Search

Field investigations and back analyses were conducted on a rockfall hazard. The flexible barrier protection system constructed along the roadside was damaged by the rockfall impact and lost its mitigation ability. Vital physical characteristics such as rockfall trajectory and kinetic energy were presumed based on the data from the aerial survey and the slope digital model. A numerical model, including slope, rockfalls, and flexible barrier, was created and thus the impacting process was reproduced. It demonstrates that the impact kinetic energy of the rockfall is only around 40 % of its design protection energy. The improper connections of members are the leading causes of damage, which prevent the flexible barrier from producing significant deformation and reduce its capacity to absorb impact force. The damage can be avoided by changing the connections of the members to improve the ability of the nets and ropes to slide and deform. The calculation results indicate that the impact resistance of the optimized model is 3 times better than the actual project. The findings can be used as a guide when designing a flexible protection system that performs better. [ABSTRACT FROM AUTHOR]

Drawing on the notions of transmedia storytelling and engagement, this study investigates how practitioners engage with the process of producing and consuming boys' love (BL) audio dramas, the trans-directional communication and interaction between producers and consumers in the transmedia BL subcultural space, and the implications of their engagement for counterculture. We contribute to the growing field of BL studies by providing insights into how practitioners can stimulate these cultural productions as a part of gender–sexuality-related counterculture in the new media space of audio dramas. We argue that the engagement of BL audio drama producers and consumers ('prosumers') features the sense of countering the predominant heteronormativity in China by producing explicit homosexual romance, actively expanding the story elements transmedially, and bringing queer members into the BL audio drama community. In this way, built by both producers and consumers together, the BL audio drama community is no longer a female-only area, but becomes a more inclusive 'third' space constituted by people with diverse sexual identities and orientations. Given its knowledge, perspectives, and experiences, the BL audio drama community, as a countercultural group, has a certain potential to bridge the divide between the female-led BL subculture and the larger queer community. [ABSTRACT FROM AUTHOR]

This paper investigates the impact of the Shanghai–Hong Kong Stock Connect (SHSC) scheme on voluntary corporate social responsibility (CSR) disclosure in China. Using a difference‐in‐differences (DiD) design, we find that companies that participate in the SHSC scheme are more inclined to voluntarily issue CSR reports. This effect is more pronounced for companies that have limited access to international markets and those with weak corporate governance. Additional analyses show that SHSC‐connected firms also produce higher quality CSR reports and achieve a better CSR performance. Our findings imply that capital market liberalisation promotes voluntary corporate disclosure for investors. [ABSTRACT FROM AUTHOR]

Audits of internal control over financial reporting (ICFR) are typically "integrated" with the audit of the financial statements (FSs)—both audits are conducted by the same audit firm, which designs procedures to satisfy the objectives of both audits simultaneously. A common assumption is that integrating the two audits is more effective and efficient than performing them separately. However, this assumption has not been tested empirically. Using a sample of Chinese companies that employ different audit firms for their FS and ICFR audits (i.e., nonintegrated auditors), we find evidence that challenges this assumption. Specifically, we find ICFR audit quality is higher for nonintegrated audits compared to integrated audits. Moreover, total audit fees are lower for nonintegrated audits, despite higher ICFR audit fees. [ABSTRACT FROM AUTHOR]

Purpose: The correlation of abnormal glucose metabolism and thyroid carcinoma, especially the aggressiveness of thyroid cancer, still remains controversial. We conducted this study to investigate the relationship between abnormal glucose metabolism parameters and differentiated thyroid carcinoma (DTC) in the Chinese population. Materials and Methods: The study was designed as a hospital-based case–control study and was approved by the Ethics Committee of our hospital and registered in the Clinical Trial Protocol Registration and Results System (Registration code: NCT 03006289). From January 1, 2018 to June 30, 2021, a total of 377 DTC patients were enrolled in the study. Demographic and general characteristics, details of thyroid surgery and histopathological results, hematological test indicators were collected. Glucose metabolism parameters were calculated. Variables were analyzed by t-test, ANOVA, chi-squared analysis and Fisher's exact test. Pearson bi-variate correlation and Spearman's correlation analysis were used for bi-variate analysis. Results: More than 40% of patients with DTC were multifocality, more than half were extra-glandular invasion, and nearly 85% complied by lymph node metastasis. The prevalence of diabetes mellitus (DM) was about 10.08% in DTC patients. It was found that the proportion of postprandial 2 h blood glucose ≥11.1mmol/L and HbA1c ≥6.5% was significantly higher than the known proportion of DM (17.8%, 16.7% vs. 10.08%). Additionally, 87.3% of the DTC patients in this study had varying degrees of insulin resistance. Further analysis found that higher T staging was associated with higher levels of area under curve of C-peptide (P = 0.029), insulin sensitivity index (P = 0.012) and C-peptide sensitivity index (P = 0.016). A delayed peak of insulin secretion was found to be positive related with capsule invasion (r = 0.206, P = 0.004). In patients without a DM history, homeostasis model assessment of insulin resistance (P = 0.017), insulin sensitivity index (P = 0.019) and C-peptide sensitivity index (P = 0.020) were statistic associated with T staging. Also, the glucose metabolism parameter at 3-hour after a meal was related to a larger number of metastatic lymph nodes. Conclusion: Abnormal glucose metabolism, namely, DM, hyperinsulinemia and insulin resistance, were significantly associated with the carcinogensis and aggressiveness of DTC. [ABSTRACT FROM AUTHOR]

