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/)

To investigate the status and epidemiological characteristics of respiratory pathogens infections in children with influenza-like illnesses (ILI) in Beijing Children′s Hospital from 2022 to 2023. A dual amplification technique was used to detect nucleic acids of seven common respiratory pathogens, including influenza A virus (Flu A), influenza B virus (Flu B), mycoplasma pneumoniae (MP), respiratory syncytial virus (RSV), parainfluenza virus (PIV), adenovirus (ADV), and Chlamydia pneumoniae (CP), in outpatient and inpatient children (aged 0-18 years) with influenza-like symptoms who sought medical care at Beijing Children′s Hospital, from January 2022 to March 2023. A total of 43 663 children were included in the study, of which 27 903 tested positive for respiratory pathogens with a total detection rate of 63.91%. Flu A had the highest detection rate of 69.93% (27 332/39 084), followed by MP about 13.22% (380/2 875). The total detection rate of RSV, PIV and ADV was 7.69% (131/1 704). Flu B had a detection rate of 0.16% (64/39 084). No CP was detected in this study. A total of 7 cases of dual infections were detected, with a detection rate of 0.41% (7/1 704). The Chi-square test was used to analyze the differences in detection rates of pathogens among different genders, age groups, and different seasons. Among the seven pathogens, only Flu A had statistically significant differences in gender ( χ2=16.712, P<0.001). The detection rates of Flu A and MP showed an increasing trend with age (both P trend<0.001), while the detection rates of RSV and PIV showed a decreasing trend with age (both P trend<0.001). Flu A had its epidemic peak in winter and spring, with detection rates of 61.30% (3 907/6 374) and 77.47% (23 207/29 958) respectively; MP and PIV had higher detection rates in autumn (25.14% and 7.64% respectively); RSV showed a relatively higher detection rate in winter (8.69%); Flu B and ADV had lower detection rates throughout the study period (0.16% and 1.17% respectively). In conclusion, children with ILI in 2022-2023 were mainly infected with a single respiratory pathogen, and occasionally dual pathogen infections were observed. Among them, the detection rate of Flu A was the highest, and only Flu A showed a gender difference in detection rate. As the age of the children patients increased, the detection rate of Flu A and MP showed an increasing trend, while RSV and PIV showed a decreasing trend. The prevalence of Flu A, Flu B, MP, PIV, and RSV were seasonal.

To investigate the status and epidemiological characteristics of respiratory pathogens infections in children with influenza-like illnesses (ILI) in Beijing Children′s Hospital from 2022 to 2023. A dual amplification technique was used to detect nucleic acids of seven common respiratory pathogens, including influenza A virus (Flu A), influenza B virus (Flu B), mycoplasma pneumoniae (MP), respiratory syncytial virus (RSV), parainfluenza virus (PIV), adenovirus (ADV), and Chlamydia pneumoniae (CP), in outpatient and inpatient children (aged 0-18 years) with influenza-like symptoms who sought medical care at Beijing Children′s Hospital, from January 2022 to March 2023. A total of 43 663 children were included in the study, of which 27 903 tested positive for respiratory pathogens with a total detection rate of 63.91%. Flu A had the highest detection rate of 69.93% (27 332/39 084), followed by MP about 13.22% (380/2 875). The total detection rate of RSV, PIV and ADV was 7.69% (131/1 704). Flu B had a detection rate of 0.16% (64/39 084). No CP was detected in this study. A total of 7 cases of dual infections were detected, with a detection rate of 0.41% (7/1 704). The Chi-square test was used to analyze the differences in detection rates of pathogens among different genders, age groups, and different seasons. Among the seven pathogens, only Flu A had statistically significant differences in gender ( χ2=16.712, P<0.001). The detection rates of Flu A and MP showed an increasing trend with age (both P trend<0.001), while the detection rates of RSV and PIV showed a decreasing trend with age (both P trend<0.001). Flu A had its epidemic peak in winter and spring, with detection rates of 61.30% (3 907/6 374) and 77.47% (23 207/29 958) respectively; MP and PIV had higher detection rates in autumn (25.14% and 7.64% respectively); RSV showed a relatively higher detection rate in winter (8.69%); Flu B and ADV had lower detection rates throughout the study period (0.16% and 1.17% respectively). In conclusion, children with ILI in 2022-2023 were mainly infected with a single respiratory pathogen, and occasionally dual pathogen infections were observed. Among them, the detection rate of Flu A was the highest, and only Flu A showed a gender difference in detection rate. As the age of the children patients increased, the detection rate of Flu A and MP showed an increasing trend, while RSV and PIV showed a decreasing trend. The prevalence of Flu A, Flu B, MP, PIV, and RSV were seasonal.

