Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

Objective:To study the infection and epidemiological characteristics of soil borne nematode disease in Sihong County, Suqian City, and to provide scientific basis for further development of prevention and control measures.Methods:In 2022, according to geographic location, Sihong County was divided into east and west areas. Jieji Town, Shiji Township, and Linhuai Town were selected from the east area, and Tianganghu Township, Meihua Town from the west area. One administrative village was selected as a survey point in each township. Using cluster sampling method, 450 permanent residents aged 3 years old and older in the village were selected as the respondents for questionnaire survey and fecal sample collection. The infection status of hookworms, roundworms, whipworms and pinworms in fecal samples were examined, transparent tape anal swab method for detecting pinworm eggs in children, and influencing factors were analyzed.Results:A total of 2 264 survey subjects were included, 18 cases of soil borne nematodes were detected as positive, with an overall positive rate of 0.80%. Among them, 15 cases were positive for hookworms, 1 case was positive for whipworms, and 2 cases were positive for pinworms, with detection rates of 0.66%, 0.04%, and 0.09%, respectively. No ascaris lumbricoides were detected. Transparent tape anal swab method was used to examine 142 children, and the positivity rate of 1.41% (2/142). By township, the detection rate of soil borne nematodes was the highest in Jieji Town, at 2.41% (11/457); the others were Meihua Town, Tianganghu Township, Shiji Township, and Linhuai Town, with detection rates of 0.89% (4/451),0.66% (3/454), 0 (0/451) and 0 (0/451), respectively. There was a statistically significant difference between different townships (χ 2 = 19.21, P < 0.001). Among the 18 positive cases of soil borne nematode, 7 were males and 11 were females, with detection rates of 0.66% (7/1 063) and 0.92% (11/1 201), respectively, the difference was not statistically significant (χ 2 = 0.47, P = 0.491). The age distribution showed the highest detection rate in the 40 - < 60 age group, at 1.42% (9/634), with statistically significant differences between different age groups (χ 2 = 6.41, P = 0.033). The occupational distribution showed the highest detection rate in farmers, at 1.46% (9/617), with statistically significant differences between different professions (χ 2 = 8.00, P = 0.034). The differences in total soil borne nematode and hookworm detection rates were statistically significant among different methods of treating human and animal feces (χ 2 = 11.01, 9.02, P = 0.003, 0.011). Conclusions:The main species of soil borne nematode infections in Sihong County, Suqian City are hookworms, with fewer infections of whipworms and pinworms, and no roundworm infections observed. There are regional differences in detection rate. In the future, it is necessary to strengthen health education for key populations, enhance health knowledge publicity, and effectively intervene to change unhealthy production and lifestyle, further reducing the infection of soil borne nematodes in Suqian City.

Objective:To investigate the correlation between cognitive function and living ability of older adult patients living in a mining community.Methods:A total of 180 older adult patients living in a mining community who received treatment during July-October 2019 were included in this study. They were randomly divided into the low-age group (< 68 years old, n = 94) and the high-age group (≥ 68 years old, n = 86). Cognitive function and living ability were evaluated using the Mini-Mental State Examination (MMSE), The Montreal Cognitive Assessment (MoCA), and the Activity of Daily Living Scale (ADL). The relationship between cognitive function and living ability was investigated using hierarchical analysis and Pearson correlation analysis. Results:The proportions of older adult patients with abnormal cognitive function identified by the MMSE and MoCA were 39.4% and 66.0%, respectively in the low-age group, and they were 32.6% and 61.6%, respectively in the high-age group. The MoCA had a greater performance in identifying abnormal cognitive function in each group than the MMSE ( χ2 = 26.69, 10.18, both P < 0.001). There were no significant differences in proportions of older adult patients with abnormal cognitive function identified by the MMSE and MoCA between low-age and high-age groups ( χ2 = 0.90, 0.36, both P > 0.05). The proportion of older adult patients with abnormal living ability was not significantly different between low-age and high-age groups (4.3% vs. 10.5%, χ2 = 2.58, P > 0.05). Compared with patients negative for MMSE items, living ability and instrumental activity of daily living increased by 7.0% and 9.4% in low-age patients positive for MMSE items (both P < 0.05). Compared with patients negative for MoCA items, living ability increased by 3.5% in low-age patients positive for MoCA items ( P < 0.05). Correlation analysis revealed that total scores of MMSE and MoCA were significantly negatively correlated with ADL score ( r = -0.26, -0.27, both P < 0.001) and instrumental activity of daily living score ( r = -0.27, -0.27, P < 0.001). Conclusion:Cognitive function and living ability are correlated in older adult patients living in a mining community. We should pay attention to the screening results of cognitive disorder in older adult patients and improve their living ability by improving their cognitive function.