This paper investigates the impact of corporate social responsibility (CSR) on corporate financial fraud in China. We find that CSR scores are negatively associated with fraudulent financial activities, suggesting that CSR firms are less likely to engage in financial fraud. The results also indicate that the negative relation is more significant for CSR performance than CSR disclosure. Additionally, we demonstrate that the negative effect of CSR is more pronounced for firms with voluntary CSR practices, continuous CSR engagements, financial pressure and internal control weaknesses. Overall, we find that CSR is an ethical behaviour that reduces financial misconduct. [ABSTRACT FROM AUTHOR]

This paper investigates the association between board characteristics and the company’s corporate social responsibility (CSR) assurance decision in China. By examining 2054 firm-years of Chinese listed companies with CSR reports from 2008 to 2012, we find that firms with a large board size, more female directors, and separation of CEO and chairman positions are more likely to engage in CSR assurance. Gender diversity also influences the CSR assurance provider choice. However, board independence and overseas background of the CEO do not affect the CSR assurance decision. Inconsistent with our prediction, firms with foreign directors are less likely to engage in voluntary CSR assurance. In summary, this research provides in-depth insights into the determinants of Chinese firms’ voluntary CSR assurance. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a worldwide epidemic disease caused by the genus Leishmania, which is still endemic in the west and northwest areas of China. Some viewpoints of the traditional taxonomy of Chinese Leishmania have been challenged by recent phylogenetic researches based on different molecular markers. However, the taxonomic positions and phylogenetic relationships of Chinese Leishmania isolates remain controversial, which need for more data and further analysis. In this study, the heat shock protein 70 (HSP70) gene and cytochrome b (cyt b) gene were used for phylogenetic analysis of Chinese Leishmania isolates from patients, dogs, gerbils, and sand flies in different geographic origins. Besides, for the interesting Leishmania sp. in China, the ultrastructure of three Chinese Leishmania sp. strains (MHOM/CN/90/SC10H2, SD, GL) were observed by transmission electron microscopy. Bayesian trees from HSP70 and cyt b congruently indicated that the 14 Chinese Leishmania isolates belong to three Leishmania species including L. donovani complex, L. gerbilli, and L. ( Sauroleishmania) sp. Their identity further confirmed that the undescribed Leishmania species causing visceral Leishmaniasis (VL) in China is closely related to L. tarentolae. The phylogenetic results from HSP70 also suggested the classification of subspecies within L. donovani complex: KXG-918, KXG-927, KXG-Liu, KXG-Xu, 9044, SC6, and KXG-65 belong to L. donovani; Cy, WenChuan, and 801 were proposed to be L. infantum. Through transmission electron microscopy, unexpectedly, the Golgi apparatus were not observed in SC10H2, SD, and GL, which was similar to previous reports of reptilian Leishmania. The statistical analysis of microtubule counts separated SC10H2, SD, and GL as one group from any other reference strain ( L. donovani MHOM/IN/80/DD8; L. tropica MHOM/SU/74/K27; L. gerbilli MRHO/CN/60/GERBILLI). The ultrastructural characteristics of Leishmania sp. partly lend support to the phylogenetic inference that Chinese Leishmania sp. is in close relationship with reptilian Leishmania. [ABSTRACT FROM AUTHOR]

Fundamental treatment for papillary thyroid carcinoma ( PTC) involves total or subtotal thyroidectomy. Iodine-131 (131 I) is routinely utilized to target remnant thyroid cancer and metastasis after thyroidectomy. The effectiveness of other therapeutic modalities remains unsatisfactory; thus, these patients have a poor prognosis. The manner in which the ability of 131 I uptake can be improved is vital for their prognosis. Bortezomib has been used as a re-differentiation agent for the treatment of patients with multiple myeloma; however, little is reported about the role of bortezomib in thyroid cancer. To evaluate the therapeutic potential of bortezomib in a human PTC cell line, expression of paired-box 8 ( Pax8) protein was determined using Western blot in PTC, normal thyroid, and anaplastic/undifferentiated thyroid carcinoma ( ATC) cells. The expression of Pax8 protein in PTC cells pretreated with bortezomib was determined using the same method. Iodine uptake was determined using 131 I radioactivity assay. The level of Pax8 protein in normal thyroid cells was significantly higher than in PTC ( P < 0.05) and ATC cells ( P < 0.05); its expression in PTC cells was also significantly higher than in ATC cells ( P < 0.05). The PTC cells in the bortezomib-treated group showed a higher expression of Pax8 protein than the control group ( P < 0.05). These findings indicate that bortezomib can increase the expression of Pax8, but does not significantly increase the iodine uptake of PTC cells. [ABSTRACT FROM AUTHOR]

