BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Adult ; Female ; Gene Expression ; Glomerulonephritis, Membranous ; etiology ; genetics ; pathology ; Hepatitis B ; complications ; Hepatitis B virus ; genetics ; metabolism ; Humans ; Male ; Middle Aged ; Mutation ; Receptors, Phospholipase A2 ; genetics ; metabolism ; Trans-Activators ; genetics ; metabolism ; Viral Regulatory and Accessory Proteins ; genetics ; metabolism

In the present study, in vitro nematicidal activity of chemical compositions from the methanol extract of Aristolochia mollissima fruits against the second stage juvenile (J2) of Meloidogyne javanica have been investigated. By using silica gel column chromatography, Sephadex LH-20 gel column chromatography methods, fourteen compounds were isolated from methanol extract of A. mollissima fruits. On the basis of spectral data, their structures were identified as aristolochic acid I (1), aristololactam I (2), aristololactam W (3), manshurolide (4), aristolactone (5), saropeptate (6), 2-(1-oxononadecyl)aminobenzoic acid (7), -sitosterol (8), sitostanetriol (9), daucosterol (10), formosolic acid (11), 5-ethyl-8,8-dimethyl nonanal (12), tetracosanoic acid,2,3-dihydroxypropyl ester (13) and tetracosanoic acid (14), respectively. It is the first time that compounds 2-4, 6-7, 9-14 are separated from A. mollissima. Furthermore, nematicidal activity of fourteen monomer compounds against J2 Meloidogyne javanica in vitro were analyzed. The compounds 1-3, 6-7 exhibited different degrees toxic effects on J2 M. javanica in vitro, especially for aristolochic acid I (1), aristololactam I (2), aristololactam W (3) with the LC₅₀ values of 45.25, 36.56, 119.46 mg·L⁻¹ after 96 h. So, A. mollissima have the potential value of developing new plant source to control root nematodes.

There is still a need for better protection against or mitigation of the effects of ionizing radiation following conventional radiotherapy or accidental exposure. The objective of our current study was to investigate the possible roles of matrix metalloproteinase inhibitor, ilomastat, in the protection of mice from total body radiation (TBI), and the underlying protective mechanisms. Ilomastat treatment increased the survival of mice after TBI. Ilomastat pretreatment promoted recovery of hematological and immunological cells in mice after 6 Gy γ-ray TBI. Our findings suggest the potential of ilomastat to protect against or mitigate the effects of radiation.
Acute Radiation Syndrome ; blood ; immunology ; prevention & control ; Animals ; Blood Cells ; drug effects ; radiation effects ; Dose-Response Relationship, Drug ; Gamma Rays ; adverse effects ; Hydroxamic Acids ; therapeutic use ; Indoles ; therapeutic use ; Matrix Metalloproteinase Inhibitors ; therapeutic use ; Mice ; Radiation Injuries, Experimental ; blood ; immunology ; prevention & control ; Radiation-Protective Agents ; therapeutic use ; Spleen ; drug effects ; immunology ; radiation effects ; Survival Analysis ; Whole-Body Irradiation

OBJECTIVETo study the relationship between surface markers of CD56 and CD19 and karyotypes and prognosis in multiple myeloma.

METHODSA total of 126 cases of newly diagnosed multiple myeloma in the first hospital of Peking university from 2011 to 2015 were enrolled in this study. Cytogenetic abnormalities and immunophenotypes were detected by using fluorescence in situ hybridization and flow cytometry respectively before chemotherapy. Bone marrow smear was used for detection of abnormal plasma cell infiltration. By combining with their basic data, the relationship between immunophenotypes, cytogenetics and prognosis of MM was analyzed.

