Comparison of the efficacy of spinal cord stimulation and dorsal root ganglion stimulation in the treatment of painful diabetic peripheral neuropathy: a prospective, cohort-controlled study.

Objective: The aim of this study was to compare the clinical outcomes of spinal cord stimulation (SCS) and dorsal root ganglion stimulation (DRG-S) in the treatment of painful diabetic peripheral neuropathy (PDPN). Methods: In this prospective cohort study, 55 patients received dorsal column spinal cord stimulation (SCS group) and 51 patients received dorsal root spinal cord stimulation (DRG-S group). The primary outcome was a Numerical Rating Scale (NRS) remission rate of ≥50%, and secondary outcomes included the effects of SCS and DRG-S on quality of life scores (EQ-5D-3L), nerve conduction velocity, and HbA1c, respectively. Results: The percentage of NRS remission rate ≥ 50% at 6 months was 80.43 vs. 79.55%, OR (95% CI): 1.06 (0.38-2.97) in the SCS and DRG-S groups, respectively, and the percentage of VAS remission rate ≥ 50% at 12 months was 79.07 vs. 80.95%, OR (95% CI): 0.89 (0.31-2.58). Compared with baseline, there were significant improvements in EQ-5D and EQ-VAS at 6 and 12 months (p < 0.05), but there was no difference in improvement between the SCS and DRG-S groups (p > 0.05). Nerve conduction velocities of the common peroneal, peroneal, superficial peroneal, and tibial nerves were significantly improved at 6 and 12 months compared with the preoperative period in both the SCS and PND groups (p < 0.05). However, at 6 and 12 months, there was no difference in HbA1c between the two groups (p > 0.05). Conclusion: Both SCS and DRG-S significantly improved pain, quality of life, and lower extremity nerve conduction velocity in patients with PDPN, and there was no difference between the two treatments at 12 months.

Microfluidic Device-Based In Vivo Detection of PD-L1-Positive Small Extracellular Vesicles and Its Application for Tumor Monitoring.

Liquid biopsy is of great significance in tumor early diagnosis and treatment stratification. PD-L1-positive small extracellular vesicles (PD-L1+ sEVs) are closely related to tumor growth and immunotherapy response, which are considered valuable liquid biopsy biomarkers. In contrast to conventional in vitro detection, in vivo detection has the ability to improve the detection efficiency and enable continuous or real-time dynamic monitoring. However, in vivo detection of PD-L1+ sEVs has multiple difficulties, such as high cell background, complex blood environments, and lack of a specific and stable detection method. Herein, the in vivo detection of PD-L1+ sEVs method was constructed, which efficiently separated sEVs based on the microfluidic device and quantitatively analyzed PD-L1+ sEVs by aptamer recognition and hybridization chain reaction. The concentration of PD-L1+ sEVs was continuously monitored, and significant differences at different stages of tumor as well as a correlation with tumor volume were found. Diseased and healthy individuals could also be effectively distinguished based on the concentration of PD-L1+ sEVs. The method with good stability, biocompatibility, and detection performance provided a powerful means for in vivo detection of PD-L1+ sEVs, contributing to the clinical diagnosis and treatment of tumor.

Identification and characterization of a novel avian nephritis virus variant in chickens with enteritis in Hunan province, China.

