematically review the effects of grief-focused interventions, applied to dementia caregivers, on emotional burden including sadness and to provide baseline information for dementia caregivers to maintain mental health by identifying the effect size of intervention using a meta-analysis.

Methods: We evaluated literature published from Jan 1, 2000, to Jun 28, 2019. Consequently, we selected five studies to conduct a systematic review. The Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields was used for conducting a quality assessment on the selected literature.

Results: The results of the quality assessment showed that the score ranged from 11 to 24 points: one strong, one good, two adequate, and one limited. When the meta-mean was compared before and after grief intervention, the effect size of the random-effect model was 0.31 (95% CI: -0.07, 0.69) showed ‘intermediate effect’, but the confidence interval was not significant.

Conclusion: The grief intervention for dementia caregivers revealed a moderate effect but it was not significant. In order to prove the effectiveness of grief intervention for dementia caregivers, a meta-analysis targeting RCT studies is needed.

Background: Classroom is where children spend much of their time in; this study aimed to identify the concentration of heavy metals in the classroom dust based on the results of various studies in the world using the published data up to years 2018.

Methods: Fifteen studies were selected for the study according to the inclusion and exclusion criteria. The mean concentration of 11 heavy metals including arsenic, barium, cadmium, cobalt, chromium, copper, iron, lead, manganese, nickel, and zinc was extracted.

Results: The highest mean concentration of heavy metal (mg/kg) in classroom dust was related to iron (3904.7, 95%CI: 3657.1-8154.3), zinc (429.9, 95%CI: 182.8-677.1) and barium (419.2, 95%CI: 274.7-253.7), respectively. Subgroup analysis showed the maximum concentration (mg/kg) of iron in Iran (16945.5), zinc in Hong Kong (2293.5), barium in China (979.8), manganese in Iran (288.9), lead in Iran (258.8), chromium in Ghana (381.3), copper in Hong Kong (274.4), nickel in Iran (50.1), cobalt in China(43.4), arsenic in China(13.7) and cadmium in Hong Kong(8.7).

Conclusion: Even safe and healthy classrooms can threaten children’s health by heavy metals. These metals are important since they are naturally found throughout the earth’s crust, accumulate in the food chain and contaminate drinking water as well as alloys in school equipment.

Background: The Severe Acute Respiratory Syndrome Coronavirus Disease 2019 (SARS-CoV-2) severely affects those above the age of 60 yr and those with other conditions. This study aimed to review the available evidence on older adult's issues in facing the COVID-19 pandemic.

Methods: The framework is based on scoping review of literature published from Jan 10 to Jul 31, 2020. Medline, Scopus, Web of Science, and Google Scholar databases and other sources of information, to identify grey literature, were selected for data collection. Two researchers independently screened all studies and extracted data. All types of studies published about SARS-CoV-2 and related to older adults’ issues were eligible.

Conclusion: In the pandemic, there is an urgent need for interventional research and innovational implementations to address issues related to providing services for older adults. This can help older adults to maintain their physical and mental health, and reduce the spread of infection in nursing homes. Further studies focusing on the rights of the older adults are needed on all issues associated with COVID-19.

Background: Leishmaniasis is one of the most important parasitic diseases in the Golestan Province, northeastern Iran. In this study, we summarize the results of studies on the disease and its causative agent Leishmania in humans, vectors and reservoirs in the Golestan Province, Iran.

Methods: We retrieved all articles related to leishmaniasis in the Golestan Province, northern Iran from 1994 to 2018 in various databases including PubMed, Scopus and Web of Science. Articles in Persian were retrieved from the IranMedex, SID and Magiran. Reference lists of relevant articles were also hand-searched. Local active researchers in the field of leishmaniasis were contacted to avoid missing any relevant articles. Overall, 54 papers were extracted, later evaluated by two research team members based on inclusion criteria. All analyses were performed using the Stata 14 software. Pooled prevalence was calculated using the metaprop command and a random-effect model. The I² statistic was used for measuring heterogeneity of studies.

Results: Ten articles in the province were related to detection of Leishmania species in patients with suspected cutaneous or visceral leishmaniasis. Fifteen articles were dedicated to identification of Leishmania species in disease reservoirs and five articles were about detection of the parasite in sand flies. The pooled prevalence of L. major in patients with acute ulcer, wild rodents and sandflies was 83%, 29% and 11%, respectively.

Conclusion: Our findings highlight the need for implementation of control measures among the reservoirs of both cutaneous and visceral leishmaniasis in the Golestan Province, Iran.

Background: The rs315952 (Ser133Ser) has been reported to influence the risk for immune-mediated as well as inflammatory diseases in many studies; however, the results remain inconsistent. The current meta-analysis was performed to give a more precise estimation for the relationship between this IL-1Ra missense variant and the risk of both types of diseases.

