OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected by glycogen storage disease (GSD) type Ia with gout as the first manifestation. METHODS: Clinical and biochemical data of the pedigree were collected. Available members of the pedigree were subjected to gene sequencing, and the result was analyzed by bioinformatics software. The pedigree was followed up for five years. RESULTS: The proband was a young female manifesting recurrent gout flare, hypoglycemia, and hypertriglyceridemia. One of her younger brothers also presented with dysplasia and hepatic adenoma. Gene sequencing revealed that the proband and her younger brother both harbored c.1022T>A (p.I1e341Asn) and c.230+5G>A compound heterozygous variants of the G6PC gene , which were inherited from their father and mother, respectively. Among these, the c.230+5G>A is an intron region variant which was unreported previously, and bioinformatics analysis showed that it may impact mRNA splicing of the gene. The proband was treated with raw corn starch, allopurinol, and fenofibrate. Gout was well controlled, and she had given birth to a baby girl without GSD. CONCLUSION GSD Ia should be considered among young gout patients with hypoglycemia and hepatomegaly, for which gene sequencing is warranted. GSD Ia has a good prognosis after comprehensive treatment with diet and medicine.
China ; Female ; Glycogen Storage Disease Type I ; Gout/genetics* ; Humans ; Hypoglycemia ; Male ; Pedigree ; Symptom Flare Up

Objective:To improve the awareness of cholesterol crystal embolism syndrome (CCE) inrheumatologists.Methods:The clinical characteristics of 40 Chinese CCE patients admitted to our department (one case) were summarize and in the literature (thirty-nine cases) were reviewed.Results:Among these 40 patients, 87.5%(35/40) were male and the mean age was (68±6) years. All patients suffered from athero-sclerosis and 87.5%(35/40) of them had precipitating factors such as endovascular intervention, vascular surgery, anticoagulant, or thrombolytic therapy. The clinical manifestations included renal insufficiency (90.0%, 36/40), blue toe syndrome (82.5%, 33/40), ulceration or gangrene (25.0%, 10/40), and livedo reticularis (15%, 6/40). Acute phase reactant was tested in 25 cases, of whom 84.0%(21/25) showed elevated C-reactive protein (CRP) and 56.0%(14/25) showed elevated erythrocyte sedimentation rate (ESR).Conclusion:Rheumatologists should be alert that CCE is one of the differential diagnosis of systemic vasculitis, especially for patients with severe atherosclerosis.

Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: ①After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. ②Univariate analysis showed that patients with grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ(2)=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ(2)=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ(2)=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ(2)=0.042, P=0.838]. ③Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions: HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade Ⅲ-Ⅳ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.
Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Myelodysplastic Syndromes ; Retrospective Studies ; Siblings ; Transplantation Conditioning ; Transplantation, Homologous

By the fourth survey of Chinese medicinal resources, new medicinal plants records of 2 genera and 5 species were reported in Tibet. They are two genera Rhynchoglossum and Asteropyrum, and five species including Rh. obliquum, A. peltatum, Urena repanda, Schefflera khasiana and Mimulus tenellus. All the voucher specimens are preserved in Herbarium of Tibet Agriculture and Animal Husbandry University.
Araliaceae ; classification ; Lamiales ; classification ; Malvaceae ; classification ; Plants, Medicinal ; classification ; Ranunculaceae ; classification ; Tibet

【Objective】To explore clinical manifestations and features of renal uric acid excretion in gout patients with obesity.【Methods】Totally 228 primary gout patients were enrolled and divided into three groups according to body mass index（BMI）. Clinical and fasting blood biochemical analysis data were collected. Indices of renal uric acid excretion were calculated according to 24 h urinary uric acid and urinary creatinine.【Results】The obese group（n = 44）was younger than overweight group（n = 88）and non-overweight group（n = 96）［43（32，57）years vs 55（45，65）years，58（45，67）years］，with earlier onset age［37（26，48）years vs 48（38，59）years］，higher serum uric acid［594（522，697）μmol/L vs 511（372，653）μmol/L］and had more hypercholesterolemia（56.8% vs 31.3%）and low density lipoproteinemia（59.1% vs 47.9%）compared with non-overweight group. The ratio of hypertriglyceridemia（43.5% and 37.5% vs 17.7%）and metabolic syndrome（50.0% and 36.4% vs 12.5%）in the overweight and obese group were both higher than non- overweight group. Fraction excretion of uric acid（FEUA）in obese group［5.5（3.6，7.4）% vs 7.0（5.2，9.8）%］was lower than non-overweight group，and the glomerular filtration load of uric acid［5.3（4.2，7.5）mg·min- 1 ·1.73 m- 2 vs 3.5（2.2，5.2）mg·min-1·1.73 m-2］in obese group was higher than that in non-overweight group（All P < 0.0167）. Multivariate regression analysis showed that overweight or obesity were negatively correlated with FEUA（All P < 0.05）.【Conclusion】High uric acid load of serum and glomerular filtration in gout patients with obesity may be due to the relative insufficiency of renal uric acid excretion.

