Transarterial chemoembolization with raltitrexed-based or floxuridine-based chemotherapy for unresectable colorectal cancer liver metastasis.

PURPOSE: To evaluate and compare the efficiency and safety of raltitrexed- or floxuridine (FUDR)-based transarterial chemoembolization (TACE) in patients with unresectable colorectal cancer liver metastasis (CRCLM). METHODS: We conducted a retrospective analysis of 81 patients with unresectable CRCLM who failed systemic chemotherapy and were treated with TACE in our department from Oct 2014 to Oct 2017. Of these, 61 patients received TACE using raltitrexed, oxaliplatin, and pirarubicin (raltitrexed group), and 20 received TACE using FUDR, oxaliplatin, and pirarubicin (FUDR group). The objective response rate (ORR), disease control rate (DCR), overall survival (OS, from the first TACE), progression-free survival (PFS, from the first TACE), and adverse reactions were evaluated and compared between the two groups, and prognostic factors for OS were analyzed. RESULTS: The ORRs of the raltitrexed group and FUDR group were 67.2 and 45.0%, respectively (P = 0.076), and the DCRs were 86.9 and 80.0%, respectively (P = 0.452). The median OS (from first TACE) was 14.0 months in the raltitrexed group and 13.0 months in the FUDR group (P = 0.556). The median PFS (from first TACE) was 2.1 months in the raltitrexed group and 2.4 months in the FUDR group (P = 0.878). Univariate and multivariate analyses showed that the primary tumor site, Child-Pugh class, and combination with local ablation (RFA or CRA) were independent significant factors affecting survival. There were no significant differences in adverse reactions between the two groups (P > 0.05), and no treatment-related death occurred in either group. CONCLUSION: TACE treatment based on raltitrexed or FUDR is an efficient and safe alternative choice for treating unresectable CRCLM.

Absorption mechanism of three curcumin constituents through in situ intestinal perfusion method.

This study aimed to investigate the absorption mechanism of three curcumin constituents in rat small intestines. Self-emulsification was used to solubilize the three curcumin constituents, and the rat in situ intestinal perfusion method was used to study factors on drug absorption, including drug mass concentration, absorption site, and the different types and concentrations of absorption inhibitors. Within the scope of experimental concentrations, three curcumin constituents were absorbed in rat small intestines through the active transport mechanism.

Collinearity analysis of allotetraploid Gossypium tomentosum and Gossypium darwinii.

Gossypium tomentosum and G. darwinii are wild allotetraploid cotton species, characterized by many excellent traits, including fiber fineness, drought tolerance, and Fusarium and Verticillium wilt resistance. Based on the construction of F2 linkage groups of G. hirsutum x G. tomentosum and G. hirsutum x G. darwinii, two genetic linkage maps were compared. As a result, we found a total of seven inverted fragments on chr02, chr05, chr08, chr12, chr14, chr16, and chr25, and three translocated fragments on chr05, chr14, and chr26. In addition, comparison of the inverted and translocated fragments revealed that the orientation of four of seven markers in G. tomentosum were consistent with G. hirsutum or G. raimondii. The orientation of one of seven inverted markers of G. darwinii was consistent with G. hirsutum, and the orientation of one of three translocated markers of G. tomentosum was consistent with G. raimondii. These results indicate that, in comparison to G. darwinii, G. tomentosum has a closer genetic relationship to G. hirsutum. These findings will be important for our understanding on the genome structure of G. tomentosum and G. darwinii, and set the scene for further in-depth genome research such as fine mapping, tagging genes of interest from wild relatives, and evolutionary study.

Mapping QTLs for drought tolerance in an F2:3 population from an inter-specific cross between Gossypium tomentosum and Gossypium hirsutum.

