BACKGROUND: Polymorphism in promoter region can change the expression of genes, which may be associated with susceptivity of diseases. Gene polymorphism of interleukin-6 (IL-6) promoter is associated with nationality and many diseases. Different nationalities often display different characteristics of gene polymorphism.OBJECTIVE: To observe the distribution of polymorphism at sites -597 and -572 in IL-6 promoter region in Tibet Tibetan population and to provide the theoretical data for Tibetan population genetics and background of immunity.DESIGN: Randomized investigation.SETTING: Institute of Anthropology, Jinzhou Medical College.PARTICIPANTS: Totally 108 healthy Tibetan teenagers were selected from Lasa and Naqu region in Tibet autonomous region from October 2003 to July 2004, including 60 males and 48 females, aged from 14-21 years. Inclusive criteria:The parents of the volunteers were healthy Tibetans after body examination. The volunteers knew the fact, agreed to participate into the trail and signed the informed consent.METHODS: 5 mL peripheral vein blood was collected from 108 Tibetan teenagers. DNA from human leucocytes was extracted by salt fractionation. IL-6 promoter including -597 and -572 fragments was amplified by polymerase chain reaction (PCR). Representative fragments were cloned then sequenced after restriction fragment length polymorphism (RFLP).MAIN OUTCOME MEASURES: Distribution of polymorphism in Tibet Tibetan population; Results after comparison with those of other nationalities including Han population.RESULTS: Data of 108 Tibetan teenagers were involved in the result analysis. ①Distribution of polymorphism on -572C/G site of IL-6 promoters in population of either sex: There were no GA and AA genotypes at site -597, but only GG genotype appeared. There were CC, CG and GG genotypes at site -572, and the frequencies were 0.63, 0.35 and 0.02 in order. Distribution of genotype with representativeness met the Hardy-Weinberg equilibrium. Allele frequencies were 0.81 and 0.19, respectively. There was no significant difference of either sex in genotype and allele frequency (P ＞ 0.05). ②Distribution of polymorphism on -597 G/A and -572 C/G in different nationalities: GG, GA, AA genotypes appeared on -597 site in England and France, and G and A allele frequencies were 0.60 and 0.40,respectively. It was significantly different from that of Tibetan in Tibet. Furthermore, Japanese had no polymorphism,which was similar to that of Hans in China (P ＞ 0.05). ③Genotype of different straps and results of DNA sequencing:Only GG genotype was found on -597 site (without the restriction site, one fragment after restriction, PCR amplification products), no GA and AA genotypes. CC, CG and GG genotypes appeared at site -572, and frequencies were 0.64,0.35 and 0.01, respectively. Distribution of genotype with representativeness met the Hardy-Weinberg equilibrium (P ＞0.05). Allele frequencies were 0.81 and 0.19, respectively. There was no significant difference of either sex in genotype and allele frequency. Distribution of gene frequency and allele frequency in IL-6 were similar between Tibetan and that of Hans, but it was significantly different from that of population in England, France and America.CONCLUSION: There are nationality differences of IL-6 gene polymorphism at sites -597 and -572. No polymorphism is found at site -597 in Tibetan. Race differences are seen at site -572, having CC, CG and GG genotypes and G allele is rate. Compared with white population, there is significant difference in genotype and allele frequency at site -572. Their characteristics are close to Hah population and Japanese, which may be associated with genetic gene of persons living in plateau.

