Poly(l-lactic acid)-based double-layer composite scaffold for bone tissue repair.

Bone defect is a serious threat to human health. Osteopractic total flavone (OTF) extracted from Rhizoma Drynariae has the effects of promoting bone formation. Panax notoginseng saponin (PNS) has the function of activating blood circulation and removing blood stasis. Therefore, combining OTF and PNS with poly(l-lactic acid) (PLLA) to prepare scaffolds containing PNS in the outer layer and OTF in the inner layer is a feasible solution to rapidly remove blood stasis and continue to promote bone formation. In addition, degradation rate of the scaffold can affect the release time of two drugs. Adding Mg particles in outer layer can control the degradation rate of the scaffold and the drug release. Therefore, a double-layer drug-loaded PLLA scaffold containing OTF in the inner layer, PNS and Mg particles in the outer layer was prepared and characterized to verify its feasibility. The experimental results showed that the scaffold can realize the rapid release of PNS and the continuous release of OTF. With the increase of Mg content, the drug release rate became faster. Animal experiments showed that the scaffold containing 5% Mg particles could effectively promote the formation of new bone in the bone defect of male New Zealand white rabbits, and the area and density of new bone formed were much better than those in the control group. These results demonstrated that the double-layer drug-loaded scaffold had good ability to promote bone repair.

Mitochondrial quality control in abdominal aortic aneurysm: From molecular mechanisms to therapeutic strategies.

Mitochondria are the energy supply sites of cells and are crucial for eukaryotic life. Mitochondrial dysfunction is involved in the pathogenesis of abdominal aortic aneurysm (AAA). Multiple mitochondrial quality control (MQC) mechanisms, including mitochondrial DNA repair, biogenesis, antioxidant defense, dynamics, and autophagy, play vital roles in maintaining mitochondrial homeostasis under physiological and pathological conditions. Abnormalities in these mechanisms may induce mitochondrial damage and dysfunction leading to cell death and tissue remodeling. Recently, many clues suggest that dysregulation of MQC is closely related to the pathogenesis of AAA. Therefore, specific interventions targeting MQC mechanisms to maintain and restore mitochondrial function have become promising therapeutic methods for the prevention and treatment of AAA.

A novel approach to analyze the association characteristics between post-spliced introns and their corresponding mRNA.

Studies have shown that post-spliced introns promote cell survival when nutrients are scarce, and intron loss/gain can influence many stages of mRNA metabolism. However, few approaches are currently available to study the correlation between intron sequences and their corresponding mature mRNA sequences. Here, based on the results of the improved Smith-Waterman local alignment-based algorithm method (SW method) and binding free energy weighted local alignment algorithm method (BFE method), the optimal matched segments between introns and their corresponding mature mRNAs in Caenorhabditis elegans (C.elegans) and their relative matching frequency (RF) distributions were obtained. The results showed that although the distributions of relative matching frequencies on mRNAs obtained by the BFE method were similar to the SW method, the interaction intensity in 5'and 3'untranslated regions (UTRs) regions was weaker than the SW method. The RF distributions in the exon-exon junction regions were comparable, the effects of long and short introns on mRNA and on the five functional sites with BFE method were similar to the SW method. However, the interaction intensity in 5'and 3'UTR regions with BFE method was weaker than with SW method. Although the matching rate and length distribution shape of the optimal matched fragment were consistent with the SW method, an increase in length was observed. The matching rates and the length of the optimal matched fragments were mainly in the range of 60%-80% and 20-30bp, respectively. Although we found that there were still matching preferences in the 5'and 3'UTR regions of the mRNAs with BFE, the matching intensities were significantly lower than the matching intensities between introns and their corresponding mRNAs with SW method. Overall, our findings suggest that the interaction between introns and mRNAs results from synergism among different types of sequences during the evolutionary process.

Transobturator tape, tension-free vaginal tape, and transvaginal tension-free vaginal tape-obturator for the treatment of female stress urinary incontinence: A systematic review and network meta-analysis.