Cotton is one of the most important natural fiber crops in the world. Its growth and yield is greatly limited by drought. A quantitative trait locus (QTL) analysis was therefore conducted to investigate the genetic basis of drought tolerance in cotton (Gossypium spp) using 188 F2:3 lines developed from an inter-specific cross between a wild cotton species, G. tomentosum, and an upland cotton, G. hirsutum (CRI-12). A genetic map was constructed using 1295 simple sequence repeat markers, which amplified 1342 loci, distributed on 26 chromosomes, covering 3328.24 cM. A field experiment was conducted in two consecutive years (2014 and 2015) and 11 morphological and physiological traits were recorded under water-limited (W1)/well-watered (W2) regimes at three growth stages (bud, flowering, and full boll). The traits measured included chlorophyll content, plant height, leaf area, leaf number, leaf fresh weight, leaf dry weight, boll weight, number of bolls per plant, and the number of fruiting branches. Sixty-seven and 35 QTLs were found under the W1 and W2 conditions, respectively. Of these, the majority exhibited partial dominance or over-dominance genetic effects for increasing the trait values. Four consistent QTLs were found under the W1 treatment on chromosomes 5, 8, 9, and 16, whereas no consistent QTL was found in W2. Thirteen QTL clusters were also identified on nine chromosomes (2, 3, 5, 6, 9, 14, 15, 16, and 21). These results will help to elucidate the genetic basis of drought tolerance in cotton.

Microarray analysis of microRNA deregulation and angiogenesis-related proteins in endometriosis.

We examined the aberrant microRNA (miRNA) expression profile responsible for the changes in angiogenesis observed in endometriotic lesions. This study revealed characteristic miRNA expression profiles associated with endometriosis in endometrial tissue and endometriotic lesions from the same patient, and their correlation with the most important angiogenic and fibrinolytic factors. miRNA expression was quantified using a microRNA array and reverse-transcription microRNA polymerase chain reaction. Levels of vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor 2 (EGFR2), phosphatase and tensin homolog (PTEN), and C-X-C chemokine receptor type 4 (CXCR4) were quantified using enzyme-linked immunosorbent assay. The endometrial tissue showed significantly lower levels of miR-200b, miR-15a-5p, miR-19b-1-5p, miR-146a-5p, and miR-200c, and higher levels of miR-16-5p, miR-106b-5p, and miR-145-5p. VEGFA was significantly upregulated, whereas EGFR2, PTEN, and CXCR4 were markedly downregulated, in the endometriotic tissues compared to that in the normal endometrial tissues. In conclusion, differences in the miRNA levels could modulate the expression of VEGFA, EGFR2, PTEN, and CXCR4, and may play an important role in the pathogenesis of endometriosis. The higher angiogenic and proteolytic activities observed in the eutopic endometrium might facilitate the implantation of endometrial cells at ectopic sites.

Molecular cloning and expression analyses of RPS3a gene from mulberry under abiotic stresses and among different mulberry varieties.

A full-length cDNA sequence coding ribosomal protein S3a of mulberry tree, which we designated MmRPS3a (GenBank accession No. KR610331), was cloned based on mulberry expressed sequence tags. Sequence analysis showed that the MmRPS3a is 1089 bp long and contains a 80-bp 5'-UTR (untranslated region) and a 220-bp 3'-UTR. Its open reading frame consists of a 789-bp encoding 262 amino acids with a predicted molecular weight of 30.053 kDa and an isoelectric point of 9.84. Homology analysis revealed that MmRPS3a gene is highly conservative in mulberry and other species including Morus notabilis, Theobroma cacao, and Ricinus communis. Phylogenetic analysis based on MmRPS3a of other species showed that mulberry had a closer relationship with Prunus persica, Arabidopsis thaliana, Solanum tuberosum, Solanum lycopersicum, and Vitis vinifera. The results of quantitative PCR analysis showed that the transcriptional level of MmRPS3a mRNA changed significantly under the conditions of hypothermia, aridity, salt stress, and varieties of differing resistances.

Fine mapping and characterization of the or gene in Chinese cabbage (Brassica rapa L. ssp pekinensis).

Orange inner leaves/heads is a qualitative trait in Chinese cabbage that is controlled by a single recessive gene. Orange head Chinese cabbage contain more carotenoids than its white head counterpart; hence, this trait is of interest to both researchers and consumers. In this study, we selected the orange head Chinese cabbage line 07A163 and the white head Chinese cabbage line Chiifu as test materials. We localized the target gene controlling the orange head trait to the A09 linkage group, with a physical distance of approximately 19.9 kb between the two markers, syau26 and syau28. This region contains six candidate genes, including Bra031539, which was predicted to encode CRTISO, a carotenoid isomerase specifically required for carotenoid biosynthesis. A comparison of the nucleic acid sequences of the two test materials revealed 88 and 7-bp deletions and 88 SNPs in the promoter region of Bra031539 in line 07A163, along with a 6-bp deletion in the first exon and early termination at the 3' end of this gene. BLAST analysis revealed that 22 amino acids were altered and 17 amino acids were lost in Bra031539 in the orange head line 07A163. We developed the BrPro1 molecular marker in the promoter region of Bra031539 that can be used for early identification of orange head materials, thereby accelerating the breeding process of orange head Chinese cabbage.

