Lower-cost genotyping technology has promoted the generation of large genetic datasets with the evolving next-generation sequencing technology. The emergence of genome-wide association studies (GWAS) has facilitated researchers’ understanding of common complex diseases. GWAS refers to finding the sequence variations present in the human genome and screening out disease-related single nucleotide polymorphisms (SNPs). These SNPs are considered as the basis for assessing the stability of complex diseases. However, a single variation is not sufficient to assess an individual’s risk of disease. Polygenic risk score (PRS) is an emerging genetic data analysis method for quantitatively estimating an individual’s genetic risk for complex diseases by comprehensively considering multiple genetic variation sites. A single-value estimate of an individual’s genetic risk for a certain phenotype can be calculated as the cumulative impact of multiple genetic variants by building a PRS model. The finally expected risk score is weighted by the strength and direction of association of each SNP with the phenotype based on the number of alleles carried by each SNP. With the continuous development of various PRS calculation methods and the constant accumulation of genomic data, PRS has received widespread attention in the field of genetics. So far, quite a few studies at home and abroad have shown that PRS is valuable in risk prediction of different types of human traits or complex diseases, and its effectiveness has been further verified in clinical applications. At present, many studies have established PRS models based on GWAS summary statistics to quantify the genetic risk of susceptibility loci and clinical characteristics on diseases such as lung cancer, breast cancer, coronary heart disease, diabetes and Alzheimer’s disease. The disease-susceptible populations can be recognized through comparing the relative risk and absolute risk of the disease in different risk groups according to the population risk stratification results. Additionally, individual-level genotype data and omics data can also be used as data sources for PRS analysis research, especially the latter can dynamically reflect the short-term or long-term effects of environmental factors on human gene expression, and has potential application value in building early warning models to assess health risks. Since the calculation of PRS involves a large amount of genomic data analysis, there are big differences in the methods for data selection, model building and validation. Different PRS construction methods and software have different performances in disease risk prediction, and even the performance of same algorithm varies across diseases. It is worth noting that the PRS model often needs to be re-evaluated and verified for different groups of people, because PRS is affected by race and region. This review combines currently published PRS-related research and algorithms to describe the basic principles of PRS, compares their construction and verification methods, and discusses their applications and prospects. As a powerful genetic risk assessment tool, PRS has great potential in analyzing the genetic code of complex diseases and achieving precise diagnosis and personalized treatment.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines. METHODS: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19. RESULTS: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004). CONCLUSIONS The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.
Adult ; COVID-19/pathology* ; China/epidemiology* ; Comorbidity ; Cough ; Cross-Sectional Studies ; Diarrhea ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight ; Bronchopulmonary Dysplasia ; China/epidemiology* ; Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Pregnancy

To analyze and evaluate predictive value of preoperative changes of serum levels of brain natri‐uretic peptide (BNP) and homocysteine (Hcy) levels for therapeutic effect and prognosis of coronary artery bypass grafting (CABG ) in patients undergoing CABG .Methods : Clinical data of 115 patients undergoing CABG in our hospital were collected .Preoperative serum levels of BNP and Hcy were compared among patients with different disease severity , therapeutic effect and prognosis .Influence of serum BNP and Hcy levels on therapeutic effect and prognosis of CABG were analyzed .Results : Compared with medium and mild disease group , there were significant rise in preoperative serum levels of BNP [ (151.86 ± 22.57) pg／L vs.(82.57 ± 10.26) pg／L vs.(283.51 ± 32.47) pg／L] and Hcy [ (18.37 ± 4.51) μmol／L vs.(12.74 ± 2. 04) μmol／L vs.(31.56 ± 5.17) μmol／L] in severe disease group , and those of medium disease group were significantly higher than those of mild disease group , P＝0.001 all ;compared with effective group and ineffective group , there were significant reductions in preoperative serum levels of BNP [ (227. 49 ± 24. 52) pg／L vs.(308.26 ± 34.12) pg／L vs.(90.13 ± 10. 75) pg／L] and Hcy [ (29. 12 ± 5. 83) μmol／L vs.(46.15 ± 7.49) μmol／L vs.(19.03 ± 3.77) μmol／L] in markedly effective group , and those of effec‐tive group were significantly lower than those of ineffective group , P＝ 0.001 all.Compared with stenotic graft group and smooth graft group , there were significant rise in preoperative serum levels of BNP [ (271. 47 ± 25.18) pg／L vs .(92.41 ± 11.06) pg／L vs.(312. 54 ± 35.06) pg／L] and Hcy [ (33.08 ± 6. 14) μmol／L vs.(20. 05 ± 3. 68) μmol／L vs.(50.21 ± 7.75 ) μmol／L ] in death group , and those of stenotic graft group were significantly higher than those of smooth graft group , P＝0.001 all .Spearman correlation analysis indicated that serum BNP and Hcy levels were significant positively correlated with severity of CHD and prognosis of CABG ( r＝0. 624～0.814 , P＜0.05 or ＜0. 01).Multifactor Logistic regression analysis indicated that serum BNP and Hcy levels were independent risk factors for prognosis after CABG in CHD patients (OR＝ 5.133 , 1. 803 , P＝ 0.001 both ).Conclusion : The higher preoperative levels of BNP and Hcy before CABG are , the worse therapeutic effects are , and the higher risk of adverse prognosis of vascular stenosis and death are .