Avian nephritis virus (ANV) infection is associated with diarrhea, uricosis, stunting, tubulonephrosis, interstitial nephritis, and mortality of chicken flocks, leading to economic losses in the poultry industry. In this study, an ANV strain designated as HNU-ANV-ML-2020 was identified in tissue samples collected from chickens with severe enteritis on a poultry farm in Hunan province, China, and analyzed. The genome of HNU-ANV-ML-2020 is 6943 nucleotides in length. It showed the highest sequence identity (88.1%) to ANV strain CHN/GXJL815/2017 (MN732559) from Guangxi province, China, while it showed less than 86% identity to other astrovirus (AstV) genome sequences available in the GenBank database. The capsid protein of this virus showed the highest sequence identity to ANV strains HQ330482 and HQ330498 from the UK (81.2% and 81.06%, respectively), while it showed only 73.9% identity to MN732559 and less than 80% identity to the capsid proteins of other AstVs available in GenBank. Further phylogenetic analysis demonstrated that HNU-ANV-ML-2020 belongs to group 4, together with ANV strains identified in Australia, Brazil, the UK, and the Netherlands. Furthermore, ANV strains identified in chickens in China were found to be separated into four distinct groups/genotypes, indicating substantial genetic divergence and a complex circulation pattern in China. The virus characterized in the present study is a novel ANV variant identified for the first time in Hunan province, China.

Anticancer activity of oleanolic acid and its derivatives modified at A-ring and C-28 position.

Oleanolic acid (OA) is a five-ring triterpenoid compound, which is widely present in plants. Due to a wide range of pharmacological activities, oleanolic acid has attracted more and more attention. However, oleanolic acid is insoluble in water and has low bioavailability, which limits its clinical application. In this review, we focus on summarizing the anti-cancer activity and mechanism of the A ring or C-28 carboxyl modified derivatives of OA since 2015, to determine the strength of its anti-cancer effectiveness and evaluate whether it could be used as a clinical anti-cancer drug.

Identification and genomic characterization of a novel porcine CRESS DNA virus from a pig suffering from diarrhea in China.

The circular replication-associated protein (Rep)-encoding ssDNA (CRESS-DNA) viruses show high diversity and have a very wide range of hosts, including all three domains of cellular life. In the present study, a novel CRESS DNA virus, provisionally named "kirkovirus HNU-XX-2020" was discovered in a growing pig with watery diarrhea. The virus has a circular genome of 2961 nucleotides (nt) and three major putative open reading frames (ORFs), encoding a Rep protein (327 amino acids), a capsid protein (175 amino acids), and one protein (209 amino acids) of unknown function. The genome showed the highest sequence similarity (68.6% identity) to the genome of porcine circo-like virus 51 (JF713719), which was identified in pig faeces, and it showed very limited sequence similarity (less than 40% identity) to other virus genomes. Further phylogenetic analysis suggested that it could be a novel member in the proposed family "Kirkoviridae".

Silencing GnT-V reduces oxaliplatin chemosensitivity in human colorectal cancer cells through N-glycan alteration of organic cation transporter member 2.

Organic cation transporter member 2 (OCT2) is an N-glycosylated transporter that has been shown to be closely associated with the transport of antitumor drugs. Oxaliplatin, a platinum-based drug, is used for the chemotherapy of colorectal cancer (CRC). However, oxaliplatin resistance is a major challenge in the treatment of advanced CRC. The aim of the present study was to better understand the mechanism underlying the chemosensitivity of CRC cells to oxaliplatin. The present study describes a potential novel strategy for enhancing oxaliplatin sensitivity involving the glycosylation of this drug transporter, specifically the modification of ß-1,6-N-acetylglucosamine (GlcNAc) residues by N-acetylglucosaminyltransferase V (GnT-V). The results revealed that the downregulation of GnT-V inhibited the oxaliplatin chemosensitivity of CW-2 cells. Furthermore, the knockdown of GnT-V caused a marked reduction in the presence of ß-1,6-GlcNAc structures on OCT2 and decreased the localization of OCT2 in the cytomembrane, which were associated with a reduced uptake of oxaliplatin in wild-type and oxaliplatin-resistant CW-2 cells. Overall, the study provides novel insights into the molecular mechanism by which GnT-V regulates the chemosensitivity to oxaliplatin, which involves the modulation of the drug transporter OCT2 by N-glycosylation in CRC cells.

Changing trends of clinicopathologic features and survival duration after surgery for gastric cancer in Northeast China.