Objective To investigate clinical characteristics and renal uric acid excretion in early-onset gout patients.Methods Consecutive inpatients with primary gout were recruited between 2013 and 2017.The patients with gout onset younger than 30 were defined as early-onset group while the others were enrolled as control group.Clinical characteristics and uric acid (UA) indicators were compared between two groups.Results Among 202 recruited patients,the early-onset group included 36 patients (17.8％).Compared with control group,the early-onset group presented more patients with obesity [13 patients (36.1％) vs.22 patients (13.3％),P＜0.05],significantly higher serum UA level [(634± 124)μmol/L vs.(527± 169).μmol/L] and glomerular load of UA[(7.2±2.8)mg· min-1 · 1.73m-2 vs.(4.4±2.2)mg· min-1 · 1.73m-2] and estimated glomerular filtration rate (GFR) [(83±21)ml· min-1 · 1.73m-2 vs.(67±21)ml· min-1 · 1.73m-2] (all P＜ 0.05),lower fractional excretion of UA [4.4％ (3.4％,6.1％) vs.7.2％ (5.2％,9.6％),P＜0.05],whereas 24h urinary UA excretion was comparable [(2 788±882)l,μmol/1.73m2 vs.(2 645±1 140)μmol/1.73m2,P=0.274].Subgroup analysis of patients without chronic kidney disease showed significantly lower fractional excretion of UA in the early-onset group [4.5％(3.3％,6.1％) vs.6.7％ (5.1％,8.7％),P＜0.05].Logistic regression analysis showed that obesity (OR=3.25) and fractional excretion of UA less than 7％ (OR=9.01,all P＜0.05) were risk factors of gout early onset.Conclusion The gout patients with early-onset younger than 30 present high serum and glomerular load of uric acid which might be due to obesity and relative under-excretion of renal uric acid.

Objective: To investigate the effects of donor-specific HLA antibodies(DSA) for graft failure in un-manipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT) and the feasible treatment for DSA. Methods: HLA antibodies were examined using the Luminex-based single Ag assay for 92 patients who were going on haplo-SCT and the correlations of graft failure and DSA among the patients who had finished SCT were analyzed. Results: Of the total 92 patients who were going on haplo-HSCT, sixteen (17.4%) patients were HLA Ab-positive, including six (6.5%) patients with antibodies corresponding to donor HLA Ags (DSA-positive). Among the patients who had finished the haplo-HSCT with conventional myeloablative conditioning regimen, the engraftment rate was significantly higher in DSA (-) patients than that in DSA (+) patients [92.3% (24/26) vs 25.0%(1/4), χ²=8.433, P=0.004] and DSA was the only factor relevant with graft failure in multiple-factor analysis [OR=12.0(95% CI 1.39-103.5), P=0.024]. Strategies to decrease antibody levels were taken for 4 patients, two were their first transplantations, and the other two patients were their second haplo-HSCT. Three of the four patients were HLA-I-DSA positive and had gained donor engraftment by means of donor platelet transfusions to decreased the level of DSA, the fourth patient with both HLA-I and HLA-II DSA also gained engraftment with the treatments of TBI, rituximab and donor platelet transfusion. Conclusion: DSA is one of the key factors of graft failure in haplo-HSCT. Donors should be selected on the basis of an evaluation of HLA antibodies before transplantation. If haplo-HSCT from donors with DSA must be performed, then recipients should be treated for DSA to improve the chances of successful engraftment.
Antibodies ; Graft vs Host Disease ; HLA Antigens ; Hematopoietic Stem Cell Transplantation ; Humans ; Tissue Donors ; Transplantation Conditioning