RESULTS(1) The median of myeloma cells in the 126 patients was 0.24（0.01-0.97）; the median of myeloma cells in 116 patients who have immunophenotype datas was 0.25（0.01-0.97）； the median of myeloma cells in CD19 positive patients was 0.11（0.01-0.53）; the median of myeloma cells in CD19 negative patients was 0.26（0.01-0.97）. The median of myeloma cells in CD19 positive patients was much lower than that in CD19 negative patients（P=0.036）. (2)In 116 patients detected by the immunophenotype, the myeloma cells expressed CD19,CD20,CD56 and CD117. Compared with CD56 negative patients(45/116,38.79%),CD56 positive patients(71/116,61.21%) had a clearly favorable disease outcome（OS was 53.0 month vs 31.0 month,P=0.016; PFS was 37.5 months vs 18.4 months, P=0.036）. (3)CD19 positive patients was 16.38%（19/116）,CD19 negative patients was 83.62%（97/116）； CD19 positive MM and CD19 negative MM had no difference in OS and PFS. (4)CD117 positive rate in CD19 positive patients was 42.11%(8/19), the CD117 positive rate in CD19 negative patients was 18.57%(18/97), the CD19 expression positively correlated with CD117 expression. (5)FISH detection was done for 67 newly diagnosed MM patients, 8 patients showed normal karyotypes(11.94%), 59 patients had abnormal karyotypes(88.06%). The most common abnormal karyotypes were IgH rearragement which occurred in 47 patients(70.15%). Other abnormal karyotypes included 1q21+, del(13q14),del(13q14.3),del(17p13) . These abnormal karyotypes occurred in 37 patients（55.22%）,31 patients（46.27%）,33 patients（49.25%） and 13 patients（19.40%） respectively. In comparison with CD19 negative MM patients, the incidence rate of 1q21+ and del(13q14.3) was significantly lower in CD19 positive patients(1q21+:33.33% vs 61.54%,P=0.016; del(13q14.3): 33.33% vs 53.85%,P=0.043）.

CONCLUSIONThe prognosis of CD56 positive MM patients is better than that of CD56 negative MM patients, CD19 negative MM has more abnormal karyotypes and bone marrow infiltration,but they have no statistical prognostic differences.

Objective: To evaluate the clinical safety and efficacy of the retrograde perfusion technique in kidney transplantation.Methods: Between January 2001 and June 2011, 24 cases of kidney transplantation with kidneys perfused using the retrograde perfusion technique due to renal artery variations or injury were selected as the observation group (retrograde perfussion roup, RP group).Twenty-two cases of kidney transplantation via conventional perfusion were chosen as the control group (antegrade perfussion group, AP group).There were no statistically significant differences in donor data between the two groups.Cold ischemia time, warm ischemia time, renal perfusion time, amount of perfusion fluid, acute renal tubular necrosis, wound infection, urinary fistula, graft kidney function, and the 1-year, 3-year, and 5-year survival rates for the grafted kidney in both groups were observed and recorded.Results: The kidney perfusion time was shorter in the RP group than that in the AP group (3.14 ± 1.00 vs.5.02 ± 1.15 min, P =0.030).There were 10 cases of acute renal tubule necrosis in the RP group and 5 in the AP group.The length of hospital stay was 40 ± 14 d in the RP group and 25 ± 12 d in the AP group.The follow-up time was 3.5-8.5 years (mean 6.25 years).The 1-, 3-, and 5-year survival rates for the grafted kidney were 95.8％, 75.5％, and 65.5％ in the RP group and 97.1％, 82.5％, and 68.4％ in the AP group, respectively (P＞0.05).Conclusions: This study indicates that retrograde perfusion is safe and practicable for cadaveric kidney harvesting and can be regarded as a better alternative or remedial measure for a poorly perfused kidney due to vascular deformity or injury.Copyright 2015, Chinese Medical Association Production.Production and hosting by Elsevier B.V.on behalf of KeAi Communications Co., Ltd.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).