BACKGROUND: Through analyzing the data from a single institution in Northeast China, this study revealed the possible clinicopathologic characteristics that influence the prognosis of patients with gastric cancer (GC). AIM: To evaluate the changing trends of clinicopathologic features and survival duration after surgery in patients with GC in Northeast China, which is a high-prevalence area of GC. METHODS: The study analyzed the difference in clinicopathologic features and survival duration after surgery of 5887 patients who were histologically diagnosed with GC at the Harbin Medical University Cancer Hospital. The study mainly analyzed the data in three periods, 2000 to 2004 (Phase 1), 2005 to 2009 (Phase 2), and 2010 to 2014 (Phase 3). RESULTS: Over time, the postoperative survival rate significantly increased from 2000 to 2014. In the past 15 years, compared with Phases 1 and 2, the tumor size was smaller in Phase 3 (P < 0.001), but the proportion of high-medium differentiated tumors increased (P < 0.001). The proportion of early GC gradually increased from 3.9% to 14.4% (P < 0.001). A surprising improvement was observed in the mean number of retrieved lymph nodes, ranging from 11.4 to 27.5 (P < 0.001). The overall 5-year survival rate increased from 24% in Phase 1 to 43.8% in Phase 3. Through multivariate analysis, it was found that age, tumor size, histologic type, tumor-node-metastasis stage, depth of invasion, lymph node metastasis, surgical approach, local infiltration, radical extent, number of retrieved lymph nodes, and age group were independent risk factors that influenced the prognosis of patients with GC. CONCLUSION: The clinical features of GC in Northeast China changed during the observation period. The increasing detection of early GC and more standardized surgical treatment effectively prolonged lifetimes.

Overexpression of ribonuclease inhibitor induces autophagy in human colorectal cancer cells via the Akt/mTOR/ULK1 pathway.

Ribonuclease inhibitor (RI), also termed angiogenin inhibitor, acts as the inhibitor of ribonucleolytic activity of RNase A and angiogenin. The expression of RI has been investigated in melanoma and bladder cancer cells. However, the precise role of RI in tumorigenesis, in addition to RI­induced autophagy, remains poorly understood. In the present study, it was demonstrated that RI positively regulated autophagy in human colorectal cancer (CRC) cells as indicated by an increase in light chain 3 (LC3)­II levels. Furthermore, RI regulated cell survival in HT29 cells. In addition, autophagy­associated proteins, including beclin­1 and autophagy­related protein 13, were increased in response to RI­induced autophagy, and the protein kinase B (Akt)/mechanistic target of rapamycin (mTOR)/Unc­51 like autophagy activating kinase (ULK1) pathway may be involved in the activation of autophagy induced by RI overexpression. Taken together, the evidence of the present study indicated that the overexpression of RI induced ATG­dependent autophagy in CRC cells via the Akt/mTOR/ULK1 pathway, suggesting that the upregulation of RI activity may constitute a novel approach for the treatment of human colorectal carcinoma.

GnT-V promotes chemosensitivity to gemcitabine in bladder cancer cells through ß1,6 GlcNAc branch modification of human equilibrative nucleoside transporter 1.

Human equilibrative nucleoside transporter 1 (hENT1) transports nucleoside analogue drugs across cellular membranes and is necessary for the uptake of many anti-tumor drugs. Gemcitabine is a frontline agent of chemotherapy for bladder cancer despite its limited efficacy due to chemoresistance, there is an acute need to decipher mechanisms underlying chemosensitivity to gemcitabinein in bladder cancer cells. Here we report a novel role for N-acetylglucosaminyltransferase V (GnT-V) in gemcitabine chemosensitivity. In this study, we found that GnT-V expression affected cell death rate to gemcitabine in different bladder cancer cells and down-regulation of GnT-V inhibited the gemcitabine sensitivity with time and dose dependent way in T24 cells. Moreover, mechanistic investigations showed that silencing GnT-V caused dramatic decrease of ß1,6 GlcNAc structure on hENT1 leading to apparently decreased accumulation of hENT1 at plasma membrane, and therefore result in less uptake of gemcitabine in T24/shRNA cells. Together, our present study indicated that GnT-V enhances gemcitabine chemosensitivity via modulation of hENT1 N-glycosylation and transport activity in T24 cells, providing new insights into how N-glycosylation drives antitumor drug sensitivity during chemotherapy for patients with cancer.