BACKGROUNDPlasmacytoid dendritic cells (pDCs) and cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to explore the frequency and function of pDC and serum cytokine network profiles in patients with acute or chronic HBV infection.

METHODSThe healthy individuals (HI group), hepatitis B envelope antigen (HBeAg)-positive chronic HBV patients in immune tolerance (IT) phase (IT group), HBeAg-positive chronic HBV patients (CHB group), and acute HBV patients (AHB group) were enrolled in this study. The frequency of cluster of differentiation antigen 86 (CD86) + pDC and the counts of CD86 molecular expressed on surface of pDC were tested by flow cytometer. The quantitative determinations of cytokines, including Fms-like tyrosine kinase 3 ligand (Flt-3L), interferon (IFN)-α2, IFN-γ, interleukin (IL)-17A, IL-6, IL-10, transforming growth factor (TGF)-β1 and TGF-β2, were performed using Luminex multiplex technology.

RESULTSIn this study, there were 13 patients in HI group, 30 in IT group, 50 in CHB group, and 32 in AHB group. Compared with HI group, HBV infected group (including all patients in IT, CHB and AHB groups) had significantly higher counts of CD86 molecular expressed on the surface of pDC (4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P < 0.001). The counts of CD86 molecular expressed on the surface of pDC in CHB group (7739.2 ± 4125.4) was significantly higher than that of IT group (6393.4 ± 1653.6, P = 0.043). Compared with IT group, the profile of cytokines of Flt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased (P = 0.012) in CHB group. The contents of IL-10, TGF-β1, and TGF-β2 in AHB group were significantly increased compared with IT and CHB groups (all P < 0.05).

CONCLUSIONSThis study demonstrated that the function of pDC was unaffected in HBV infection. The enhanced function of pDC and IFN-α2 might involve triggering the immune response from IT to hepatitis active phase in HBV infection. Acute patients mainly presented as down-regulation of the immune response by enhanced IL-10 and TGF-β.

OBJECTIVETo evaluate the effect of Fuzheng Kang'ai Formula (, FZKA) plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations.

METHODSA randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage IIIB/IV non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib (250 mg/day orally) plus FZKA (250 mL, twice per day, orally); 35 cases] or G group (gefitinib 250 mg/day orally; 35 cases) according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival (PFS)] and secondary endpoints [median survival time (MST), objective response rate (ORR), disease control rate (DCR) and safety] were observed.

RESULTSNo patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months (95% CI 3.30-21.69) vs. 8.4 months (95% CI 6.30-10.50; log-rank P<0.01), MST of 21.5 months (95% CI 17.28-25.73) vs. 18.3 months (95% CI 17.97-18.63; log-rank P<0.01). ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively (P>0.05). The most common toxic effects in the GF group and G group were rash or acne (42.8% vs. 57.1%, P>0.05), diarrhea (11.5% vs. 31.4%, P<0.05), and stomatitis (2.9% vs. 8.7%, P>0.05).

CONCLUSIONPatients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.

OBJECTIVETo evaluate the renal protective effect of Tangshenkang Granule () in a rat model of diabetic nephropathy (DN).