Objective: To investigate the feasibility of establishing a model of allograft penile transplantation in adult beagle dogs and explore the conditions for constructing a stable animal model of penis transplant. METHODS: Following the principles of similarity, repeatability, feasibility, applicability, and controllability in the construction of experimental animal models, we compared the major anatomic features of the penis of 20 adult beagle dogs with those of 10 adult men. Using microsurgical techniques, we performed cross-transplantation of the penis in the 20 (10 pairs) beagle dogs and observed the survival rate of the transplanted penises by FK506+MMF+MP immune induction. We compared the relevant indexes with those of the 10 cases of microsurgical replantation of the amputated penis. RESULTS: High similarities but no statistically significant differences were observed in penile anatomic features between the 20 beagle dogs and 10 men. All the 10 cases of cross-transplantation of the penis were successfully completed in the 20 beagle dogs, of which the transplanted glans survived with normal micturition in 12 but developed necrosis in the other 8; the success rate of one-time venous anastomosis was 95.0% (38/40) and that of one-time arterial anastomosis was 87.5% (35/40), with an average vascular anastomosis time of (71.0±9.0) minutes, a mean operation time of (133.0±10.3) minutes, and a mean blood loss of (135.8±41.4) ml. In the 10 cases of penile replantation, the success rate of one-time venous anastomosis was 100% (20/20) and that of one-time arterial anastomosis was 90.0% (18/20), with an average vascular anastomosis time of (65.0±7.9) minutes, a mean operation time of (117.4±10.0) minutes, and a mean blood loss of (85.0±10.8) ml. In the 12 cases of replantation of the amputated penis, the success rate of one-time venous anastomosis was 100% (24/24) and that of one-time arterial anastomosis was 95.8% (23/24), with an average vascular anastomosis time of (79.0±17.6) minutes, a mean operation time of (125.0±20.6) minutes, and a mean blood loss of (140.0±44.3) ml. No statistically significant differences were found in the relevant indexes among the three groups. CONCLUSIONS The anatomic structure of the corpus cavernosum penis of beagle dogs is highly similar to that of men, almost the same in cross-section anatomy. Microsurgical replantation and allograft transplantation of the penis were both successfully performed in beagle dogs, which showed similar operative indexes to those of human penile replantation. The construction of the allograft penile transplantation model in adult beagle dogs is feasible clinically, with the advantages of operability and repeatability.
Adult ; Anastomosis, Surgical ; Animals ; Arteries ; surgery ; Dogs ; Feasibility Studies ; Graft Survival ; Humans ; Male ; Microsurgery ; Models, Animal ; Necrosis ; etiology ; Operative Time ; Penis ; anatomy & histology ; pathology ; transplantation ; Postoperative Complications ; etiology ; Replantation ; Survival Rate ; Urination ; Veins ; surgery

