ALBI Grade Is Associated with Clinical Outcomes of Critically Ill Patients with AKI: A Cohort Study with Cox Regression and Propensity Score Matching.

Background: The albumin-bilirubin (ALBI) grade has surfaced as a viable substitute for assessing liver functional reserve in individuals afflicted with hepatocellular carcinoma (HCC). ALBI grade also demonstrates the capacity to stratify distinct patient subcohorts bearing disparate prognostic implications in not only HCC but also other inflammatory diseases like acute pancreatitis. However, the association between ALBI grade and clinical outcomes of acute kidney injury (AKI) remains mysterious. Methods: The dataset was sourced from the Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV) version 2.0. ALBI grade was calculated in a nomogram utilizing albumin and bilirubin. In order to ascertain the connection between ALBI grades and clinical outcomes of patients with AKI, Cox proportional hazards regression analysis was employed with in-hospital, 30- and 90-day mortality as end points, respectively. The Kaplan-Meier (K-M) curve was employed to gauge the cumulative incidence of mortality based on various ALBI grades. To explore potential nonlinear relationships, the Restricted Cubic Spline (RCS) approach was adopted. Furthermore, a subgroup analysis was conducted to validate the durability of the correlation between ALBI grade and in-hospital mortality. Furthermore, equilibrium of confounding variables was also achieved through the application of propensity score matching (PSM). Results: The study encompassed a total of 12,518 patients (ALBI grade 1 : 2878, grade 2 : 6708, and grade 3 : 2932). Patients with heightened ALBI grades displayed a significant correlation with increased mortality in both univariate and various multivariate Cox regression models. RCS depicted a predominantly linear relationship. The robustness of the correlation was also affirmed across multifarious subpopulations through subgroup analysis. The association still remains after PSM. Conclusion: Elevated ALBI grade was associated with worse clinical outcomes of critically ill patients with AKI.

Germline variants profiling of BRCA1 and BRCA2 in Chinese Hakka breast and ovarian cancer patients.

OBJECTIVE: To investigate the prevalence and spectrum of BRCA1 and BRCA2 mutations in Chinese Hakka patients with breast and ovarian cancer. METHODS: A total of 1,664 breast or ovarian cancer patients were enrolled for genetic testing at our hospital. Germline mutations of the BRCA gene were analysed by next-generation sequencing, including the coding regions and exon intron boundary regions. RESULTS: The 1,664 patients included 1,415 (85.04%) breast cancer patients and 245 (14.72%) ovarian cancer patients, while four (0.24%) patients had both the breast and ovarian cancers. A total of 151 variants, including 71 BRCA1 variants and 80 BRCA2 variants, were detected in the 234 (14.06%) patients. The 151 variants included 58 pathogenic variants, 8 likely pathogenic variants, and 85 variants of unknown significance (VUS). A total of 56.25% (18/32) and 65.38% (17/26) of pathogenic variants (likely pathogenic variants are not included) were distributed in exon 14 of BRCA1 and exon 11 of BRCA2, respectively. The most common pathogenic variants among this Hakka population are c.2635G > T (p.Glu879*) (n = 7) in the BRCA1 gene and c.5164_5165del (p.Ser1722Tyrfs*4) (n = 7) in the BRCA2 gene among the Hakka population. A hotspot mutation in the Chinese population, the BRCA1 c.5470_5477del variant was not found in this Hakka population. The prevalence and spectrum of variants in the BRCA genes in the Hakka patients are different from that in other ethnic groups. CONCLUSIONS: The most common pathogenic variant in this population is c.2635G > T in the BRCA1 gene, and c.5164_5165delAG in the BRCA2 gene in this population. The prevalence and spectrum of variants in the BRCA1 and BRCA2 genes in the Hakka patients from southern China are different from those in other ethnic groups.

Effects of Stem Cell Therapy on Diabetic Mellitus Erectile Dysfunction: A Systematic Review and Meta-analysis.