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 value of nerve conduction velocity testing combined with F-waves, H-reflexes, and sympathetic skin responses in electroneuromyography in the diagnosis of diabetic peripheral neuropathy.Methods:A total of 212 patients with diabetic peripheral neuropathy who received treatment at Fenyang Hospital of Shanxi Province (Fenyang Hospital Affiliated to Shanxi Medical University) from October 2022 to October 2023 were included in this study. These patients were divided into an asymptomatic group ( n = 100) and a symptomatic group ( n = 112) based on the presence or absence of peripheral neuropathy symptoms. Additionally, 100 healthy individuals who underwent physical examinations at the same hospital during this period were included in the control group. Motor nerve conduction velocities were measured for the median nerve, ulnar nerve, tibial nerve, and common peroneal nerve, while sensory nerve conduction velocities were assessed for the median nerve, ulnar nerve, superficial peroneal nerve, and gastrocnemius nerve. F-waves were recorded for the median and tibial nerves. The H-reflexes of the tibial nerve and sympathetic skin response were also evaluated. Differences in motor nerve conduction velocity, sensory nerve conduction velocity, F-waves, H-reflexes, and sympathetic skin responses among the different groups were compared. Results:In the asymptomatic and symptomatic groups, motor conduction velocities were lower ( F = 390.32, 264.63, 228.58, 714.30), distal motor latencies were longer ( F = 316.87, 106.88, 108.58, 217.86), compound muscle action potential amplitudes were lower ( F = 113.38, 59.58, 14.92, 10.36), sensory conduction velocities were slower ( F = 568.87, 532.74, 973.75, 1181.27), sensory nerve action potential amplitudes were lower ( F = 229.53, 309.97, 251.07, 414.82), F-waves were longer ( F = 653.96, 538.20), H-wave latencies were longer ( F = 401.54), and sympathetic skin response latencies were also longer ( F = 147.93, 98.85) compared with those in the control group (all P < 0.05). There were significant differences in motor nerve conduction velocity ( t = 7.33, 13.31), distal motor latency ( t = 13.56, 4.34), compound muscle action potential amplitude ( t = 2.98, 2.99) of the tibial nerve and common peroneal nerve between the asymptomatic and symptomatic groups (all P < 0.05). Significant differences were also observed in the sensory nerve conduction velocity ( t = 12.85, 13.70, 11.08, 15.66) and sensory nerve action potential amplitude ( t = 20.15, 20.26, 8.96, 18.55) of the median nerve, ulnar nerve, gastrocnemius nerve, and superficial peroneal nerve (all P < 0.05). Additionally, differences in F-waves of the median and tibial nerves were significant ( t = 31.96, 13.70, both P < 0.05). The abnormal detection rate of nerve conduction velocity test in the asymptomatic group was 86% (86/100), while the abnormal detection rate of combined nerve conduction velocity test, F-waves, H-reflexes, and sympathetic skin response was 91% (91/100). In the symptomatic group, the abnormal detection rate of nerve conduction velocity test alone was 90.18% (101/112), and the abnormal detection rate of combined nerve conduction velocity test, F-waves, H-reflexes, and sympathetic skin responses was 98.21% (110/112). The abnormal detection rate of combined therapy in the symptomatic group was significantly higher than that in the asymptomatic group ( χ2 = 5.58, P = 0.018). Conclusion:Neuroelectromyography has high diagnostic value for diabetic peripheral neuropathy. The use of F-waves, H-reflexes, and sympathetic skin responses, in conjunction with nerve conduction velocity testing, can enhance the early diagnosis of diabetic peripheral neuropathy in patients who do not exhibit peripheral neuropathy symptoms.