Background Vandetanib is the first US Food and Drug Administration approved agent to treat advanced or metastasized thyroid cancer. To gain a better understanding of the drug, we conducted a systematic review of its efficacy and safety in patients with thyroid cancers. Methods Trial data was retrieved from Pubmed, EMBASE, Medline, China National Knowledge Infrastructure, and the Cochrane database without restrictions on language. A systematic review of the literature was performed to assess median progression-free survival ( PFS) and adverse events associated with vandetanib therapy for advanced or metastasized thyroid cancers. Results Vandetanib statistically prolonged PFS in comparison with the placebo (30.5 vs. 19.3 months, hazard ratio 0.46), It even prolonged PFS in surgically unresectable or metastatic differentiated thyroid cancer cases compared with the placebo (11.1 vs. 5.9 months, hazard ratio 0.63). Rash, diarrhea, neutropenia, and hypertension were the most frequent side effects. Conclusion Vandetanib can significantly improve PFS. Though it has some side effects, it is still a promising agent in the treatment of advanced or metastasized thyroid cancer, especially in those with metastasized or advanced medullary thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Backgrounds: As patients attending hospitals of different grades in China may receive different medical care, we investigated the clinical efficacy and safety of routine insulin therapy in patients with type 2 diabetes who were treated at grade 2 and grade 3 (highest grade) hospitals in China.Methods: 2683 patients with type 2 diabetes were enrolled in a multicenter, nonrandomized, open-label, noninterventional, 12-week clinical trial performed at 62 Chinese hospitals. Patients were divided into two groups according to the hospitals' grading. Data were analyzed for efficacy (changes and normalization of glycated hemoglobin [HbA1c] and changes in fasting plasma glucose and 2-h postprandial blood glucose [PBG] levels from baseline to the final visit) and for safety (hypoglycemia).Results: After 12 weeks of routine human insulin (SciLin) therapy, decreases in mean HbA1c and PBG levels were significantly greater in patients treated at second-grade hospitals (all P < 0.001 vs. third-grade hospitals), and the HbA1c success rate (<7%) was significantly higher (46.94% vs. 38.85%; P = 0.0002). However, patients treated at second-grade hospitals had more weight gain (0.29 kg vs. 0.04 kg; P < 0.0001) and a higher incidence of total hypoglycemic events (21.82% vs. 16.79%; P = 0.0002).Conclusions: Routine insulin treatment of patients with type 2 diabetes in China demonstrates acceptable safety and effectiveness, improving blood glucose control with a low incidence of severe hypoglycemia. Patients treated at second-grade hospitals had a greater HbA1c success rate than those treated at third-grade hospitals, but with more weight gain and more hypoglycemic events. [ABSTRACT FROM AUTHOR]

Abstract: This work describes a simple method to yield large amounts of the isolate MHOM/CN/90/SC10H2 amastigotes-like forms in axenic cultures using promastigotes as the starting population. The isolate MHOM/CN/90/SC10H2, used in this study, belongs to an undescribed species of Leishmania endemic to hill foci in China. The method describes induced extracellular amastigote transformation of this isolate. The rounded parasite obtained in axenic culture was morphologically similar, even at the ultrastructural level, to intracellular amastigotes. Moreover, the axenic amastigotes remained viable as verified by the stage-specific genes (gp46 and p4 genes) with RT-PCR. A 70–80kDa protein was recognized by polyclonal antibody HRP-IgG only in axenic-derived amastigotes and not in promastigotes. [Copyright &y& Elsevier]

