Palladium catalyzed stereoselective intramolecular [3 + 2] cycloaddition reactions of (E) & (Z)-ene-vinylidenecyclopropanes.

A palladium-catalyzed ring-opening cyclization of (E) & (Z)-ene-vinylidenecyclopropanes has been developed via an intramolecular [3 + 2] cycloaddition process in the presence of a sterically bulky biaryl phosphine ligand, stereoselectively affording fused cis- & trans-bicyclo[4.3.0] skeletal products in good yields with a broad substrate scope and good functional tolerance. A plausible reaction mechanism was proposed on the basis of previous work and the DFT calculations.

Simultaneous or Staged Decompressions for Patients with Tandem Spinal Stenosis.

OBJECTIVE: To compare the clinical effects of cervical decompression first, lumbar decompression first, or simultaneous decompression of both lesions in the treatment of tandem spinal stenosis (TSS). METHODS: This is a retrospective analysis. From January 2013 to December 2018, 51 TSS patients underwent our surgery and postoperative investigation. Among the 51 subjects, 27 females and 24 males, aged 49-77 years with an average age of 66.3 ± 6.8, were selected. According to the different operation sequences, all patients were divided into three groups. In simultaneous operation group, five patients underwent cervical and lumbar vertebrae surgery at the same time. In first cervical surgery group, 28 patients underwent cervical vertebra surgery first, followed by lumbar spine surgery after a period of recovery. And in first lumbar surgery group, 18 patients underwent lumbar vertebrae surgery first. The choice for neck surgery is posterior cervical single-door vertebroplasty, the surgery of lumber is plate excision and decompression needle-rod system internal fixation. The outcome measures are visual analogue scale (VAS), Japanese Orthopaedic Association cervical (JOA-C) and lumbar (JOA-L) scores, which were assessed at 3 months and 1 year after the operation by telephone interview. In addition, operative time, estimated blood loss, and hospital stay were also recorded. RESULTS: All the patients in the study had surgery performed successfully by the same group of orthopaedic surgeons. The preoperative VAS scores of simultaneous operation group, first cervical surgery group, and first lumbar surgery group were 8.00 ± 1.00, 8.36 ± 0.68, and 8.17 ± 0.71 (P > 0.05). The preoperative JOA-C scores were 7.00 ± 2.35, 6.54 ± 1.53, and 7.83 ± 1.04 (P < 0.05). And the preoperative JOA-L scores were 7.20 ± 2.17, 4.64 ± 2.36, and 5.78 ± 1.22 respectively (P < 0.05). During the final 1-year follow-up, the JOA-C improvement rates of simultaneous operation group, first cervical surgery group, and first lumbar surgery group were 85.68% ± 5.44%, 84.27% ± 5.02%, and 83.34% ± 10.25%, respectively (P > 0.05), and the JOA-L improvement rates were 80.04% ± 3.35%, 81.65% ± 3.74%, and 80.21% ± 4.76% (P > 0.05). The difference among them was not statistically significant. In addition, operation time (OP), blood loss (BL), and hospital stay (HS) in the simultaneous operation group were 245.00 ± 5.00 min, 480.00 ± 27.39 mL, and 16.60 ± 0.55 days, respectively. While those parameters in the first cervical surgery group were 342.50 ± 18.18 min, 528.21 ± 43.97 mL, and 22.75 ± 2.15 days, and in the first lumbar surgery group they were 346.11 ± 24.77 min, 519.44 ± 43.99 mL, and 22.89 ± 1.64 days. The average blood loss in simultaneous operation group was less (P > 0.05); meanwhile, the operation time and hospital stay time were significantly shorter in the simultaneous operation group than in the first cervical surgery group and first lumbar surgery group (P < 0.05). Only one case of fat liquefaction occurred in first cervical surgery group, which healed spontaneously after a regular change of dressing for 1 month. CONCLUSIONS: Under the condition of ensuring the surgical effect, the choice of staged surgery or concurrent surgery according to the patients' own symptoms of cervical and lumbar symptoms could both obtain satisfactory results, and the damage of simultaneous surgery was less than that of staged surgery.

