AbstractBackgroundImmune checkpoints play crucial roles in immune escape of cancer cells. However, the exact prognostic values of expression and methylation of programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1) and PD-L2 in low-grade glioma (LGG) have not been defined yet.MethodsA total of 514 LGG samples from TCGA dataset containing both PD-1, PD-L1 and PD-L2 expression, DNA methylation, and survival data were enrolled into our study. The clinical significance of PD-1/PD-Ls expression and methylation in LGG were explored. Besides, the correlation between PD-1/PD-Ls expression and methylation with the infiltration levels of tumor-infiltrating immune cells (TIICs) was assessed. Moreover, GO enticement analysis of PD-1/PD-Ls co-expressed genes was performed as well. R 3.6.2 and GraphPad Prism 8 were applied as main tools for the statistical analysis and graphical exhibition.ResultsPD-1/PD-Ls had distinct co-expression patterns in LGG tissues. The expression and methylation status of PD-1/PD-Ls seemed to be various in different LGG subtypes. Besides, upregulated PD-1/PD-Ls expression and hypo-methylation of PD-1/PD-Ls were associated with worse survival in LGG patients. In addition, PD-1/PD-Ls expression was revealed to be positively associated with TIICs infiltration, while their methylation was negatively associated with TIICs infiltration. Moreover, the PD-1/PDLs correlated gene profiles screening and Gene Ontology (GO) enrichment analysis uncovered that PD-1/PDLs and their positively correlated gene mainly participated in immune response related biological processes.ConclusionsHigh expression and hypo-methylation of PD-1/PD-Ls significantly correlated with unfavorable survival in LGG patients, suggesting LGG patients may benefit from PD1/PD-Ls checkpoint inhibitors treatment.

Periampullary diverticula (PAD) often detected during endoscopic retrograde cholangiopancreatography (ERCP), and ERCP remains the primary approach to treating bile duct stones, and papilla cannulation plays a critical role in the success of ERCP. PAD can reduce the cannulation success rate. Needle knife precut greatly promoted the clinical application of precut incision. However, this approach also increases the risk of various adverse events. The present study aimed to compare the perioperative outcomes of pancreatic duct guide wire-assisted needle knife precut and conventional needle knife precut for PAD with difficult cannulation. A total of 230 cases of PAD with difficult cannulation of the duodenal papilla diagnosed by ERCP between June 2009 and December 2021 were retrospectively reviewed. The exclusion criteria were set as follows: patients with ERCP history, coagulopathy prothrombin time two times longer or platelet (PLT) count ≤70×109/L, or an inability to tolerate endoscopy due to severe heart/lung diseases. Pancreatic duct guide wire-assisted needle knife precut (Group A) was performed in 135 cases, and conventional needle knife precut (Group B) was performed in 95 cases. All clinical data were analyzed retrospectively. SPSS20.0 statistical software was used for the t-test and analysis of variance. P<0.05 was considered statistically significant. The operating time of the needle knife precut was significantly shorter in Group A (18.44±6.65 min) compared with Group B (32.05±13.15 min, P<0.01). Moreover, the success rate of the cannulation was markedly higher in Group A (100%, 135/135) compared with Group B (78.9%, 75/95). Intraoperative complications occurred in 15 (11.1%) and 26 (27.4%) cases in Groups A and B, respectively (P<0.01). Postoperative complications occurred in 10 (7.4%) and 17 (17.9%) cases in Groups A and B, respectively (P<0.01). Our results showed notable differences in the operating time, success rate of cannulation, intraoperative complication rates, and postoperative complication rates between the two approaches. Pancreatic duct guide wire-assisted needle knife precut appeared to be a safe and effective modality for PAD with difficult cannulation in the duodenal papilla.