Hereditary spherocytosis (HS) is a common, hereditary hemolytic anemia (HHA) that is attributed to the disturbance of five erythrocyte membrane proteins. HS is also common in Guangxi, China. Target region capture high-throughput sequencing technology was used to analyze genetic mutations found in HS patients. Pedigree analysis was also performed, in some cases, to provide an optimized approach for the etiological diagnosis of complex, hereditary hemolytic anemia. Blood samples from the probands and their families were assessed by laboratory tests, target region capture high-throughput sequencing technology, and Sanger sequencing. We detected 79 HS patients from 37 unrelated families. The mutations observed in these patients were found mainly in four HS-related genes. These included SLC4A1, which was mutated in 31.65% of patients (25/79), SPTA1 (30.78% (24/79)), EPB42 (6.33% (5/79)), and SPTB (5.06% (4/79)). Composite genotype was observed in 26.58% (21/79) of patients and included mutations in two or more HS-related genes or mutations in HS-related genes combined with thalassemia or G6PD deficiency. No significant differences in clinical symptoms were found among patients of various genotypes except total bilirubin. Mean reticulocyte volume (MRV) and mean sphered cell volume (MSCV) of the composite genotype were significantly different from other groups. A total of 28 mutation types were found in HS-related genes. Using high-throughput sequencing technology, we also found some cases that had been misdiagnosed. MRV and MSCV are more significant in compound mutations as sensitive determinants of HS. High-throughput sequencing technology can be used to provide a more effective etiological diagnostic method for HS, with high efficiency and specificity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Neck pain is common and can have a significant impact on patients' physical functionality, mobility, and quality of life (QOL). In clinical practice, traditional Chinese mind and body exercise (TCMBE) is a combination of different types of exercise based on traditional Chinese medicine, including qigong, tai chi, the 12-words-for-life-nurturing exercise, and so on, and many studies have found that it is safe and effective at helping patients with neck pain., Objective: The aim of this study was to investigate the effectiveness of TCMBE on pain intensity, functional mobility, and QOL in individuals with neck pain., Methods: The PubMed, MEDLINE, PEDro, and Embase databases were systematically searched for relevant studies. Randomized controlled trials reporting the effects of TCMBE on pain intensity, functional mobility, and QOL in individuals with neck pain were included. Screening, data extraction, and literature quality assessments were performed independently by two reviewers. RevMan5.4 software was used for data analysis., Results: Six studies with 716 participants met the inclusion criteria. Compared with the control groups, TCMBE had no therapeutic advantage in improving pain intensity (visual analogue scale: mean difference (MD) = 1.8, 95% confidence interval (CI): -7.70 to 11.46, and P  = 0.70); functional mobility (neck disability index: MD = 0.15, 95% CI: -6.37 to 6.66, and P  = 0.96; neck pain and disability scale: MD = 1.31, 95% CI: -4.10 to 6.71, and P  = 0.64); or 36-item short-form health survey (SF-36) scores for physical function (MD = 5.58, 95% CI: -8.03 to 19.18, and P  = 0.42), general health (MD = 1.87, 95% CI: -4.99 to 8.72, and P  = 0.59), body pain (MD = 2.26, 95% CI: -3.80 to 8.32, and P  = 0.46), vitality (MD = 6.24, 95% CI: -1.49 to 13.98, and P  = 0.11), social function (MD = 8.06, 95% CI: -4.85 to 20.98, and P  = 0.22), role physical (MD = -1.46, 95% CI: -8.54 to 5.62, and P  = 0.69), or role emotional (MD = 6.5, 95% CI: -3.45 to 16.45, and P  = 0.2). However, TCMBE was less effective at improving mental health results based on the SF-36 survey (MD = 3.37, 95% CI: 0.5 to 6.24, and P  = 0.02)., Conclusions: Based on the meta-analysis, there is insufficient evidence to support the clinical use of TCMBE in improving pain intensity and enhancing functional mobility and QOL in individuals with neck pain., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Yu-Hua Xie et al.)

Approximately 35% of patients fail to attain ideal initial blood glucose control under metformin monotherapy. The objective of this observational study is to simulate the optimal protocol of metformin according to the different renal function.The population pharmacokinetics of metformin was performed in 125 subjects with type 2 diabetes mellitus. Plasma concentrations of metformin were quantified by high-performance liquid chromatography. A population pharmacokinetic model of metformin was developed using NONMEN (version 7.2, Icon Development Solutions, USA). Monte Carlo simulation was used to simulate the concentration-time profiles for doses of metformin for 1000 times at different stages of renal function.The mean population pharmacokinetic parameters were apparent clearance 53.0 L/h, apparent volume of distribution 438 L, absorption rate constant 1.4 hour and lag-time 0.91 hour. Covariate analyses revealed that estimated glomerular filtration rate (eGFR) and bodyweight as individual factors influencing the apparent oral clearance: CL/F = 53.0 × ( bodyweight/75) × (eGFR/102.5)EXP(0.1797). The results of the simulation showed that patients should be prescribed metformin 2550 mg/d (t.i.d.) vs 3000 mg/d (b.i.d.) as the minimum doses for patients with augmented renal clearance.eGFR had a significant impact on metformin pharmacokinetics. Patients administered metformin twice a day require higher total daily doses than those with a regimen of 3 times a day at each stage of kidney function.

A new species of the xenodermatid snake genus Achalinus Peters, 1869 is described from Yunnan Province, Southwest China, based on a single male specimen. The new species is assigned to the genus Achalinus on the basis of absence of preocular and postocular, subcaudals arranged in single row, and results of phylogenetic analyses of mitochondrial DNA CO1 sequence data. Achalinus pingbianensis sp. nov. differs from its congeners by the combination of following morphological characters: absence of a loreal, internasals subequal to that between prefrontals and dorsal scales strongly keeled, 23 rows throughout. Currently, 13 species are in the genus Achalinus, further taxonomical and phylogenetic studies based on more extensive samples and more markers will help understand the cryptic diversity and clarify their interspecific relationships.

