Application of artificial intellengence and deep learning in opthalmology / 国际眼科杂志(Guoji Yanke Zazhi)

@#With the development and prevalence of artificial intelligence(AI), the application of AI has become a global trend in medical field recent years. The combination of AI and clinical medicine is becoming a hot spot in medical research. It is remarkable that the AI based on deep learning(DL)has achieved great accomplishments in image recognition, speech recognition and natural language processing, especially the application of convolutional neural network(CNN)in image recognition. CNN has been applied to the detection and diagnosis of various of ophthalmological diseases such as diabetic retinopathy, retinopathy of prematurity, glaucoma and age-related macular degeneration. Meanwhile, there are many public databases on ocular including large amount of images of fundus photographs, optical coherence tomography and visual field for researchers to train and test the AI algorithms. However, training the algorithm based on AI technology is still costly and time-consuming. The medical ethic of AI is another challengefor its application. Although DL has bought revolutionary change in ophthalmology field, it still has a long way to go for its world wide application. The article aims to synthesize the researches on the applications of AI technology in ophthalmology, and give a review on the present situation, existing problems and future outlook.

The effect of edaravone on the inflammasome NLRP3 and blood brain barrier associated protein after embolic stroke in rat / 医学研究生学报

ObjectiveIn cerebral ischemia, free radicals form in large quantities and activate the inflammasome nod-like recepter protein 3(NLRP3), thereby exacerbating brain damage. Edaravone has the effect of scavenging free radicals, but the relationgship between its neuroprotective effect and inflammasome NLRP3 has not been reported. To study the neuroprotective effects of edaravone on inflammasome NLRP3 and associated protein of the blood-brain barrier against cerebral ischemia injury.Methods60 male Sprague-Dawley rats were randomly divided into Sham group, cerebral embolism group and edaravone group, respectively. Rat thromboembolic MCAO models were established and edaravone (3mg/kg) was intravenous injected immediately after occlusion and 4 hours after occlusion. In the sham group, cervical blood vessels were separated only, and no embolus was injected. At 24 hours after thrombi injected, mNSS score was used to evaluate neurological function deficits. Brain infarct volume was estimated by TTC staining. The expression of inflammasome NLRP3, occludin and ZO-1 was detected by Western blot. Immunohistochemistry was used to measure IgG leakage.ResultsThe mNSS score and infarct volume of cerebral embolism group at 24 hours after stroke were significantly higher than Sham group (P<0.05). The expression of inflammasome NLRP3 in the brain increased (P<0.05), occludin and ZO-1 blood brain barrier associated protein decreased (P<0.05), and IgG leakage increased. But compared with cerebral embolism group, the mNSS score（4.50±2.12 vs 6.50±1.35, P<0.05）and infarct volume （19.29±11.92 vs 29.99±7.56, P<0.05）decreased when treated with edaravone. Edaravone treatment significantly attenuated inflammasome NLRP3 expression in cerebral ischemic area (0.97±0.47 vs 1.58±0.86, P<0.05), degradation of BBB components (occludin, ZO-1) (1.04±0.19 vs 0.53±0.09, 0.66±0.05 vs 0.30±0.04,P<0.05) and IgG leakage decreased.ConclusionInflammasome NLRP3 play an important role in acute cerebral ischemia injury. Edaravone may provide neuroprotection by inhibiting expression of inflammasome NLRP3 and degradation of associated protein of blood brain barrier.