METHODSForty male Sprague-Dawley rats were randomly divided into control, DN, Tangshenkang and benazepril groups. DN model was established in the rats of DN, Tangshenkang and benazepril groups. Tangshenkang Granule solution and benazepril hydrochloride solution were intragastrically administered daily to the rats in the Tangshenkang and benazepril groups for 8 weeks, respectively. Urinary albumin and creatinine were detected. The albumin/creatinine (ACR) was calculated in addition to 24 h urinary protein (24-h UPr), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and creatinine clearance rate (Ccr). Right kidneys were harvested for pathological observation using periodic acid-silver methenamine-Masson staining. The average glomerular diameter (DG), average glomerular (AG) and mesangial areas (AM) were measured. The thickness of glomerular basement membrane (TGBM) was detected using transmission electron microscope.

RESULTSCompared with rats in the control group, rats in the DN group showed significantly decreased body weight, increased hypertrophy index, 24-h urinary volume, 24-h UPr, ACR, Scr, BUN, Ccr, blood lipids as well as renal pathological indices including DG, AG, AM, AM/AG and TGBM (P <0.05). Compared with the DN group, the weights of rats in the Tangshenkang and benazepril groups were significantly increased, and the renal hypertrophy indices were significantly decreased (P <0.05). The 24-h urinary volumes, ACR, 24-h UPr, Scr, BUN, Ccr, LDL, DG, AG, AM and TGBM were obviously decreased (P <0.05). Compared with the benazepril group, the Tangshenkang group showed significantly decreased levels of ACR, 24-h UPr, AG and AM (P <0.05).

CONCLUSIONSTangshenkang Granule decreased the urinary protein, attenuated the high glomerular filtration rate and improved lipid metabolism in DN rats, and prevented further injury induced by diabetic nephropathy.

Albuminuria ; complications ; Animals ; Basement Membrane ; drug effects ; metabolism ; Blood Urea Nitrogen ; Body Weight ; drug effects ; Creatinine ; blood ; urine ; Diabetic Nephropathies ; blood ; drug therapy ; physiopathology ; urine ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypertrophy ; Kidney Function Tests ; Kidney Glomerulus ; drug effects ; pathology ; physiopathology ; Lipid Metabolism ; drug effects ; Lipids ; blood ; Male ; Rats, Sprague-Dawley

Objective To investigate the clinical data, risk factors for bleeding following endoscopic treatment of colorectal polyps (diameter ≥ 1.0 cm) and feature analysis for carcinogenesis of adenomatous polyps. Method It was analyzed retrospectively that the clinical data, endoscopic characteristics, risk factors for bleeding and features for carcinogenesis of adenomatous polyps in 741 patients with a total of 884 colorectal polyps (diameter ≥ 1.0 cm) of our hospital from January 1, 2014 to January 1, 2016, which were resected under endoscope. Result Univariate analysis of colorectal polyps resected under endoscope on intraoperative and delayed bleeding, we found that gender (P = 0.017), location (P = 0.011), size (P = 0.004), lobulated or not (P = 0.010), resection methods under endoscope (P = 0.029) were statistically significant deviation between the two groups; taking the polyp as observation unit,multivariate Logistic regression analysis of their clinical data and endoscopic characteristics, we found gender (P = 0.012, OR^ = 2.671, 95% CI = 1.246 ~ 5.728) was an independent risk factor, men are more prone to bleeding than women; it was a protective factor for the location of polyps is sigmoid colon compared to rectum (P = 0.011, OR^ = 0.348, 95% CI = 0.154 ~ 0.786), and it was a risk factor for the polyps whose diameters ≥ 3.0 cm compared to among 1.0 ~ 1.9 cm. Univariate analysis of the features for carcinogenesis of colorectal adenomatous polyps, we found that surface lobulated or not (P = 0.001), surface smooth or not (P = 0.017), Yamada classification (P = 0.008) were statistically significant deviation, and the logistic regression analysis identified surface lobulation (P = 0.001, OR^ = 6.556, 95% CI = 2.326 ~ 18.475) was an independent risk factor for carcinogenesis of adenomatous polyps. Conclusion Resection of colorectal polyps under endoscope is a safe treatment method. Taking the polyp as observation unit, gender is an independent risk factor of colorectal polyps resected under endoscope on intraoperative and delayed bleeding, men are more prone to bleeding than women; the larger the diameters of polyps are, the higher the bleeding rates could be. Surface lobulation of colorectal adenomatous polyps are more likely lead to carcinogenesis.