BACKGROUND: Stem cell is considered a potential therapy for treating erectile dysfunction (ED), including diabetic mellitus erectile dysfunction (DMED), which was investigated in some preclinical studies. Several trials introduced stem cell into clinical practice, but divergences emerged. AIM: To further investigate the therapeutic effects of stem cell on DMED in preclinical studies and investigate some possible factors that influence curative effects. METHODS: The literature research was conducted in Web of Science and PubMed to retrieve studies utilizing stem cell to treat DMED. Revman 5.3 was used to perform subgroup analysis of intracavernosal pressure/mean artery pressure (ICP/MAP) and structural changes. Publication bias was assessed with Egger's test, funnel plot, and sensitivity analysis by Stata 15.0. OUTCOMES: The ICP/MAP and structural changes before and after stem cell treatment. RESULTS: Of 2,115 studies retrieved, 23 studies are eligible. Plus 10 studies from a meta-analysis published in 2016, 33 studies were enrolled. Pooled analysis showed that stem cell ameliorates damaged ICP/MAP (WMD 0.26; 95% CI 0.23-0.29; P < .001) and structural changes induced by diabetes. Subgroup analysis indicated that adipose-derived mesenchymal stem cell (ADSC) may have better efficacy than bone marrow-derived mesenchymal stem cell (BMSC) (χ2= 4.21, P = .04; ADSC WMD 0.28, 95% CI [0.24-0.32] vs BMSC WMD 0.22 95% CI [0.17-0.26]). Transplantation type, diabetes type, and cell number make no difference to curative effects. Gene modification and therapy combination proved promising in improving the therapeutic effects of stem cell. CLINICAL TRANSLATION: The evidence reminded that ADSC may be prior to BMSC in clinical trials and autotransplantation is probably not compulsory in the clinical practice of stem cell. STRENGTHS AND LIMITATIONS: The study number and sample size are large enough. However, high degree of heterogeneity remains after subgroup analysis. CONCLUSION: This meta-analysis suggests the efficacy of stem cell therapy for DMED and the possible superiority of ADSC over BMSC in erection restoration and structure renovation. Yao C, Zhang X, Yu Z, et al., Effects of Stem Cell Therapy on Diabetic Mellitus Erectile Dysfunction: A Systematic Review and Meta-analysis. J Sex Med 2022;19:21-36.

Association of ALDH2 rs671 and MTHFR rs1801133 polymorphisms with hypertension among Hakka people in Southern China.

BACKGROUND: Genetic factors play an important role in susceptibility to hypertension. Herein, the association between acetaldehyde dehydrogenase 2 (ALDH2) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hypertension was analyzed among Hakka population in southern China. METHODS: A total of 3057 hypertensive patients and 2215 controls were enrolled. The ALDH2 rs671 and MTHFR rs1801133 genotyping were analyzed using gene chip. Relevant information and medical records of these subjects were collected. RESULTS: Hypertensive patients with ALDH2 rs671 G/A heterozygous had lower systolic blood pressure (SBP) than other genotypes (P < 0.001), while hypertensive patients with A allele had lower diastolic blood pressure (DBP) than patients with G allele (P < 0.001). The level of plasma homocysteine (Hcy) in patients with MTHFR CC, CT and TT genotypes showed an increasing trend (P < 0.001). The ALDH2 G/A genotype in the co-dominant model (adjusted OR 1.251, 95% CI 1.024-1.528, P = 0.028) and ALDH2 A/A genotype in the recessive model (adjusted OR 1.221, 95% CI 1.008-1.478, P = 0.041) were significant risk factors for the presence of hypertension. The MTHFR C/T genotype in the co-dominant model (adjusted OR 1.307, 95% CI 1.039-1.643, P = 0.022) and MTHFR C/T and T/T genotypes in the dominant model (adjusted OR 1.281, 95% CI 1.146-1.430, P < 0.001) were significant risk factors for the presence of hypertension. Further, logistic regression analysis showed that age, smoking, alcohol consumption, hyperhomocysteinemia, and high level of serum TG, Apo-A1, Apo-B were significant risks for hypertension. CONCLUSIONS: In summary, ALDH2 rs671 G/A, A/A genotypes and MTHFR rs1801133 C/T, T/T genotypes may be risk factors for hypertension in this Chinese Hakka population.

GSTP1 c.313A > G mutation is an independent risk factor for neutropenia hematotoxicity induced by anthracycline-/paclitaxel-based chemotherapy in breast cancer patients.

BACKGROUND: The link between glutathione S-transferase P1 (GSTP1) c.313A > G polymorphism and chemotherapy-related adverse events remains controversial. The goal of this study was to assess how this variant affected the toxicity of anthracycline-/paclitaxel-based chemotherapy in patients with breast cancer. METHODS: This study retrospectively investigated pharmacogenetic associations of GSTP1 c.313A > G with chemotherapy-related adverse events in 142 breast cancer patients who received anthracycline and/or paclitaxel chemotherapy. RESULTS: There were 61 (43.0%), 81 (57.0%), 43 (30.3%), and 99 (69.7%) patients in the T0-T2, T3-T4, N0-N1, and N2-N3 stages, respectively. There were 108 (76.1%) patients in clinical stages I-III and 34 (23.9%) patients in clinical stage IV. The numbers of patients with luminal A, luminal B, HER2 + , and triple-negative breast cancer (TNBC) were 10 (7.0%), 77 (54.2%), 33 (23.2%), and 22 (15.5%), respectively. The numbers of patients who carried GSTP1 c.313A > G A/A, A/G, and G/G genotypes were 94 (66.2%), 45 (31.7%), and 3 (2.1%), respectively. There were no statistically significant differences in the proportion of certain toxicities in patients with A/G, G/G, and A/G + G/G genotypes, except for neutropenia, in which the proportion of patients with A/G + G/G (χ2 = 6.586, P = 0.035) genotypes was significantly higher than that with the AA genotype. The logistic regression analysis indicated that GSTP1 c.313A > G mutation (A/G + G/G vs. A/A genotype) (adjusted OR 4.273, 95% CI 1.141-16.000, P = 0.031) was an independent variable associated with neutropenia. CONCLUSIONS: The findings of this study indicate that the GSTP1 c.313A > G mutation is an independent risk factor for neutropenia hematotoxicity in breast cancer patients induced by anthracycline-/paclitaxel-based chemotherapy.