Genotyping of RhD-negative blood samples diagnosed by serological tests from patients waiting for kidney transplantation / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the accuracy of serological and molecular approaches to identification of RhD-negative patients waiting for kidney transplantation.</p><p><b>METHODS</b>A total of 103 RhD-negative blood samples by serological test were collected from patients waiting for kidney transplantation between January, 2006 and January, 2016. Quantitative PCR and sequencing were used to verify the results of RHD genotyping, and the false negative rates of the serological and molecular methods for RhD genotyping were compared.</p><p><b>RESULTS</b>Among the 103 blood samples, true RhD negativity (with all the 10 exons missing) was found in 56 samples (54.5%), and false RhD negativity (RhD positivity with loss, repetition, or missense mutation in the 10 exons) in 47 samples (45.6%). In the 47 false RhD-negative cases, weak D was detected in 1 case (2.1%), partial D in 13 cases (27.7%), and D-elution in 33 cases (70.2%). The detection rates of RhD negativity differed significantly between the serological and molecular methods (P<0.05).</p><p><b>CONCLUSION</b>Serological test is associated with a high false negative rate in detecting RhD blood group, and the use of the molecular approach has important clinical significance in accurate RhD genotyping for patients waiting for renal transplantation.</p>

ROC curve-based evaluation of platelet parameters for predicting delayed renal graft function / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the value of evaluating 5 platelet parameters in predicting delayed graft function (DGF) in patients following kidney transplantation.</p><p><b>METHODS</b>We retrospectively analyzed the pre- and postoperative (within 2 months) data of 330 renal transplant recipients. The cases with DGF and those without were analyzed to assess the association between relationship between DGF following transplantation and the variations of blood platelet parameters including platelet count (PLT), large platelet ratio (P-LCR), mean platelet volume (MPV), platelet volume distribution width (PDW) and platelet hematocrit (PCT).</p><p><b>RESULTS</b>The DGF and non-DGF cases were comparable for the platelet parameters before the operation. On postoperative day 7 when the diagnosis of DGF was made, PLT (P<0.05) and PCT (P<0.02) were significantly lower while MPV (P<0.01), PDW (P=0.036) and P-LCR (P=0.01) significantly higher in DGF group than in non-DGF group. The AUCs of P-LCR (0.611±0.047), PDW (0.603±0.048) and MPV (0.762±0.037) were significantly higher than the reference area (P<0.05) with cut-off values of 34.80%, 12.95fl and 11.55fl, respectively. MPV showed a high sensitivity, specificity and Youden index for predicting DFG; PDW and P-LCR had a high sensitivity but a low specificity for predicting DFG with a modest diagnostic value. PLT and PCT, with AUCs of were 0.37 and 0.38, respectively, did not have a predictive value for DGF.</p><p><b>CONCLUSIONS</b>Significant variations in platelet parameters occur in the event of DGF in renal transplant recipients, and monitoring the postoperative changes in MPV, PDW, and P-LCR can help in early diagnosis and treatment of DGF. MPV has a moderate value (0.7-0.9) in predicting DGF, and a MPV>11.55 fl suggests the risk of DGF.</p>

Relationship between polymorphism of HLA-A, -B, -DRB1 alleles and susceptibility of children to acquired aplastic anemia / 中国实验血液学杂志

The aim of this study was to identify the relationship between susceptibility of children to acquired aplastic anemia (AA) and HLA-A, -B, -DRB1 alleles. 80 children with AA were enrolled in this study. Among of them, 34 patients collected from tissue typing test centers of Nanfang Hospital; 46 patients were diagnosed at Department of Pediatrics of Sun Yat-Sen Memorial Hospital. In these patients, 48 were males, 32 were females, and with average age 8.1 years old, 6 cases were non-severe AA (nSAA), 74 case were severe AA (SAA). The healthy control group consisted of 109 donors who were from the same area. All the patients and healthy controls were of Han Chinese, and all were unrelated individuals. The polymerase chain reaction sequence specific primers (PCR-SSP) was used to analyze the polymorphism of HLA-A, -B and -DRB1 alleles. Pearson Chi-square or continuity correction or two-sided Fisher's exact test were used. The results showed that the genotype frequency of HLA-B*48:01 and DRB1*09:01 were significantly higher in children with AA as compared with healthy controls (P < 0.05). The genotype frequency of HLA-B*51:01, DRB1*03:01 and DRB1*11:01 were significantly lower in children with AA as compared with healthy controls (P < 0.05). Besides, the results also demonstrated that the genotype frequencies of HLA-B*48:01 and DRB1*09:01 were significantly higher in SAA as compared with controls, the genotype frequencies of B*51:01, DRB1*03:01 and DRB1*11:01 were significantly lower in SAA, as compared with controls. In conclusion, HLA-B*48:01 and DRB1*09:01 are related with children AA, and may be susceptible alleles to the development of children AA. Besides, the expression of HLA-B*51:01, DRB1*03:01 and DRB1*11:01 are low in children with AA, whether they are relative protection alleles of children needs to be further studied.