Objective To investigate the association between total homocysteine (tHcy) level in plasma and methylenetetrahydrofolate reductase ( MTHFR ) C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus (T2DM) accompanied by dyslipidemia. Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively. Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C. Plasma tHcy and lipid levels were measured as well. The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test. Plasma tHcy level of T2DM patients who carried the different genotypes was compared by Student's t test. Results Finally, 82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study. There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism in T2DM patients ( t =2.27, P =0.02). Moreover, the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677 TT genotype was significantly higher than that in those with CT+CC genotype (13.62±6.97 vs . 10.95±3.62 μmol/L, t =2.20, P =0.03); while for patients without dyslipidemia, comparison of the tHcy level between those who carried the above two alleles showed no significantly difference (13.34±6.03 vs . 12.04±5.09 μmol/L, t =1.08, P =0.29). Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.

Background/aims: Thiamine-responsive megaloblastic anemia syndrome is a rare autosomal recessive disorder resulting from mutations in SLC19A2, and is mainly characterized by megaloblastic anemia, diabetes, and progressive sensorineural hearing loss., Methods: We study a Chinese Zhuang ethnicity family with thiamine-responsive megaloblastic anemia. The proband of the study presented with anemia and diabetes, similar to his late brother, as well as visual impairment. All clinical manifestations were corrected with thiamine (30 mg/d) supplementation for 1-3 months, except for visual impairment, which was irreversible. The presence of mutations in all exons and the flanking sequences of the SLC19A2 gene were analyzed in this family based on the proband's and his brother's clinical data. Computer analysis and prediction of the protein conformation of mutant THTR-1. The relative concentration of thiamine pyrophosphate in the proband's whole blood before and after initiation of thiamine supplement was measured by high performance liquid chromatography (HPLC)., Results: Gene sequencing showed a homozygous mutation in exon 6 of the SLC19A2 gene (c.1409insT) in the proband. His parents and sister were diagnosed as heterozygous carriers of the c.1409insT mutation. Computer simulation showed that the mutations caused a change in protein conformation. HPLC results suggested that the relative concentration of thiamine pyrophosphate in the proband's whole blood after thiamine supplement was significantly different (P=0.016) from that at baseline., Conclusions: This novel homozygous mutation (c.1409insT) caused the onset of thiamine-responsive megaloblastic anemia in the proband., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Objective: The goal of the genetic investigation was to identify the associations of serum lipid levels and DPP-4 variants in Chinese type 2 diabetes patients., Methods: We detected four variants of the DPP4 gene in 190 Chinese individuals with type 2 diabetes and tested for an association with dyslipidemia in 82 selected samples. Data including basic information, HbA1c, FPG, serum lipid parameters were collected. Statistical analysis was performed by SPSS 13.0 through ANOVA and χ 2 test., Results: The genetic polymorphism of rs4664443, rs3788979, rs7608798 and rs1558957 in Chinese type 2 diabetes were consistent with Hardy-Weinberg equilibrium. The CT genotype of rs4664443 suffered from higher serum TG (P=0.013), LDL (P=0.044) and ApoB (P=0.006) levels, whereas the TT genotype of rs7608798 exhibited a lower serum TG level (P=0.037). For rs3788979, the serum TG level (P=0.034) and BMI (P=0.04) were significantly different among genotypes. Moreover, serum TG and TC levels and BMI showed a positive correlation with the number unfavorable alleles, and individuals with more than two unfavorable alleles had higher TG (P=0.004), TC (P=0.011), and BMI (P=0.044) values., Conclusions: This is the first study to investigate DPP4 allelic distributions and their association with dyslipidemia in Chinese type 2 diabetes patients, which may have clinical significance., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Congenital dysfibrinogenemia (CD) is a qualitative fibrinogen disorder caused by an abnormal fibrinogen molecule structure, leading to dysfunctional blood coagulation. This study describes 3 cases of dysfibrinogenemia identified in the unrelated Chinese pedigrees.Routine coagulation screening tests were performed on the probands and their families. The antigens and functionality of fibrinogen was measured using an immunoturbidimetry assay and the Clauss method, respectively. To identify the genetic mutation responsible for these dysfibrinogens, genomic DNA extracted from the blood was analyzed using PCR amplification and direct sequencing. The presence of the mutant chains was determined using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectroscopy. Purified plasma fibrinogen of 3 probands was analyzed using SDS-PAGE, fibrinogen clottability, fibrin polymerization, fibrinopeptide release, and scanning electron microscopy (SEM).The 3 probands had a long thrombin time. Levels of functional fibrinogen were found to be very low, while the fibrinogen antigen was within the normal range. DNA sequencing revealed a heterozygous Arg16His substitution in the fibrinogen Aα chain (FGA). The mutant chains were found to be expressed using MALDI-TOF mass spectroscopy. SDS-PAGE did not reveal any difference in the molecular weights of 3 polypeptide chains between normal and abnormal fibrinogens. Fibrinogen clottability showed a slower fibrin clot formation than the healthy control. Fibrin polymerization, after addition of thrombin, showed a prolonged lag phase and decreased final turbidity. The kinetics of fibrinopeptides release revealed a decreased amount of the released fibrinopeptide A. SEM of the patient's fibrin clot was found to be abnormal.Results indicate that the 3 probands with dysfibrinogenemia were caused by mutations of Aα chain Arg16His. Mutation of this fibrinogen induced dysfunction of plasma fibrinogen., Competing Interests: The authors have no conflicts of interest to disclose.