OBJECTIVE: To explore the effects of aquaporin 4( APQ4) in rat toxic brain edema induced by subacute 1,2-dichloroethane( 1,2-DCE) exposure. METHODS: Thirty-two specific pathogen free healthy adult female SD rats were randomly divided into control( 8 rats),low-dose( 12 rats) and high-dose( 12 rats) groups. The treatment groups were exposed to 1,2-DCE( low-dose: 600 mg / m3; high-dose: 1 800 mg/m3,nose-only) and the control group was exposed to fresh air by dynamic inhalation for 8 hours per day for consecutive 7 days. After exposure,histopathologic changes were examined in the cerebral cortex. Real-time polymerase chain reaction was used to detect the mRNA relative expression of matrix metalloproteinase 2( MMP2),Na-K-Cl cotransporter-1( NKCC1) and AQP4. The Western blotting was used to detect the expression of AQP4 protein in the cerebral cortex. RESULTS: The pathological results showed that the cerebral cortex tissues were loose around the peripheral vessels and the vessels tissue space appeared widen in low-dose exposure group. The pathological change was more serious in high-dose group than low-dose group,with obvious loosen vessels and vacuole. Compared with those of the control group and the low-dose group,the relative expression level of MMP2 mRNA in the high-dose group increased significantly[( 1. 07 ± 0. 41) vs( 1. 56 ± 0. 55),( 1. 21 ± 0. 59) vs( 1. 56 ± 0. 55),P <0. 05],while the the relative expression level of AQP4 mRNA in the high-dose group significantly decreased [( 1. 03 ±0. 25) vs( 0. 81 ± 0. 12),( 1. 00 ± 0. 20) vs( 0. 81 ± 0. 12),P < 0. 05]. The relative expression levels of NKCC1 mRNA in all groups showed no statistical difference [( 1. 03 ± 0. 31) vs( 1. 14 ± 0. 43) vs( 1. 36 ± 0. 50),P > 0. 05]. The relative expression level of AQP4 protein in the high-dose group was lower than that of the control group [( 0. 80 ± 0. 25) vs( 1. 19 ± 0. 42),P < 0. 05]. CONCLUSION: The brain edema induced by subacute inhalation of 1,2-DCE is of mixed types with vasogenic edema as its main symptom. Its pathogenesis is related to the changes of AQP4 expression.

OBJECTIVE: To study the metabolic characteristics of 5-bromo-2-fluorobenzonitrile in vitro and compare the differences between rats and human,and for the purpose of providing data for poison effect research and extrapolating poison effect of 5-bromo-2-fluorobenzonitrile from animals to human being. METHODS: Equilibrium dialysis method was used to analyze the protein binding ratio of 5-bromo-2-fluorobenzonitrile in the plasma of rats and humans in the groups of low dose,medium dose and high dose which were treated with mass concentration of 5-bromo-2-fluorobenzonitrile at 500,5 000 and 50 000 μg / L respectively. Metabolic incubation systems of SD rat microsomes and human liver microsomes were established in vitro. When the mass concentration of 5-bromo-2-fluorobenzonitrile in the systems was 800 μg / L,the concentration of liver microsome was 0. 5 g / L; after being incubated for 0,10,30,60 and 90 min with the involvement of the regeneration system of nicotinamide-adenine dinucleotide phosphate in the incubation systems,the metabolic reaction was stoped. The residual amounts of 5-bromo-2-fluorobenzonitrile were analyzed and metabolic half-life of 5-bromo-2-fluorobenzonitrile incubating with liver microsomes in vitro was figured out. RESULTS: Protein binding ratio of 5-bromo-2-fluorobenzonitrile in the groups of low dose,medium dose and high dose were( 83. 5 ± 0. 9) %,( 88. 8 ± 0. 3) % and( 88. 6 ± 0. 3) % in rats plasma,and( 85. 2 ± 0. 1) %,( 89. 0 ± 0. 1) % and( 91. 1 ± 0. 4) % in human plasma. Both in rat plasma and human plasma,the protein binding ratio of 5-bromo-2-fluorobenzonitrile in the groups of medium dose and high dose were significantly increased than that in the low-dose group( P < 0. 01). In human plasma,the protein binding ratio of 5-bromo-2-fluorobenzonitrile in the high-dose group significantly increased than that in the medium-dose group( P < 0. 01). In the groups of low dose and high dose,the protein binding ratio of 5-bromo-2-fluorobenzonitrile in human plasma significantly increased than that in rats plasma( P < 0. 01). Absolute differences in protein binding ratio of 5-bromo-2-fluorobenzonitrile between the rat plasma and the human plasma were no more than 2. 5% in the same dose groups. Metabolic half-life of 5-bromo-2-fluorobenzonitrile incubating with rats and human liver microsomes and control solution in vitro were respectively( 58. 6 ± 1. 6),( 59. 2 ± 1. 5) and( 65. 0 ± 6. 3) min,which shows no significant differences( P < 0. 05). CONCLUSION: The potein binding ratio and metabolism of 5-bromo-2-fluorobenzonitrile in liver microsomes in rat plasma is similar to those in human plasma. Both in the plasmas of rats and humans,5-bromo-2-fluorobenzonitrile has high protein binding ratio,and 5-bromo-2-fluorobenzonitrile is not metabolized in liver microsomes of either rats or humans.