Objective To discuss the feasibility and accuracy of left atrial appendage (LAA)ejection fraction by real-time 3 dimensional imaging (3D-EF),and tissue velocity of the LAA wall by tissue Doppler imaging (TDI)via transesophageal echocardiography (TEE)in assessing LAA functions.Methods A total number of 76 patients with atrial fibrillation (AF)were included in the study consecutively and underwent TEE for LAA investigations.3D-EF,fractional area change by 2 dimensional imaging (2D-FAC),peak emptying velocity (PEV),LAA tissue velocity by TDI at the mid-portion of lateral wall (TDI-L),mid-portion of septal wall (TDI-S)and the apical tip (TDI-A)were calculated.Results Statistic analysis showed the following results:1 )2D-FAC,3D-EF,PEV,TDI-L,TDI-S and TDI-A were all significantly higher in patients with sinus rhythm than those with AF during the TEE examinations (all P <0.05),and significantly higher in patients without spontaneous echo contrast (SEC)than those who had SEC (all P <0.05);2)The results of 3D-EF showed a good correlation with 2D-FAC (r=0.727,P =0.000),and their correlations with PEV were similar (2D-FAC and PEV:r =0.685;3D-EF and PEV:r =0.632,both P =0.000);3)TDI-A [(14.95±4.63)cm/s]were significantly higher than TDI-L [(12.62±3.96)cm/s]and TDI-S [(12.68±3.59)cm/s](both P =0.000).The correlations of TDI-A with PEV,2D-FAC and 3D-EF were all marked higher than those of TDI-L and TDI-S (with PEV:r=0.840 vs r=0.564,r=0.524;with 2D-FAC:r=0.701 vs r=0.486,r=0.504;with 3D-EF:r=0.753 vs r=0.493,r=0.522,all P <0.05). Conclusions 3D TEE is feasible and reliable in assessing LAA emptying function.The best location for LAA tissue velocity evaluation is the apical tip.

Objective:To explore teaching methods to improve the teaching effect in view of many difficulties in learning medical statistics for clinical medical students.Methods:Taking the clinical medical students of the same grade as the research objects, the students were randomly divided into two groups by cluster sampling in class, i.e. control group and experimental group. The traditional teaching methods and the scenario-based interactive learning software teaching methods were used respectively. The scores of medical statistics courses examinations and the statistical errors in responding to projects of extracurricular research activities were compared between the two groups. SPSS 19.0 was performed for statistical analysis.Results:The results of subject achievements of the students in the experimental group (74.08±11.19) were higher than those in the control group (63.82±10.10) ( t=3.926, P<0.001), especially the comprehensive capabilities of the innovative analysis questions and the multiple-choice questions. The statistical errors of the students in the experimental group was less than those in the control group. There were significant differences between the two groups in the estimation of sample size ( χ2=4.189, P=0.041), statistical design ( χ2=5.558, P=0.018) and data analysis ( χ2=3.971, P=0.046). Conclusion:The results suggest that scenario-based interactive learning software is helpful to improve teaching efficiency, and enhance students' ability to analyze and solve practical problems by using medical statistics knowledge.