Anti-MICA antibodies: risk factors for sensitization and the impact on renal transplantation outcomes / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the risk factors for sensitization of anti-MICA antibodies and their impact on the outcomes of renal transplantation.</p><p><b>METHODS</b>Luminex flow cytometry were used to identify 10 MICA antibodies and evaluate the antibody specificity in 98 uremic patients positive or negative for anti-MICA antibodies undergoing kidney transplantation. The factors contributing to MICA sensitization were analyzed, and the incidence of acute rejection and graft function recovery time were compared between the positive and negative cases for anti-MICA antibodies.</p><p><b>RESULTS</b>Of the 98 uremic patients, 16 (16.3%) were positive for anti-MICA antibodies. The positive and negative cases showed significant differences in the history of blood transfusion, pregnancy, transplantation, and PRA status (P<0.05). In the 38 renal transplant recipients, 6 experienced acute graft rejection, which was reversed by methylprednisolone pulse therapy; of the 10 recipients positive for anti-MICA antibodies, 4 showed acute graft rejection as compared to 2 out of the 28 recipients negative for anti-MICA antibodies (P=0.031). The cases positive for anti-MICA antibodies showed a significantly longer graft function recovery time than the negative cases (14.6∓4.7 vs 8.2∓4.5 days, P=0.001).</p><p><b>CONCLUSIONS</b>Blood transfusion, pregnancy, and transplantation all contribute to the production of anti-MICA antibodies. Patients positive for anti-MICA antibodies may require strict HLA matching and more potent immunosuppressive drugs to prevent renal graft rejection and improve graft survival.</p>

Expression of human leukocyte antigen gene in 94 patients with cerebral infarction / 中华神经医学杂志

Objective To discuss the relationship between human leukocyte antigen (HLA) gene heredity and morbidity of cerebral infarction by a random survey on the allele expression of HLA-A, B and DRB1 seats of patients with cerebral infarction. Methods The genotypes of HLA-A, B and DRB1 alleles in 94 patients with cerebral infarction and 122 healthy blood donors were detected by polymerase chain reaction-sequencing based typing (PCR-SBT) method. Results Sixteen alleles in HLA -A locus,32 alleles in HLA -B locus and 25 alleles in HLA -DRB1 locus expressed themselves in these patients with cerebral infarction. The gene frequency of HLA -A*1102 in patients was lower than that in healthy controls, and negative association was found between HLA -A* 1102 allele and cerebral infarction (RR=0.06,P=0.019). Conclusion The research reveals susceptibility association of HLA -A*1102 with patients having cerebral infarction, displaying close genetic immunity correlation between HLA alleles and pathogenesis of cerebral infarction. So, the research in this paper is useful in the clinical prediction of this disease.

KIR/HLA ligand matching and acute rejection after kidney transplantation / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of KIR/HLA ligand matching which mediates activated or inhibitory signal pathways on acute rejection (AR) after kidney transplantation.</p><p><b>METHODS</b>HLA and KIR genotype assortments were analyzed in 53 donor/recipient pairs of kidney transplantation. The recipients were divided into AR group (GI, n=19) and stable renal function group (GII, n=34) based on the early graft function. The impact of donor HLA, recipient KIR and distinct KIR/HLA class I ligand combinations on acute rejection after kidney transplantation was studied.</p><p><b>RESULTS</b>No significant differences were found in donor HLA-C1/2, HLA-A3, HLA-A11, or HLA-Bw4 between GI and GII groups. The frequency for KIR2DL2/2DS2 and KIR genotype assortment (AA) of the recipients in GI group were significantly lower than that in GII group (26.3% vs 55.9%, P=0.038; 31.6% vs 67.6%, P=0.011). The incidence of AR was significantly lower in donor HLA-C1/1 than in non-C1/1 (31.6% vs 46.7%, P>0.05), and lower in recipient KIR genotype assortment (AA) than in non-AA (20.7% vs 52.2%, P=0.011). A significant higher number of matches for the KIR2DL2/ HLA-C1 and KIR2DL3/HLA-C1 were observed in GII group (P=0.030, P=0.028).</p><p><b>CONCLUSION</b>Distinct KIR/HLA class I ligand combinations between the donor and recipient (such as KIR2DL2/ HLA-C1 and KIR2DL3/HLA-C1) may reduce the incidence of AR. A good KIR/HLA class I ligand matching will benefit the survival of the renal allograft.</p>