Methods: Relevant publications were retrieved through a literature search in Web of Science, Medline, PubMed, Scopus, EMBASE, and Google scholar search engines, between 2000 and 2019. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association.

Results: Twenty-two studies, including 2622 cases with and 3854 controls were identified. The IL-1Ra Ser133Ser variant does not confer an increased overall risk for immune-mediated and inflammatory diseases. This variant was statistically associated with decreased risk of systemic lupus erythematosus (under allelic, codominant heterozygous, and dominant models) or ankylosing spondylitis (in allelic and recessive models)(OR<1). Moreover, alleles, as well as genotypes of the IL-1Ra Ser133Ser variant, may confer an increased risk of immune-mediated and inflammatory diseases in Hispanics. However, this variant was not associated with susceptibility to immune-mediated and inflammatory diseases in both Asians and Arabs.

Conclusion: The pooled results fail to support the hypothesis that the IL-1Ra Ser133Ser variant is associated with the overall risk of immune-mediated and inflammatory diseases. Performing large scale replication and meta-analysis of functional variants within this gene is encouraged to further investigate the influence of IL-1Ra SNPs on overall disease susceptibility.

Background: Disasters have many health consequences such as suicide ideation as one of the relatively common psychological consequences after natural disasters, especially earthquakes. This study aimed to determine the prevalence of post-earthquake suicidal ideation in affected people.

Methods: Related keywords of this systematic review and meta-analysis in English and their Persian equivalents were searched in the data resources including Google Scholar, SID, Magiran, Scopus, PubMed, and Web of Science from Jan 2014 to May 2019. The STROBE checklist was used to evaluate the quality of the articles. The I² index was used to determine the heterogeneity and the random-effects model was used in meta-analysis. Statistical analysis was conducted in the STATA software version 14.

Results: Overall, 14347 subjects including 6662 males and 7715 females with the mean age of 23.88 ± 15.81yr old were assessed. The prevalence of post-earthquake suicidal ideation was 20.34% (95% CI: 13.60-27.08, P<0.001, I²=99.1). The prevalence of suicidal ideation showed a decreasing trend based on the year of the study and the duration of post-earthquake follow-up.

Conclusion: Although the prevalence of post-earthquake suicidal ideation showed a decreasing trend, the probability of incidence of these thoughts in the long-term is still noticeable. Therefore, implementing a surveillance system is recommended to monitor the mental health status of earthquakes survivors for the possibility of suicidal thoughts in the short and long term recovery phase.

Background: To investigate the therapeutic and diagnostic value of caspase-12 and study of growth differentiation factor-15 (GDF-15) in patients with acute myocardial infarction (AMI).

Methods: Overall 78 patients with AMI admitted to Weifang People's Hospital Brain Hospital, Weifang, China from Apr 2016 to Apr 2019 were enrolled as AMI group. Seventy five non-AMI people undergoing physical examination during the same period were enrolled as non-AMI group. The expression levels of caspase-12 and GDF-15 were detected and compared. The correlation between the expressions of GDF-15, caspase-12 and clinical characteristics and efficacy was detected. Single and combined detection of GDF-15 and caspase-12 were performed analyze their role in the early diagnosis, the prediction of efficacy, and the guidance of clinical therapy.

Results: After treatment, the levels of GDF-15 and caspase-12 in AMI group were significantly lower than those before treatment (P<0.001). The expression levels of GDF-15 and caspase-12 were significantly correlated with blood pressure (P<0.05). The expression levels of GDF-15 and caspase-12 were significantly negatively correlated with clinical efficacy in AMI group. The diagnostic value of combined detection of GDF-15 and caspase-12 was higher than that of single diagnosis. The levels of serum caspase-12 and GDF-15 proteins were significantly up-regulated in AMI patients. With the better therapeutic effect, the levels of serum caspase-12 and GDF-15 proteins decreased significantly.

Conclusion: The levels of serum caspase-12 and GDF-15 proteins may be a key indicator in the clinical diagnosis of acute myocardial infarction and may also be used to guide the treatment of AMI patients and predict the therapeutic efficacy.

Background: Repeated research while using the same methodology can be useful and it can enable relevant conclusions in the same health care system. The aim of our study was to perform comparative analysis of the agreement between admission and discharge diagnostic groups in period 2014-2017 with period 2006-2013 in the Clinical Center of Kragujevac, Serbia.

Methods: The 5% simple, random sample was made from the basic set of all hospital reports from Clinical Centre Kragujevac, Serbia, in the period 01.01. 2014 - 31.12. 2017 (n=10228). The first four digits of ICD-10 codes at admission and discharge were compared for agreement. We used discharge diagnosis as a "golden standard". Statistical analysis was performed using Cohen’s Kappa statistic.