Quantitative candidate gene association studies of metabolic traits in Han Chinese type 2 diabetes patients.

Recent genome-wide association studies have identified many loci associated with type 2 diabetes mellitus (T2DM), hyperuricemia, and obesity in various ethnic populations. However, quantitative traits have been less well investigated in Han Chinese T2DM populations. We investigated the association between candidate gene single nucleotide polymorphisms (SNPs) and metabolic syndrome-related quantitative traits in Han Chinese T2DM subjects. Unrelated Han Chinese T2DM patients (1975) were recruited. Eighty-six SNPs were genotyped and tested for association with quantitative traits including lipid profiles, blood pressure, body mass index (BMI), serum uric acid (SUA), glycated hemoglobin (HbA1c), plasma glucose [fasting plasma glucose (FPG)], plasma glucose 120 min post-OGTT (P2PG; OGTT = oral glucose tolerance test), and insulin resistance-related traits. We found that CAMTA1, ABI2, VHL, KAT2B, PKHD1, ESR1, TOX, SLC30A8, SFI1, and MYH9 polymorphisms were associated with HbA1c, FPG, and/or P2PG; GCK, HHEX, TCF7L2, KCNQ1, and TBX5 polymorphisms were associated with insulin resistance-related traits; ABCG2, SLC2A9, and PKHD1 polymorphisms were associated with SUA; CAMTA1, VHL, KAT2B, PON1, NUB1, SLITRK5, SMAD3, FTO, FANCA, and PCSK2 polymorphisms were associated with blood lipid traits; CAMTA1, SPAG16, TOX, KCNQ1, ACACB, and MYH9 polymorphisms were associated with blood pressure; and UBE2E3, SPAG16, SLC2A9, CDKAL1, CDKN2A/B, TCF7L2, SMAD3, and PNPLA3 polymorphisms were associated with BMI (all P values <0.05). Some of the candidate genes were associated with metabolic and anthropometric traits in T2DM in Han Chinese. Although none of these associations reached genome-wide significance (P < 5 x 10(-8)), genes and loci identified in this study are worthy of further replication and investigation.

Construction and characterization of a bacterial artificial chromosome library for the allotetraploid Gossypium tomentosum.

Gossypium tomentosum is a wild allotetraploid species with the (AD)5 genome. It is characterized by many useful traits including finer fiber fineness, drought tolerance, and Fusarium and Verticillium resistance. We constructed the first bacterial artificial chromosome library for Gossypium tomentosum. With high quality and broad coverage, this library includes 200,832 clones, with an average insert size of about 122 kb and fewer than 3% empty clones. Our library is approximately 10-fold the size of the (AD)5-genome (2400 Mb) and provides a 99.7% probability of isolating genes of interest or their sequences. Seven of eight simple sequence repeats markers that are located on five different chromosomes and linked with resistance to Verticillium wilt could amplify the 50 superpools and obtained one to five hits. This high capacity library will be an important genomic resource for classifying and analyzing the evolution of allotetraploid cotton species as well as for isolating disease-resistance and drought-tolerance genes.

Effect of high-intensity exercise on interleukin-15 expression in rabbit synovia.

The objective of this study was to examine the effect of high-intensity exercise on interleukin-15 (IL-15) expression in rabbit synovia. We utilized 24 New Zealand white rabbits, which were randomly divided equally into high-intensity exercise and control groups. The former were forced to run for 60 min/day over 4 weeks at the speed of 30 m/min. The histological changes of cartilage and knee joint synovia were investigated with hematoxylin and eosin staining. Immunohistochemistry and enzyme-linked immunosorbent assays were performed to measure IL-15 expression. From these analyses, we identified knee articular cartilage damage and synovitis in the high-intensity exercise group. This group also exhibited higher IL-15 expression in their synovial fluid and tissues than was observed in the control group (P < 0.05). These results suggested that high-intensity exercise might lead to synovitis and articular cartilage damage, and that IL-15 overexpression in synovia might be associated with post-traumatic osteoarthritis.