[Effects of nitrogen fertilizer application rate on nitrogen use efficiency and grain yield and quality of different rice varieties]. / æ°®è‚¥æ°´å¹³å¯¹ä¸åŒåŸºå› åž‹æ°´ç¨»æ°®ç´ åˆ©ç”¨çŽ‡ã€äº§é‡å’Œå“è´¨çš„å½±å“.

To provide scientific basis for reasonable application of nitrogen and create varieties with high N use-efficiency, an experiment was carried out to study the effects of nitrogen fertilizer application rate on grain yield, N use rate and quality of different rice varieties. Four different genotypic rice varieties, Nipponbare, N70, N178 and OM052 were used as tested material and three levels of nitrogen application rate (0, 120, 270 kg·hm-2) were conducted. Urea as nitrogen source was applied as basal (70%) and panicle (30%) fertilizer. The results showed that nitrogen fertilizer could raise yield mainly because of the increased effective panicles and filled grains per panicle. When the N application rate was 120 and 270 kg·hm-2, OM052 had the largest grain yield among four varieties, being 41.1% and 76.8% higher, respectively compared with control. Difference in grain yield among four varieties was due to the difference of nitrogen use efficiency. Under 120 and 270 kg·hm-2 nitrogen levels, Nipponbare had the lowest grain yield and N agronomic efficiency (NAE, 40.90 g·g-1 and 18.56 g·g-1), which was a variety with low N use-efficiency. On the contrary, OM052 had the highest grain yield and NAE (145.9 g·g-1 and 81.24 g·g-1), was a variety with high N use-efficiency. N fertilizer application increased the amylose content and protein content, lengthened gel consistency, reduced chalky kernel, chalkiness, and alkali digestion value. With the increase of N fertilizer application, hot paste viscosity, peak viscosity, consistence viscosity and breakdown viscosity were decreased gradually, and setback viscosity was increased. Correlation analysis showed that the yield and yield components had more significant correlations with appearance quality, cooking and eating quality under low N level. This study confirmed that OM052 was a double high variety with extremely high N agronomic efficiency and yield. Reasonable application of nitrogen fertilizer could significantly increase effective panicles and filled grains per panicle, improve rice quality, and ensure high yield and superior quality simultaneously.

[Detection of SALL4 mRNA expression in leukemia by real-time fluorescent quantitative PCR].

This study was purposed to establish a real-time fluorescent quantitative PCR (FQ-PCR) for quantifying SALL4 mRNA and to investigate its expression in different types of leukemia patients. SALL4 mRNA expression were measured in 60 leukemia patients of different periods and 10 normal controls sequentially by FQ-PCR. The results showed that the expression of SALL4 mRNA in de novo leukemia patients and relapsed patients was higher than that in controls (P < 0.05), which was significantly decreased at complete remission (CR). In relapsed patients, the expression of SALL4 mRNA increased slightly higher than that in de novo leukemia group, but the difference was not statistically significant (P > 0.05). However, the expression of SALL4 mRNA was low in CLL, T-ALL and AML-M3. The expression pattern of BMI-1 was same as SALL4, and the expression of BMI-1 positively correlated with that of SALL4 in leukemia (r = 0.825, P < 0.01). It is concluded that the detection of SALL4 gene expression in acute and chronic leukemia by real-time gTR-PCR displays high sensitivity and specificity. SALL4 gene may be one of indicators for monitoring the therapeutic outcome of partial leukemia and minimal residual disease.