Objective To investigate the situation and the causes of neonatal death in Henan Province.Methods This study retrospectively analyzed the clinical data of 277 neonates who died at 18 hospitals in Henan Province in 2017.Distribution and causes of neonatal deaths,differences between perinatal conditions of premature and term/post-term infants,causes of early (＜ 7 d) and late (7-28 d) neonatal deaths and the differences in neonatal death cases between Maternal and Child Health Care Hospitals and General/Children's Hospitals were analyzed.We used t,rank-sum and Chi-square test (or corrected Chi-square test,or Fisher's exact test) for statistical analysis.Results (1) A total of 50 993 newboms were admitted to the 18 hospitals in 2017,297 of which died with a mortality of 5.82‰.After excluding 20 cases with uncertain birth or maternal pregnancy history or clinical data,277 cases with complete data were analyzed.Among them,168 (60.6％) were preterm neonates and 109 (39.4％) were term/post-term ones.Early and late neonatal deaths accounted for 74.0％ (205 cases) and 26.0％ (72 cases),respectively.(2) The top five causes of neonatal deaths were infection (78 cases,28.2％),asphyxia (54 cases,19.5％),neonatal respiratory distress syndrome (NRDS,33 cases,11.9％),severe congenital malformations (26 cases,9.4％) including cyanotic congenital heart diseases,digestive malformations,airway malformations and neural tube defects and pulmonary hemorrhage (23 cases,8.3％).Among them,the top three causes of early neonatal deaths were asphyxia (48 cases,23.4％),infection (43 cases,21.0％) and NRDS (33 cases,16.1％),while the main causes of late neonatal deaths were infection (35 cases,48.6％),major congenital malformations (9 cases,12.5％) and chromosome abnormities/inherited metabolic diseases (7 cases,9.7％).(3) Maternal complications during pregnancy accounted for 79.1％ (219 cases) and the predominant types were pregnancy-induced hypertension (43 cases,19.6％),followed by infection (36 cases,16.4％),placental-related conditions (32 cases,14.6％),gestational diabetes mellitus (23 cases,10.5％),hypothyroidism (20 cases,9.1％),fetal distress (18,8.2％),twin-twin transfusion syndrome (10 cases,4.6％) and cholestasis syndrome (9 cases,4.1％).(4) Compared with the term/post-term cases,the preterm cases had higher proportions of multiple births [27.4％ (46/168) vs 6.4％ (9/109),x2=14.016,P ＜ 0.05],assisted reproduction [7.1％ (12/168) vs 0.9％ (1/109),x2=4.421,P ＜ 0.05] and maternal hypertensive disorders of pregnancy [21.4％ (36/1 68) vs 6.4％ (7/109),x2=11.353,P ＜ 0.05],infection [16.7％ (28/168) vs 7.3％ (8/109),x2=4.295,P ＜ 0.05] and twin-to-twin transfusion syndrome [6.0％ (10/168) vs 0.0％ (0/109),x2=6.707,P ＜ 0.05].(5) Among all the early neonatal deaths,preterm cases had a higher incidence of NRDS than term/post-term neonates [20.3％ (27/133) vs 8.3％ (6/72),x2=1 1.937,P ＜ 0.05],but lower incidence of meconium aspiration syndrome (MAS),severe congenital malformations and chromosome abnormalities/inherited metabolic diseases [0.8％ (1/133) vs 5.6％ (4/72),x2=4.508;3.8％ (5/133) vs 16.7％ (12/72),x2=10.233;1.5％ (2/133) vs 6.9％ (5/72),~=4.172;all P ＜ 0.05].Among the late neonatal deaths,the incidence of severe intracranial hemorrhage in preterm infants was higher than that in term/post-term neonates [7.1％ (3/42) vs 0.0％ (0/30),x2=2.205,P ＜ 0.05].(6) Compared with the cases in General/Children's Hospitals,those in Maternal and Child Health Care Hospitals showed a higher proportion of preterm neonatal deaths [67.3％ (105/156) vs 52.1％ (63/121),x2=6.010,P ＜ 0.05],younger gestational age [(32.8±5.3) weeks vs (34.6±4.9) weeks,t=3.072,P ＜ 0.05],lower birth weight [(2 132.6± 1 014.5) g vs (2 409.4±987.3) g,t=-2.513,P ＜ 0.05],and higher average age of death [M(P25-P75),3 (1-8) d vs 2 (1-4) d,Z=3.710,P ＜ 0.05].Conclusions Neonatal death occurs mainly within one week after birth in those with maternal complications.Late preterm deaths and term/post-term cases account for nearly half of total neonatal deaths.The causes of death for preterm and term/post-term newborns vary with postnatal age.Infection,asphyxia and severe congenital malformations are important causes of neonatal deaths.

Objective: To investigate the relationship between monokine induced by interferon⁃gamma (MIG) level and coronary slow flow phenomenon ( CSFP) . Methods: 80 patients diagnosed with CSFP and 54 patients with normal CAG were selected as the CSFP group and no⁃CSFP group respectively in this study. Coronary slow flow was determined quantitatively by thrombolysis in myocardial infarction (TIMI) frame count (TFC) method. The clinical characteristics and biochemical indexes , including serum CD40L and Interferon⁃γ (IFN⁃γ) , monokine induced by interferon⁃gamma (MIG) levels were measured , and the relationship between interferon⁃γ induced monocyte level and CSFP were analyzed. Results: The serum levels of CD40L , IFN⁃γand MIG in the CSFP group were higher than those in the no⁃CSFP group ( P = 0. 001) . The MIG levels were positive correlated with mean TFC ( r =0. 879 ,P = 0. 009) . Multivariate logistic regression analysis showed that MIG was an important risk factor for CSFP (β = 0. 874 ,P = 0. 011) . The ROC curve analyses indicated that the MIG levels had diagnostic value in patients with CSFP , the area under the curve ( AUC) was 0. 793 , the sensitivity was 0. 79% and the specificity was 76. 0% , and 95% CI 0. 714 - 0. 872. Conclusion Chemokine CD40L , IFN⁃ γ and MIG may be involved in the process of vascular inflammation and arteriosclerosis. MIG is an important influencing factor of CSFP and participated in the occurrence and development of CSFP.