Analysis of natural killer cell immunoglobulin-like receptor genes in Chinese / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the genotypes of natural killer cell immunoglobulin-like receptor (KIR) genes and their frequencies in Chinese subjects and explore the mechanism of the actions of nature killer cells.</p><p><b>METHODS</b>The DNA samples were obtained from 67 randomly selected unrelated Chinese Han individuals for genotyping of the KIR genes using PCR with sequence-specific primers (PCR-SSP), and the frequencies of the KIR genes in these Chinese subjects were compared with the reported frequencies in populations of other nationalities.</p><p><b>RESULTS</b>Sixteen KIR genes were identified in these Chinese subjects, and 87.5% of these genes were expressed at frequencies above 0.35. Fourteen functional KIR genes combined into 25 KIR genotypes, among which the most frequent genotype KIR-2DL1-2DL3-2DL4-3DL1-3DL2-3DL3-2DS4 showed a frequency of 0.373, while the frequencies of all the other genotypes were no greater than 0.09. Comparison of the KIR combinations in Chinese Han population with those of Japanese, Korean, and Caucasians populations identified 8.93% of the KIR combinations shared by all these populations; the Chinese, Koreans and Caucasians shared 5.36% common KIR combinations, whereas only 1.79% common combinations were found in Chinese and Caucasians. In this study, 16 new gene combinations were identified (25.28%).</p><p><b>CONCLUSION</b>This study shows the high-frequency distribution of a single KIR gene polymorphism. The KIR combination KIR-2DL1-2DL3-2DL4-3DL1-3DL2-3DL3-2DS4 has the highest frequency in Chinese, Japanese, Korean and Caucasian populations, indicating that inhibitory signal transduction pathway plays an important role in the function of the natural killer cells. This study provide clues for new approaches for improving the prognosis of kidney transplantation by enhancing or inhibiting the function of the natural killer cells instead of life-time usage of immunosuppressive agents.</p>

Expression and analysis of HLA-A, B and DRB1 genes in patients with chronic myelogenous leukemia in Guangdong area / 中国实验血液学杂志

To study the gene polymorphism of HLA-A, B, DRB1 alleles in patients with chronic myelogenous leukemia and to explore the correlation of HLA with chronic myelogenous leukemia, the polymerase chain reaction-reverse sequence specific oligonucleotide (PCR-RSSO) was used to analyze the polymorphism of HLA-A, B, DRB1 alleles of 293 CML Patients and 406 randomized and synchronous blood donors (healthy and unrelated with patients) from Guangdong Han population. The results indicate that the gene frequency of HLA-A*24 in CML group was 15.53% lower than that of control group (22.09%, RR = 0.63, p = 0.005); the gene frequency of HLA-B*13 in CML group was 10.41% higher than that of control group (6.74%, RR = 1.68, p = 0.016). The gene frequency of HLA- DRB1*14 in CML group was 7.51% lower than that of control group (11.89%, RR = 0.58, p = 0.008). The differences were all statistically significant. It is concluded that the gene frequency of HLA-A*24, HLA- DRB1*14 in CML patients is significantly lower than normal people in Guangdong. The gene frequency of HLA-B*13 in CML patients is significantly higher than normal people in Guangdong. Further study is needed to make sure whether HLA-A*24 and HLA- DRB1*14 are protective gene markers for CML acquisition on Guangdong Chinese Han population and whether HLA-B*13 is a gene marker for CML susceptibility on this population.