Results: In the period 2014-2017, agreement between diagnosis among the most ICD10 groups increased in comparison with the period 2006-2013. Disagreements between diagnosis in the period 2014-2017 in comparation with period 2006-2013 was associated with increased length of stay in the hospital (7.5 vs. 9.1 days, P<0.01), patients were younger (54 vs 49.6 yr, P<0.01), number of males declined (26.3% vs 16.2%, P<0.05), kappa value decreased in XV ICD10 group and XI ICD10 group and kappa value increased in XIV ICD10 group.

Conclusion: Agreement between admission and discharge diagnosis among the most ICD10 diagnostic groups increased. Introduction of a new web application has increased the quality of data, but interpreting it requires the skill of researchers. Further research should identify modifiable causes of discrepancy between admission and discharge diagnoses.

Background: During the long–time home quarantine due to COVID–19, preschool-age children can be easily stricken by negative emotions, which give rise to aggressive behaviors. Aggressive behaviors are of different types at the preschool stage. We aimed to investigate the differences of emotion regulation strategies among children age 3–6 yr old with different aggression types and explore the relationship between emotion regulation strategies and aggressive behaviors.

Methods: The aggressive behaviors of 1,187 children sampled (event sampling method) from 5 kindergartens in five cities in Henan Province of China were observed on the spot in 2020. Three aggression types (i.e., physical, verbal, and indirect) were selected to conduct a questionnaire survey on emotion regulation strategies and discuss the differences among aggressive children in emotion regulation strategies.

Results: Children of different genders are significantly different in aggressive behaviors and problem solving, as well as children at different age levels in self–comfort, passive reaction, and negative regulation strategies. Significant interaction exists between gender and aggression but not in negative regulation strategy; significant interaction also exists between age and aggression but not in cognitive reconstruction, substitutive activity, and aggressive behavior. Significant differences exist among children of different aggression types in positive and negative regulation strategies. The discrimination accuracy of emotion regulation strategies for aggression types is 66.5%.

Conclusion: Significant differences exist among 3-6-yr-old aggressive children in emotion regulation strategies, and emotion regulation strategies can effectively distinguish aggressive children of different types.

Background: We aimed to investigate the factors affecting healthcare utilization among patients with single and multiple chronic diseases using the Andersen healthcare utilization model.

Methods: We used a combination of the data from the sixth and seventh Korea National Health and Nutrition Survey (2014–2016). The study population was 3,901 patients with single chronic disease and 1,829 patients with multiple chronic diseases as defined by the WHO. Participants were aged 19 yr or older. Multiple regression analysis was employed using the Andersen model to identify factors affecting healthcare utilization (inpatient and outpatient).

Results: According to the Andersen model (comprising predisposing, enabling, and need factors and health behaviors), the factors that increased outpatients with single chronic disease were female, being aged 65 yr or older, having basic livelihood security benefit, immobility, and poor subjective health status. Factors that increased inpatients with single chronic disease were being aged under 65, having private insurance, immobility, poor subjective health status, and nondrinking. Moreover, factors that increased outpatients and inpatients with multiple chronic diseases were female, being aged under 65, immobility, and poor subjective health status and immobility, poor subjective health status, nondrinking, and not engaging in physical activity, respectively.

Conclusion: We identified factors affecting outpatient and inpatient care utilization among patients with single and multiple chronic diseases, using the Andersen healthcare utilization model. The findings can be used as foundational data to develop preventive and management strategies in healthcare utilization among patients with single and multiple chronic diseases.

Methods: The sample of respondents included 240 Montenegrin male soldiers (32.5yr±9.5), who were measured at the sports dispensaries within the barracks of Montenegrin Army around the country in the spring of 2020, was classified into eight numerically equal subsamples according to their military specialty. The sample of variables included five anthropometric measures, which were necessary to calculate two derived body composition indicators: Body Mass Index (BMI) and Body Fat Percentage (FAT %). Using the one-way ANOVA and Post Hoc test with Taki’s model, the variables were analyzed.

Background: Illness can provoke a crisis response that affects condition acceptance, treatment and recovery. Patients’ sense of coherence can influence this and has been explored across patient cohorts internationally. However there are few studies that examine these effects in patients with hepatic cirrhosis. This study investigated sense of coherence and social support of patients with hepatic cirrhosis.

Methods: The psychological status of 146 patients admitted to the Digestive System Department, First Affiliated Hospital of Harbin Medical University, Harbin, China from Mar 2016 to Mar 2019 with hepatic cirrhosis was assessed using the Sense of Coherence (SOC-13), Social Support Rating Scale (SSRS) and crisis assessment scales.

Results: There was a low level of crisis response in patients with hepatic cirrhosis that was influenced by age, disease course, education level and Child-Pugh grade and negatively correlated with sense of coherence and social support.