Objective: To explore the clinical phenotype of a family affected with congenital dysfibrinogenemia and potential mutations underlying the disease., Methods: Coagulation testing and hepatorenal function testing were conducted on 18 individuals from three generations. Plasma fibrinogen was extracted and analyzed with SDS-PAGE electrophoresis. All of the exons and flanking sequences of fibrinogen FGA, FGB, FGG genes were analyzed by PCR, and the products were subjected to Sanger sequencing., Results: Hepatorenal function, prothrombin time and activated partial thromboplastin time of the proband were all normal. However, his thrombin time was significantly prolonged. Fibrinogen activity was decreased, while the concentration of antigen was in the normal range. The results of his mother, brother, and nephew were similar. DNA sequencing has confirmed that the proband, his mother, brother, and nephew have all carried a g.5877G>A mutation in the exon 8 of the FGG gene, which resulted in replacement of arginine (Arg) by histidine (His) at position 275., Conclusion: The Arg275His mutation of the fibrinogen gamma chain probably underlies the pathogenesis of congenital dysfibrinogenemia in this family.

Background: Osmotic fragility testing based on flow cytometry was recently introduced for the screening of hereditary spherocytosis (HS). This study was undertaken to evaluate the clinical diagnostic value of a flow-cytometric osmotic fragility test for HS., Methods: Peripheral blood was collected from 237 subjects at the First Affiliated Hospital of Guangxi Medical University, including 56 HS patients, 86 thalassemia patients and 95 healthy controls. The samples were examined by flow-cytometric osmotic fragility test and the percentage of residual red blood cells was used to determine HS. Peripheral blood smears were performed to examine the red blood cell morphology., Results: With clinical diagnosis of HS as the gold standard and the percentage of residual red blood cells <23.6% as the diagnostic threshold in the flow-cytometric osmotic fragility test, the sensitivity of the flow-cytometric osmotic fragility test for HS was 85.71% and the specificity was 97.24%., Conclusion: The flow-cytometric osmotic fragility test combined with a red blood cell morphology test by peripheral blood smear could be a simple, practical and accurate laboratory screening method for HS., (© 2015 S. Karger AG, Basel.)

Background: Hereditary spherocytosis is usually diagnosed based on a combination of clinical and family histories, physical examination, and laboratory data. Milder or atypical cases can be difficult to diagnose., Methods: We report one case each of mild and moderate hereditary spherocytosis whose diagnoses were made by the First Affiliated Hospital, Guangxi Medical University in China., Results: In case 1, laboratory test results were as follows: hemoglobin 81.40 g/l, mean corpuscular hemoglobin concentration 339.00 g/l, mean corpuscular volume 82.88 fl, reticulocyte count 19%, mean sphered corpuscular volume 71.66 fl, total bilirubin 57.60 μmol/l, and blood smears showed increased spherocytosis. In case 2, laboratory test results were as follows: hemoglobin 133.10 g/l, mean corpuscular hemoglobin concentration 358.60 g/l, mean corpuscular volume 96.75 fl, reticulocyte count 17%, mean sphered corpuscular volume 77.78 fl, total bilirubin 62.50 μmol/l, and blood smears showed increased spherocytosis., Conclusions: Mild and moderate hereditary spherocytosis can be easily misdiagnosed. Assessment of total, direct, and indirect serum bilirubin, erythrocyte morphology and red cell characteristics (particularly mean corpuscular volume and mean sphered corpuscular volume) clearly distinguishes hereditary spherocytosis from autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, thalassemia, and autoimmune hepatitis., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Leishmania species belong to the family Trypanosomatidae and cause leishmaniasis, a geographically widespread disease that infects humans and other vertebrates. This disease remains endemic in China. Due to the large geographic area and complex ecological environment, the taxonomic position and phylogenetic relationship of Chinese Leishmania isolates remain uncertain. A recent internal transcribed spacer 1 and cytochrome oxidase II phylogeny of Chinese Leishmania isolates has challenged some aspects of their traditional taxonomy as well as cladistics hypotheses of their phylogeny. The current study was designed to provide further disease background and sequence analysis., Methods: We systematically analyzed 50 cytochrome b (cyt b) gene sequences of 19 isolates (16 from China, 3 from other countries) sequenced after polymerase chain reaction (PCR) using a special primer for cyt b as well as 31 sequences downloaded from GenBank. After alignment, the data were analyzed using the maximum parsimony, Bayesian and netwok methods., Results: Sequences of six haplotypes representing 10 Chinese isolates formed a monophyletic group and clustered with Leishmania tarentolae. The isolates GS1, GS7, XJ771 of this study from China clustered with other isolates of Leishmania donovani complex. The isolate JS1 was a sister to Leishmania tropica, which represented an L. tropica complex instead of clustering with L. donovani complex or with the other 10 Chinese isolates. The isolates KXG-2 and GS-GER20 formed a monophyletic group with Leishmania turanica from central Asia. In the different phylogenetic trees, all of the Chinese isolates occurred in at least four groups regardless of geographic distribution., Conclusions: The undescribed Leishmania species of China, which are clearly causative agents of canine leishmaniasis and human visceral leishmaniasis and are related to Sauroleishmania, may have evolved from a common ancestral parasite that came from the Americas and may have split off earlier than the other old world Leishmania. Our results also suggest the following: the isolates GS7, GS1 and XJ771 occur as part of the L. donovani complex; the JS1 isolate is L. tropica; and the isolate GS-GER20 identified as Leishmania gerbilli is close to KXG-2 which is L. turanica.

