Objective To analyze the antibody responses in guinea pigs vaccinated with recombi-nant vaccinia virus( rTT) strains expressing transmitted/founder ( T/F) HIV-1 membrane proteins in combi-nation with gp140 protein.Methods Guinea pigs were primed with rTT strains and boosted twice with gp140 protein in every four weeks.Serum samples were collected from guinea pigs before immunization and in 2, 6 and 10 weeks after the last immunization for the detection of HIV-1-specific binding antibodies, neu-tralizingantibodiesandtherelativeavidityofantibodies.Results (1)Thebindingantibodiesspecificto HIV-1 B′/C, B, AE subtypes were efficiently induced by the immunization of rTT-B, rTT-C and rTT-CON vaccinia strains in combination with gp140 protein.The antibody titers ranged from 111 430 to 1 024 000. More antibodies against HIV-1 B′/C and AE subtypes were induced in guinea pigs by the immunization of rTT-C and rTT-CON strains in combination with gp140 protein than those by using rTT-B strain prime-protein boost strategy (P<0.05).No significant differences with the titers of HIV-1 B subtype specific antibody were observed among the guinea pigs immunized with the three strategies.( 2 ) High titers of SF162 and ZM109 neutralizing antibodies were induced in guinea pigs immunized with rTT-B, rTT-C and rTT-CON vac-cinia strains in combination with gp140 protein, ranging from 83.76 to 649.30.No significant differences were found among the three groups.(3) The HIV-1 V1V2-gp70 specific antibodies associated with protec-tive immunity were induced by immunization of the three virus prime-protein boost strategies.No significant differences were observed among them.(4) Antibodies induced in guinea pigs by immunization of the three strategies showed strong affinity to membrane proteins of HIV-1 B′/C, B, AE subtype strains.No significant differences were found among the three immunization strategies.Conclusion A strong humoral immune re-sponse was induced in guinea pigs primed with recombinant vaccinia virus strains expressing T/F virus HIV-1 membrane proteins and boosted with gp140 protein.

Objective To investigate the diagnosis and treatment of idiopathic chronic colonic pseudo-obstruction(ICCPO). MethodsIn this study 69 patients admitted for “constipation” were finally found falling into one of the 4 groups: 11 cases of outlet obstructive constipation, 16 cases of slow transit constipation, 26 cases of mixed type, and 16 of ICCPO. ResultsThe main symptoms of these 16 ICCPO cases were intractable constipation, compared with that in other entities ICCPO tends to affect patients at younger age, with shorter clinical course, and often needs surgical intervention due to intractable bowel obstruction, usually total colectomy. ConclusionsICCPO, STC and mixed constipation are different clinical entities. The differentiation of ICCPO from other entities is sometimes very difficult especially when patients are suffering from acute onset of bowel obstruction.