The role of fibroblast activation protein in progression and development of osteosarcoma cells.

To investigate the expression levels of fibroblast activation protein (FAP) in human osteosarcoma tissues and its possible correlations with clinical pathological characteristics of patients with osteosarcoma, and to explore the potential effects of FAP on progression and development of osteosarcoma. Immunohistochemistry (IHC) assay was initially performed to detect the expression levels of FAP in 66 tumor tissues and adjacent non-tumor tissues. Patients were sequentially divided into two groups based on different expression levels of FAP. The correlations between the expression levels of FAP and the clinical pathological characteristics were investigated, and the role of FAP in proliferation, migration, and invasion of osteosarcoma cells was assessed via colony formation, MTT, wound healing, and transwell assays, respectively. The possible effects of FAP on tumor growth and metastasis were evaluated in vivo. We further attempted to reveal the underlying mechanism of FAP involved in tumor growth through bioinformatics and IHC assays. High expression levels of FAP were noted in human osteosarcoma tissues. It also was unveiled that FAP was significantly associated with the tumor size (P = 0.005*) and clinical stage (P = 0.017*). Our data further confirmed that knockdown of FAP remarkably blocked proliferation, migration, and invasion of osteosarcoma cells in vitro, and suppressed tumor growth and metastasis in mice via AKT signaling pathway. The possible role of FAP in progression and development of osteosarcoma could be figured out. Our data may be helpful to develop a novel therapeutic target for the treatment of osteosarcoma.

Interleukin-22 receptor 1 is expressed in multinucleated giant cells: A study on intestinal tuberculosis and Crohn's disease.

BACKGROUND: It is challenging to distinguish intestinal tuberculosis from Crohn's disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)-23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM: To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS: We analysed 133 patients with intestinal tuberculosis, 128 with Crohn's disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1ß rs1143627, TGFß rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS: The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION: High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.

The Polymorphism rs17525495 of LTA4H Is Associated with Susceptibility of Crohn's Disease instead of Intestinal Tuberculosis in a Chinese Han Population.

BACKGROUND: Because of the similarity of intestinal tuberculosis and Crohn's disease in disease phenotype, differential diagnosis has always been a clinical problem. Arachidonic acid metabolites play an important role in the inflammatory response of intestinal tuberculosis and Crohn's disease. Recent studies have shown that the polymorphism locus in the promoter region of LTA4H gene affects LTB4 expression level and the susceptibility to extrapulmonary tuberculosis. Thus, we identified a total of 148 patients with intestinal tuberculosis, 145 with Crohn's disease, and 700 normal controls in this study. METHODS: All the study participants were local Han people from Jiangxi Province in the past eleven years. DNA was extracted from the paraffin-embedded specimens or the whole blood. The LTA4H promoter SNP (rs17525495) was genotyped with TaqMan assay. RESULTS: The T-alleles frequency was not significantly increased in patients with intestinal tuberculosis compared with healthy control group (p=0.630; OR=1.07; 95%CI=0.81-1.41), while patients with Crohn's disease have significantly increased T allele frequency compared with healthy population (p=0.032; OR=1.34; 95%CI=1.03-1.75). During treatment, the presence of the T allele significantly increased the proportion of Crohn's patients requiring glucocorticoids (p<0.05). CONCLUSIONS: The T allele of LTA4H gene SNP (rs17525495) is a risk factor for Crohn's disease instead of intestinal tuberculosis. More importantly, there may be a potential association of the different genotypes of rs17525495 with the treatment efficacy of 5-ASA and glucocorticoids in patients with Crohn's disease. The association between LTA4H polymorphism and drugs therapeutic effects might contribute to the practice of precision medicine and the prediction of clinical outcomes.