OBJECTIVE: To systematically review the safety and effectiveness of tension-free vaginal tape (TVT), transobturator tape (TOT), and transvaginal tension-free vaginal tape-obturator (TVT-O) in the treatment of stress urinary incontinence (SUI). METHODS: The PubMed, Embase, The Cochrane Library, Web of Science, WanFang Data, and CNKI were electronically searched. A total of 22 trials involving 3709 patients were included. RESULTS: The objective cure rate was better with TVT than with TOT and TVT-O. The incidence of postoperative thigh/groin pain was lower with TVT than with TOT and TVT-O, but the incidence of dysuria was higher with TVT than with TVT-O. The incidence of lower urinary tract infection was higher with TVT than with TOT. CONCLUSION: Tension-free vaginal tape may have a better outcome compared to TOT and TVT-O, but the risk of dysuria and lower urinary tract infection is higher with SUI.

Interobserver variability in target volume delineation in definitive radiotherapy for thoracic esophageal cancer: a multi-center study from China.

PURPOSE: To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies. METHODS: Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC). RESULTS: Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI 0.32-0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI 0.45-0.83, P = 0.005) but the DSC of GTV-T and CTV remained constant in most cases. CONCLUSION: Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions.

Identification of crucial long non-coding RNAs and mRNAs along with related regulatory networks through microarray analysis in esophageal carcinoma.

Esophageal carcinoma (EC) is a tremendous threat to human health and life worldwide. Long non-coding RNAs (lncRNAs) have been identified as crucial players in carcinomas including EC. An in-depth understanding on regulatory networks of lncRNAs contributes to the better management of EC. In this text, 2052 lncRNAs and 3240 mRNAs were found to be differentially expressed in 5 EC tumor tissues versus adjacent normal tissues by microarray analysis. Moreover, 297 carcinoma-related genes were screened out according to pathway and disease annotation analyses. In addition, 410 potential lncRNA-mRNA cis-regulation pairs and 395 lncRNA-mRNA trans-regulation pairs were screened out. Among these genes, 14 trans-regulated and 19 cis-regulated genes were found to be related with carcinomas. Additionally, 42 possible lncRNA-mRNA trans-regulation pairs and 26 cis-regulation pairs were found to be related with carcinomas. Also, 4 differentially expressed transcription factors in EC and lncRNAs possibly regulated by these transcription factors were screened out. Moreover, plenty of common upregulated or downregulated lncRNAs and mRNAs in EC were identified by comparative analysis for our microarray outcomes and previous high-throughput data. Furthermore, we demonstrated that ENST00000437781.1 knockdown inhibited cell proliferation and facilitated cell apoptosis by downregulating SIX homeobox 4 (SIX4) and ENST00000524987.1 knockdown had no influence on anoctamin 1 calcium activated chloride channel (ANO1) expression in EC cells. In conclusion, we identified some crucial lncRNAs and genes along with potential regulatory networks of lncRNAs/genes, deepening our understanding on pathogenesis of EC.

Efficacy of ureterocalicostomy in treating secondary long-segment upper ureteral stricture.

OBJECTIVE: To evaluate the efficacy and safety of ureterocalicostomy for long-segment upper ureteral stricture. METHODS: A total of 13 patients underwent ureterocalicostomy for long-segment upper ureteral stricture, and a long-term follow-up was carried out to observe postoperative results, complications and renal function at 6 months after surgery. RESULTS: Among the 13 patients undergoing ureterocalicostomy, 12 achieved successful results with surgery. Nine of the 12 received open surgery and 3 patients received laparoscopic surgery. During the perioperative period, 3 patients developed fever while 2 patients had hematuria and irritation in lower urinary tract, and all improved after symptomatic treatment. The 12 patients with successful surgeries achieved remission of hydronephrosis without anastomotic stricture. At 6 months after surgery, the 12 patients had significantly decreased serum creatinine and cystatin C levels and markedly increased estimated glomerular filtration rate, as compared with those before surgery (P<0.05). CONCLUSION: Ureterocalicostomy is an effective, safe, optional treatment strategy for secondary long-segment upper ureteral stricture.

Second-line treatment strategy for urothelial cancer patients who progress or are unfit for cisplatin therapy: a network meta-analysis.

BACKGROUND: Second-line treatment for urothelial carcinoma (UC) patients is used if progression or failure after platinum-based chemotherapy occurs or if patients are cisplatin-unfit. However, there is still no widely accepted treatment strategy. We aimed to analyze the effectiveness and safety of second-line treatment strategies for UC patients. METHODS: The PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) that included UC patients who were cisplatin-ineligible or unfit up to April 19, 2019. The primary outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). RESULTS: Thirteen trials that assessed 3502 UC patients were included. This study divided the network comparisons into three parts. The first part contained studies comparing taxanes and other interventions; the second part assessed investigator's choice chemotherapy (ICC)-related comparisons; and the third part assessed best support care (BSC). In the OS results of the first part, pembrolizumab (87.5%), ramucirumab plus docetaxel (74.6%), and atezolizumab (71.1%) had a relative advantage. Pembrolizumab also had advantages in ORR and severe adverse effect (SAE) results. Vinflunine and ramucirumab plus docetaxel had a relatively high surface under the cumulative ranking curve (SUCRA) rank by exploratory cluster analysis. CONCLUSIONS: This study concluded that atezolizumab and pembrolizumab are superior to other treatments, mainly in OS results, but no treatment confers a significant advantage in PFS. Pembrolizumab still has relative advantages in ORR and SAE results compared to ICC. Due to limitations, more studies are necessary to confirm the conclusions.

Dosimetric comparison of TomoDirect, helical tomotherapy, VMAT, and ff-IMRT for upper thoracic esophageal carcinoma.

BACKGROUND: The new TomoDirect (TD) modality offers a nonrotational option with discrete beam angles. We aim to compare dosimetric parameters of TD, helical tomotherapy (HT), volumetric-modulated arc therapy (VMAT), and fixed-field intensity-modulated radiotherapy (ff-IMRT) for upper thoracic esophageal carcinoma (EC). METHODS: Twenty patients with cT2-4N0-1M0 upper thoracic esophageal squamous cell carcinoma (ESCC) were enrolled. Four plans were generated using the same dose objectives for each patient: TD, HT, VMAT with a single arc, and ff-IMRT with 5 fields (5F). The prescribed doses were used to deliver 50.4 Gy/28F to the planning target volume (PTV50.4) and then provided a 9 Gy/5F boost to PTV59.4. Dose-volume histogram (DVH) statistics, dose uniformity, and dose homogeneity were analyzed to compare treatment plans. RESULTS: For PTV59.4, the D2, D98, Dmean, and V100% values in HT were significantly lower than other plans (all p < 0.05), and those in TD were significantly lower than VMAT and ff-IMRT (all p < 0.05). However, there was no significant difference in the D2 and Dmean values between VMAT and ff-IMRT techniques (p > 0.05). The homogeneity index (HI) differed significantly for the 4 techniques of TD, HT, VMAT, and ff-IMRT (0.03 ± 0.01, 0.02 ± 0.01, 0.06 ± 0.02, and 0.05 ± 0.01, respectively; p  < 0.001). The HI for TD was similar to HT (p = 0.166), and had statistically significant improvement compared to VMAT (p < 0.001) and ff-IMRT (p = 0.003). In comparison with the 4 conformity indices (CIs), there was no significant difference (p > 0.05). For PTV50.4, the D2 and Dmean values in HT were significantly lower than other plans (all p < 0.05), and those in TD were significantly lower than VMAT and ff-IMRT (all p < 0.05). However, there was no significant difference in the D2 and Dmean values between VMAT and ff-IMRT techniques (p > 0.05). No D98 and V100% parameters differed significantly among the 4 treatment types (p > 0.05). HT plans were provided for statistically significant improvement in HI (0.03 ± 0.01) compared to TD plans (0.05 ± 0.01, p = 0.003), VMAT (0.08 ± 0.03, p < 0.001), ff-IMRT (0.08 ± 0.01, p < 0.001). The HI revealed that TD was superior to VMAT and ff-IMRT (p < 0.05). The CI differed significantly for the 4 techniques of TD, HT, VMAT, and ff-IMRT (0.59 ± 0.10, 0.69 ± 0.11, 0.64 ± 0.09, and 0.64 ± 0.11, respectively; p = 0.035). The best CI was yielded by HT. We found no significant difference for the V5, V10, V15, V30, and the mean lung dose (MLD) among the 4 techniques (all p > 0.05). However, the V20 differed significantly among TD, HT, VMAT, and ff-IMRT (21.50 ± 7.20%, 19.50 ± 5.55%, 17.65 ± 5.45%, and 16.35 ± 5.70%, respectively; p = 0.047). Average V20 for the lungs was significantly improved by the TD plans compared to VMAT (p = 0.047), and ff-IMRT (p = 0.008). The V5 value of the lung in TD was 49.30 ± 13.01%, lower than other plans, but there was no significant difference (p > 0.05). The D1 of the spinal cord showed no significant difference among the 4 techniques (p = 0.056). CONCLUSIONS: All techniques are able to provide a homogeneous and highly conformal dose distribution. The TD technique is a good option for treating upper thoracic EC involvement. It could achieve optimal low dose to the lungs and spinal cord with acceptable PTV coverage. HT is a good option as it could achieve quality dose conformality and uniformity, while TD generated superior conformality.

