Hemophilia A with reduced coagulation factor Ⅺ: a case report and literature review / 中国输血杂志

【Objective】 To investigate the possible molecular pathogenesis of a child with hemophilia A accompanied by coagulation factor Ⅺ reduction by testing coagulation-related indicators and genotyping in the child and his family. 【Methods】 Peripheral blood from the patient and his parents for detection of coagulation factors Ⅷ, Ⅸ, Ⅺ, Ⅻ, VWF∶Ag, lupus anticoagulants and F VIII, F XI inhibitors were collected. All exons and flanking sequences of the genes encoding FⅧ and FⅪ were sequenced and bioinformatically analyzed. 【Results】 The child had low FⅧ and FⅪ activity and no parental abnormalities were observed. The sequencing results showed that there was a c. 1834(exon12) C>T heterozygous mutation in the FⅧ gene and a c. 1817 (exon15) G>A heterozygous mutation in the FⅪ gene, which was de novo. Bioinformatics analysis shows that the FⅪ mutation changes the original protein structure and increases the number of carboxyl groups. 【Conclusion】 For patients with prolonged APTT, in addition to excluding factors that interfere with APTT testing, all coagulation factors related to APTT should be tested to clarify the diagnosis.

Systematic review and meta-analysis of health state utility for global patients with hemophilia / 中国药房

OBJECTIVE To systematically sort out and evaluate the health state utility of hemophiliac patients， and to provide reliable parameters for conducting pharmacoeconomic evaluation and health technology assessment. METHODS Retrieved from CNKI， Wanfang data， VIP， CBM， PubMed， Embase， the Cochrane Library， Scopus and Web of Science databases， relevant literature about the measurement of health state utility in hemophiliac patients was collected from the inception to February 2023. After screening literature， extracting data and evaluating the quality of literature， meta-analysis was performed for health state utility with Stata 15.1 software. RESULTS Thirty-eight papers were finally included， with the highest and lowest health utility values of 0.90 and 0.46， respectively. Those studies mostly adopted the EuroQol Five Dimensions Questionnaire （EQ-5D） （73.7%）. Results of meta-analysis showed that health state utility of global hemophiliac patients was 0.69，95% confidence interval was 0.65- 0.74； those of patients with mild， moderate and severe hemophilia were 0.79， 0.70， and 0.64， respectively； health state utility for patients with inhibitors （0.64） was lower than that of patients without inhibitors （0.69）； health state utility for the Chinese patient population was 0.55， which was higher than that of Iranian patients （0.46）， but lower than those of other developed countries. CONCLUSIONS There is some heterogeneity in the results of the studies across countries/regions， with higher health state utility in developed countries than in developing countries. As the severity of hemophilia increases， the trend of decreasing health state utility is obvious.

Current Situation and Prospect of Pharmacoeconomic Evaluation of Hemophilia in China / 罕见病研究

In 2018, hemophilia, one of the first ones, entered into the catalogue of Rare Disease in China. However, drug accessibility and affordability have been the challenges for hemophilia patients. Therefore, a comprehensive evaluation of the cost and efficacy of hemophilia drugs is essential to push forward the appropriate application of hemophilia drugs. In the article, we have teased out the existing process of the review and approval of hemophilia drugs; have examined the procedures for the drug entry into the medical insurance policy; have systematically searched the pharmacoeconomic evaluation studies of hemophilia in published literature in both China and overseas; and have comprehensively analyzed the quality, the content of evaluation, and challenges of pharmacoeconomic studies of hemophilia in China. At last, we discuss the prospect for the future based on the following three aspects: developing a special model of hemophilia, obtaining the health utility from various sources, and establishing the threshold of willingness to pay for rare diseases, hoping to provide reference and examples to the research into pharmacoeconomic evaluation of hemophilia in China.

Current Status and Discussion of Hemophilia Aid System / 罕见病研究

Hemophilia is a hereditary bleeding disorder where the only effective treatment is factor replacement therapy. The main contradiction of hemophilia in China is the contradiction between the increasing demand for quality of life of hemophilia patients and insufficient medical insurance, medical treatment and medicine. Expensive treatment costs are the main reason for patients to "be impoverished due to illness" and "return to poverty due to illness". This article analyzes the current status of the hemophilia aid system through the existing literature data and existing patient aid projects. Cooperation of social insurance, social relief and high-quality medical services is critical to a complete hemophilia comprehensive medical aid system, so that hemophilia patients can receive standardized diagnosis and treatment, and try to achieve the close quality of life as normal.

Analysis of hemophilia case information of Shandong province / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To summarize the general condition, regional distribution, prevalence and clinical characteristics of Shandong province based on hemophilia case registry information.</p><p><b>METHODS</b>A retrospective study was carried out on 1979 hemophilia patients registered at Shandong Hemophilia Registration Center.</p><p><b>RESULTS</b>The 1979 cases have included 1704 hemophilia A and 275 hemophilia B patients. Hemophilia A was characterized as severe in 1021 patients (59.9%), moderate in 483 patients (28.4%), and mild in 200 patients (11.7%); while hemophilia B was characterized as severe in 125 patients (45.4%), moderate in 116 patients (42.2%), and mild in 34 patients (12.4%). The median age was 23 years (ranging from 1 month to 81 years), and most were young patients. Joint deformity occurred in 963 patients, and 948 patients had a family history of hemophilia. All counties of Shandong province had patients except for Changdao county and Fushan district of Yantai city. The prevalence of Heze city and Dongying city (3.39/100 000 and 3.05/100 000, respectively) were relatively higher.</p><p><b>CONCLUSION</b>The above data revealed epidemiological and clinical characteristics of Shandong Province. Patient-centered registry system allowed a more detailed and accurate patient information, and promoted the comprehensive care of hemophilia, which also suggested the necessity for the establishment and improvement of the National Hemophilia Registry System.</p>

