Early and accurate diagnosis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation is crucial for the prognosis of patients. This study identified a potential biomarker for the severity of aGVHD after human leukocyte antigen (HLA)-haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). We included 20 healthy subjects and 57 patients who underwent haplo-PBSCT. Of these patients, 22 developed aGVHD after haplo-PBSCT. The results showed that patients with aGVHD had significantly increased levels of Tim-3+/Perforin+/Granzyme B+CD8+ T cells, but significantly decreased Galectin-9. The differences in Galectin-9 and Tim-3+/Granzyme B+CD8+ T cells between grade I-II aGVHD and III-IV aGVHD were also significant. In vitro, the apoptosis of CD8+ T cells from aGVHD patients was significantly increased after Tim-3/Galectin-9 pathway activation, which decreased Granzyme B secretion. As revealed by univariate analysis, the level of Tim-3+CD8+ T cells was a risk factor for severe aGVHD. ROC analysis demonstrated that high levels of Tim-3+CD8+ T cells had a significant diagnostic value for severe aGVHD, with an area under the curve of 0.854 and cut-off value of 14.155%. In conclusion, the binding of Tim-3 with exogenous Galectin-9 can promote apoptosis of CD8+ T cells and affect the secretion of Granzyme B. Tim-3+CD8+ T cells have the potential to serve as immunological markers for assessing the severity of aGVHD after haplo-PBSCT and identifying patients at a higher risk for severe aGVHD.

Abstract The surfactant-polymer-based (S/P) fracturing fluid combines the advantages of the surfactant-based and polymer-based fracturing fluids. In this study, the synergistic tackifying of cationic surfactants and carboxymethyl hydroxyethyl cellulose and the potential application in hydraulic fracturing fluid was investigated. Firstly, cetyltrimethylammonium chloride (CTAC) and salicylic acid (SA) with a weight ratio of 4:1 were optimized as the main agent of the small molecule surfactant gel, which was then mixed with carboxymethyl 2-hydroxyethyl ether cellulose (CMHEC) and salicylic acid (SA) to obtain the S/P gel. The proppant suspension performance, gel-breaking properties, salt-resistance and thermal stability of the optimized S/P were evaluated to confirm their potential application in the hydraulic fracturing fluid. These results showed that the performance of the S/P fracturing fluid system was much better than the performance of the surfactant fracturing fluid and also the performance of polymer fracturing fluid.

RESUMO OBJETIVO Neste estudo, investigamos a função do COL6A3 na mobilidade celular e na via PI3K/AKT em osteossarcomas. METODOLOGIA A expressão relativa do COL6A3 foi obtida a partir de dados GEO em tecidos de osteossarcoma. O RNA de interferência (siRNA) foi utilizado para reduzir a expressão do COL6A3 nas células, e o teste de contagem de células kit-8 (CCK-8) e a análise de formação de colônias foram realizados para examinar o potencial de proliferação celular. Além disso, o Transwell comprovou os efeitos do si-COL6A3 na invasão celular e migração em células de osteossarcoma. Para medir os níveis de expressão das proteínas e mRNAs, utilizamos transcriptase reversa quantitativa (qRT-PCR) e western blot. RESULTADOS O COL6A3 foi regulado nos tecidos e células do osteossarcoma quando comparado com o controle normal. A redução de COL6A3 reduziu a proliferação e a capacidades de formação de colônias em relação ao COL6A3 sem interferência. Do Mesmo modo, ao contrário do observado no grupo si-con, a invasão e migração celular foram inibidas no grupo si-COL6A3. Além disso, o resultado do western blot sugere que a via PI3K/AKT foi manipulada, medindo a expressão proteica dos marcadores relacionados à PI3K/AKT, devido à inibição do COL6A3. CONCLUSÃO O COL6A3 desempenha um papel crucial na modulação de vários aspectos da progressão do osteossarcoma, o que pode representar um possível tratamento eficaz para a doença.

SUMMARY OBJECTIVE In this study, we aimed to investigate the role of COL6A3 on cell motility and the PI3K/AKT signaling pathway in osteosarcoma. METHODS The relative expression of COL6A3 was achieved from a GEO dataset in osteosarcoma tissue. siRNA technology was applied to decrease the COL6A3 expression in cells, and cell counting kit-8 (CCK-8) assay and colony formation analysis were used to examine the cell proliferation potential. Knockdown COL6A3 made the proliferation and colony formation abilities worse than the COL6A3 without interference. Likewise, in contrast to the si-con group, cell invasion and migration were inhibited in the si-COL6A3 group. Moreover, the western blot results suggested that the PI3K/AKT signaling pathway was manipulated by measuring the protein expression of the PI3K/AKT pathway-related markers, due to the COL6A3 inhibition. CONCLUSION COL6A3 plays a crucial role in modulating various aspects of the progression of osteosarcoma, which would provide a potentially effective treatment for osteosarcoma.