Dual functions of ZmNF-YA3 in photoperiod-dependent flowering and abiotic stress responses in maize.

Nuclear factor-Y (NF-Y) transcription factors are important regulators of several essential biological processes, including embryogenesis, drought resistance, meristem maintenance, and photoperiod-dependent flowering in Arabidopsis. However, the regulatory mechanisms of NF-Ys in maize (Zea mays) are not well understood yet. In this study, we identified an NF-Y transcription factor, ZmNF-YA3. Genome-wide analysis showed that ZmNF-YA3 bound to >6000 sites in the maize genome, 2259 of which are associated with genic sequences. ZmNF-YA3 was found to interact with CONSTANS-like (CO-like) and flowering promoting factor1 (FPF1) through yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assays. Quantitative real-time reverse transcription-PCR (qRT-PCR) combined with yeast one-hybrid assay and EMSA suggested that NF-YA3 could promote early flowering by binding to the FLOWERING LOCUS T-like12 (FT-like12) promoter in maize. Morerover, we also showed that ZmNF-YA3 could improve drought and high-temperature tolerance through binding to the promoter regions of bHLH92, FAMA, and the jasmonic acid activator MYC4, respectively. These results contribute to a comprehensive understanding of the molecular mechanisms and regulatory networks of NF-Y transcription factors in regulating maize flowering time and stress response in maize.

The significance of De Ritis (aspartate transaminase/alanine transaminase) ratio in predicting pathological outcomes and prognosis in localized prostate cancer patients.

PURPOSE: To illustrate whether De Ritis (aspartate transaminase-AST/alanine transaminase-ALT) ratio is useful in risk stratification of localized prostate cancer and propose an easy predictive model for biochemical recurrence-free survival (BCRFS). METHODS: In total, 438 patients who underwent radical prostatectomy were included in this study. Blood samples including AST and ALT were collected 1-7 days before surgery. An elevated AST and ALT value was defined as over 40 or 56 IU/L. RESULTS: The median AST and ALT value was 18.5 (16-22) and 14 (11-18) IU/L. In total, 15 patients (3.4%) and 9 patients (2.1%) exhibited elevated AST value and ALT value. The median De Ritis ratio was 1.33 (1.11-1.60), and ROC curve indicated the best cutoff of 1.325 in predicting the occurrence of biochemical recurrence. Higher De Ritis ratio was found to be related to older age (p < 0.001), higher tumor stages (p < 0.001) and Gleason Score (p < 0.001), presence of seminal invasion (p < 0.001), positive surgical margin (p < 0.001) and lymph node metastasis (p = 0.003). Multivariate logistic regression confirmed that De Ritis ratio was an independent predictor for final Gleason Score (p < 0.001), and multivariate Cox regression demonstrated De Ritis ratio as an independent risk factor for BCRFS. A simple predictive model which incorporated De Ritis ratio, pathological tumor stage and final Gleason Score could help risk stratification for BCRFS. CONCLUSION: Higher De Ritis ratio could be predictive for worse pathological outcomes and higher BCR in localized prostate cancer patients. A predictive model which incorporates De Ritis ratio, Gleason Score and pathological tumor stage could help risk stratification for BCRFS.

Dual functions of the ZmCCT-associated quantitative trait locus in flowering and stress responses under long-day conditions.