Mechanism investigation of platelet apoptosis inhibition by N-Arachidonoylethanolamine / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of N- Arachidonoylethanolamine (ANA) on inhibiting platelets (PLT) apoptosis under standard blood bank storage conditions.</p><p><b>METHODS</b>Samples taken from collected apheresis PLT by the Amicus instrument were split into three parts. An aliquot of 0.5 μmol/L ANA were added to one part of storage PLT as the ANA group; an aliquot of 0.5 μmol/L ANA and 1 μmol/L SR141716 was added to the another part as the ANA + SR141716 group; and the third part without ANA and SR141716 as the control group. These samples were stored on a flat-bed shaker at (22 ± 2) ⁰C for 7 days. The expression of phosphatidyl serine (PS) positive, phospho (p)-Akt, Akt, p-Bad, Bad, caspase-3, caspase-9, cytochrome C (Cyt-C) and BCL-XL interaction with Bak were detected.</p><p><b>RESULTS</b>The rate of PLT PS positive in ANA group decreased significantly than that in control group[ (8.29 ± 1.44) % vs (14.24 ± 2.47) %, P<0.05]. The release of Cyt-C from mitochondria to cytosol in ANA group decreased significantly compared with control group[ (3.29 ± 1.44) % vs (15.24 ± 3.40) %, P<0.05]. Also the expressions of p-Akt and p-Bad in ANA group increased significantly than those in control group[ (71.33 ± 10.26) % vs (35.00 ± 6.00) %, P<0.05; (39.00 ± 9.64) % vs (10.33 ± 1.53) %, P<0.05, respectively]. Higher amounts of Bak protein were co-precipitated with BCL-XL in ANA group than that in control group (about 2.6 fold, P<0.05). The expressions of cleaved caspase- 9 and caspase- 3 in ANA group decreased significantly than those in control group[ (9.63 ± 1.47) % vs (23.24 ± 2.47) %, P<0.05; (6.30 ± 1.40) % vs (13.20 ± 2.50) %, P<0.05, respectively]. There were no significantly changes between ANA+SR141716 and control groups (P>0.05).</p><p><b>CONCLUSION</b>ANA protected PLTs from apoptosis as a result of inhibiting the release of Cyt-C from mitochondria to cytosol by modifying the expressions of apoptosis-relative proteins.</p>

Identification of a novel HLA allele, HLA-B*4086, and investigation of its family pedigree / 复旦学报（医学版）

Objective To identify a novel HLA allele, HLA-B*4086, in Chinese population and to investigate its pedigree. Methods An exceptional reaction pattern was detected in routine HLA typing of a CMDP (China Marrow Donor Programme) sample by PCR-sequence specific oligonucleotide primer (PCR-SSOP) assay. A new HLA-B allele was confirmed by sequence-based typing. Then family investigation was performed. Results DNA sequencing confirmed a new HLA allele. Compared with the closest macthing allele HLA-B*40060101, the novel allele has a difference at nt419 (A→T) in exon 3, which resulted in an amino acid change from Tyr to Phe at codon 140. Family investigation indicated the new allele derives from mother of the carrier. Conclusions One novel HLA allele was confirmed by sequencing based typing and it had been designated as HLA-B*4086 by the WHO Nomenclature Committee. This novel allele was inherited from mother of the carrier.

The expression of ICAM-1,CEA and CD31 in peritumoral tissues of rectal cancer / 中国现代普通外科进展

Objective:In order to study mechanism of hematogenous metastasis of rectum cancer.Methods:8 specimens of human rectum cancer and 6 specimens of rectum in normal human were examined.The immunohistochemical SP method was employed in study of the expression of ICAM1,CEA and CD31 in the peritumoral rectum tissues and lymphy nodes.Results:The intercellular role in the adhesion molecule-1(ICAM-1)and carcinoma embryonic antigen(CEA) were expressed on the vascular endothelial cells of peritumoral rectum tissues and peritumoral lymph nodes in the rectum cancer.CD31 are expressed on the vascular endothelial cells of rectum tissues from normal human with the same intensity of cancer peritumoral rectum tissues.Conclusion:This study showed that ICAM-1 and CEA seemed to play a stable role in the adhesion effect between cancer cells and endothelial cells.It is not clear whether CD31 plays a role in the interaction between cancer cells and endothelial cells.

Expression of CEA,ICAM-1 on lymphatic endothelial cells in rectum cancer of human / 中国现代普通外科进展

Objeetive:To study the expression of cell adhesion molecules on the lymphatic endothelial cells In the rectum cancer and peritumoral lymph nodes as well as their relationship with the diffusion of cancer cellS. Methods: In this Study the immunhistochemistry method was employed to observe the expression of CEA, ICAM-1 and CD31 on rectum cancer lymphatic endo-thelial cells. Results :The results demonstrated that CEA and lCAM-1 were highly expressed on the lynphatio endothelial cells in the peritumoral rectum tissues and lymph nodes. It was, howev-er,negative in normal lymphatic endothelial cells. CD31 was expressed on both lymphatic endothe-Ilal cells in the periturmral rectum tissues and lymph nodes and vessel endothelial cells of the normal human. Conelusion: The study suggests that there are relationships between the dis-semination of cancer cells and excession of CEA, lCAM-1 and CD31 in lymphatic endothelial cells.The CAE and ICAM-1 seem to induce stable adhesion between oancer cells and endothelial cells.