Objective:To learn about the iodine nutritional status of pregnant women in Suqian City, Jiangsu Province, and to provide evidence for scientific supplementation of iodine of pregnant women.Methods:From May 2016 to July 2020, five sampling districts were divided in each county (district) of Suqian City according to the oriation of east, west, south, north and center each year. One township (street) was selected from each district, and 20 pregnant women who lived in the local area for more than half a year were selected from each township (street). The 30 g of household salt samples of pregnant women and 5 ml of urine samples at random once were collected to test the salt iodine and urinary iodine content.Results:A total of 2 483 household salt samples of pregnant women were tested, and the median salt iodine was 23.9 mg/kg; among them, 2 454 were iodized salt, and the coverage rate of iodized salt was 98.8%; the qualified iodized salt was 2 383, the qualified rate of iodized salt was 97.1%, and the consumption rate of qualified iodized salt was 96.0%. There were statistically significant differences in coverage rate of iodized salt, qualified rate of iodized salt and consumption rate of qualified iodized salt between different years (χ 2 = 10.55, 13.23, 11.37, P < 0.05). A total of 2 483 urine samples of pregnant women were tested, and the median urinary iodine was 167.6 μg/L, which was at the appropriate iodine level. However, the median urinary iodine of pregnant women in 2020 was 146.7 μg/L, lower than the WHO/UNICEF/ICCIDD recommendation standard (150 μg/L). The differences of median urinary iodine of pregnant women in different years, pregnancy periods and regions were statistically significant ( H = 26.08, 8.17, 19.87, P < 0.05). Conclusions:The coverage rate of iodized salt, qualified rate of iodized salt and consumption rate of qualified iodized salt in Suqian City , meet the national standard for eliminating iodine deficiency disorders. Iodine nutrition of pregnant women in Suqian City is at an appropriate iodine level, but some pregnant women may have iodine deficiency.

Objective:To understand the iodine nutritional status and the prevalence of goiter and thyroid nodules among children in Suqian City, and to provide a basis for prevention and treatment of iodine deficiency disorders.Methods:From May 2019 to July 2020, the counties (districts) in Suqian City were divided into 5 areas according to east, west, south, north, and middle, each area selected 1 township (street) every year, and 40 non-boarding students aged 8 - 10 years were selected (balanced age and gender) from 1 primary school from each township (street). Children's urine samples and household salt samples were collected to detect urinary iodine and salt iodine contents, and some children were subjected to thyroid examination and height and weight measurements.Results:A total of 1 999 urine samples were collected from children aged 8 to 10 years, and the median urinary iodine was 221.0 μg/L. There was a statistically significant difference among different counties (districts, H = 147.89, P < 0.05). A total of 1 999 edible salt samples were collected from children's homes, and the salt iodine content was (24.01 ± 4.55) mg/kg. Among them, iodized salts was 1 979, the coverage rate of iodized salt was 99.00%; the qualified iodized salts was 1 910, and the iodized salt qualified rate was 96.51%, and the consumption rate of qualified iodized salt was 95.55%. A total of 1 000 cases of children's thyroid were examined, and 22 cases of goiter, 51 cases of solid thyroid nodules, and 54 cases of thyroid cyst were detected, and the detection rates were 2.20%, 5.10%, and 5.40%, respectively. There were significant differences in the detection rates of solid nodules and cysts beteen different counties (districts, χ 2 = 16.41, 37.66 , P < 0.05), but there was no significant difference in the detection rates of goiter (χ 2 = 8.65 , P > 0.05). According to Spearman correlation analysis, children's thyroid volume was positively correlated with height and weight ( r = 0.403, 0.315, P < 0.05). Conclusions:The iodine nutrition of children in Suqian City is at an excessively suitable level of iodine, and the salt iodine monitoring indicators meet the national iodine deficiency disorders elimination standards (the coverage rate of iodized salt ≥ 95%, and the consumption rate of qualified iodized salt > 90%). The children's thyroid volume is affected by factors such as height and weight.

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.

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integra-tion of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation,and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, hap-lotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.