Abstract Paired basic amino acid-cleaving enzyme 4 (PACE4), a proprotein convertase, is involved in the activation of aggrecanases (ADAMTS-4 and ADAMTS-5) in osteoarthritic and cytokine-stimulated cartilage. Activated aggrecanases cause aggrecan degradation and thus, contribute to osteoarthritis (OA). In this study, we investigated the association between PACE4 gene polymorphisms and OA risk. One single-nucleotide polymorphism (rs4965833) in the PACE4 gene was genotyped in 432 OA patients and 523 healthy controls using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Quantitative reverse transcription PCR (qRT-PCR) was used to determine the relative expression of PACE4 in blood samples from 90 OA patients (30 for each genotype). The relative expression level of PACE4 mRNA was higher in the GG genotype as compared to the AA/AG group. Moreover, the PACE4 rs4965833 polymorphism was associated with increased risk of OA, especially among individuals aged ≥55 years and with a body mass index ≥25. There was no significant association between the PACE4 rs4965833 polymorphism and clinical parameters of OA patients, such as erythrocyte sedimentation rate, C-reactive protein, Visual Analog Scale for pain and Lequesne’s index. In conclusion, the rs4965833 polymorphism in the 3’-UTR of PACE4 is associated with OA susceptibility.

Abstract In this paper, a novel zwitterionic copolymer AM/SSS/THDAB clay hydration dispersion inhibitor was synthesized by copolymerization of tris hydroxyethyl diallyl ammonium bromide (THDAB), sodium p-styrene sulfonate (SSS) and acrylamide (AM) initiated in an aqueous solution. The copolymer was characterized by FT-IR, GPC, TGA-DSC and SEM. Results demonstrated that molecular weight of AM/SSS/THDAB was 43674 g/mol and its temperature resistance ability was up to 225 °C. Evaluation experiments showed that AM/SSS/THDAB has an excellent clay hydration inhibitive performance. Methods including particle size analysis and SEM were utilized to study its dispersion inhibition mechanism by using sodium montmorillonite (Na-MMT). Results indicated that the micro-structure of Na-MMT has been successfully changed by AM/SSS/THDAB. In a word, the superior inhibition property makes the novel clay hydration dispersion inhibitor promised in water-based drilling fluids.

Abstract The goal of this research was to investigate the linkage disequilibrium between rs9263726 and HLA-B*58:01 in different Chinese ethnic groups (Han, Tibet, and Hui) and to study the feasibility of rs9263726 replacing HLA-B*58:01 as an efficient indicator of potential allopurinol hypersensitivity syndrome. In this study, rs9263726 and HLA-B*58:01 were detected in all samples. For samples of individuals whose rs9263726 genotypes were not consistent with HLA-B*58:01, we did high-resolution typing of HLA-B gene to further confirm the correlation of rs9263726 genotype and special HLA-B alleles. We confirmed that the linkage disequilibrium between rs9263726 and HLA-B*58:01 was more significant in the Han ethnic group (r2=0.886, D’=1.0) than in the Tibet and Hui ethnic groups (for Tibetan, r2=0.606, D’=0.866; for Hui, r2=0.622, D’=0.924). For Han Chinese, samples with the GG genotype of rs9263726 did not carry HLA-B*58:01, while AA genotype samples were homozygous carriers of HLA-B*58:01. However, GA genotype samples of rs9263726 required a more sophisticated HLA-B genotyping assay before it was possible to identify whether they were HLA-B*58:01 carriers or not. For Tibetan and Hui, the linkage disequilibrium between rs9263726 and HLA-B*58:01 was not significant. Therefore, rs9263726 cannot replace HLA-B*58:01 in these two groups.

CONTEXTO:Hemangiomas cavernosos da glândula adrenal são tumores neoplásicos raros, benignos. A apresentação clínica dos hemangiomas adrenais é geralmente vaga e muitas vezes eles são descobertos acidentalmente por exame imagiológico realizado por outras razões.RELATO DE CASO:Nós relatamos um caso de hemangioma adrenal não funcional encontrado por acaso em um homem de 37 anos de idade com histórico de um ano de dor de cabeça e hipertensão. Foi detectada massa adrenal direita por meio de ressonância magnética. Exame físico e todos os valores de laboratoriais estavam normais. O paciente foi submetido a cirurgia laparoscópica para ressecção da glândula adrenal direita. Avaliação histopatológica confirmou hemangioma adrenal cavernoso.CONCLUSÃO:A maioria dos hemangiomas cavernosos de glândula adrenal são não funcionais e muitas vezes descobertos por acaso. Embora raras, essas massas adrenais benignas devem ser parte de um diagnóstico diferencial de neoplasias suprarrenais. O tratamento adequado para o hemangioma adrenal cavernoso é a remoção cirúrgica.

CONTEXT:Cavernous hemangiomas of the adrenal gland are rare benign neoplastic tumors. The clinical presentation of adrenal hemangiomas is usually vague, and they are often discovered incidentally through imaging examination s performed for other reasons.CASE REPORT:We report the case of a non-functional adrenal hemangioma found incidentally in a 37-year-old man with a one-year history of headache and hypertension. A right adrenal mass was detected by means of magnetic resonance imaging. Physical examination and all laboratory values were unremarkable. The patient underwent laparoscopic right adrenal gland resection. Histopathological evaluation confirmed adrenal cavernous hemangioma.CONCLUSIONS:Most occurrences of cavernous hemangiomas of the adrenal gland are non-functional and often discovered incidentally. Although rare, these unusual benign adrenal masses should form part of the differential diagnosis of adrenal neoplasms. The proper treatment for adrenal cavernous hemangioma is surgical removal.

Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer.