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/)

Tumor has become the major reasons cause of death,and its vaccine has become the effective tracts of treatment and prevention by enhancing the immune response of patients.However,most vaccines which are recombination subunit protein antigens are poorly immunogenic and difficult to induce a robust immune response in patients with compromised immune systems,resulting in poor marketing approval.The core component of the vaccine adjuvant can greatly enhance the strength,speed and duration of the immune response,thus becoming the key to the development of an ideal tumor vaccine.Most tumor vaccines are combined with tradition adjuvant such as aluminum,MF59 and AS adjuvant,but their products and patents are monopolized by large foreign companies.We found that natural adjuvants have many unique advantages,such as good biocompatibility and biodegradability,promoting the maturation of dendritic cell and the secretion of immune cytokines,significantly enhancing the tumor vaccine immune response,etc.In this paper,the application and future development of natural polysaccharides,saponins,flavonoid and plant virus-like particles in cancer vaccines were reviewed,which may lay a solid foundation for the development of the original and innovative adjuvants with domestic independent intellectual property rights.

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R² = 0.033; P = 0.018), followed by acute kidney injury (AKI; R² = 0.032; P = 0.011) and plasma MIP-1β level (R² = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
Acute Kidney Injury/complications* ; Bacteria/classification* ; Chemokine CCL4/blood* ; Community-Acquired Infections/microbiology* ; Humans ; Lung ; Microbiota/genetics* ; Pneumonia, Bacterial/diagnosis* ; Prognosis ; RNA, Ribosomal, 16S/genetics*

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objective:To investigate the clinical characteristics and outcome of novel coronavirus pneumonia (COVID-19)patients with different body mass index (BMI), and to provide the basis for disease assessment and prognosis.Methods:The clinical data of 541 patients with COVID-19 diagnosed in Xiaogan Hospital Affiliated to Wuhan University of Science and Technology from January 16 to March 28, 2020 were collected. The patients were divided into normal weight group, overweight group, and obesity group according to BMI. The clinical characteristics and outcomes of the three groups were compared. The correlation between BMI and clinical classification was analyzed by ordinal logistic regression.Results:There were 288 cases (53.23%) in normal weight group, 193 cases (35.67%) in overweight group, and 60 cases (11.09%) in obesity group. Compared with normal weight group, overweight and obesity groups displayed higher proportion of hypertension, with increased levels of white blood cells, neutrophils, C reactive protein, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and triglyceride in laboratory test results, and higher proportion of severe and critical illness ( P<0.05 or P<0.01). After adjusting for age, gender, and underlying diseases, regression analysis showed that higher BMI predicted more severe clinical classification ( OR=1.079, 95% CI 1.010-1.154). Conclusion:In COVID-19 patients, overweight and obese patients are more likely to develop into severe and critical illness, suggesting that obesity may be an important risk factor affecting the clinical outcome of COVID-19.

Objective:To summarize the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) infected with Delta variant, so as to provide further references for clinical diagnosis and treatment.Methods:A real-world study was conducted to analyze the characteristics of 166 COVID-19 patients infected with Delta variant at Guangzhou Eighth People’s Hospital, Guangzhou Medical University.Results:The study enrolled 5 asymptomatic cases, 123 non-severe cases (mild and moderate type), and 38 severe cases (severe and critical type). Among these patients, 69 (41.6%) were male and 97 (58.4%) were female, with a mean age of 47.0±23.5 years. Thirty-nine cases (23.5%) had received 1 or 2 doses of inactivated vaccine. The incidence of severe COVID-19 cases was 7.7% in 2-doses vaccinated patients, which was lower than that of 11.5% in 1-dose and 26.8% in unvaccinated patients. The proportion of severe cases in 2 dose-vaccinated patients was 7.7%, which was lower than that of 11.5% in 1-dose vaccinated patients and 26.8% in unvaccinated patients, but the difference was not significant ( P>0.05). The most common clinical symptom was fever (134 cases, 83.2%), and 39.1% of cases presented with high-grade fever (≥39 °C); other symptoms were cough, sputum, fatigue, and xerostomia. The proportion of fever in severe cases was significantly higher than that of non-severe cases (97.4% vs. 76.4%, P<0.01). Similarly, the proportion of severe cases with high peak temperature (≥39 ℃) () was also higher than that of non-severe cases (65.8% vs. 30.9%, P<0.01). The median minimal Cycle threshold (Ct) values of viral nucleic acid N gene and ORFlab gene were 20.3 and 21.5, respectively, and the minimum Ct values were 11.9 and 13.5, respectively. Within 48 h of admission, 9.0% of cases presented with decreased white blood cell counts, and 52.4% with decreased lymphocyte counts. The proportions of increased C-reactive protein, serum amyloid A, interleukin 6, and interleukin 10 were 32.5%, 57.4%, 65.3%, and 35.7%, respectively. The proportions of elevated C-reactive protein, serum amyloid A and interleukin-6 in severe cases were significantly higher than those in non-severe cases ( P<0.01). Logistic regression analysis showed that older age and higher peak temperature were associated with a higher likelihood of severe cases ( OR>3, 95% CI: 2-7, P<0.01). In terms of treatment, traditional Chinese medicine (TCM) was used in 97.6% of non-severe cases and 100% in severe cases. Other treatments included respiratory and nutritional support, immunotherapy (such as neutralizing antibodies and plasma of recovered patients). The median times from admission to progression to severe cases, of fever clearance, and of nucleic acid conversion were 5 days, 6 days and 19 days, respectively. No deaths were reported within 28 days. Conclusions:The symptoms of Delta variant infection in Guangzhou are characterized by a high proportion of fever, high peak temperature, long duration of fever, high viral load, a long time to nucleic acid conversion, and a high incidence of severe cases. The severe cases exhibit a higher percentage of elderly patients, a longer duration of fever and have a higher fever rate and a higher hyperthermia rate than non-severe cases. Age and hyperthermia are independent risk factors for progression to severe disease. The combination of TCM and Western medicine can control the progression of the disease effectively.