The objective is to integrate all the eligible studies and investigate whether the programmed cell death 1 (PDCD-1) gene polymorphisms (PD 1.3 G/A, PD 1.5 C/T, and PD 1.9 C/T polymorphism) are correlated with ankylosing spondylitis risk (AS). Ankylosing spondylitis is a chronic inflammatory disease, and several genetic and environmental factors play an important role in the development and progression of AS. Significant associations between PDCD-1 gene polymorphisms (PD 1.3 G/A, PD 1.5 C/T or PD 1.9 C/T) and AS risk have been reported; however, some of these results are controversial. A systematic online search was performed using PubMed, EMBASE, Web of Science, and the Cochrane Library to identify case-control studies investigating the relationship between PD 1.3 G/A, PD 1.5 C/T, and PD 1.9 C/T polymorphisms and the susceptibility of AS. The pooled odds ratio (OR) with 95 % confidence interval (CI; 95 %) was calculated to assess the associations, and subgroup meta-analyses were performed according to the ethnicity of the study populations. Five studies involving 909 cases and 982 controls met the inclusion criteria after assessment by two reviewers. Overall, there were no significant associations between PD 1.3 G/A and PD 1.5 C/T polymorphisms and AS risk. With regard to PD 1.9 C/T polymorphism, a significant association was found under the allele contrast model (T vs. C: OR 1.74, 95 % CI 1.48-2.06, P < 0.001), heterozygote model (CT vs. CC: OR 2.43, 95 % CI 1.65-3.59, P < 0.001), homozygote model (TT vs. CC: OR 1.87, 95 % CI 1.30-2.71, P = 0.001), and dominant model (CT/TT vs. CC: OR 2.29, 95 % CI 1.65-3.18, P < 0.001). In the subgroup analysis of ethnicity, no significant associations were found between PD 1.3 G/A, PD 1.5 C/T polymorphisms, and AS risk in either Asian or Caucasian populations. However, our study suggested that PD 1.9 C/T polymorphism was significantly associated with AS in Asian populations (T vs. C: OR 1.72, 95 % CI 1.46-2.04, P < 0.001; CT vs. CC: OR 2.44, 95 % CI 1.56-3.82, P < 0.001; TT vs. CC: OR 1.88, 95 % CI 1.30-2.73, P = 0.001; and CT/TT vs. CC: OR 2.29, 95 % CI 1.58-3.32, P < 0.001) but not in Caucasian populations. The PD 1.9 C/T polymorphism may be involved in susceptibility to AS, particular in Asian populations; however, no significant associations were found between PD 1.3 G/A, PD 1.5 C/T polymorphisms, and AS risk in either Asians or Caucasians.

Summary Objective To investigate the contribution of needle electrode electromyography (EMG) in the diagnosis of vaginismus. Methods The electromyograhic activity of ischio-cavernosus and bulbo-cavernosus muscles was recorded by using a concentric needle EMG on 9 women with vaginismus, then compared to the EMG activity of no vaginismus women. The agreement between the needle electrode EMG and clinical exam was assessed by measuring the Cohen Kappa coefficient. Results The EMG was abnormal in 7 women presenting vaginismus by showing a significant reactivity after stimulating the vaginal introitus. A hyperexcitability was found in 4 cases. The EMG and clinical findings presented a high level of agreement. Conclusion The pelvic floor muscles in vaginismus patients showed an increased EMG activity at rest and on induction of vaginismus. The needle electrode EMG can be useful for the diagnosis of vaginismus.

Objectives The feasibility and safety of direct needle insufflation to create pneumoretroperitoneum was assessed by an imaging study and clinical experience. Methods A total of 10 patients without previous retroperitoneal surgery or diseases received computed tomography scans of the retroperitoneum 2 cm above the iliac crest. Distances between quadratus lumborum and colon (Q-C distance) were measured in the supine and lateral positions. Changes of Q-C distance were calculated when the patient was changed from the supine to the lateral position. Operative charts on 38 retroperitoneoscopic procedures were collected prospectively to assess complications related to direct needle insufflation, which was performed by inserting a 14 G Veress needle blindly along the posterior axillary line 2 cm above the iliac crest. Results Q-C distance increased from 8.7 to 27.3 mm (left side) and 4.6 to 18.1 mm (right side) when the patient was changed from the supine to the lateral position, both P values <0.05. An average distance of 23 mm between colon and quadratus lumborum was found when patients were lying laterally. The misplacement of a Veress needle was encountered in 1 patient, in which a prefascia insufflation resulted in conversion of the endoscopic procedure. Needle puncture caused no visceral or great vessel injury. Conclusions Significant anterior movement of the colon was found when patients were changed from the supine to the lateral position. It provided a window for inserting the Veress needle blindly into the retroperitoneum. The high success rate (97%) and low complication rate of direct needle insufflation were found in actual clinical applications. We considered needle insufflation a safe and effective method of establishing a pneumoretroperitoneum for any retroperitoneoscopic procedure.