BACKGROUND: Photoperiodism refers to the ability of plants to measure day length to determine the season. This ability enables plants to coordinate internal biological activities with external changes to ensure normal growth. However, the influence of the photoperiod on maize flowering and stress responses under long-day (LD) conditions has not been analyzed by comparative transcriptome sequencing. The ZmCCT gene was previously identified as a homolog of the rice photoperiod response regulator Ghd7, and associated with the major quantitative trait locus (QTL) responsible for Gibberella stalk rot resistance in maize. However, its regulatory mechanism has not been characterized. RESULTS: We mapped the ZmCCT-associated QTL (ZmCCT-AQ), which is approximately 130 kb long and regulates photoperiod responses and resistance to Gibberella stalk rot and drought in maize. To investigate the effects of ZmCCT-AQ under LD conditions, the transcriptomes of the photoperiod-insensitive inbred line Huangzao4 (HZ4) and its near-isogenic line (HZ4-NIL) containing ZmCCT-AQ were sequenced. A set of genes identified by RNA-seq exhibited higher basal expression levels in HZ4-NIL than in HZ4. These genes were associated with responses to circadian rhythm changes and biotic and abiotic stresses. The differentially expressed genes in the introgressed regions of HZ4-NIL conferred higher drought and heat tolerance, and stronger disease resistance relative to HZ4. Co-expression analysis and the diurnal expression rhythms of genes related to stress responses suggested that ZmCCT and one of the circadian clock core genes, ZmCCA1, are important nodes linking the photoperiod to stress tolerance responses under LD conditions. CONCLUSION: Our study revealed that the photoperiod influences flowering and stress responses under LD conditions. Additionally, ZmCCT and ZmCCA1 are important functional links between the circadian clock and stress tolerance. The establishment of this particular molecular link has uncovered a new relationship between plant photoperiodism and stress responses.

Experimental demonstration of iterative post-equalization algorithm for 37.5-Gbaud PM-16QAM quad-carrier Terabit superchannel.

We experimentally demonstrate a quad-carrier 1-Tb/s solution with 37.5-GBaud PM-16QAM signal over 37.5-GHz optical grid at 6.7 b/s/Hz net spectral efficiency. Digital Nyquist pulse shaping at the transmitter and post-equalization at the receiver are employed to mitigate the impairments of joint inter-symbol-interference (ISI) and inter-channel-interference (ICI) symbol degradation. The post-equalization algorithms consist of one sample/symbol based decision-directed least mean square (DD-LMS) adaptive filter, digital post filter and maximum likelihood sequence estimation (MLSE), and a positive iterative process among them. By combining these algorithms, the improvement as much as 4-dB OSNR (0.1nm) at SD-FEC limit (Q(2) = 6.25 corresponding to BER = 2.0e-2) is obtained when compared to no such post-equalization process, and transmission over 820-km EDFA-only standard single-mode fiber (SSMF) link is achieved for two 1.2-Tb/s signals with the averaged Q(2) factor larger than 6.5 dB for all sub-channels. Additionally, 50-GBaud 16QAM operating at 1.28 samples/symbol in a DAC is also investigated and successful transmission over 410-km SSMF link is achieved at 62.5-GHz optical grid.

Electroabsorption-modulated widely tunable DBR laser transmitter for WDM-PONs.

We present an InP based distributed Bragg reflector (DBR) laser transmitter which has a wide wavelength tuning range and a high chip output power for wavelength division multiplexing passive optical network (WDM-PON) applications. By butt-jointing InGaAsP with 1.45 µm emission wavelength as the material of the grating section, the laser wavelength can be tuned for over 13 nm by the DBR current. Accompanied by varying the chip temperature, the tuning range can be further enlarged to 16 nm. With the help of the integrated semiconductor optical amplifier (SOA), the largest chip output power is over 30 mW. The electroabsorption modulator (EAM) is integrated into the device by the selective-area growth (SAG) technique. The 3 dB small signal modulation bandwidth of the EAM is over 13 GHz. The device has both a simple tuning scheme and a simple fabrication procedure, making it suitable for low cost massive production which is desirable for WDM-PON uses.

[The influence of in awake and sleeping to the thresholds of ASSR].

OBJECTIVE: To explore the difference of the threshold of auditory steady-state evoked responses (ASSR) in awake and sleeping. METHOD: Fifteen adults (30 ears) with normal hearing were selected to ASSR test. ASSR parameters: carrier frequency (CM)are 0.5, 1.0, 2.0, 3.0, 4.0, 6.0 kHz, modulation frequency (FM) are 46.81 Hz. The test was performed in two different status (in awake and sleeping). RESULT: In awake, the thresholds of ASSR with FM of 46 Hz are significantly lower than 81 Hz (P < 0.01); In sleeping, the thresholds of ASSR with FM of 81 Hz are lower than 46 Hz above 2 kHz CM (P < 0.05), which thresholds were close to pure tone. CONCLUSION: To select low modulate (46 Hz) frequency in awake, and use high modulate (81 Hz) frequency in sleeping. When perform ASSR test, the test values are closer to the actual hearing threshold.