Objective:To investigate the characteristic of mild cognitive impairment (MCI) in the adults aged 48 years and over in a coal mine community, and to analyze its associated risk factors.Methods:From July to October 2019, a questionnaire survey for basic information was conducted among 180 middle-aged and elderly adults who met the inclusion criteria in the Datong coal mine community. The cognitive function was evaluated by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The effects of gender, age, years of education, sleep, living alone, physical exercise, social activities, smoking and drinking status, body mass index and chronic diseases on cognitive level were analyzed by single factor stratification and multiple linear regression.Results:There was no significant difference in the positive rate of MCI screened by MMSE and MoCA in the age groups of 48-<64, 64-<72 and 72-90 (original and corrected P>0.05); The positive rate of MCI in MoCA screening (64.4%, 66.7%, 60.9%) was significantly higher than that in MMSE (35.6%, 45.6%, 28.1%) (all P<0.05); MMSE was positively correlated with MoCA score ( r=0.762, P<0.001). With the increase of age, the scores of memory, execution and visual space detected by MoCA decreased significantly (all P<0.05), while the scores of attention, language and orientation did not change significantly (all P>0.05). Univariate stratification showed that the significant influencing factors of MMSE or MoCA scores were gender, age, years of education and sleep status (all P<0.05). Multiple linear regression analysis showed that gender ( βMMSE=-0.192; βMoCA=-0.140), years of education ( βMMSE=0.209; βMoCA=0.328) and sleep status( βMMSE=-0.162; βMoCA=-0.136) were risk factors affecting MMSE and MoCA scores ( P<0.05). Conclusions:More middle-aged and elderly adults with MCI might be observed in a coal mine community, and the main characteristics of MCI are impaired memory, executive function and visual space. To prevent and reduce the occurrence of dementia, early interventions of MCI should be carried out among the adults with female, old age, low years of education and poor sleep quality.

ObjectiveTo investigate the value of prothrombin time-international normalized ratio to albumin ratio (PTAR) in evaluating the prognosis of patients with decompensated cirrhosis. MethodsA retrospective analysis was performed for the clinical data of 172 patients with decompensated cirrhosis who were admitted to The Second Affiliated Hospital of Kunming Medical University from April 2016 to April 2017, including sex, age, etiology, complications, and first examination of laboratory markers after admission. With death as the outcome event, the patients were divided into survival group with 98 patients and death group with 74 patients according to the outcome of the disease after 2 years of follow-up. The influencing factors for prognosis were analyzed, and the value of PTAR in predicting the prognosis of patients with decompensated cirrhosis were evaluated. The t-test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. Univariate and multivariate Cox regression analyses were performed for related variables. The receiver operating characteristic (ROC) curve was plotted and the area under the ROC curve (AUC) was calculated, and the optimal cut-off value was determined according to the sensitivity and specificity of the ROC curve. The Kaplan-Meier survival curve analysis was performed to compare 2-year survival rate between patients with different values of PTAR, indocyanine green retention rate at 15 minutes (ICGR15), and Model for End-Stage Liver Disease (MELD) score, and the log-rank test was used for comparison between groups. ResultsCompared with the survival group, the death group had significantly higher PTAR (Z=-7.823, P＜0.001), ICGR15 (t=3.458, P=0.001), and MELD score (t=5.921, P＜0.001). PTAR, ICGR15, and MELD score had optimal cut-off values of 0.05, 41.00%, and 37.25, respectively, in predicting 2-year prognosis, with AUCs of 0849, 0.651, and 0.724, respectively. The survival analysis showed that the high-PTAR (PTAR≥0.05) group had a significantly lower survival rate than the low-PTAR (PTAR＜0.05) group (χ2=60.07, P＜0.001). The multivariate Cox regression analysis showed that PTAR ≥0.05 was an independent risk factor for death within 2 years (hazard ratio = 2.564, 95% confidence interval: 1.276-5.151, P=0.008). ConclusionPTAR ≥0.05 can be used as an independent predictive factor for death within 2 years in patients with decompensated cirrhosis, and PTAR has a relatively high value in predicting the prognosis of patients with decompensated cirrhosis.