Background Diabetic retinopathy (DR) has become the main cause of blindness in the world,But the etiology of DR is still not clear,and the results of the studies on the risk factors of DR are not completely consistent.Fully understanding the risk factors of DR has an important clinical value for the prevention and treatment of DR.Objective This study was to analyze the prevalence rate and risk factors of DR inpatients with type 2 diabetes and provide a basis for the establishment of ophthalmic intervention programs and measures for diabetic inpatients.Methods Cross sectional study was performed.Four hundred and seventy three patients with type 2 diabetes in the department of endocrinology,Dongguan People's Hospital from July 2011 to July 2012 were included.The patients were divided into DR group and non diabetic retinopathy (NDR) group.The DR group was subdivided into mild,moderate and severe non-proliferative DR (NPDR) group and proliferative DR (PDR) group.The sex and age of patients,course of diabetes,body mass index (BMI),systolic blood pressure,diastolic blood pressure,fasting blood glucose (FBG),2 hours postprandial blood glucose (2 h PBG),glycosylated hemoglobin (HbA1 c),fasting insulin,2 hours postprandial insulin,high density lipoprotein cholesterol,low density lipoprotein cholesterol,apolipoprotein A1 (APOA1),APOB,alpha lipoprotein,total cholesterol,three glycerol,urea nitrogen,creatinine,uric acid,percentage of neutrophil,24 hours urinary albumin total (ALBU-24 h) and ALBU were detected.Logistic regression was used to analyze the relationship between DR and various factors,and the risk factors of DR were screened out.Results The prevalence of DR inpatients with type 2 diabetes was 28.33％,the prevalence of mild,moderate and severe NPDR were 2.54％,16.28％ and 4.23％,respectively,the prevalence of PDR was 5.29％.The prevalence of DME was 10.36％ in the DR patients.The course of diabetes,the levels of serum lipoprotein,creatinine,ALBU-24 h and ALBU were statistically significant between DR group and NDR group (all at P＜0.05).By stepwise Logistic regression analysis,the course of disease,FBG were identified as the independent risk factors of DR (course of disease:odds ratio [OR] =1.155,95 ％ confidence interval [CI]:1.067-1.251;FBG:OR =1.313,95％ CI:1.071-1.610).Conclusions The course of diabetes,lipoprotein,creatinine,ALBU-24h,ALBU are closely related to the occurrence and development of DR.The course of diabetes and FBG are the independent risk factors of DR.

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.

OBJECTIVETo observe the effects of electroacupuncture (EA) pretreatment on the intestinal function, inflammatory reaction and blood lactic acid in the patients of colorectal cancer surgery.

METHODSSixty patients of colorectal cancer laparotomy at selective period, aged from 18 to 59 years old were selected. According toⅠ-Ⅲ grade of American Society of Anesthesiologists (ASA), the patients were randomized into group A (total intravenous anesthesia), group B[total intravenous anesthesia combined with EA pretreatment at Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39) on the right side] and group C[total intravenous anesthesia combined with EA pretreatment at Zhongwan (CV 12), Tianshu (ST 25), Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39) on the right side], 20 cases in each one. The total intravenous anesthesia was applied to all of the three groups. EA pretreatment was used one day before surgery and 30 min before surgery at corresponding acupoints in the group B and group C separately, 30 min each time. After surgery, the recovery time of bowel sound, the recovery time of flatus, the recovery time of defecation, the duration of diet fasting, the time of peritoneal drainage tube withdrawal and the total peritoneal drainage volume were observed in the three groups. The venous blood was collected to determine white blood cell count (WBC) and neutrophil count (NEUT) before surgery (T), 24 h after surgery (T) and on the 5th day after surgery (T) separately. The arterial blood was collected to determine the level of lactic acid before surgery (T), after peritoneal douching (T) and 24 h after surgery (T)separately.

RESULTSThe recovery time of bowel sound, the recovery time of flatus, the duration of diet fasting and the time of peritoneal drainage tube withdrawal in the group C were apparently earlier than those in the group A (all<0.05). WBC and NEUT at Tin the group C were apparently less than those in the group A (both<0.05). The differences in lactic acid at T, Tand Twere not significant statistically in comparison of the three groups (all>0.05).

CONCLUSIONSThe total intravenous anesthesia combined with EA pretreatment at Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Tianshu (ST 25) and Zhongwan (CV 12) reduce the recovery time of bowel sound, the recovery time of flatus, the duration of diet fasting and the time of peritoneal drainage tube withdrawal so as to improve the recovery of intestinal function, reduce WBC in 24 h after surgery and alleviate inflammatory reaction. This therapy has no influence on blood lactic acid.

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 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.

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/ ).
Humans ; Prognosis ; Genotype ; Polymorphism, Single Nucleotide/genetics* ; Quantitative Trait Loci ; Colorectal Neoplasms ; Tumor Microenvironment ; Aminopeptidases/metabolism* ; Minor Histocompatibility Antigens/genetics*

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.