Genetic diversity and relationship analysis of Gossypium arboreum accessions.

Simple sequence repeat techniques were used to identify the genetic diversity of 101 Gossypium arboreum accessions collected from India, Vietnam, and the southwest of China (Guizhou, Guangxi, and Yunnan provinces). Twenty-six pairs of SSR primers produced a total of 103 polymorphic loci with an average of 3.96 polymorphic loci per primer. The average of the effective number of alleles, Nei's gene diversity, and Shannon's information index were 0.59, 0.2835, and 0.4361, respectively. The diversity varied among different geographic regions. The result of principal component analysis was consistent with that of unweighted pair group method with arithmetic mean clustering analysis. The 101 G. arboreum accessions were clustered into 2 groups.

Characterization and development of chloroplast microsatellite markers for Gossypium hirsutum, and cross-species amplification in other Gossypium species.

Cotton is an important economic crop worldwide; its fiber, commonly known as cotton lint, is the main natural source for the textile industry. Sixty chloroplast microsatellites were identified and characterized from the complete sequence of the Gossypium hirsutum chloroplast genome using a bioinformatic approach. Twenty chloroplast microsatellite loci were polymorphic in the 66 Gossypium germplasm accessions. A total of 85 alleles were detected, with allele numbers varying from 2-7 per locus. Polymorphism information content varied from 0.02-0.66, with a mean of 0.48. Additionally, transferability of the 20 polymorphic chloroplast microsatellite primers was evaluated in other 31 Gossypium species. Sixteen markers were successfully amplified across all species tested, while the remaining 4 markers cross-amplified in most species tested. These polymorphic chloroplast microsatellite markers may be useful tool for studies of individual identification, genetic diversity, evolution, conservation genetics, and molecular breeding in Gossypium.

Effects of high intensity exhaustive exercise on SOD, MDA, and NO levels in rats with knee osteoarthritis.

The aim of this study was to investigate the impact of high intensity exhaustive exercise on nitric oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD) expression in rats with knee osteoarthritis. Sprague Dawley rats were randomly divided into control (N = 5) and model (N = 35) groups; the model group was further divided into quiet (N = 5), low- (N = 15) and high- (N = 15) intensity exhaustive exercise groups. The low- and high-intensity groups were randomly divided into pre-exercise (N = 5), immediate post-exercise (N = 5), and 24-h post-exercise (N = 5) groups according to different time points for detection. NO, MDA, and SOD levels were compared between each group. The SOD levels in the quiet, low-, and high-intensity exhaustive exercise groups were lower than that in the control group, whereas the NO and MDA levels were higher in the former groups than in the controls (P < 0.05). The SOD level in the 24-h post-low intensity exhaustive exercise group was higher than that in the 24-h post-high intensity exhaustive exercise group, whereas the NO and MDA levels were lower in the 24-h post-low intensity than in the post-high intensity exercise group (P < 0.05). Overall, the results demonstrated that with the increase of exercise intensity, the SOD activity in the rats with knee osteoarthritis decreased gradually, whereas the MDA and NO levels gradually increased. Thus, the greater the exercise intensity, the more serious the impact on knee osteoarthritis.

Genetic diversity of wild soybean populations in Dongying, China, by simple sequence repeat analysis.

Annual wild soybean (Glycine soja Sieb. et Zucc.), the ancestor of cultivated soybean (G. max), is believed to be a potential gene source for further improvement of soybean to cope with environmental stress. In this study, 10 simple sequence repeat (SSR) markers were used to evaluate the genetic diversity and population genetic structure in five wild soybean populations using 195 accessions collected from Dongying, China. Ten SSR markers yielded 90 bands, with an average of nine bands per marker. The percentage of polymorphic loci (P) was 97.78%, the distribution of expected heterozygosity (HE) was 0.1994-0.4460 with an average of 0.3262, and the distribution from Shannon's information index (I) was 0.3595-0.6506 with an average of 0.5386. The results showed that wild soybean had a high degree of genetic diversity at the species level. Nei's differentiation coefficient (FST) was 0.1533, and gene flow (Nm) was 1.3805, which indicated that genetic variation mainly existed within populations and that there was a certain level of gene exchange between populations. Some genetic differentiation occurred among populations, although this was not significant. Cluster analysis indicated that there was no significant correlation between the genetic structure of wild soybean populations and their geographic distribution, and the clustering results may be relatively consistent with the habitats of the accessions. In the present study, the genetic diversity of wild soybeans showed a broad genetic base and enables suggestions for the conservation of this plant to be made.

Construction of a tissue engineered intervertebral disc with high biological activity using an allogeneic intervertebral disc supplemented with transfected nucleus pulposus cells expressing exogenous dopamine beta-hydroxylase.

This study addressed the in vitro construction and biological activity of tissue engineered intervertebral discs with exogenous human dopamine beta-hydroxylase (DBH) nucleus pulposus cells. pSNAV2.0-DBH expression plasmids were utilized to enhance the survival rates of intervertebral disc tissue cells. Various concentrations of transfected nucleus pulposus cells were injected into the discs, and DBH mRNA expression was determined using polymerase chain reaction amplification. Polysaccharide content and total collagen protein content in the engineered disc nucleus pulposus tissue were determined. The visible fluorescence intensities of the 1 x 10(5) and 1 x 10(6) groups vs the 1 x 10(4) group were significantly increased (P < 0.05); no significant difference was observed between the 1 x 10(5) and 1 x 10(6) groups (P > 0.05) at 7 days after injection. DBH mRNA expression could be detected in the all but the EGFP control group at 14 days culture. No significant difference was observed in the protein content between the 1 x 10(4) and the control groups at various times, while the protein content was significantly higher in the 1 x 10(5) vs the control and the 1 x 10(4) groups at 7-, 14-, and 21-day cultures. These results demonstrate that a tissue engineered intervertebral disc with high biological activity can be constructed by utilizing allogeneic intervertebral discs stored in liquid nitrogen and a 1 x 10(5) transfected nucleus pulposus cell complex with in vitro culture for 14 days. This model can be used in animal experiments to study the biological activity of the engineered discs.

Protective effect and mechanism of probucol in the treatment of spinal cord injury.

To investigate the effects of probucol on the treatment of spinal cord injury in rat, 80 rats were randomly divided into two groups of 40: a group treated with probucol and a control group. Allen's method was used to establish a rat model of spinal cord injury. After establishment, probucol (500 mg·kg(-1)·day(-1)) was intraperitoneally injected into the treatment group rats for 1 week, while the same amount of saline was used to treat the control group. On days 1, 7, 14, 21, and 28 after treatment, the function of rats' spinal cord was evaluated according to the Bresnahan locomotor rating scale. Serum protein and mRNA levels of the cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-17] were measured using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. Protein levels of IFN-γ, TNF-α, IL-17, and the downstream markers signal transducer and activator of transcription (STAT)-1 and STAT-3 were measured using western blot. In addition, the oxidative stress-related parameters, superoxide dismutase (SOD) and malondialdehyde (MDA), were also measured. It was found that compared to control group, rats from the treatment group had significantly lower levels of IFN-γ, TNF-α, and IL-17 (P < 0.05) on days 1 and 7, as well as lower MDA levels and higher SOD activity on days 7, 21, and 28 (P < 0.05). In summary, probucol improved the recovery of locomotion function after spinal cord injury in rats through downregulation of inflammation and upregulation of anti-oxidative activity.

Effects of p-chlorophenoxyisobutyric acid, arabinogalactan, and activated charcoal on microspore embryogenesis in kale.

To improve embryogenesis in microspore cultures of kale (Brassica oleracea L. var. acephala DC.), 6-benzylaminopurine (6-BA), naphthaleneacetic acid (NAA), arabinogalactan (AG), p-chlorophenoxyisobutyric acid (PCIB), and activated charcoal (AC) were added to the medium using four varieties of kale. The results showed that the addition of AG (0.1-0.2 g/L), AC (0.1-0.2 g/L) or a combination of 6-BA (0.1-0.2 mg/L) and NAA (0.1-0.2 mg/L) promoted embryo-genesis. Adding 40 µM PCIB or a combination of 40 µM PCIB and 0.2 g/L AC to NLN-13 medium at pH 5.8 effectively enhanced embryogenesis. Treatment with a combination of 40 µM PCIB and 10 mg/L AG gave the highest rate of embryonic induction, especially in genotype "Y007," which showed a twelve-fold increase in yield.