Analysis of STR loci expression after allogeneic cord blood hematopoietic stem cell transplantation / 中国实验血液学杂志

The purpose of this study was to analyze the STR loci expression after allergenic cord hematopoietic stem cell transplantation in patient with Ducennes muscular dystropy (DMD) patient. PCR-SSO was used to identify the HLA antigens and alleles, STR-PCR was used to detect the chimera status. Quantity analysis of donor chimeras was performed by multiplex PCR amplification of STR marker and capillary electrophoresis with fluorescence detection. The results showed that patient appear to be HLA identical to the donor cord blood at the tested level. Persistent full donor chimerism was found in breast bone marrow. The patient with stable MC (DC < 5%) had a probability of long term survival with molecular remission MC status appeared in forearm muscle, tongue, liver, spleen, stomach, right temporal lobe, diaphragmatic muscle, bronchus, left ventricle and right kidney. In conclusion, the donor gene can express in parenchymatoas organs, the donor chimerism was detected in breast bone marrow and some other organs.

Factors responsible for inter-individual variations in dosage/concentration of tacrolimus in renal transplant recipients / 南方医科大学学报

<p><b>OBJECTIVE</b>To identify the factors responsible for the inter-individual variations in the dosage/concentration of tacrolimus in renal transplant recipients.</p><p><b>METHODS</b>This study involved renal transplant recipients receiving immunosuppressive therapy with the tacrolimus, mycophenolate and prednisone regimen after the operation. The gender, age, height, body weight, tacrolimus dosage, hormone dosage, diarrhea, blood lipids, liver function, renal function, albumin, and hematocrit of the patients were recorded at different time points, namely in early stage (3, 7, 14, and 30 days postoperatively, 118 cases), at 3 months (103 cases), 6 months (75 cases) and over one year (119 cases) after the operation. The concentrations of tacrolimus and gene polymorphisms at CYP3A5, MDR1 3435, MDR1 2677 and MDR1 1236 were also determined in these patients. Multiple linear regression was used for analysis of these factors with tacrolimus concentration/dosage*body surface area as the independent variable.</p><p><b>RESULTS</b>Patients in early stage following renal transplantation showed rather poor fitting of the stepwise regression model, which increased obviously 3 months after the operation and further increased till reaching a stable level at 6 months. Multiple factors were found to affect tacrolimus concentration/dosage in the early postoperative stage, during which period these factors underwent drastic variations and became stable 3 months later. In terms of pharmacogenomics, the major factors affecting tacrolimus concentration/dosage included MDR1 3435, MDR1 2677 and MDR1 1236 polymorphisms, which vastly varied between the patients early after the operation. Of these polymorphic sites, CYP3A5 produced only minor effects on tacrolimus concentration/dosage, and was not included as an active factor until the stable phase (over 1 year) following the transplantation; MDR1 3435 was found to be the predominant factor affecting tacrolimus metabolism in the stable phase. Age, liver function, albumin and hematocrit were found to be positively correlated to the independent variable tacrolimus concentration/dosage*body surface area, and identified as important factors responsible for the intra-individual variation of tacrolimus dosage/concentration.</p><p><b>CONCLUSION</b>The variations in the factors affecting tacrolimus dosage/concentration after renal transplantation are consistent with the clinical features of the patients, and these factors vary with the postoperative stages. Pharmacogenomic factors produce the most conspicuous effect on tacrolimus dosage/concentration, and agents that may interfere with tacrolimus metabolism should be avoided after the operation. Age, liver function, albumin and hematocrit are also important factors responsible for the variation of tacrolimus dosage/concentration.</p>