Conclusion: Liver cirrhosis patients had a low level of crisis response. As the level of crisis response in is correlated with patients' sense of coherence, social support and educational level, careful assessment, tailored educational interventions and mobilizing of family support are important to maximize responses to illness and thus improve quality of life.

Background: Interests between pain and frailty have been increasing in aging or aged societies. This study aimed to identify the prevalence of pain and frailty and to find the influence of pain on frailty.

Methods: Subjects were selected with aged 65 yr or older among pooled Korea Health Panel data from 2009 to 2013. The prevalence of pain was determined by combining some pain and extreme pain and also, frailty was defined when subjects had at least one of the following 6-domain frailty: physical inactivity, mobility reduction, dependence of daily life, depression, multimorbidity, and disability.

Results: The prevalence of pain and frailty was 56.1% and 59.8%. It was significantly higher in female (66.1% and 65.2%) and the oldest-old (69.4% and 71.8%). After adjusting for gender, age group, spouse, illiteracy, and economic activity, odds ratios of frailty for some pain and extreme pain were 2.8 (95% CI 2.6-3.0) and 10.5 (95% CI 8.0-13.8) in total subjects. The odds ratios of each 6-domain frailty for some and extreme pain were also significant. Among them, mobility reduction was 5.1 (95% CI 4.5-5.8) and 16.5 (95% CI 13.6-20.1), and dependence of daily life was 3.9 (95% CI 3.5-4.5) and 12.4 (95% CI 10.2-15.1).

Conclusion: Among the elderly, prevalence of frailty (59.8%) was somewhat higher than that of pain (56.1%). Female and oldest-old had higher prevalence of pain and frailty. In addition, some pain and extreme pain had a decisive influence on frailty and each 6-domain frailty. Therefore, pain control is essential to prevent or manage frailty.

Background: Weight control is crucial for osteoarthritis management. This study investigated weight control methods in postmenopausal Korean osteoarthritis patients and examined their correlation with subjective health status and figure recognition, obesity, quality of life (QoL), and hemodynamic variables.

Methods: One thousand six hundred and seventy-eight female postmenopausal osteoarthritis patients participated in the 2018 Korea National Health and Nutrition Examination Survey. A frequency analysis was conducted for weight control methods, and phi coefficients for crossover analyses or Cramer’s V coefficient were calculated to identify the relationships between weight-control-related variables and subjective health status and QoL. Using independent t-tests, we examined the relationships of weight control methods with hemodynamic variables.

Results: Postmenopausal osteoarthritis patients’ preferred weight control methods were exercise, meal volume reduction, functional diet consumption, and the skipping of meals. Osteoarthritis patients who performed exercise demonstrated improved subjective figure recognition and health status, body weight, and recent 2-week discomfort, QoL, and hemodynamic variables (systolic blood pressure and fasting glucose, hemoglobin A1C, total cholesterol, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein [hs-CRP] levels). However, patients who attempted weight control by food volume reduction made relatively harder efforts to lose weight but were more likely to view themselves as obese, and demonstrated higher pain levels, anxiety/depression, and recent 2-week discomfort. Further, they exhibited lower triglyceride levels, as did patients who skipped meals.

Conclusion: Overall, Korean postmenopausal osteoarthritis patients’ preferred weight control methods were exercise and reduced food intake. Although reduced food intake was effective for weight control, exercise improved mental health and hemodynamics, particularly inflammation (hs-CRP) levels.

Background: Escherichia coli is one of the most frequent causes of many common bacterial infections. As a potential reservoir, hospital wastewater is considered for the dissemination of bacterial pathogens such as E. coli. Therefore, research on hospital waste’s bacteria by low-cost, rapid and easy molecular typing methods such as multilocus variable-number tandem-repeat analysis (MLVA) can be helpful for the study of epidemics.

Methods: E. coli strains were isolated from hospital wastewater sources in Tehran, Iran, over a 24-month sampling period (Jun 2014- Jun 2016) and identified by standard bacteriological methods. The diversity of repeated sequences of seven variable-number tandem-repeat (VNTR) loci was studied by MLVA method base on polymerase chain reaction (PCR).

Results: Overall, 80 E. coli isolates were discriminated into 51 different genotypes. Analysis of the MLVA profiles using a minimum spanning tree (MST) algorithm showed two clonal complexes with 71 isolates and only nine isolates were stayed out of clonal complexes in the form of a singleton. High genotypic diversity was seen among E. coli strains isolated from hospital wastewaters; however, a large number of isolates showed a close genetic relationship.

Conclusion: MLVA showed to be a rapid, inexpensive and useful tool for the analysis of the phylogenetic relationships between E. coli strains under the study.

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