Objective:To investigate the people's cardiopulmonary resuscitation (CPR) ability in Hunan Province and whether there are differences in the skill level of CPR among respondents of different ages and education levels.Methods:A self-made questionnaire was conducted to survey people in Hunan Province by means of WeChat from May 2018 to April 2019. The questionnaire referred to 2016 National consensus on cardiopulmonary resuscitation in China issued by Cardiopulmonary Resuscitation Specialized Committee of Chinese Research Hospital Association and 2017 version of American Heart Association (AHA) CPR operational guide, and combined with the CPR assessment scale of Hunan Provincial People's Hospital. The contents of the survey included the basic information of the subjects, the common knowledge and skills of first aid, the willingness to learn CPR skills and implement CPR, and the operational requirements of high quality CPR, etc. Results:A total of 6 563 people received the on-site first aid knowledge questionnaire, and 4 355 people completed and submitted the questionnaire. The recovery rate was 66.36%, of which 3 602 valid questionnaires were from IP in Hunan Province, and the qualified rate was 82.71%. Among the subjects, 1 532 were men (42.53%) and 2 070 were women (57.47%). The majority aged group from 19 to 30 (59.41%) and from 31 to 50 (36.70%). 307 were rural (8.52%) and 3 295 were urban (91.48%); and the majority levels of education were senior or technical secondary school (38.26%) and undergraduate or junior college (44.50%). Of the 3 602 respondents, 39.09% indicated that they had been exposed to CPR knowledge and only 0.36% indicated that they did not wish to participate in CPR training. 69.93% of the respondents said they would actively to help if they wet cardic arrest, and 97.92% of those were willing to do so if the patients were relatives or friends. The survey results showed that only 8.91% of respondents chose relatively high-quality CPR options (chest compressions were performed first, the pressing point was located in the sternum of the midpoint of bilateral nipple line, the pressing frequency was 100-120 times/min, pressing depth was 5-6 cm, the ratio of chest compression to artificial ventilation was 30∶2). Among these people, the correct rate was higher in the ages of 31-50 years old and ≤ 18, 19-30 than those ≥51 years old (12.71% vs. 0%, 6.87%, 8.70%, χ2 = 41.420, P < 0.01). The correct rate of education at graduate level and above was higher than those in junior middle school and below, high school or technical secondary school, undergraduate or junior college (19.57% vs. 2.07%, 3.41%, 13.72%, χ2 = 152.262, P < 0.01). Conclusions:The public in Hunan Province have a strong sense of first aid, and some of the theoretical knowledge of CPR. People between 31 years old and 50 years old of age and with graduate education and above know more about CPR, but the overall mastery of CPR skills is poor. It is necessary to further improve the ability of the public as the first witness by teaching various skills of CPR in various forms.

Acute myocardial infarction with cardiogenic shock (AMI-CS) refers to the rapid decrease in cardiac output in a short period of time, and it leads to severe insufficient perfusion of various organs and causes systemic microcirculatory dysfunction, which is the most common cause of the death of patients with acute myocardial infarction (AMI). At present, the main strategy for clinical treatment of AMI-CS is revascularization, which reduces the mortality of AMI-CS. However, myocardial ischemia and reperfusion can cause ischemia/reperfusion (I/R) injury, induce myocardial mitochondrial dysfunction, and a large amount of reactive oxygen species (ROS) accumulation. Mitochondrial-mediated apoptosis of cardiomyocytes is the main reason of cardiomyocyte death during reperfusion injury. This article summarizes the role of mitochondrial in AMI-CS, which focus on three aspects of mitochondrial permeability transition pore (mPTP) opening, mitochondrial autophagy and mitochondrial fusion/division. It is expected to provide new ideas for clinical AMI-CS and identify potential complications targets.