Expression of major histocompatibility complex class I-related chain A antibody in patients with end-stage renal disease and its clinical implications / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the frequency of major histocompatibility complex class I-related chain A (MICA) antibody in patients with end-stage renal disease (ESRD).</p><p><b>METHODS</b>Luminex flow cytometry and beads loaded with 11 MICA antigens were used to identify the MICA antibody and evaluate the antibody specificity in 110 patients with ESRD.</p><p><b>RESULTS</b>The positivity rate of MICA antibody was 40% (12/30) in PRA-positive patients, significantly higher than the rate of 17.5% (14/80) in PRA-negative patients (chi(2)=6.120, P=0.013). MICA-specific antibodies against 10 of the 11 MICA antigens were detected in 26 MICA antibody-positive patients, and 26.92% of the MICA antibody-positive patients had antibodies with single-specificity and 73.08% had polyspecific antibodies. Three MICA antibody-positive patients with cadaveric kidney transplantation showed good function of the graft without acute rejection 2 months after the operation.</p><p><b>CONCLUSION</b>The positivity rate of MICA antibody is significantly higher in PRA-positive patients, suggesting a strong correlation between MICA and PRA positivity. The MICA antibodies are polyspecific and probably consist of IgM and IgG. These data can be used as prospective data for these ESRD patients considering potential renal transplantation, and may facilitate further investigation of the association of MICA with renal transplantation.</p>

Effects of the HLA antibodies on allograft acute rejection after cadaveric liver transplantation / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of perioperative HLA antibody changes on acute allograft rejection in cadaveric liver transplantation.</p><p><b>METHODS</b>Totally 134 patients received modified piggyback liver transplantation and enzyme-linked immunosorbent assay was performed for HLA antibody detection before and the 1, 7, 14 and 30 days after operation. B ultrasound-guided liver biopsy was employed for diagnosis of acute allograft rejection, and the perioperative changes of HLA antibodies were evaluated for their effect on allograft acute rejection.</p><p><b>RESULTS</b>Of the 44 recipients with preoperative positivity for HLA antibodies, acute rejection occurred in 56.8% of the patients, as compared with 25.9% in those negative for HLA antibody (P=0.001). The patients who became positive for HLA antibody postoperatively had a rate of acute rejection of 60%, which was significantly higher than that in those persistently negative for HLA antibody (18.6%, P=0.003).</p><p><b>CONCLUSION</b>HLA antibody positivity before transplantation may contribute to acute rejection episode in liver transplantation, and persistent posttransplant HLA antibody positivity is closely associated with the occurrence of acute rejection.</p>

Relationship between the genetic background of donor KIR recipient HLA and the outcomes in HLA-identical sibling HSCT / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the genetic background of donor KIR/recipient HLA and the outcomes in HLA-identical sibling HSCT.</p><p><b>METHODS</b>HLA genotype was determined by polymerase chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP) and/or PCR-sequence-specific primer (PCR-SSP). Donor KIR genotype was determined by PCR-SSP. A retrospective study was carried out to analyze the outcomes of 59 patients with various hematologic malignancies received non T-cell-depleted transplant from HLA-identical sibling donors.</p><p><b>RESULTS</b>Incidence of grade II-IV acute graft-versus-host disease (aGVHD) was significantly lower in patients of KIR/HLA matched group than in KIR/HLA mismatched group (32% vs 78%, P = 0.026). The incidence of grade II-IV aGVHD (24% vs 61%, P = 0.018) and fungus infection (14% vs 44%, P = 0.028) were significantly lower in Bw4 matched group than in Bw4 mismatched group. In myeloid diseases, Bw4 matched patients had much lower incidence of fungus infection (12% vs 80%, P = 0.002) compared with Bw4 mismatched patients, and C2 matched patients had higher overall survival (OS) compared with C2 mismatched patients (P = 0.01).</p><p><b>CONCLUSIONS</b>Donor KIR/recipient HLA genetic background is correlated with the outcomes of HLA-identical sibling HSCT in incidences of grade II-IV aGVHD, fungus infection and OS. KIR/HLA matched patients may have lower incidence of aGVHD. Bw4 matched patients may have lower incidences of aGVHD and fungus infection. C2 matched patients may have longer OS.</p>

HLA class I and II polymorphism and haplotypes in Guangdong Han population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the polymorphism and haplotypes of HLA class I and II in Guangdong Han population and detect the HLA-A, B, Cw and DRB1 allele frequencies.</p><p><b>METHODS</b>An auto semi-quantitative PCR-sequence speacific oligonucleotide probe(PCR-SSOP) method was adopted in exploring the HLA-A, B, Cw and DRB1 genotypes of the samples from 160 bone marrow donors.</p><p><b>RESULTS</b>Twelve HLA-A, 23 B, 11 Cw and 13 DRB1 alleles were obtained. A total of 9 HLA-A-B, 20 Cw-B, 7 A-Cw, and 8 A-DRB1, 9 B-DRB1, 10 Cw-DRB1 haplotypes were found.</p><p><b>CONCLUSION</b>HLA class I and II alleles in Guangdong Han population have plenty of polymorphisms. The haplotype distribution possesses territory characteristic.</p>

Therapy of Duchenne muscular dystrophy with umbilical cord blood stem cell transplantation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a Duchenne muscular dystrophy(DMD) patient's muscular regeneration, dystrophin expression and locomotive variation before and after he underwent umbilical cord blood stem cell transplantation in order to assess the therapeutic effect.</p><p><b>METHODS</b>A 12-year-old DMD boy who could not walk for 3 years was confirmed by gene analysis and dystrophin protein immune test on his muscle. He had no other chronic disease. By HLA matching, a piece of umbilical cord blood stem cell with 6 HLA sites matching to the boy was found in Guangdong Umbilical Cord Blood Bank. The number of the nucleated cells of the umbilical cord blood stem cell was 24.08x 10(8). After pretreatment for the DMD boy with busulfan, cyclophosphamide and rabbit anti-human thymocyte globulin, the allergenic cord blood stem cells were transplanted into him by intravenous injection. Cyclosporin A, methylprednisolone, MMF, prostaglandin E1 and ganciclovir were given after the transplantation. At the same time, Gran, the granulocytic cell stimulating factor, and gamma globulin were administered. The biochemistry profile including serum creatine kinase (CK), the reconstruction of blood making, the deletion exon of DMD gene, the regenerating muscles, the dystrophin protein expression, and the locomotive function of the DMD boy were tested regularly.</p><p><b>RESULTS</b>(1) The white blood cells (WBC) of peripheral blood decreased gradually to zero after pretreatment. In a period of 15 days after transplantation, the neutrophil increased to 0.5x 10(9)/L; at 25 days, WBC increased to normal level. Blood platelet was more than 20x 10(9)/L at 22 days. The hemoglobin rose to 85-100 g/L. At 140 days, sternal puncture revealed the rapid growth of neutrophil, blood platelet and hemoglobin. (2)At 140 days, the blood type of the DMD boy transformed from type O to type AB (the donor's blood type being AB). There was no grafe versus host reaction. (3) At 18, 30, 43, 55, 74 and 233 days after transplantation, the PCR-short tandem repeat test of the boy's peripheral blood DNA showed that his genotype was completely the same as the donor's. The results of PCR-short tandem repeat tests of the bone marrow cells DNA by sternal puncture at 140, 183 and 235 days were the same as those of the blood DNA. (4) At 60 days, DMD gene analysis by PCR showed that the defected DMD gene (exon 19 deletion) had been corrected by the umbilical cord stem cells transplantation. (5) At 75 days, the biopsy of calf muscle showed there were myoblast cells and muscular tubes growing. The dystrophin expressions were weak, but a few of them were strong. DNA analysis showed that the donor's gene DNA accounted for 1%-13%. At 126 days, obviously increased dystrophin positive muscular fibers of the boy were found. The donor's fibers rose to 2.5%-25%. (6) The serum CK of the boy declined from 5735 U/L to 274 U/L. (7) At 100 days, physical examination revealed improvement in his arms and legs.</p><p><b>CONCLUSION</b>The therapy of Duchenne muscular dystrophy with allogeneic umbilical cord blood hematopoietic stem cell transplantation may reset up the blood-making function, decrease the serum CK level, restore the dystrophin in muscles, and improve the locomotive function of the DMD boy. These data suggest that the allogeneic umbilical cord blood hematopoietic stem cell transplantation may benefit the DMD boys.</p>