Programmed-cell-death 1 (PD-1) expression is associated not only with T-cell activation but with exhaustion. Specifically, PD-1+ T cells present an exhausted phenotype in conditions of chronic antigen exposure, such as tumor microenvironments and chronic viral infection. However, the immune status regarding exhaustion of PD-1+CD8+ T cells in chronic autoimmune diseases including idiopathic inflammatory myopathies (IIMs) remains unclear. We aimed to clarify the role of PD-1+CD8+ T cells and PD-1 ligand (PD-L1) in IIMs. We showed that PD-1+ cells infiltrated into PD-L1-expressing muscles in patients with IIMs and immune checkpoint inhibitor-related myopathy. According to the peripheral blood immunophenotyping, the PD-1+CD8+ cell proportions were comparable between the active and inactive patients. Of note, PD-1+CD8+ cells in the active patients highly expressed cytolytic molecules, indicating their activation, while PD-1−CD8+ cells expressed low levels of cytolytic molecules in the active and inactive patients. A part of PD-1+CD8+ cells expressed the HMG-box transcription factor TOX highly and presented the exhausted phenotype in the active patients. Among PD-1+CD4+ T cells, PD-1highCXCR5−CD45RO+CD4+ peripheral helper T cells were increased in the active patients. PD-L1-deficient mice developed severer C-protein-induced myositis (CIM), a model of polymyositis, with abundant infiltration of PD-1+CD8+ cells expressing cytolytic molecules than wild-type mice, indicating pathogenicity of the PD-1+CD8+ cells and the protective role of PD-L1. The deficiency of IFNγ, a general PD-L1-inducer, impaired muscular PD-L1 expression and exacerbated CIM, indicating IFNγ-dependent muscular PD-L1 regulation. IFNγ-induced PD-L1 on myotubes was protective in an established muscle injury model. In conclusion, PD-1+CD8+ T cells rather than PD-1−CD8+ T cells were a pathogenic subset of IIMs. Muscular PD-L1 was regulated by IFNγ and exerted protective properties in IIMs.

The role of palladium precursors (e.g. chloride — PdCl 2; acetylacetonate — Pd(acac) 2; nitrate — Pd(NO 3) 2) in the catalytic properties of Pd/Al 2O 3 and Pd/CeO 2/Al 2O 3 catalysts toward CO oxidation was herein investigated. The characterization techniques used for mapping the Pd sites were H 2 and CO chemisorption, infrared spectroscopy (FTIR) of CO adsorbed, and temperature-programmed desorption (TPD). Unsteady-state CO oxidation was carried out by temperature-programmed surface reaction (TPSR). The nature of palladium precursors and their interaction with CeO 2 affected the metallic dispersion and the site morphologies. Highly dispersed metal particles ( d>50%) were obtained by using palladium chloride and acetylacetonate precursors on Pd/Al 2O 3 catalysts. Pd(1 0 0) and Pd(1 1 1) were the major palladium crystallite orientations in these samples, but a larger amount of low coordination sites located on Pd(1 0 0) faces was observed for the ex-chloride sample. These sites accounted for the oxidation of CO at very low temperatures on Pd-Cl catalyst. In the presence of ceria, the Pd dispersion was a function of the way in which each Pd precursors interacted with CeO 2. A two-fold decrease of dispersion was obtained to ex-chloride sample, while a two-fold increase to ex-nitrate and the same dispersion to ex-acetylacetonate samples were otherwise observed. The metallic redispersion may be the result of the occupancy of ceria oxygen vacancies by the palladium crystallites. Ultimately, the interaction with ceria redispersed Pd crystallites in a more organized bi-dimensional structure with the predominance of (1 1 1) orientation. Due to the transient conditions of the reaction, ceria did not promote, as expected, the oxidation of CO. Ceria reduced species (Ce 3+) were not able to help CO oxidize at lower temperatures due to lack of oxygen into its lattice. Thus, the highest rates for CO oxidation were only observed at higher temperatures for the Pd/CeO 2/Al 2O 3 catalysts, a result of a combination of strong competition for oxygen molecules, which have replenished the ceria lattice, and the low activity of Pd(1 1 1) sites.