Malignant tumors are diseases that seriously threaten human health and social development. Traditional tumor therapies such as surgery, radiotherapy, chemotherapy and targeted therapy cannot fully meet the needs of clinical treatment, and emerging immunotherapy has become a research hotspot in the field of tumor treatment. Immune checkpoint inhibitors (ICIs) have been approved as a tumor immunotherapy method for the treatment of various tumors, such as lung cancer, liver cancer, stomach cancer and colorectal cancer, etc. However, during the clinical use of ICIs, only a small number of patients experienced durable responses, which also led to drug resistance and adverse reactions. Therefore, the identification and development of predictive biomarkers is crucial to improve the therapeutic efficacy of ICIs. The predictive biomarkers of tumor ICIs mainly include tumor biomarkers, tumor microenvironment biomarkers, circulation-related biomarkers, host environmental biomarkers and combinatorial biomarkers. They are of great significance for screening, individualized treatment and prognosis evaluation of tumor patients. This article reviews the advances of predictive markers for tumor ICIs therapy.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms ; Biomarkers ; Immunotherapy/methods* ; Biomarkers, Tumor/genetics* ; Prognosis ; Tumor Microenvironment

The estimated new cases of breast cancer (BC) patients were 2.26 million in 2020, which accounted for 11.7% of all cancer patients, making it the most prevalent cancer worldwide. Early detection, diagnosis and treatment are crucial to reduce the mortality, and improve the prognosis of BC patients. Despite the widespread use of mammography screening as a tool for BC screening, the false positive, radiation, and overdiagnosis are still pressing issues that need to be addressed. Therefore, it is urgent to develop accessible, stable, and reliable biomarkers for non-invasive screening and diagnosis of BC. Recent studies indicated that the circulating tumor cell DNA (ctDNA), carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), extracellular vesicles (EV), circulating miRNAs and BRCA gene from blood, and the phospholipid, miRNAs, hypnone and hexadecane from urine, nipple aspirate fluid (NAF) and volatile organic compounds (VOCs) in exhaled gas were closely related to the early screening and diagnosis of BC. This review summarizes the advances of the above biomarkers in the early screening and diagnosis of BC.
Humans ; Female ; Biomarkers, Tumor ; Early Detection of Cancer ; Breast Neoplasms/diagnosis* ; Prognosis ; MicroRNAs/genetics*

Tumor is a serious threat to human health. At present, surgical resection, chemoradiotherapy, targeted therapy and immunotherapy are the main therapeutic strategies. Monoclonal antibody has gradually become an indispensable drug type in the clinical treatment of cancer due to its high efficiency and low toxicity. Phage antibody library technology (PALT) is a novel monoclonal antibody preparation technique. The recombinant immunoglobulin variable region of heavy chain (VH)/variable region of light chain (VL) gene is integrated into the phage vector, and the antibody is expressed on the phage surface in the form of fusion protein to obtain a diverse antibody library. Through the process of adsorption-elution-amplification, the antibody library can be screened to obtain the antibody molecule with specific binding antigen as well as its gene sequence. PALT has the advantages of short antibody production cycle, strong plasticity of antibody structure, large antibody yield, high diversity and direct production of humanized antibodies. It has been used in screening tumor markers and preparation of antibody drugs for breast cancer, gastric cancer, lung cancer and liver cancer. This article reviews the recent progress and the application of PALT in tumor therapy.
Humans ; Bacteriophages/genetics* ; Immunoglobulin Variable Region/genetics* ; Gene Library ; Antibodies, Monoclonal/therapeutic use* ; Immunotherapy ; Peptide Library