Decrease of chronic graft-versus-host disease by adding anti-human thymocyte globulin to the conditioning regimen / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the influence of adding anti-human thymocyte globulin (ATG) into conditioning regimen on graft-versus-host disease (GVHD) and life quality of the patients of allo-peripheral blood stem cell transplantation (PBSCT).</p><p><b>METHODS</b>Patients were distributed into study (19 cases) and control (24 cases) groups at random. Median dose of rabbit ATG was added to the conditioning regimen based on the fludara, busufan and cyclophosphamide (FBC) in study group, and no ATG in the control group. Acute and chronic GVHD disease and Karnofsky scores were compared between two groups after allo-PBSCT.</p><p><b>RESULTS</b>The patients in the study group received a mean of 6.0 (3 - 9) x 10(8)/kg mononucleated cells and 5.5 (4.5 - 7.5) x 10(6)/kg in the control group. The mean CD(34)(+) cells number was 5.5 (3.0 - 6.5) x 10(5)/kg in the study and 5.0 (3.0 - 7.0) x 10(6)/kg in the control group respectively. Eighteen patients in the study group and in the control group were successfully engrafted. The mean time of absolute neutrophil count recovered more than 500/ micro l was 13 days and 12 days respectively. Acute GVHD occurred in 6 patients of the study group, and 15 of the control group. Seven patients suffered from chronic GVHD and 14 got 90 Kanrofsky scores in a mean of 250 days follow-up in the study group, and 19 patients GVHD and 4 patients respectively in a mean of 440 days follow-up in the control group. There was a significant difference for acute and chronic GVHD and life quality between the two groups.</p><p><b>CONCLUSIONS</b>Addition of anti-thymocyte globulin to the FBC conditioning regimen had no effect on stem cells engraftment but could decrease acute and chronic GVHD and improve patients life quality.</p>

A probability analysis for HLA matching in adult stem cell transplantation treating nervous genetic diseases / 中国实验血液学杂志

The aim of this study was to investigate the clinical feasibility of adult stem cell transplantation for lethal mono-gene inherited disease, Duchenne muscular dystrophy (DMD). A total of 30 blood samples from DMD patients were genotyped with HLA-A,-B and -DR alleles by means of polymerase chain reaction-reverse sequence specific oligonucleotide (PCR-RSSO). The HLA gene types in 30 DMD patients were compared with those of 668 unrelated donors from Umbilical Cord Blood Center of Guangdong Province and 34 910 unrelated donors from Chinese Bone Marrow Bank. The results showed that HLA gene of the DMD group was inherited in normal distribution. There was no striking difference of HLA-A, -B and -DR alleles expression between the DMD patients group and control healthy group. 25% of the DMD patients got suitable donors for stem cell transplantation, in which 15 patients found donors with >or= 5/6 HLA match at the Umbilical Cord Blood Center of Guangdong Province, i.e. occupying 50% of the total. Eight patients got 6/6 HLA matching donors at the Chinese Bone Marrow Bank, i.e. occupying 26% of the total. It is concluded that stem cells transplantation therapy for DMD patients is feasible, which will benefit these patients suffered from the lethal neuromuscular disease, and create a new way to treat this tough nervous system disease.

Progress on the study of HLA-Cw--review / 中国实验血液学杂志

HLA-Cw belongs to classic HLA-I gene, HLA-Cw molecules have high polymorphism like HLA-A and B molecules. They distribute extensively on the surfaces of karyote, not only presenting endogenetic antigen to CD8+ T cells to induce specific killing effect, but also participating in immunologic reaction as the ligands of killer cell immunoglobulin-like receptor (KIR). Thus it has been valued for their relations to diseases and the functions in transplantation immunity, anti virus and anti-tumor immunity.