Allogeneic CAR-T cells with of HLA-A/B and TRAC disruption exhibit promising antitumor capacity against B cell malignancies.

BACKGROUND: Although chimeric antigen receptor T (CAR-T) cells have been proven to be an effective way of treating B cell malignancies, a lot of patients could not benefit from it because of failure in CAR-T cell manufacturing, disease progression, and unaffordable price. The study aimed to explore universal CAR-T cell products to extend the clinical accessibility. METHODS: The antitumor activity of CRISPR/Cas9-edited allogeneic anti-CD19 CAR-T (CAR-T19) cells was assessed in vitro, in animal models, and in patients with relapsed/refractory (R/R) acute B cell lymphoblastic leukemia (B-ALL) or diffuse large B cell lymphoma. RESULTS: B2M-/TRAC- universal CAR-T19 (U-CAR-T19) cells exhibited powerful anti-leukemia abilities both in vitro and in animal models, as did primary CD19+ leukemia cells from leukemia patients. However, expansion, antitumor efficacy, or graft-versus-host-disease (GvHD) was not observed in six patients with R/R B cell malignancies after U-CAR-T19 cell infusion. Accordingly, significant activation of natural killer (NK) cells by U-CAR-T19 cells was proven both clinically and in vitro. HLA-A-/B-/TRAC- novel CAR-T19 (nU-CAR-T19) cells were constructed with similar tumoricidal capacity but resistance to NK cells in vitro. Surprisingly, robust expansion of nU-CAR-T19 cells, along with rapid eradication of CD19+ abnormal B cells, was observed in the peripheral blood and bone marrow of another three patients with R/R B-ALL. The patients achieved complete remission with no detectable minimal residual disease 14 days after the infusion of nU-CAR-T19 cells. Two of the three patients had grade 2 cytokine release syndrome, which were managed using an IL-6 receptor blocker. Most importantly, GvHD was not observed in any patient, suggesting the safety of TRAC-disrupted CAR-T cells generated using the CRISPR/Cas9 method for clinical application. CONCLUSIONS: The nU-CAR-T19 cells showed a strong response in R/R B-ALL. nU-CAR-T19 cells have the potential to be a promising new approach for treating R/R B cell malignancies.

The correlation between the main and minor lesions of synchronous multiple gastric neoplasms assessed gastroscopically and microscopically.

BACKGROUND: Patients with early gastric cancer (EGC) are at high risk of developing synchronous multiple gastric neoplasms (SMGNs) after undergoing endoscopic submucosal dissection (ESD). However, most previous studies have had small sample sizes, and few have focused on association studies. AIMS: This study aimed to analyze the associations between SMGN lesion data from patients with EGC treated with ESD and their correlation coefficients. METHODS: The clinical ESD data from two hospitals from January 2008 to January 2021 were retrospectively analyzed. The main lesions were defined as those with a significant depth of infiltration. The larger tumor diameter was considered the main lesion if the lesions had the same infiltration depth. RESULTS: Of the 1013 post-ESD cases examined, 95 cases (223 lesions) had SMGN, and 25 patients had more than three lesions. For the correlation analysis, 190 lesions were included. The study revealed a similarity in pathological type between main and minor lesions (rs = 0.37) and a positive correlation in infiltration depth (rs = 0.58). The mean diameter sizes of the main and minor lesions were 20.7 ± 8.3 mm and 13.1 ± 6.4 mm, respectively, with statistically significant differences (P < 0.001). A linear correlation was observed between the diameter size and a linear regression model was constructed, producing r = 0.38 [95% confidence interval (CI) 0.19-0.54], b = 0.29 (95% CI 0.14-0.44), t = 3.94, P < 0.001]. A correlation was identified between the vertical distribution of the main and minor lesions, the horizontal distribution, and the gross endoscopic morphology (ϕc = 0.25, P = 0.02; ϕc = 0.32, P < 0.001; ϕc = 0.60, P < 0.001). CONCLUSIONS: The correlation coefficients for microscopic characteristics were higher than those for gastroscopy. There is a significant positive correlation between the main and minor lesions regarding pathological stage and depth of infiltration, respectively. The spatial distribution of the lesions and the gastroscopic morphology were similar.

Classification of Isatis indigotica Fortune and Isatis tinctoria Linnaeus via comparative analysis of chloroplast genomes.