Objective: To evaluate the clinical safety and efficacy of the retrograde perfusion technique in kidney transplantation.Methods: Between January 2001 and June 2011, 24 cases of kidney transplantation with kidneys perfused using the retrograde perfusion technique due to renal artery variations or injury were selected as the observation group (retrograde perfussion roup, RP group).Twenty-two cases of kidney transplantation via conventional perfusion were chosen as the control group (antegrade perfussion group, AP group).There were no statistically significant differences in donor data between the two groups.Cold ischemia time, warm ischemia time, renal perfusion time, amount of perfusion fluid, acute renal tubular necrosis, wound infection, urinary fistula, graft kidney function, and the 1-year, 3-year, and 5-year survival rates for the grafted kidney in both groups were observed and recorded.Results: The kidney perfusion time was shorter in the RP group than that in the AP group (3.14 ± 1.00 vs.5.02 ± 1.15 min, P =0.030).There were 10 cases of acute renal tubule necrosis in the RP group and 5 in the AP group.The length of hospital stay was 40 ± 14 d in the RP group and 25 ± 12 d in the AP group.The follow-up time was 3.5-8.5 years (mean 6.25 years).The 1-, 3-, and 5-year survival rates for the grafted kidney were 95.8％, 75.5％, and 65.5％ in the RP group and 97.1％, 82.5％, and 68.4％ in the AP group, respectively (P＞0.05).Conclusions: This study indicates that retrograde perfusion is safe and practicable for cadaveric kidney harvesting and can be regarded as a better alternative or remedial measure for a poorly perfused kidney due to vascular deformity or injury.Copyright 2015, Chinese Medical Association Production.Production and hosting by Elsevier B.V.on behalf of KeAi Communications Co., Ltd.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).

OBJECTIVE: Tiny cerebral aneurysms are difficult to embolize because the aneurysm's sac is too small for a single small coil, and coils within the aneurysm may escape from the confinement of a stent. This study was performed to introduce the stent-assisted coil-jailing technique and to investigate its effect on the coil embolization of tiny intracranial aneurysms. MATERIALS AND METHODS: Sixteen patients with tiny intracranial aneurysms treated with the stent-assisted coil-jailing technique between January 2011 and December 2013 were retrospectively reviewed and followed-up. RESULTS: All aneurysms were successfully treated with the coil-jailing technique, and at the end of embolization, complete occlusion of the aneurysm was achieved in 9 cases (56.3%), incomplete occlusion in 6 (37.5%), and partial occlusion in 1 (6.3%). Intraprocedural complications included acute thrombosis in one case (6.3%) and re-rupture in another (6.3%). Both complications were managed appropriately with no sequela. Follow-up was performed in all patients for 3-24 months (mean, 7.7 months) after embolization. Complete occlusion was sustained in the 9 aneurysms with initial complete occlusion, progressive thrombosis to complete occlusion occurred in the 6 aneurysms with initial near-complete occlusion, and one aneurysm resulted in progressive thrombosis to complete occlusion after initial partial occlusion. No migration of stents or coils occurred at follow-up as compared with their positions immediately after embolization. At follow-up, all patients had recovered with no sequela. CONCLUSION: The stent-assisted coil-jailing technique can be an efficient approach for tiny intracranial aneurysms, even though no definite conclusion regarding its safety can be drawn from the current data.
Adult ; Aged ; Cerebral Angiography ; Embolization, Therapeutic/*instrumentation ; Female ; Follow-Up Studies ; Humans ; Intracranial Aneurysm/pathology/*therapy ; Magnetic Resonance Angiography ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Stents ; Treatment Outcome