Effect of the mixture of bone marrow mesenchymal stromal cells and annulus fibrosus cells in repairing the degenerative discs of rabbits.

The aims of this study were to investigate the effect of a mixture of bone marrow mesenchymal stem cells (BMSCs) and annulus fibrosus cells (AFCs) in repairing the degenerative discs of rabbits, and to provide an experimental basis for its clinical application. BMSCs from rabbits were cultured in vitro and mixed with AFCs. The animal model of degenerative intervertebral disc was built by aspirating the nucleus pulposus (L3-4, L4-5, L5-6, and L6-7) through a posterolateral approach. Mixtures of BMSCs and AFCs (group A), BMSCs alone (B), or saline (C) were injected into test discs, and changes evaluated by plain radiographs, magnetic resonance imaging, and histology. After two weeks, each group showed typical internal disc disruption; stenosis of the intervertebral space, weakening T2 disc signal, decreased disc height and expression of type II collagen and glycosaminoglycan, and fibrosis of the nucleus pulposus. After cell transplantation, the disc heights in groups A and B were regained; however, they continued to decrease in group C. The transplanted cells survived in the discs, proliferated after transplantation, and produced copious matrix. Macroscopic and histological evaluations confirmed structural and nuclear preservation in cell-transplanted discs. The secretions and expressions of Type Ⅱ collagen and glycosaminoglycan in group A were statistically significant higher than those in group B (Type Ⅱ collagen, group A 141.6 ± 5.87, group B 139.8 ± 8.65, P = 0.004; glycosaminoglycan, group A 3.008 ± 0.35, group B 2.94 ± 0.29, P = 0.003). Expression of type II collagen and glycosaminoglycan was significantly greater in group A than group B. Therefore, co-transplantation of BMSCs and AFCs can restore the extracellular matrix, making this approach superior to transplantation of BMSCs alone, which may be beneficial for the therapy of intervertebral disc degeneration.

Development and characterization of microsatellite markers for the Chinese endangered medicinal plant Tetrastigma hemsleyanum.

Tetrastigma hemsleyanum (Vitaceae) is an endangered medicinal plant endemic to China. Because of its widely known efficacy for treating many health problems, wild resources of this species are currently undergoing a rapid decline. Few studies have been conducted examining the population genetics or development of microsatellite loci for this plant. In this study, 14 microsatellite loci were isolated and characterized for T. hemsleyanum using a double-suppression PCR method. Polymorphisms were tested with a total of 50 individuals from 2 natural populations. The number of alleles per locus ranged from 3-9, with an average of 7 alleles per locus. The observed and expected heterozygosity per locus ranged from 0-1 and from 0.068-0.803, respectively. The polymorphism information content value varied from 0.215-0.760. These loci may facilitate further genetic studies of populations of T. hemsleyanum and provide guidance for their conservation.

Characteristics of immune cell changes before and after immunotherapy and their clinical significance in patients with unexplained recurrent spontaneous abortion.

To investigate the characteristics of immune cells before and after immunotherapy and their clinical significance in patients with unexplained recurrent spontaneous abortion (URSA), an analysis of 67 URSA patients, 67 sporadic spontaneous abortion (SA) patients, and 22 normal nonpregnant women (as controls) was conducted. URSA patients underwent immunotherapy using paternal lymphocytes. Peripheral blood from patients and controls was examined for lymphocytes and other markers of immune status. Before the immunotherapy, lymphocyte counts, CD4:CD8 cell ratios, and the relative proportion of natural killer (NK) cells were significantly higher in the URSA patient group than in the SA patient and control groups (P < 0.05). After the therapy, all of these three measures were decreased, whereas the percentage of T cells was increased, and statistically significant differences before and after the immunotherapy were detected (P < 0.05). Therefore, the immune system appears to be activated in the URSA patients, and the abnormal immunologic state in the URSA patients is more severe than in the SA patients. The alterations in T and NK cells may be involved in the etiopathogenesis of URSA. Lymphocyte immunotherapy appears to be an effective treatment for URSA patients.