BACKGROUND: Isatis tinctoria Linnaeus and Isatis indigotica Fortune are very inconsistent in their morphological characteristics, but the Flora of China treats them as the same species. In this work, a new technology that differs from conventional barcodes is developed to prove that they are different species and to clarify their classification. RESULTS AND METHODS: I. indigotica was indistinguishable from I. tinctoria when using ITS2. CPGAVAS2 was used to construct the chloroplast genomes. MAFFT and DnaSP were used to calculate nucleotide polymorphism, the chloroplast genomes of the two have high diversity in the rpl32 ~ trnL-UAG short region. When using this region as a mini barcode, it was found that there are obvious differences in the base numbers of I. tinctoria and different ploidy I. indigotica were found, but diploid and tetraploid I. indigotica had the same number of bases. Moreover, the reconstruction of the maximum likelihood (ML) tree, utilizing the mini-barcode, demonstrated that I. tinctoria and both diploid and tetraploid I. indigotica are located on distinct branches. The genome size of tetraploid I. indigotica was approximately 643.773 MB, the heterozygosity rate was approximately 0.98%, and the repeat sequence content was approximately 90.43%. This species has a highly heterozygous, extremely repetitive genome. CONCLUSION: A new method was established to differentiate between I. indigotica and I. tinctoria. Furthermore, this approach provides a reference and basis for the directional breeding of Isatis.

Adjuvant cytokine-induced killer cell immunotherapy improves long-term survival in patients with stage I-II non-small cell lung cancer after curative surgery.

BACKGROUND AIMS: Non-small cell lung cancer (NSCLC) remains the most common cancer worldwide, with an annual incidence of around 1.3 million. Surgery represents the standard treatment in early-stage NSCLC when feasible. However, because of cancer recurrence, only approximately 53% of patients with stage I and II NSCLC survive 5 years after radical surgery. The authors performed a retrospective study to investigate the impact of cytokine-induced killer (CIK) cell immunotherapy on the long-term survival of patients with stage I-II NSCLC after curative resection. METHODS: Fifty-seven patients with NSCLC were included in the study, with 41 and 16 in the control and CIK groups, respectively. Clinical characteristics were compared using a t-test and χ2 test. Survival analysis of patients with NSCLC was performed using the Kaplan-Meier method. The phenotypes and anti-tumor functions of CIK cells were evaluated by flow cytometry. RESULTS: Patients in the CIK group exhibited significantly longer overall survival (OS) and better disease-free survival (DFS) than those in the control group. Subgroup analysis indicated that patients with a higher risk of recurrence benefited more from CIK treatment and attained longer OS and DFS compared with those in the control group. No severe adverse events related to CIK treatment occurred. CIK cells contained a higher proportion of CD3+CD56+ natural killer (NK) T cells and CD3+ and CD8+ T cells and a lower proportion of CD3-CD56+ NK cells compared with peripheral blood mononuclear cells. CIK cells exhibited potent tumor-killing ability, with longer contact times with tumor cells and a greater number of cells exposed to tumor cells. CONCLUSIONS: The authors' data suggest that adjuvant CIK cell therapy is a safe and effective therapeutic strategy for improving OS and DFS in patients with stage I-II NSCLC after curative resection.

Validation of the EKFC equation for glomerular filtration rate estimation and comparison with the Asian-modified CKD-EPI equation in Chinese chronic kidney disease patients in an external study.

OBJECTIVES: The aim of this study is to determine whether new European Kidney Function Consortium (EKFC) equation is more applicable than Asian-modified CKD-EPI equation in clinical practice, having a higher accuracy in estimating GFR in our external CKD population. METHODS: We calculated estimated GFREKFC and GFRCKD-EPI independently using the EKFC and Asian-modified CKD-EPI formulas, respectively. The clinical diagnostic performance of the two equations was assessed and compared by median bias, precision, accuracy (P30) and so on, using 99mTc-DTPA dual plasma sample clearance method as a reference method for GFR measurement (mGFR). The equation that met the following targets was superior: (1) median bias within ± 3 mL/min/1.73 m2; (2) P30 > 75%; and (3) better precision and 95% limits of agreement in Bland-Altman analysis. RESULTS: Totally, 160 CKD patients were recruited in our external cohort. GFREKFC was highly related to mGFR, with a regression equation of GFREKFC=mGFR × 0.87 + 5.27. Compared with the Asian-modified CKD-EPI equation, EKFC equation demonstrated a wider median bias (-1.64 vs. 0.84 mL/min/1.73 m2, p < 0.01) that was within 3 mL/min/1.73 m2 and not clinically meaningful. Furthermore, the precision (12.69 vs. 12.72 mL/min/1.73 m2, p = 0.42), 95% limits of agreement in Bland-Altman analysis (42.4 vs. 44.4 mL/min/1.73 m2) and incorrect reclassification index of the two target equations were almost identical. Although, EKFC equation had a slightly better P30 (80.0% vs. 74.4%, p = 0.01). CONCLUSIONS: The overall performance of EKFC equation is acceptable. There is no clinically meaningful difference in the performance of the Asian-modified CKD-EPI and EKFC equations within the limits imposed by the small sample size.