Objective:To ananlyze the toxic effects and mechanisms of Cr (Ⅵ) subchronic exposure based on metabonomics techniques.Methods:Twenty-nine female Sprague-Dawley rats were randomly divided into control group, low dose group and high dose group, 10, 9, 10, respectively. The control group, low dose group and high dose group were treated with 0, 10, 50 mg/L Cr (Ⅵ) for 90 days respec tively. The serum samples of rats with different dose of Cr (Ⅵ) treatment were detected Using UPLC-Q-TOF-MS/MS technique and data was analyzed by PCA, PLS-DA and OPLS-DA to compare with metabolic profile in different Cr (Ⅵ) dose treatments. Pathway analysis was performed using MetaboAnalyst 4.0 software.Results:UPLC-Q- TOF-MS/MS has stable detection performance and reliable experimental data. The control group, low Cr (Ⅵ) and high Cr (Ⅵ ) metabolic profiles of rats serum differences was obviously, and there is significant difference of serum metabolic profile among rats treated with different dose of Cr (Ⅵ) . 18 differential metabolites were screened between Cr (Ⅵ) low dose group and control group, 23 differential metabolites between Cr (Ⅵ) high dose group and control group. Compared to control group, there were 13 differential metabolites in both Cr (Ⅵ) high dose group and Cr (Ⅵ ) low dose group, such as 3-Hydroxy-11Z-octadecenoylcarnitine, Anserine, Farnesyl pyrophosphate, Linoleoyl ethanolamid e, Linoleyl carnitine, Lithocholate 3-O-glucuronide, LysoPC [20∶2(11Z, 14Z) ], LysoPC[20∶3 (5Z, 8Z, 11Z) ], LysoPC[22∶2(13Z, 16Z) ], PG[16∶0/22∶5(7Z, 10Z, 13Z, 16Z, 19Z) ], PI[18∶1 (11Z) /20∶4(5Z, 8Z, 11Z, 14Z) ], PI[20∶3(5Z, 8Z, 11Z) /18∶0], Serotonin. These differential metabolites were related to Glycerophospholipid metabolism, Tryptophan metabolism, Pentose and glucuronate interconversions, Terpenoid backbone biosynthesis.Conclusion:Cr (Ⅵ) subchronic exposure could induce the significant difference of serum metabolic profile. The differential metabolites induced by Cr (Ⅵ) subchronic ex- posure were mainly related to amino acid and lipid metabolism.

Objective:To ananlyze the toxic effects and mechanisms of Cr (Ⅵ) subchronic exposure based on metabonomics techniques.Methods:Twenty-nine female Sprague-Dawley rats were randomly divided into control group, low dose group and high dose group, 10, 9, 10, respectively. The control group, low dose group and high dose group were treated with 0, 10, 50 mg/L Cr (Ⅵ) for 90 days respec tively. The serum samples of rats with different dose of Cr (Ⅵ) treatment were detected Using UPLC-Q-TOF-MS/MS technique and data was analyzed by PCA, PLS-DA and OPLS-DA to compare with metabolic profile in different Cr (Ⅵ) dose treatments. Pathway analysis was performed using MetaboAnalyst 4.0 software.Results:UPLC-Q- TOF-MS/MS has stable detection performance and reliable experimental data. The control group, low Cr (Ⅵ) and high Cr (Ⅵ ) metabolic profiles of rats serum differences was obviously, and there is significant difference of serum metabolic profile among rats treated with different dose of Cr (Ⅵ) . 18 differential metabolites were screened between Cr (Ⅵ) low dose group and control group, 23 differential metabolites between Cr (Ⅵ) high dose group and control group. Compared to control group, there were 13 differential metabolites in both Cr (Ⅵ) high dose group and Cr (Ⅵ ) low dose group, such as 3-Hydroxy-11Z-octadecenoylcarnitine, Anserine, Farnesyl pyrophosphate, Linoleoyl ethanolamid e, Linoleyl carnitine, Lithocholate 3-O-glucuronide, LysoPC [20∶2(11Z, 14Z) ], LysoPC[20∶3 (5Z, 8Z, 11Z) ], LysoPC[22∶2(13Z, 16Z) ], PG[16∶0/22∶5(7Z, 10Z, 13Z, 16Z, 19Z) ], PI[18∶1 (11Z) /20∶4(5Z, 8Z, 11Z, 14Z) ], PI[20∶3(5Z, 8Z, 11Z) /18∶0], Serotonin. These differential metabolites were related to Glycerophospholipid metabolism, Tryptophan metabolism, Pentose and glucuronate interconversions, Terpenoid backbone biosynthesis.Conclusion:Cr (Ⅵ) subchronic exposure could induce the significant difference of serum metabolic profile. The differential metabolites induced by Cr (Ⅵ) subchronic ex- posure were mainly related to amino acid and lipid metabolism.