Objective To discuss the possibility for regeneration of knee joint with normal function under bionics biomechanical environment. Methods Seven normal rabbits with two metal frames respectively mounted on their femur and tibia of single (right) side leg by two threading pins of 1.5 mm diameter were used. Then the external artificial joints, containing two four-bar-linkage inside and outside of the knee to simulate motion trajectory of the joint in sagital plane were connected with the two preset fixed frames before osteotomy. The arthro-cartilage of the knee joint, crucial ligaments, semi-lunar fibro-cartilages, and partial under-cartilage-osseous intra articular capsule were cut off during osteotomy, with the patella, sesamoid bones remained intact. Insertion sites of muscle tendons were not invaded as far as possible, and capsules with ligaments outside were kept complete when the incision wound was closed by suture. The rabbits could move freely after osteotomy. The range of motion (ROM) of the knees in sagital plane and bony gap between the femur and tibia were measured by X-Ray films during the fracture healing after osteotomy. Results External artificial knee joints were successfully installed on right legs of 6 rabbits among the seven. The rabbits moved freely after osteotomy under the control of minimal invasive external artificial joint in bionics trajectory. The average angles between femoral shaft and tibial shaft at the 1st week after osteotomy were from (144.7±15.62)° in extremely flexed position to (44.2±25.77)° in extremely extended position, with ROM of (100.5±29.03)°. At the 12th week, the average angles were from (139.4 ± 12.92)° in extremely flexed position to (40.4±22.04)° in extremely extended position, with ROM of (99.0±23.39)°. No significant differences were displayed in flexed/extended position and ROM between the 1st and 12th week, with the bony gaps of the knees still existed but decreased significantly from (4.03±1.84) mm at the 1st week to (2.32±1.05) mm at the 12th week. In contrast, bony gaps of the opposite knees were not changed significantly, which were (1.27±0.22) mm on average. At the end of 16th week after osteotomy, the external artificial joints were removed. Newly born cartilage, with white color and smooth surface, were covered at lower end of the femur and upper end of the tibia. Typical trochlear surface appeared at the front side of regenerated cartilage corresponding to the posterior surface of the patella. And the regenerated fibro-bundle linkage similar with ligament, which started from bony structure of regenerated lower end of the femur and inserted into regenerated upper end of the tibia, was observed in each rabbit. At the 25th week, the average angles between femoral shaft and tibial shaft were from (148.3 ± 4.75)° in extremely flexed position to (48.30±17.57)° in extremely extended position, with ROM of (100.0±20.80)°. In the opposite (left) leg, the average angles between femoral shaft and tibial shaft were from (148.3±7.5)° in extremely flexed position to (21.6±9.09)° in extremely extended position, with ROM of (126.7±6.88)°, and the average bony gap of the knees after osteotomy was (1.4±0.59) mm, while that of the opposite (left) knees was (0.92±0.35) mm. Conclusions The external artificial joint with bionics trajectory could reserve the space for regeneration of rabbit knee joint by providing motion modeling environment, and proved the stress adaption during fracture healing. The present results indicated that regeneration of the knee joint after intra-capsular osteotomy in bionics biomechanical environment was possible.

Objective To determine the efficacy of temozolomide (TMZ) in treating patients with glioblastoma using carmustine (BCNU) as control, and examine the effect of O6-methylguanine-DNA methyltransferase (MGMT) expression on the prognosis of patients with glioblastoma. Methods Two hundred and eighty-three patients with pathologically confirmed glioblastoma,admitted to and received treatment without chemotherapeutics in our hospital from January 2004 to January 2009, were enrolled in our study; TMZ was used in 97 patients and BCNU in 186 patients.The glioma tissues were examined for MGMT protein expression by immunohistochemistry.All patients in these 2 groups were performed long-term follow-up for survival time of the patients, tumor response and drug safety. Results In patients of the TMZ treatment group,the median survival time was (19.2±0.6) months,the 2-year survival rate 31％ (30/97),the 5-year survival rate 6.2％ (6/97) and the objective response rate 75.26％ (73/97); while in patients of the BCNU treatment group,the median survival time of was (15.6±0.6) months,the 2-year survival rate 14％ (26/186),the 5-year survival rate 0.5％ (1/186),and objective response rate 45.16％ (84/186); the cumulative survival rate of patients received TMZ treatment was significantly higher than that of patients received BCNU treatment (P＜0.05);the objective response rate between the 2 groups was obviously different (x2=24.753, P=0.000); the incidence of hypoleukocytosis in patients received TMZ treatment was significantly lower than that in patients received BCNU treatment (x2=15.681,P=0.000). Conclusion TMZ shows more efficient oobjective response as compared with BCNU, with less adverse reaction and better tolerability.Therefore,it is an ideal drug of postoperative adjuvant chemotherapy for malignant glioma.