Copy number variation characterization and possible candidate genes in miscarriage and stillbirth by next-generation sequencing analysis.

BACKGROUND: The present study aimed to explore the etiological relationship between miscarriage and stillbirth and copy number variations (CNVs), as well as provide useful genetic guidance for high-risk pregnancy. METHODS: In total, 659 fetal samples were recruited and subjected to DNA extraction and CNV sequencing (CNV-seq), relevant medical records were collected. RESULTS: There were 322 cases (48.86%) with chromosomal abnormalities, including 230 with numerical abnormalities and 92 with structural abnormalities. Chromosomal monosomy variations mainly occurred on sex chromosomes and trisomy variations mainly occurred on chromosomes 16, 22, 21, 18, 13 and 15. In total, 41 pathogenic CNVs (23 microdeletions and 18 microduplications) were detected in 27 fetal tissues. The rates of numerical chromosomal abnormalities were 29.30% (109/372), 32.39% (57/176) and 57.66% (64/111) in < 30-year-old, 30-34-year-old and ≥ 35-year-old age pregnant women, respectively, and increased with an increasing age (p < 0.001). There was statistically significant difference (χ2 = 7.595, p = 0.022) in the rates of structural chromosomal abnormalities in these groups (13.71%, 18.75% and 7.21%, respectively). The rates of numerical chromosomal abnormalities were 45.44% (219/482), 7.80% (11/141) and 0% (0/36) in the ≤ 13 gestational weeks, 14-27 weeks and ≥ 28 weeks groups, respectively, and decreased with respect to the increasing gestational age of the fetuses (p < 0.001). CONCLUSIONS: The present study has obtained useful and accurate genetic etiology information that will provide useful genetic guidance for high-risk pregnancies.

High Levels of Serum Triglyceride, Low-density Lipoprotein Cholesterol, Total Bile Acid, and Total Bilirubin are Risk Factors for Gallstones.

BACKGROUND: This study aimed to identify the risk factors for gallstone disease in the Hakka population in the Meizhou area of China. METHODS: In total, 816 patients with gallstone disease and 818 control participants were included in the study, and their serum lipid levels were measured. Data on age, gender, and risk factors for gallstone disease (such as smoking and drinking history and the prevalence of hypertension) were recorded. RESULTS: Of the 1,634 enrolled individuals, age 13 - 101 years, 727 were men and 907 were women. Serum triglyceride (TG) (p < 0.001), low-density lipoprotein-cholesterol (LDL-C) (p = 0.043), total bile acid (TBA) (p < 0.001), and total bilirubin (T-BIL) (p < 0.001) levels showed significant differences between the patients and controls. However, age, the proportion history of drinking and smoking; the prevalence of hypertension and diabetes mellitus; and serum levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), and Apo-A1/Apo-B were similar between the two groups. The frequencies of gallstones in the common bile duct (χ2 = 13.909, p < 0.001) and intrahepatic bile ducts (χ2 = 8.289, p = 0.004) showed significant differences between male and female patients, but the distribution of gallstones of different sizes was similar between the two groups. Serum TBA (p < 0.001) and T-BIL (p < 0.001) levels were higher in patients with gallstones in the common bile duct than in those with gallstones in the gall bladder and intrahepatic bile ducts. Logistic regression analysis indicated that participants with high serum TG, LDL-C, TBA, and T-BIL levels had a significantly higher risk of gallstone disease. CONCLUSIONS: High serum levels of TG, LDL-C, TBA, and T-BIL are found to be the main risk factors for gallstone formation in our study.

Clinical Value of Serum CEA, CA24-2 and CA19-9 in Patients with Colorectal Cancer.