Background: Leishmaniasis is a vector-borne disease, which is still endemic in the west and northwest area of China. Canines are the major reservoirs of Leishmania, the etiological agent of human visceral leishmaniasis. Phlebotomus chinensis is the main transmission vector of zoonotic visceral leishmaniasis (ZVL)., Methods: In this study, rK39 dip-stick, ELISA and PCR methods were used to investigate the prevalence of canine leishmaniasis (CanL) in Beichuan County, Sichuan Province, China., Results: Among the 86 dogs which were included in the study, 13 dogs were positive using the dip-stick test (15.12%), while 8 dogs were positive using ELISA (9.30%) and 19 dogs were positive for PCR (22.03%). In total, 32 dogs were positive for one or more tests (37.21%). Interestingly, phylogenetic analysis based on the partial 7SL RNA fragment provided evidence that an undescribed Leishmania species, which is clearly a causative agent of CanL and human visceral leishmaniasis, does exist in China. This result is consistent with our previous study., Conclusions: Our work confirmed that canine leishmaniasis is still prevalent in Beichuan County. Further control is urgently needed, as canine leishmaniasis is of great public health importance. The phylogenetic analysis based on 7SL RNA segment provides evidence for the existence of an undescribed Leishmania sp. in China.

Leishmaniasis is a geographically widespread disease, caused by protozoan flagellates of the genus Leishmania. This disease still remains endemic in China, especially in the west and northwest frontier regions. To date, the phylogenetic relationships among Chinese Leishmania isolates are still unclear, and the possible taxonomic diversity remains to be established. In this study, the ITS1-5.8S fragments of ten isolates collected from different foci in China were determined. To infer the phylogenetic relationships among them, seven sequences of Chinese Leishmania isolates retrieved from GenBank were also included. Both parsimony and Bayesian analyses reveal an unexpected but strongly supported clade comprising eight newly determined isolates, which is sister to other members of subgenus Leishmania. In combination with genetic distance analysis, this provides evidence of the occurrence of an undescribed species of Leishmania. Our results also suggest that (1) the isolate IPHL/CN/77/XJ771 from Bachu County, Xinjiang Uygur Autonomous Region is not Leishmania infantum but Leishmania donovani; (2) the status referring to an isolate MRHO/CN/88/KXG-2 from a great gerbil in Karamay as Leishmania turanica, formerly based on multilocus enzyme electrophoresis, is recognized; (3) an earlier finding demonstrating the L. donovani identity of isolate MHOM/CN/80/801 from Kashi city is corroborated; (4) the three isolates from eastern Jiashi County, Xinjiang Uygur Autonomous Region, causing desert type of zoonotic visceral leishmaniasis (see Wang et al., Parasitol Int (in press), 2010), belong to L. donovani instead of L. infantum. In addition, the results of this study make an important contribution to understanding the heterogeneity and relationships of Chinese Leishmania isolates, further indicating that the isolates from China may have had a more complex evolutionary history than expected.

Objective: To examine the distribution of intron 4 polymorphism in endothelial nitric oxide synthase (eNOS) gene in mainland Chinese and Singapore Chinese and its association with diabetic nephropathy (DN)., Methods: Peripheral blood samples were collected from 237 diabetes patients with the diabetic duration longer than 10 years, 87 mainland Chinese who visited the Qilu Hospital, Shandong province, and diabetic duration and blood sugar control-matched 150 Singapore Chinese who visited the Singapore National University Hospital. DNA extraction, PCR, cloning, and sequencing were conducted., Results: The 27 bp repeat polymorphism in intron 4 was tri allelic (a, b, and c alleles) in the Singapore Chinese while biallelic (a and b alleles) in the mainland Chinese. A third allele-allele c, with six 27 bp repeats was found. Significant difference was identified in the a allele distribution between the mainland and the Singapore Chinese (P < 0.001), but the intron 4 polymorphism didn't show any association with DN., Conclusion: The intron 4 polymorphism is tri allelic, and the a allele distribution is not significantly associated with DN.