Chemisorption-Induced Formation of Biphenylene Dimer on Ag(111).

We report an example that demonstrates the clear interdependence between surface-supported reactions and molecular-adsorption configurations. Two biphenyl-based molecules with two and four bromine substituents, i.e., 2,2'-dibromobiphenyl (DBBP) and 2,2',6,6'-tetrabromo-1,1'-biphenyl (TBBP), show completely different reaction pathways on a Ag(111) surface, leading to the selective formation of dibenzo[e,l]pyrene and biphenylene dimer, respectively. By combining low-temperature scanning tunneling microscopy, synchrotron radiation photoemission spectroscopy, and density functional theory calculations, we unravel the underlying reaction mechanism. After debromination, a biradical biphenyl can be stabilized by surface Ag adatoms, while a four-radical biphenyl undergoes spontaneous intramolecular annulation due to its extreme instability on Ag(111). Such different chemisorption-induced precursor states between DBBP and TBBP consequently lead to different reaction pathways after further annealing. In addition, using bond-resolving scanning tunneling microscopy and scanning tunneling spectroscopy, we determine with atomic precision the bond-length alternation of the biphenylene dimer product, which contains 4-, 6-, and 8-membered rings. The 4-membered ring units turn out to be radialene structures.

Long-term clinical efficacy of cytokine-induced killer cell-based immunotherapy in early-stage esophageal squamous cell carcinoma.

BACKGROUND AIMS: In this retrospective clinical study, the authors investigated the impact of cytokine-induced killer (CIK) cell-based immunotherapies on the long-term survival of patients with esophageal squamous cell carcinoma (ESCC). METHODS: A total of 87 patients with ESCC who received comprehensive treatment were enrolled in the study. Of these patients, 43 were in the control group and 44 were in the CIK treatment group. Flow cytometry analysis was performed to detect the phenotype and anti-tumor function of CIK cells. Clinical characteristics were compared between these two groups, and the survival estimates of ESCC patients were determined using Kaplan-Meier analysis. RESULTS: CIK cells contained a high proportion of the main functional fraction (CD3+CD56+ group) and exhibited a strong killing ability for esophageal cancer cells in vitro. Importantly, overall survival (OS) and progression-free survival (PFS) were significantly higher in the CIK group than in the control group in early-stage ESCC. However, patients with advanced-stage ESCC did not benefit from CIK cell-based therapy in terms of OS and PFS compared with the control group. CONCLUSIONS: These results demonstrate that CIK cells combined with conventional treatments potentially prolong long-term survival of patients and may serve as a combined therapeutic approach for the treatment of early-stage ESCC.

Association of BIRC5 Gene Polymorphism with the Collateral Circulation and Severity of Large Artery Atherosclerotic Stroke.

Objectives: The collateral circulation near the cerebral artery occlusion can contribute to the relief of the symptoms and signs of stroke. Genetic factors play a decisive role in the difference in collateral circulation. Survivin, encoded by the baculoviral inhibitor of apoptosis (IAP) repeat-containing 5 gene (BIRC5), plays an important role in maintaining long-term endothelial integrity and homeostasis and as an angiogenic factor in the treatment of vascular diseases. We hypothesized that genetic variations in the BIRC5 gene may contribute to severity by influencing the collateral circulation. This study aimed at examining how the polymorphism of the BIRC5 gene correlated with the collateral circulation and severity of large artery atherosclerotic stroke. Methods: This study enrolled 428 patients with large artery atherosclerotic stroke. There are no statistical differences in age, sex, social behavior, such as smoking and drinking, between the groups classified by the collateral circulation and by the severity of stroke (P > 0.01). Direct sequencing was performed for the genotyping of single nucleotide polymorphism (SNP) of BIRC5 (rs2071214). The enrolled patients were divided into several subgroups based on the collateral flow grading system from the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR), the results of the National Institutes of Health Stroke Survey (NIHSS) (6 as a threshold), and the score of the modified Rankin scale (mRS) (for the prediction of prognosis, 2 as a threshold). Differences among subgroups were identified through logistic regression. Results: The analysis of collateral circulation revealed the significant correlation of SNP of rs2071214 with the development of poor collateral circulation of large artery atherosclerotic stroke in the additive model (GG vs. AA, odds ratio (OR) = 3.592, 95% confidence interval (CI) = 1.410-9.150, and P=0.007) and the recessive model (GG vs. AA/GA, OR = 3.313, 95% CI = 1.420-7.727, and P=0.006). The analysis of stroke severity exposed the significant role of the SNP of rs2071214 in increasing stroke severity in the dominant model (GA/GG vs. AA, OR = 1.658, 95% CI = 1.017-2.703, and P=0.043) and the additive model (GA vs. AA, OR = 1.717, 95% CI = 1.021-2.888, and P=0.042). However, the analysis of the short-term outcome indicated that three genetic models were not associated with short-term outcomes in the additive model (GA vs. AA, P=0.815, GG vs. AA, and P=0.336), the dominant model (GA/GG vs. AA and P=0.589), and the recessive model (GG vs. AA/GA and P=0.342). Conclusion: Our findings identified the SNP of rs2071214 of the BIRC5 gene as a risk factor for the poor compensatory ability of collateral circulation and a predictor of stroke severity in large artery atherosclerotic stroke, which suggested that the SNP of rs2071214 can serve as an innovative therapeutic target for patients with acute ischemic stroke.

The ensemble learning model is not better than the Asian modified CKD-EPI equation for glomerular filtration rate estimation in Chinese CKD patients in the external validation study.

OBJECTIVE: To assess the clinical practicability of the ensemble learning model established by Liu et al. in estimating glomerular filtration rate (GFR) and validate whether it is a better model than the Asian modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in a cohort of Chinese chronic kidney disease (CKD) patients in an external validation study. METHODS: According to the ensemble learning model and the Asian modified CKD-EPI equation, we calculated estimated GFRensemble and GFRCKD-EPI, separately. Diagnostic performance of the two models was assessed and compared by correlation coefficient, regression equation, Bland-Altman analysis, bias, precision and P30 under the premise of 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) dual plasma sample clearance method as reference method for GFR measurement (mGFR). RESULTS: A total of 158 Chinese CKD patients were included in our external validation study. The GFRensemble was highly related with mGFR, with the correlation coefficient of 0.94. However, regression equation of GFRensemble = 0.66*mGFR + 23.05, the regression coefficient was far away from one, and the intercept was wide. Compared with the Asian modified CKD-EPI equation, the diagnostic performance of the ensemble learning model also demonstrated a wider 95% limit of agreement in Bland-Altman analysis (52.6 vs 42.4 ml/min/1.73 m2), a poorer bias (8.0 vs 1.0 ml/min/1.73 m2, P = 0.02), an inferior precision (18.4 vs 12.7 ml/min/1.73 m2, P < 0.001) and a lower P30 (58.9% vs 74.1%, P < 0.001). CONCLUSIONS: Our study showed that the ensemble learning model cannot replace the Asian modified CKD-EPI equation for the first choice for GFR estimation in overall Chinese CKD patients.

Single-molecule detection of cancer mutations using a novel PCR-LDR-qPCR assay.

Detection of low-abundance mutations in cell-free DNA is being used to identify early cancer and early cancer recurrence. Here, we report a new PCR-LDR-qPCR assay capable of detecting point mutations at a single-molecule resolution in the presence of an excess of wild-type DNA. Major features of the assay include selective amplification and detection of mutant DNA employing multiple nested primer-binding regions as well as wild-type sequence blocking oligonucleotides, prevention of carryover contamination, spatial sample dilution, and detection of multiple mutations in the same position. Our method was tested to interrogate the following common cancer somatic mutations: BRAF:c.1799T>A (p.Val600Glu), TP53:c.743G>A (p.Arg248Gln), KRAS:c.35G>C (p.Gly12Ala), KRAS:c.35G>T (p.Gly12Val), KRAS:c.35G>A (p.Gly12Asp), KRAS:c.34G>T (p.Gly12Cys), and KRAS:c.34G>A (p.Gly12Ser). The single-well version of the assay detected 2-5 copies of these mutations, when diluted with 10,000 genome equivalents (GE) of wild-type human genomic DNA (hgDNA) from buffy coat. A 12-well (pixel) version of the assay was capable of single-molecule detection of the aforementioned mutations at TP53, BRAF, and KRAS (specifically p.Gly12Val and p.Gly12Cys), mixed with 1,000-2,250 GE of wild-type hgDNA from plasma or buffy coat. The assay described herein is highly sensitive, specific, and robust, and potentially useful in liquid biopsies.

Efficacy of cascade-primed cell infusion as an adjuvant immunotherapy with concurrent chemotherapy for patients with non-small-cell lung cancer: A retrospective observational study with a 5-year follow-up.

BACKGROUND: Clinical studies have shown the efficacy of combination therapy for various malignancies. In this study, the characteristics, safety and feasibility of use of cascade-primed (CAPRI) cells for the combination treatment of non-small-cell lung cancer (NSCLC) were evaluated both in vitro and in vivo. METHODS: Sixty-five patients with stage II-IV NSCLC were recruited. Of these patients, 31 patients received CAPRI cell therapy combined with chemotherapy (CAPRI group), and the other 34 patients constituted the control group and received chemotherapy alone. This study primarily aimed to evaluate the overall survival (OS), progression-free survival (PFS), short-term responses and treatment efficacy. RESULTS: CD83, CD1a, CD80 and CD86 marker levels were significantly upregulated in CAPRI cells. Interferon-γ expression levels were highest in CD3+CD8+ cells (33.77% ± 4.40%). Furthermore, interleukin-2 levels were highest in CD3+CD56+ cells (26.73% ± 6.63%), whereas perforin expression levels were similar in CD3+CD8+ and CD3+CD56+ cells. Furthermore, CAPRI cells had a better anti-tumor potential in CD3+CD56+ cells and displayed the highest expression levels of CD107a to H460 and A549 cell lines. The 5-year OS was significantly greater in the CAPRI group than in the control group (P = 0.008), and the PFS of two groups exhibited a significant difference (P = 0.007). Median OS (48 versus 31.6 months; P = 0.004) and PFS (48 versus 36.4 months; P = 0.016) differed between these two groups. Moreover, treatment-associated toxicities were mild and well-tolerated by patients with NSCLC. CONCLUSION: CAPRI cell therapy potentially prolongs the survival of patients with NSCLC when combined with chemotherapy.

Prediction of blood-based biomarkers and subsequent design of bisulfite PCR-LDR-qPCR assay for breast cancer detection.

BACKGROUND: Interrogation of site-specific CpG methylation in circulating tumor DNAs (ctDNAs) has been employed in a number of studies for early detection of breast cancer (BrCa). In many of these studies, the markers were identified based on known biology of BrCa progression, and interrogated using methyl-specific PCR (MSP), a technique involving bisulfite conversion, PCR, and qPCR. METHODS: In this report, we are demonstrating the development of a novel assay (Multiplex Bisulfite PCR-LDR-qPCR) which can potentially offer improvements to MSP, by integrating additional steps such as ligase detection reaction (LDR), methylated CpG target enrichment, carryover protection (use of uracil DNA glycosylase), and minimization of primer-dimer formation (use of ribose primers and RNAseH2). The assay is designed to for breast cancer-specific CpG markers identified through integrated analyses of publicly available genome-wide methylation datasets for 31 types of primary tumors (including BrCa), as well as matching normal tissues, and peripheral blood. RESULTS: Our results indicate that the PCR-LDR-qPCR assay is capable of detecting ~ 30 methylated copies of each of 3 BrCa-specific CpG markers, when mixed with excess amount unmethylated CpG markers (~ 3000 copies each), which is a reasonable approximation of BrCa ctDNA overwhelmed with peripheral blood cell-free DNA (cfDNA) when isolated from patient plasma. The bioinformatically-identified CpG markers are located in promoter regions of NR5A2 and PRKCB, and a non-coding region of chromosome 1 (upstream of EFNA3). Additional bioinformatic analyses would reveal that these methylation markers are independent of patient race and age, and positively associated with signaling pathways associated with BrCa progression (such as those related to retinoid nuclear receptor, PTEN, p53, pRB, and p27). CONCLUSION: This report demonstrates the potential utilization of bisulfite PCR-LDR-qPCR assay, along with bioinformatically-driven biomarker discovery, in blood-based BrCa detection.

Polarization of granulocytic myeloid-derived suppressor cells by hepatitis C core protein is mediated via IL-10/STAT3 signalling.

Myeloid-derived suppressor cells (MDSCs) have been described as suppressors of T-cell function in many malignancies. Impaired T-cell responses have been observed in patients with chronic hepatitis C virus infection (CHC), which is reportedly associated with the establishment of persistent HCV infection. Therefore, we hypothesized that MDSCs also play a role in chronic HCV infection. MDSCs in the peripheral blood of 206 patients with CHC and 20 healthy donors were analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMCs) of healthy donors cultured with hepatitis C virus core protein (HCVc) were stimulated with or without interleukin 10 (IL-10). Compared to healthy donors and certain CHC patients with sustained viral response (SVR), CHC patients without SVR presented with a dramatic elevation of G-MDSCs with the HLA-DR-/low CD33+ CD14- CD11b+ phenotype in peripheral blood. The frequency of G-MDSCs in CHC patients was positively correlated with serum HCVc, and G-MDSCs were induced from healthy PBMCs by adding exogenous HCVc. Furthermore, we revealed a potential mechanism by which HCVc mediates G-MDSC polarization; activation of ERK1/2 resulting in IL-10 production and IL-10-activated STAT3 signalling. Finally, we confirmed that HCVc-induced G-MDSCs suppress the proliferation and production of IFN-γ in autologous T-cells. We also found that the frequency of G-MDSCs in serum was associated with CHC prognosis. HCVc maintains immunosuppression by promoting IL-10/STAT3-dependent differentiation of G-MDSCs from PBMCs, resulting in the impaired functioning of T-cells. G-MDSCs may thus be a promising biomarker for predicting prognosis of CHC patients.

Kinetic Control over Morphology of Nanoporous Graphene on Surface.

On-surface synthesis of high-quality nanoporous graphene (NPG) for application in nanotechnology and nanodevices remains challenging. Rational design of molecular precursors and proper kinetic control over the reaction process are the two key factors to tune the synthesis. Herein, we report a detailed study of the coupling reactions of a planar halogen-substituted nanographene molecular precursor, hexaiodo-peri-hexabenzocoronene (I6 -HBC), on the Au(111) surface in the synthesis of NPG. The influence of three basic kinetic processes - molecular adsorption, migration, and coupling - on the synthesis was investigated. The results show that the HBC molecules deposited at low temperature predominantly desorb from the Au(111) surface during the annealing process, whereas depositing the precursor molecules onto a hot surface (700 K) can lead to the formation of NPG. However, at such a high surface temperature, simultaneous intermolecular dehydrogenative coupling between HBC monomers can hinder the ordered growth of NPG through Ullmann coupling. Moreover, the deposition rate of the precursors greatly influences the growth morphology of the NPG nanostructures.

Panax notoginseng Saponins Attenuate Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in Human SH-SY5Y Cells by Regulating the Expression of Inflammatory Factors through miR-155.

Panax notoginseng saponins (PNS) have been widely used in China to treat stroke. Accumulating evidence has found that microRNA (miR)-155 plays critical roles in the pathology of ischemic stroke. Here we investigated whether PNS plays a protective effect against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced focal inflammation and injury in SH-SY5Y cells by regulating miR-155 expression. Treatment with PNS at a concentration less than 160 µg/mL had no effect on the proliferation of SH-SY5Y cell. In OGD/R-induced SH-SY5Y cells, 160 µg/mL PNS treatment promoted cell proliferation and cell cycle progression, as well as decreased inhibited apoptosis and miR-155 expression. However, overexpression of miR-155 attenuated the promotion effects of PNS on cell proliferation and cell cycle, apoptosis inhibition in OGD/R-induced SH-SY5Y cells. Moreover, 160 µg/mL PNS treatment decreased the levels of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) in OGD/R-induced SH-SY5Y cells, whereas overexpression of miR-155 reversed PNS-induced decreases in the levels of IL-1ß, IL-6, and TNF-α in OGD/R-treated SH-SY5Y cells. In conclusion, PNS attenuated OGD/R-induced injury in human undifferentiated SH-SY5Y cells by regulating the expression of inflammatory factors through miR-155.

The Effect of Vascular Morphology on Selective Left Vertebral Artery Catheterization in Right-sided Radial Artery Cerebral Angiography.

BACKGROUND: The aim of this study is to determine, via retrospective study, the effects of vascular morphology and related factors on the success of selective arterial catheterization of the left vertebral artery when approached via right-sided radial artery cerebral angiography. METHODS: Patients who had undergone diagnostic cerebral angiography were enrolled, and their medical history, catheter type, and vessel morphology were analyzed. RESULTS: A total of 205 patients were enrolled in this study from February 2014 to December 2015. After exclusion according to defined criteria, 161 patients were incorporated into the final analysis. Selective catheterization of the bilateral subclavian artery and the bilateral common carotid artery were conducted successfully in all patients, and the success rate of selective catheterization of the left vertebral artery was 82.0%. The success rate of the left vertebral artery catheterization was positively correlated with the angle between the left vertebral artery and the left subclavicular artery (P < 0.001), with 90° serving as a demarcation point, and this was higher in patients without innominate artery distortion (90.2-75.0%), although this finding was not statistically significant. However, the morphology of the aortic artery did not affect the success rate of selective catheterization of the left vertebral artery (P = 0.189), and there was no significant difference (P = 0.231) in the success rate of selective catheterization if the left vertebral artery was predominant (91.0%, 81/89) or balanced (84.7%, 61/72). A total of 0.9% (2/161) of the patients experienced surgery-related complications. Both these patients exhibited bleeding at the puncture point when they were deflated 2 hr after the operation. They were pressurized and depressurization was again conducted for an appropriate period of time. CONCLUSIONS: The angle between the left vertebral artery and the left subclavicular artery is the primary vessel-associated morphological factor affecting the success rate of selective catheterization of the left vertebral artery in the right-sided radial artery cerebral angiography, while innominate artery distortion also had some more limited impact on this success rate.

Efficacy and Safety of a Novel Catheter for Transradial Cerebral Angiography.

BACKGROUND: The goal of this study is to evaluate the safety and efficacy of a novel catheter for right radial artery approach cerebral angiography. METHODS: Patients from the Neurology Department of The Second Affiliated Hospital of Guangxi Traditional Chinese Medical University who underwent diagnostic cerebral angiography of either the left vertebral artery dominant type or balanced type were enrolled in this study. RESULTS: A total of 167 patients were treated between February 2016 and December 2017, of whom 44 were excluded based on study exclusion criteria and 123 were enrolled in the present analysis. Bilateral subclavian artery catheterization and bilateral common carotid artery catheterization were conducted successfully in all 123 patients. The success rate of selective catheterization of the left vertebral artery was 87.8% (108/123). The success rate of selective catheterization of the right vertebral artery using the novel catheter was 89.0% (73/82). The average fluoroscopy time was 6.5 ± 3.4 min, the average operation duration was 47 ± 3.7 (range 50-90) min, and the average dosage of contrast agent was 112.3 ± 8.1 mL. One patient exhibited an absence of pulse in the punctual radial artery after the removal of the arterial compression band, but there was no evidence of ischemia of the distal hand. One patient who was undergoing dual anti-platelet drug treatment suffered from bleeding at the puncture point when deflated for 2 hr after operation; this patient was re-pressurized and re-timed. CONCLUSIONS: This novel catheter improved the success rate of selective left vertebral artery catheterization, and allowed for simplification of the relevant surgical steps. The controllability of this novel catheter was satisfactory, and its associated surgical risk was found to be low.

Validation of the full-age spectrum equation in the approximation of glomerular filtration rate in Chinese patients with chronic kidney disease.