BACKGROUND: To investigate the clinical value of serum concentration of carcinoembryonic antigen (CEA), carbohydrate antigen 24-2 (CA24-2), and carbohydrate antigen 19-9 (CA19-9) in the detection of colorectal cancer (CRC). METHODS: The serum levels of tumor markers and KRAS/NRAS/PIK3CA/BRAF gene mutations were detected in patients with colorectal cancer. Clinical medical records in colorectal cancer patients were collected. RESULTS: A total of 2,281 patients were recruited in the study, included 1,578 colorectal cancer patients and 703 controls. CEA, CA24-2, and CA19-9 concentrations were significantly higher in the colorectal cancer group than in the control group. The sensitivity of these tumor markers sorted in descending order was CEA>CA19-9>CA24-2. The best specificity was CA24-2, followed by CA19-9 and CEA, with all were more than 92%. The combination of CEA, CA19-9, and CA24-2 ranked the best sensitivity and specificity for colorectal cancer diagnosis. The prediction equation excluding the risk of colorectal cancer was. Probability (normal) = Exp (-5.47 - 0.28*CEA - 0.11*CA242 + 0.001*CA199)/(1+ Exp (-5.47 - 0.28*CEA - 0.11*CA242 + 0.001*CA199)). Besides, there were no significant differences in age, gender, histology type, differentiation, depth of invasion, and TNM stage in KRAS/ NRAS, BRAF, and PIK3CA mutations compared with wild type. CONCLUSIONS: Serum CEA, CA24-2, and CA19-9 are valuable indicators for predicting the risk of colorectal cancer.

Molecular analysis of alpha- and beta-thalassemia in Meizhou region and comparison of gene mutation spectrum with different regions of southern China.

BACKGROUND: Thalassemia is a group of inherited autosomal recessive hemolytic anemia disease caused by reduced or absent synthesis of globin chain/chains of hemoglobin. Only few studies showed the molecular characterization of α- and ß-thalassemia in Meizhou city of China. METHODS: A total of 22,401 individuals were collected; hematological and hemoglobin electrophoresis analysis and thalassemia genetic testing were performed. RESULTS: Eleven thousand and thirty (49.24%) cases with microcytosis (mean corpuscular volume (MCV) < 82 fl), 11,074 (49.44%) cases with hypochromia (mean corpuscular Hb (MCH) < 27 pg) in 22,401 subjects, 11,085 cases with abnormal hemoglobin results were identified in subjects aged ≥6 months. 7,322 (32.69%) subjects harbored thalassemia mutations, including 4,841 (21.61%) subjects with α-thalassemia, 2,237 (9.99%) with ß-thalassemia, and 244 (1.09%) with α-thalassemia combined ß-thalassemia. 18 genotypes of α-thalassemia mutations and 27 genotypes of ß-thalassemia mutations were characterized. The most frequent α gene mutation was --SEA (64.69%), followed by -α3.7 (19.93%), -α4.2 (7.73%), αCS α (3.97%), and αWS α (2.83%). The six most common ß-thalassemia mutations were IVS-II-654 (C>T) (39.79%), CD41-42 (-TCTT) (33.02%), -28 (A>G) (10.38%), CD17 (A>T) (9.08%), CD27-28 (+C) (2.14%), and CD26 (G>A) (2.02%). In addition, MCV and MCH were sensitive markers for α- and ß-thalassemia except for -α3.7 /αα, -α4.2 /αα, αCS α/αα, αWS α/αα, and ßCap+40-43 /ßN . CONCLUSIONS: The --SEA , -α3.7 , and -α4.2 deletions were the main mutations of α-thalassemia, while IVS-II-654 (C>T), CD41-42 (-TCTT), -28 (A>G), and CD17 (A>T) mutations of ß-thalassemia in Meizhou. There were some differences in thalassemia mutation frequencies in Meizhou city from other populations in China.

Clinical and biochemical indexes of 11 COVID-19 patients and the genome sequence analysis of the tested SARS-CoV-2.

BACKGROUND: At present, SARS-CoV-2 epidemic in the world rapidly spread. It is a serious global public health emergency. METHODS: In this study, we described the clinical characteristics of 11 COVID-19 patients hospitalized in the Meizhou People's Hospital, and viral genome sequences of SARS-CoV-2 from these patients were analyzed. RESULTS: Of the 11 patients, six cases developed fever, 9 cases developed a cough, and two cases developed headache and chills. Four patients (36.4%) had underlying diseases. Pneumonia is the most common complication. The laboratory test results showed that there were no adult patients with increased lymphocyte/lymphocyte percentage (LYM/LYM%). Most patients had normal total protein (TP) and albumin (ALB), but only two patients had decreased. Most patients had increased or normal levels of erythrocyte sedimentation rate (ESR), C reactive protein (CRP), activated partial thromboplastin time (APTT), fibrinogen (FIB), creatine kinase isoenzymes (CK-MB), and lactate dehydrogenase (LDH). Neutrophil (NEU) (r = 0.664, p = 0.026), CK-MB (r = 0.655, p = 0.029) and blood urea nitrogen (BUN) (r = 0.682, p = 0.021) were significantly associated with SARS-CoV-2 virus cycle threshold (Ct) value. Multiple sequence alignment (MSA) shows that two different SNPs were identified at positions 8781 and 28144, and have a complete linkage genetic form of 8781C-28144T and 8781T-28144C. CONCLUSIONS: The reports of the 11 COVID-19 patients in our hospital will provide useful information for the diagnosis, treatment, and drug development of SARS-CoV-2.