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.

Objective:To investigate the manifestations of liver injury in hospitalized patients with coronavirus disease 2019 (COVID-19), to investigate the prognosis indicators of the disease, and to provide the reference for clinical diagnosis and treatment.Methods:From January 10 to February 14, 2020, at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, the data of 333 hospitalized patients with COVID-19 were collected. The changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil), indirect bilirubin (IBil) and albumin of the first liver function test after admission and the reexaminations of liver function test during hospitalization period in patients with liver injury were retrospectively analyzed. Student t test and Chi-square test were used for statistical analysis. Results:Liver injury occurred in 39.6% (132/333) of COVID-19 patients. There was no statistically significant difference in the rate of liver injury between patients in intensive care unit (ICU) and in general ward (45.6%, 26/57 vs. 38.4%, 106/276; χ2=1.026, P>0.05). 67.4% (89/132) of COVID-19 patients with liver injury presented with increased ALT or AST level on admission. During hospitalization, the level of ALT was higher than that of the first examination after admission ((60.28±50.44) U/L vs. (42.25±32.21) U/L), and the difference was statistically significant ( t=-3.230, P<0.05). The levels of ALT and AST of 71.2% (94/132) patients were both <80 U/L, which indicated that most of the patients showed mild liver injury. The patients with elevated level of TBil, DBil and IBil accounted for 3.9% (13/333), 5.4% (18/333) and 2.4% (8/333) of the COVID-19 patients, respectively. The albumin level of COVID-19 patients with liver injury during hospitalization was lower than that of the first examination after admission ((31.8±5.1) g/L vs. (33.7±5.4) g/L), and the difference was statistically significant ( t=2.712, P<0.05). The albumin levels at first examination on admission and reexamination during hospitalization of patients in ICU were both significantly lower than those of patients in general ward ((29.3±3.7) g/L vs. (34.8±5.1) g/L and (27.6±2.8) g/L vs. (32.9±5.1) g/L), and the differences were statistically significant ( t=4.928 and 4.783, both P<0.05). Conclusions:The incidence of liver injury in COVID-19 patients is high. A slight increase in aminotransferase levels is particularly common. Bilirubin abnormality is relatively rare and mild. The level of albumin may be one of the indicators for the severity and prognosis of COVID-19.

Objective:To find out the obstacle factors in its clinical application according to the clinical situation of the application of urinary catheter fixation device.Methods:From September 2018 to October 2018, 19 nurses working in the urology ward of Peking University First Hospital were selected for a semi-structured interview. Based on the theoretical domain framework, the interview outline was formulated and the content was analyzed, and the topic was extracted again.Results:This study identified obstacle factors related to 5 areas of the theoretical domain framework, namely "knowledge, social or professional role and identity, motivation and goals, environmental factors and social influence". The themes were extracted again, respectively: "the system level of evidence implementation (organizational factors, training, product categories) needs to be optimized, the level of willingness of users (patients) for evidence implementation needs to be improved and the sustainability of evidence application needs to be strengthened".Conclusions:The factors that affect the clinical application of urinary catheter fixation devices are multiple, and future research needs to formulate targeted intervention plans based on evidence according to obstacles identified.

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

Objective To explore the barriers in the clinical use of evidence-based urethral catheter cleaning. MethodsThe interview outline was developed based on the Theoretical Domains Framework (TDF) from September to October 2018. Totally 19 nurses working in the Department of Urinary Surgery at Peking University First Hospital was selected for semi-structural interview by convenient sampling, and content analysis was conducted based on the results. ResultsA total of 4 barriers related to 4 domains under the TDF were found in this study, namely, social / professional roles and identities, confidence in results, environmental factors and resources, and social impact. The subjects were extracted on this basis, which were lack of knowledge conversion process and norms in the department, poor self-management ability in the patients, and insufficient catheter cleaning resources. ConclusionsThe clinical use of evidence-based urethral catheter cleaning is affected by multiple factors, including systems, patients and resource availability. Departments need to explore and develop the norms for knowledge transformation, improve the self-management ability of postoperative patients, provide sufficient resources for catheter cleaning, and promote the clinical use of evidence-based urethral catheter cleaning.