Cholesteryl ester transfer protein (CETP) is a key participant in the reverse transport of cholesterol from the peripheral tissues to the liver. To understand further the role that CETP gene plays in the pathogenesis of coronary heart disease (CHD), the promoter region, all 16 exons and adjacent intronic regions of CETP gene were screened for single nucleotide polymorphisms (SNPs) in 203 CHD patients and 209 healthy volunteers by the combination of PCR, denaturing high performance liquid chromatography (DHPLC), molecular cloning, and DNA sequencing. A novel missense mutation in the CETP gene was identified. This mutation (L(296)Q) was caused by a T-to-A conversion at codon 296 of exon 10 which resulted in the replacing of the codon for leucine (CTG) with the codon for glutamine (CAG). Further studies found that there was a significant increase in the mutant allele frequency in the CHD patients compared with that in the controls (0.160 vs. 0.091,cgr;(2) = 9.014, P = 0.003), and the odds ratio to develop CHD was 1.83 for the (296)Q allele carriers vs. (296)LL homozygotes. Statistical analyses also demonstrated that the mutant (296)Q allele carrier patients displayed significantly higher total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) concentrations than noncarrier patients. All these results suggest that the Q(296) mutation in CETP gene was closely related to CHD, and the identification of new mutations in the CETP gene will afford the opportunity to investigate the relationship between CETP gene and CHD.

Hepatic lipase (HL) is a lipolytic enzyme involved in the catabolism of plasma lipoproteins, and is an important determinant of high density lipoproteins(HDL) concentration and low density lipoproteins(LDL) subclass distribution. Accordingly, HL activity may influence body's susceptibility to coronary artery disease (CAD). Association on the single nucleotide polymorphisms (SNPs) in the HL gene to post-heparin plasma HL activity and the plasma HDL-cholesterol concentration have been investigated thoroughly, but to date, little is known about th is in Chinese. In present study, the SNPs of the HL gene were analyzed. The promoter region and all the 9 exons with their flanking sequences of the HL gene were amplified from the Chinese patients with CAD and normal controls by PCR technique, and the PCR products were detected by denaturing high performance liquid chromatography (DHPLC) and sequenced with a dideoxy terminal termination method. As the result, a novel SNP-2T right curved arrow C in the promoter of HL gene was found. Compared with the control group, more CAD patients carried the -2C allele(TC+CC) (57.9% versus 42.7%, chi(2) =4.181, df=2, =0.041). The prevalence of the -2C allele was significantly higher in the CAD patients than in control subjects (chi(2)=3.988, df=1, P=0.046) and the odds ratio(OR) of -2C allele associated with the risk of CAD is 1.58 [95% confidence interval(CI): 1.01-2.47]. The -2C allele homozygous carriers in the CAD patients had a significantly higher HDL-cholesterol level than the noncarriers [(1.13-/+0.24) mmol/L versus (0.91-/+0.14) mmol/L, P<0.05]. These suggest that a T right curved arrow C substitution at -2 of the HL promoter may be associated with th e variation of HDL-cholesterol concentration and therefore affect the risk of CAD in Chinese.

Coronary heart disease is a complex disease reflecting the interaction of multiple genes with the environment (e.g. diet, life style). Lipoprotein lipase (LPL) plays an important role in lipid metabolism and the pathogenesis of coronary atherosclerosis. Recent associations between single-nucleotide polymorphisms in the LPL gene and heart disease have been reported, but little is known in Chinese. The LPL gene spans >26 kb, with an mRNA of 3549 bp. In the present study, we screened 5155 bp (565 bp of 5' flanking region, nine exons and donor- and acceptor-splice sites, and some intronic bases) in 160 Chinese patients with confirmed coronary heart disease and 150 age- and gender-matched controls. Thirteen of the sixteen single-nucleotide polymorphisms that we found have not been previously reported. In males, significant (P<0.05) differences between the coronary heart disease patients and controls were found for five single-nucleotide polymorphisms: -421G>A (5' flanking region); +13,577C>A (intron 2); +16,052G>A, R192Q (exon 5); +16,173C>G and +16,177T>C (intron 5). In females, significant differences between the patients with coronary heart disease and controls were found for only the -421G>A and +16,052G>A (R192Q) mutations. Among the coronary heart disease males, significant (P<0.05) associations were found between the low-HDL high-triglyceride (LHDL/HTG) phenotype and the non-LHDL/HTG trait for the 5' flanking-421G, the intron 2+13,577C, and the exon 5+16,052G mutations, with odds-ratios (ORs)[confidence intervals] of 3.90[1.12-13.66], 3.38[1.22-9.40], and 3.22[1.04-10.01], respectively; no corresponding associations were found in females. There were 69, 51, 57 and 41 unphased haplotype patterns in male coronary heart disease, male control, female coronary heart disease and female control groups, respectively; the computer program PM-Plus found the heterogeneity model by far the best fit (P<0.0001 in males, >0.01 in females). These data show that some single-nucleotide polymorphisms in the LPL gene among Chinese are associated with abnormal lipid and lipoprotein profiles and predisposition to coronary heart disease, a genetically heterogeneous complex disease, and that they are gender-specific.