Introduction: To investigate the validity of the full age spectrum (FAS) equation in determining the glomerular filtration rate (GFR) in Chinese patients with chronic kidney disease (CKD) and to compare the performance of FAS equation and the technetium-99m-diethylene triamine pentaacetic acid (Tc-99m-DTPA) renal dynamic imaging method. Methods: The GFR was determined by three methods in the same day: (a) Tc-99m-DTPA dual plasma sample clearance method (mGFR); (b) FAS equation (eGFR1); (c) Tc-99m-DTPA renal dynamic imaging method (eGFR2). The mGFR was used as the reference standard. The Bland-Altman method, concordance correlation coefficient and regression equation were applied to evaluate the validity of the estimated glomerular filtration rate (eGFR). The bias, precision and accuracy were analyzed to compare the performances of eGFR1 and eGFR2. Results: A total of 162 subjects were enrolled in this study. The eGFR1 was correlated well with mGFR (concordance correlation coefficient was 0.896, p < 0.0001) and the regression equation was mGFR = -0.374 + 1.029eGFR1 (p < 0001). The Bland-Altman analysis proved good agreement between the eGFR1 and mGFR. In comparison with eGFR2, the eGFR1 showed better performance on bias (-1.22 vs. 8.92, p < 0001), precision (15.69 vs. 18.36, p = 0.047) and 30% accuracy (75.31% vs. 59.26%, p = 0.0009) in all participants. Conclusions: The FAS equation is valid in determining the glomerular filtration rate in Chinese patients with chronic kidney disease. The Tc-99m-DTPA renal dynamic imaging method is less accurate than the FAS equation and cannot be employed as the reference method in assessing the performance of FAS equation.

[Association of single nucleotide polymorphisms of SCN1A gene with therapeutic effect of carbamazepine among ethnic Zhuang Chinese patients with epilepsy].

OBJECTIVE: To assess the association of single nucleotide polymorphisms of SCN1A gene with therapeutic effect of carbamazepine among ethnic Zhuang Chinese patients with epilepsy. METHODS: Peripheral blood samples were taken from 186 epileptic patients for whom 66 cases standard regime of carbamazepine treatment was effective. Genotypes of rs3812718 and rs1813502 loci of the SCN1A gene were determined by Mass ARRAY-IPLEX and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Correlation between genotypes of patients and efficacy of carbamazepine treatment was analyzed. RESULTS: Three genotypes (GG, GA and AA) were detected at both rs3812718 and rs1813502 loci of the SCN1A gene. A significant difference was found in allelic distribution (chi-square=17.810, P=0.000) and genotypic distribution (chi-square=17.873, P=0.000) of the rs3812718 locus between the effective group and ineffective group. No such difference was found with the rs1813502 locus (chi-square=1.606, P=0.206; chi-square=1.546, P=0.462, respectively). Compared with the GG+GA genotype, the AA genotype at rs3812718 locus significantly reduced the antiepileptic efficacy of carbamazepine (OR=3.776, 95%CI: 2.007-7.105). Among the 66 patients who were responsive to carbamazepine treatment, those with the AA genotype for rs3812718 or rs1813502 shown no significant difference in their blood concentration of carbamazepine compared with those with the GG+GA genotype (t=1.562, P=0.125; t=0.843, P=0.562, respectively). rs3812718 and rs1813502 were not in strong linkage disequilibrium. CONCLUSION: Polymorphisms of rs3812718 of the SCN1A gene is associated with carbamazepine resistance among ethnic Zhuang Chinese epilepsy patients from Baise region.

Clinical value of 99Tcm-MIBI gated myocardial perfusion imaging in evaluating sarcoglycanopathy.

AIM: The purpose of this study was to analyse the diagnostic value of gated myocardial perfusion imaging (G-MPI) in the evaluation of myocardial injury in sarcoglycanopathy. MATERIALS AND METHODS: Twenty-eight patients diagnosed with sarcoglycanopathy were evaluated using 99m- -methoxyisobutylisonitrile(99Tcm-MIBI) G-MPI. The data was processed into tomographic images, and the left ventricular function was analysed using quantitative gated SPECT (QGS) to assess the degree of impairment in myocardial and cardiac function. RESULTS: The images of 23 of the patients (82.1%) were positive. Two hundred and twenty-nine sub-segments with abnormal lesions were detected out of 391 cardiac sub-segments of these 23 positive cases. According to the segmental abnormalities, the cases were divided into two cases (8.7%) with single abnormal wall segment, six cases (26.1%) with two abnormal wall segments, and 15 cases (65.2%) with three or more abnormal wall segments or scattered lesions. CONCLUSIONS: 99Tcm-MIBI G-MPI can objectively show impaired myocardium in patients with sarcoglycanopathy. Therefore, this method is helpful for early diagnosis and follow-up of myocardial damage.