The present systematic review and meta-analysis aimed to evaluate the available evidence base on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) combined with either endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or endoscopic ultrasound using the EBUS scope-guided fine-needle aspiration (EUS-B-FNA) for diagnosing and staging mediastinal diseases.PubMed, Web of Science, and Embase were searched to identify suitable studies up to June 30, 2019. Two investigators independently reviewed articles and extracted relevant data. Data were pooled using random effect models to calculate diagnostic indices that included sensitivity and specificity. Summary receiver operating characteristic (SROC) curves were used to summarize the overall test performance.Data pooled from up to 16 eligible studies (including 10 studies of 963 patients about EBUS-TBNA with EUS-FNA and six studies of 815 patients with EUS-B-FNA) indicated that combining EBUS-TBNA with EUS-FNA was associated with slightly better diagnostic accuracy than combining it with EUS-B-FNA, in terms of sensitivity (0.87, 95%CI 0.83 to 0.90 vs. 0.84, 95%CI 0.80 to 0.88), specificity (1.00, 95%CI 0.99 to 1.00 vs. 0.96, 95%CI 0.93 to 0.97), diagnostic odds ratio (413.39, 95%CI 179.99 to 949.48 vs. 256.38, 95%CI 45.48 to 1445.32), and area under the SROC curve (0.99, 95%CI 0.97 to 1.00 vs. 0.97, 95%CI 0.92 to 1.00).The current evidence suggests that the combination of EBUS-TBNA with either EUS-FNA or EUS-B-FNA provides relatively high accuracy for diagnosing mediastinal diseases. The combination with EUS-FNA may be slightly better.

The biomorphic mineralization technique is a powerful tool that allows to synthetize inorganic materials using as templates some structures of biological origin. This work presents kinetics results obtained during the liquid-phase hydrogenation of cyclohexene using a novel Pd–Al catalyst supported on biomorphic carbon.The catalysts have been prepared by a reactive method, using cellulose as carbonaceous precursor of the biomorphic support. The influence of the time and decomposition temperature (600–800°C) of cellulose under hydrogen atmosphere has been studied. The characterization results indicate that the synthesis of these biomorphic materials produce solids with high microporosity. The metallic dispersion of the Pd nanoparticles is strongly dependent on the preparation conditions (i.e. heating rate, thermal decomposition temperature and time) of the carbonaceous precursor.The kinetic study has covered the effect of the hydrogen pressure and temperature, and was carried out using a real-time in situ Raman probe. The developed kinetic model considers the non-competitive adsorption between hydrogen and cyclohexene in two different types of Pd metallic sites. The model explains all the experimental results obtained, providing a rational explanation for the variation of the kinetic orders and apparent activation energy obtained using the empirical power-law model.

Background:Recently, EUS-guided fine-needle biopsy (EUS-FNB) using a Franseen needle was developed for histological tissue acquisition. However, the yield of a 25G Franseen needle when acquiring histological core tissue has been unclear.Patients and Methods:We performed a prospective, multicenter, and observational cohort study that included 100 solid lesions scheduled for EUS-FNB using a 25G Franseen needle at eight centers in Hokkaido, Japan. Only EUS-FNB specimens acquired at the first pass were evaluated without a rapid on-site evaluation. The tissue acquisition rate, acquisition rate of an adequate specimen for histological assessment, the quality of tissue sample, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic accuracy, and adverse events were evaluated.Results:We analyzed a total of 100 solid lesions in 100 patients. The patients were 57 males and 43 females with a median age of 70 years. The technical success rate was 100%. The tissue acquisition rate was 95.0%. The acquisition rate of an adequate specimen for histological assessment was 82.0%. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy were 87.0%, 100%, 100%, 40.0%, and 88.0%, respectively. The adverse event rate was 1.0%, and it was reported in only one patient who had a moderate pancreatic fistula.Conclusions:EUS-FNB using the 25G Franseen needle was feasible, and adequate histological core tissue samples were acquired with this method.