Association between aldehyde dehydrogenase 2 gene rs671 G>A polymorphism and alcoholic liver cirrhosis in southern Chinese Hakka population.

BACKGROUND: Alcoholic liver cirrhosis (ALC) endangering people's health. The association between aldehyde dehydrogenase 2 (ALDH2) gene polymorphisms and ALC is not clear. To analyze the relationship between ALDH2 and ALC among Hakka population in southern China. METHODS: A total of 292 ALC patients and 278 controls were included in the study. The ALDH2 gene rs671 polymorphism was analyzed by polymerase chain reaction (PCR)-gene chip. Relevant information and medical records of these participants were collected. RESULTS: The ALC patients had higher percentage of smoking, lower prevalence of hypertension, higher level of alanine aminotransferase (ALT), aspertate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bile acid (TBA), total bilirubin (Tbil), and direct bilirubin (Dbil), lower level of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) than controls. The proportions of the G/A genotype (p = 0.017), G/A plus A/A genotype (p = 0.023) and A allele (p = 0.031) were significantly higher in ALC patients than that of controls. ALC patients with G/A genotype had higher TC, HDL-C, and Apo-A1 than those with G/G genotype, while with A allele had higher HDL-C, and Apo-A1 than those with G allele. Logistic regression analysis indicated that ALDH2 SNP rs671 G/A plus A/A genotypes (A allele carriers) (OR 2.030, 95% CI 1.109-3.715, p = 0.022) in the dominant model was the risk factor for ALC. CONCLUSIONS: ALDH2 A allele (G/A + A/A genotypes) increased the risk of developing ALC among Hakka people in southern China. The results should enrich the relevant data and provide valuable information for the future related research.

Simultaneous detection of Marburg virus and Ebola virus with TaqMan-based multiplex real-time PCR method.

BACKGROUND: Marburg virus (MARV) and Ebola virus (EBOV) are acute infections with high case fatality rates. It is of great significance for epidemic monitoring and prevention and control of infectious diseases by the development of a rapid, specific, and sensitive quantitative PCR method to detect two pathogens simultaneously. METHODS: Primers and TaqMan probes were designed according to highly conserved sequences of these viruses. Sensitivity, specificity, linear range, limit of detection, and the effects of hemolysis and lipid on real-time qPCR were evaluated. RESULTS: The linearity of the curve allowed quantification of nucleic acid concentrations in range from 103 to 109  copies/ml per reaction (MARV and EBOV). The limit of detection of EBOV was 40 copies/ml, and MARV was 100 copies/ml. It has no cross-reaction with other pathogens such as hepatitis b virus (HBV), hepatitis c virus (HCV), human papillomavirus (HPV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), cytomegalovirus (CMV), and human immunodeficiency virus (HIV). Repeatability analysis of the two viruses showed that their coefficient of variation (CV) was less than 5.0%. The above results indicated that fluorescence quantitative PCR could detect EBOV and MARV sensitively and specifically. CONCLUSIONS: The TaqMan probe-based multiplex fluorescence quantitative PCR assays could detect EBOV and MARV sensitively specifically and simultaneously.

APOE gene ɛ4 allele (388C-526C) effects on serum lipids and risk of coronary artery disease in southern Chinese Hakka population.

OBJECTIVE: To analyze the relationship of Apolipoprotein E (APOE) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene polymorphisms with coronary artery disease (CAD). METHODS: 1,129 CAD patients and 1,014 non-CAD controls were included in the study, and relevant information and medical records were collected. The single-nucleotide polymorphisms (SNPs) were analyzed, including rs429358, rs7412 in APOE gene and rs2306283, rs4149056 in SLCO1B1 gene. RESULTS: The CAD patients' average age was 66.3 ± 10.7 years, while 65.5 ± 12.0 years in controls. The frequencies of APOE allele ɛ3, ɛ4, and ɛ2 were 83.01%, 10.08%, and 6.91% respectively. There were statistically significant differences in genotype ɛ3/ɛ4 (χ2  = 8.077, p = 0.005) in CAD patients compared with the controls. The SLCO1B1 genotype *1b/*1b and haplotype *1b showed the highest frequency in the study sample. Moreover, ε4 carriers had significantly lower HDL-C, Apo-A1 levels than ε3 carriers among CAD patients, while ε2 carriers showed lower LDL-C, Apo-B level, and higher Apo-A1/Apo-B level than ε3 and ε4 carriers. In controls, ε2 carriers showed lower LDL-C and Apo-B level, higher Apo-A1, and Apo-A1/Apo-B level than ε4 carriers. Logistic regression analysis showed that high LDL-C and Apo-B level, low HDL-C level, smoking, and the ε4 allele were risks for the presence of CAD. CONCLUSIONS: APOE ε4 allele may be associated with susceptibility to CAD in southern Chinese Hakka population. It indicated that the APOE SNPs rs429358 and rs7412 are associated with CAD, but not SNPs rs2306283 and rs4149056 of SLCO1B1 gene.

Dihydropyrimidine dehydrogenase (DPYD) gene c.1627A>G A/G and G/G genotypes are risk factors for lymph node metastasis and distant metastasis of colorectal cancer.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) acts as the key enzyme catabolizing pyrimidines, and may affect the tumor progression. DPYD gene mutations affect DPD activity. The relationship between DPYD IVS14+1G>A, c.1627A>G, c.85T>C and lymph node metastasis (LNM) and distant metastasis (DM) of colorectal cancer (CRC) was investigated. METHODS: A total of 537 CRC patients were enrolled in this study. DPYD polymorphisms were analyzed by polymerase chain reaction (PCR)-Sanger sequencing. The relationship between DPYD genotypes and clinical features of patients, metastasis of CRC was analyzed. RESULTS: About DPYD c.1627A>G, A/A (57.7%) was the most common genotype, followed by A/G (35.6%), G/G (6.7%) genotypes. In c.85T>C, T/T, T/C, and C/C genotypes are accounted for 83.6%, 16.0%, and 0.4%, respectively. Logistic regression analysis revealed that DPYD c.1627A>G A/G and G/G genotypes in the dominant model (A/G + G/G vs. A/A) were significant risk factors for the LNM (p = 0.029, OR 1.506, 95% CI = 1.048-2.165) and DM (p = 0.039, OR 1.588, 95% CI = 1.041-2.423) of CRC. In addition, DPYD c.1627A>G polymorphism was more common in patients with abnormal serum carcinoembryonic antigen (CEA) (>5 ng/ml) (p = 0.003) or carbohydrate antigen 24-2 (CA24-2) (>20 U/ml) level (p = 0.015). CONCLUSIONS: The results suggested that DPYD c.1627A>G A/G, G/G genotypes are associated with increased risk of LNM and DM of CRC.

The Serum Tumor Markers in Combination for Clinical Diagnosis of Lung Cancer.

BACKGROUND: To explore the clinical value of combined detection of serum tumor markers in lung cancer, including carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), cytokeratin 19 fragment (CYFRA 21-1), neuron specific enolase (NSE), and squamous carcinoma antigen (SCCA). METHODS: The expression levels were compared among groups, and the combined effects of these tumor markers in the diagnosis of lung cancer were analyzed. In addition, EGFR gene mutations were detected in some patients with NSCLC. RESULTS: There were 776 patients (age 59.78 ± 10.39 years) with lung cancer and 794 controls (age 58.26 ± 15.73 years) included in our study. In this study, tumor markers were detected in lung cancer patients and controls. Individual sensitivity of the tumor markers sorted in descending order were CEA > CYFRA21-1 > CA15-3 > NSE, and the specificities were NSE > CYFRA21-1 > CEA > CA15-3. The combination of CEA + CA15-3 + CYFRA21-1 + NSE ranked the highest in the sensitivity index (75.00%) and specificity index (98.61%) in lung cancer. In adenocarcinoma, the area under the ROC curve (AUROC) of CEA (0.665) and CYFRA21-1 (0.631) were higher than those of CA15-3 (0.559) and NSE (0.507). In squamous carcinoma, the AUC of CYFRA21-1 (0.722) and SCC (0.628) were higher than those of CEA (0.579), CA15-3 (0.524), and NSE (0.552). In small cell carcinoma, the AUC of NSE (0.654) was higher than those of CEA (0.616), CYFRA21-1 (0.555), and CA15-3 (0.482). CONCLUSIONS: These serum tumor markers are valuable indicators in the clinical use. The combination of tumor markers can be used as a method to improve the effectiveness of clinical diagnosis for lung cancer.

The SNPs rs429358 and rs7412 of APOE gene are association with cerebral infarction but not SNPs rs2306283 and rs4149056 of SLCO1B1 gene in southern Chinese Hakka population.

BACKGROUND: Apolipoprotein E (ApoE) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) regulate lipid metabolism. However, the relationship between genetic polymorphisms of APOE and SLCO1B1 and cerebral infarction (CI) remains unclear. METHODS: A total of 938 CI patients and 1028 control participants were included in the study. The rs429358 and rs7412 single nucleotide polymorphisms (SNPs) in the APOE gene and rs2306283 and rs4149056 SNPs in the SLCO1B1 gene were analyzed by fluorescence polymerase chain reaction (PCR). RESULTS: The genotype ɛ3/ɛ3 was the most common APOE genotype, with ɛ3 being the allele with the highest frequency, followed by ɛ4 and ɛ2. Statistically significant differences of genotype ɛ2/ɛ2 (χ2 = 3.866, P = 0.049), ɛ2/ɛ3 (χ2 = 20.030, P < 0.001), ɛ3/ɛ4 (χ2 = 16.960, P < 0.001), and ɛ4/ɛ4 (χ2 = 4.786, P = 0.029) between CI patients and controls were detected. The SLCO1B1 genotype *1b/*1b and haplotype *1b showed the highest frequency in the study sample. There was no statistically significant difference in the frequencies of SLCO1B1 genotypes and haplotypes among CI patients comparing with controls. Moreover, ε4 carriers had significantly higher low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (Apo-B) and lower apolipoprotein A1 (Apo-A1)/Apo-B levels than ε2 and ε3 carriers, but ε2 carriers showed lower LDL-C and Apo-B and higher Apo-A1/Apo-B than ε3 and ε4 carriers. Further, logistic regression analysis revealed that high LDL-C, high ApoB, smoking, hypertension and the ε4 allele were risks for the presence of CI. CONCLUSIONS: This study indicated that the APOE SNPs rs429358 and rs7412 may be associated with susceptibility to cerebral infarction in southern Chinese Hakka population.

Analysis of genotype distribution of thalassemia and G6PD deficiency among Hakka population in Meizhou city of Guangdong Province.

OBJECTIVE: The aim of the study was to explore genotype distribution thalassemia and G6PD deficiency in Meizhou city, China. METHODS: A total of 16 158 individuals were involved in thalassemia genetic testing. A total of 605 subjects were screened for common Chinese G6PD mutations by gene chip analysis. Genotypes and allele frequencies were analyzed. RESULTS: A total of 5463 cases carried thalassemia mutations were identified, including 3585 cases, 1701 cases, and 177 cases with α-, ß-, and α + ß-thalassemia mutations, respectively. --SEA (65.12%), -α3.7 (19.05%), and -α4.2 (8.05%) deletion were the main mutations of α-thalassemia, while IVS-II-654(C â†’ T) (40.39%), CD41-42(-TCTT) (32.72%), -28(A â†’ G) (10.11%), and CD17(A â†’ T) (9.32%) mutations were the principal mutations of ß-thalassemia in Meizhou. There were significant differences in allele frequencies in some counties. Genetic testing for G6PD deficiency, six mutation sites, and one polymorphism were detected in our study. A total of 198 alleles with the mutation were detected among 805 alleles (24.6%). G6PD Canton (c.1376 G â†’ T) (45.96%), G6PD Kaiping (c.1388 G â†’ A) (39.39%), and G6PD Gaohe (c.95 A â†’ G) (9.09%) account for 94.44% mutations, followed by G6PD Chinese-5 (c.1024 C â†’ T) (4.04%), G6PD Viangchan (c.871G â†’ A) (1.01%), and G6PD Maewo (c.1360 C â†’ T) (0.51%). There were some differences of the distribution of G6PD mutations among eight counties in Meizhou. CONCLUSIONS: The --SEA , -α3.7 , and -α4.2 deletion were the main mutations of α-thalassemia, while IVS-II-654(C â†’ T), CD41-42(-TCTT), -28(A â†’ G), and CD17(A â†’ T) mutations were the principal mutations of ß-thalassemia in Meizhou. G6PD c.1376 G â†’ T, c.1388 G â†’ A, and c.95 A â†’ G were the main mutations of G6PD deficiency. There were some differences of the distribution of thalassemia and G6PD mutations among eight counties in Meizhou.

Circulating microRNA expression profiling and bioinformatics analysis of patients with coronary artery disease by RNA sequencing.

BACKGROUND: MicroRNAs play a vital role in coronary artery disease. Abnormal expression of microRNAs has been found to be associated with the occurrence of CAD. METHODS: We identified significantly differentially expressed microRNAs in plasma between 40 patients with CAD and 10 controls with NCA using RNA sequencing. The differentially expressed microRNAs were analyzed for Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. RESULTS: Fifty cDNA libraries were constructed and sequenced, and a total of 1871.82 M raw reads were obtained, and 2135 microRNAs were found. Compared to the expressed microRNAs of NCA controls, 159 microRNAs were differentially expressed in CAD patients, including 119 upregulated microRNAs and 40 downregulated microRNAs. The top 10 upregulated miRNAs were miR-144-3p, miR-34a-5p, miR-15b-3p, miR-22-3p, miR-29b-3p, miR-1270, miR-6891-5p, miR-106a-5p, miR-15b-5p, and hsa-miR-499b-3p. The top ten downregulated miRNAs were miR-4437, miR-6842-3p, miR-4664-3p, miR-671-3p, miR-219a-1-3p, miR-7848-3p, miR-664a-3p, miR-1284, miR-361-3p, and miR-6780a-5p. The target genes of differentially expressed microRNAs were related to many basic biological terms, such as biological process, cellular component, and molecular function. According to the KEGG pathway analysis, the most enriched pathways of the differentially expressed microRNAs were endocytosis, focal adhesion, axon guidance, and so on. Furthermore, six upregulated and two downregulated microRNAs were detected by qRT-PCR (Quantitative Real-time PCR) and ROC analysis for diagnosing CAD. CONCLUSION: The results suggest that the expression levels of some microRNAs may play a vital role in the physiological and pathological course of CAD. Our study may provide useful information for the diagnosis and treatment of CAD.

Expression profiling and bioinformatics analysis of circulating microRNAs in patients with acute myocardial infarction.

OBJECTIVE: Acute Myocardial Infarction (AMI) is the most severe type of coronary atherosclerotic heart diseases. MiRNA is a class of endogenous noncoding small molecule RNA, which plays an important regulatory role in the development of some diseases. METHODS: We examined the miRNA expression profiles in 16 patients with AMI compared with 6 non-AMI controls using RNA sequencing. RESULTS: Compared with the miRNA expression profiles of non-AMI controls, a total of 181 differentially expressed miRNAs were discriminated in AMI patients, of which 96 upregulated miRNAs and 85 downregulated miRNAs. The top ten upregulated miRNAs were as follows: miR-449a-5p, miR-126-5p, miR-93-5p, miR-199a-3p, miR-4454, miR-6880-3p, miR-3135a, miR-548ad-5p, miR-4508, and miR-556-5p; while the top ten downregulated were as follows: miR-6805-5p, miR-1228-5p, miR-939-5p, miR-615-3p, miR-6780a-5p, miR-6857-3p, miR-5088-55p, miR-7155-3p, miR-184, and miR-4525. And the qRT-PCR results of differentially expressed miRNAs showed the same result as high-throughput sequencing data. For these 181 differentially expressed miRNAs, 19 841 target genes were predicted by GO analysis. The enrichment analysis revealed 2061 involved in biological processes, 353 in molecular function and 303 in cellular components. To identify biological pathways in AMI as compared to non-AMI, the target genes of differentially expressed miRNAs were mapped to the classical signal transduction pathway in KEGG, indicating that 214 classes were enriched. ROC analysis showed that the circulating miRNAs had the important value for AMI diagnosis and supported the previous conclusions that circulating miRNAs were effective to diagnose the AMI as a novel biomarker. CONCLUSIONS: Our findings require further research to confirm. It may provide a meaningful reference for the diagnosis and treatment of AMI.

Frequency of BRCA1 and BRCA2 Mutations in Individuals with Breast and Ovarian Cancer in a Chinese Hakka Population Using Next-Generation Sequencing.

BACKGROUND: It is necessary to investigate the frequency of BRCA1 and BRCA2 mutations in Hakka populations due to the variations in breast cancer epidemiology and genetics. METHODS: 359 breast cancer patients and 66 ovarian cancer patients were included in this retrospective clinical study. Mutations of BRCA1 and BRCA2 were detected in blood samples by semiconductor sequencing. RESULTS: The sensitivity of tumor markers including CEA, CA15-3, CA12-5, and CA199 for screening breast cancer was 16.44, 15.11, 8.44, and 7.56%, the combination of these 4 tumor markers reached the highest sensitivity index (31.11%). For ovarian cancer, the tumor markers were CA12-5 (54.05%), HE-4 (54.05%), CA72-4 (51.35%), and CEA (2.70%) in order of decreasing sensitivity. Moreover, the combination of these 4 tumor markers has the best sensitivity (75.68%) for screening ovarian cancer. In breast cancer patients, we found 5 (1.39%) patients with mutations in BRCA1, 13 (3.62%) mutations in BRCA2, and the total carrier rate is 5.01% (18/359). For ovarian cancer patients, the corresponding results were 3 (4.54%) mutations, 2 (3.03%) mutations, and 7.58% (5/66), respectively. The proportion of BRCA mutations was 5.41% (23/425) in breast and ovarian cancer patients of a Hakka population. The pathogenic, likely pathogenic, and benign mutations, and mutations of uncertain significance in this study mainly occurred in exon 14 of the BRCA1 gene, and exon 10 and exon 11 of the BRCA2 gene. CONCLUSIONS: Understanding the spectrum and frequency of BRCA1 and BRCA2 mutations in a Hakka population will assist in the prevention and control of hereditary breast and ovarian cancers in this population.