DRD4 promotes chemo-resistance and cancer stem cell-like phenotypes by mediating the activation of the Akt/ß-catenin signaling axis in liver cancer.

BACKGROUND: Liver cancer stem cells (LCSCs) significantly impact chemo-resistance and recurrence in liver cancer. Dopamine receptor D4 (DRD4) is known to enhance the cancer stem cell (CSC) phenotype in glioblastoma and correlates with poor prognosis in some non-central nervous system tumors; however, its influence on LCSCs remains uncertain. METHODS: To investigate the gene and protein expression profiles of DRD4 in LCSCs and non-LCSCs, we utilized transcriptome sequencing and Western blotting analysis. Bioinformatics analysis and immunohistochemistry were employed to assess the correlation between DRD4 expression levels and the pathological characteristics of liver cancer patients. The impact of DRD4 on LCSC phenotypes and signaling pathways were explored using pharmacological or gene-editing techniques. Additionally, the effect of DRD4 on the protein expression and intracellular localization of ß-catenin were examined using Western blotting and immunofluorescence. RESULTS: DRD4 expression is significantly elevated in LCSCs and correlates with short survival in liver cancer. The expression and activity of DRD4 are positive to resistance, self renewal and tumorigenicity in HCC. Mechanistically, DRD4 stabilizes ß-catenin and promotes its entry into the nucleus via activating the PI3K/Akt/GSK-3ß pathway, thereby enhancing LCSC phenotypes. CONCLUSIONS: Inhibiting DRD4 expression and activation offers a promising targeted therapy for eradicating LCSCs and relieve chemo-resistance.

Exploring the therapeutic potential of isoorientin in the treatment of osteoporosis: a study using network pharmacology and experimental validation.

BACKGROUND: Isoorientin (ISO) is a glycosylated flavonoid with antitumor, anti-inflammatory, and antioxidant properties. However, its effects on bone metabolism remain largely unknown. METHODS: In this study, we aimed to investigate the effects of ISO on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in vitro and bone loss in post-ovariectomy (OVX) rats, as well as to elucidate the underlying mechanism. First, network pharmacology analysis indicated that MAPK1 and AKT1 may be potential therapeutic targets of ISO and that ISO has potential regulatory effects on the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways, as well as oxidative stress. ISO was added to RAW264.7 cells stimulated by RANKL, and its effects on osteoclast differentiation were evaluated using tartrate-resistant acid phosphatase (TRAP) staining, TRAP activity measurement, and F-actin ring analysis. Reactive oxygen species (ROS) production in osteoclasts was detected using a ROS assay kit. The effects of ISO on RANKL-triggered molecular cascade response were further investigated by Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescence staining. In addition, the therapeutic effects of ISO were evaluated in vivo. RESULTS: ISO inhibited osteoclastogenesis in a time- and concentration-dependent manner. Mechanistically, ISO downregulated the expression of the main transcription factor for osteoclast differentiation by inhibiting MAPK and PI3K/AKT1 signaling pathways. Moreover, ISO exhibited protective effects in OVX-induced bone loss rats. This was consistent with the results derived from network pharmacology. CONCLUSION: Our findings suggest a potential therapeutic utility of ISO in the management of osteoclast-associated bone diseases, including osteoporosis.

Can the Sterilization Protocol Be Improved to Enhance the Healing of Allograft Tendons? An In Vivo Study in Rabbit Tendons.

BACKGROUND: Peracetic acid and irradiation are common sterilization methods for allograft tendons; however, under some conditions, both methods adversely affect the fiber arrangement and ultimate load of the tendon. An in vitro study showed that low-dose peracetic acid combined with irradiation may be less detrimental to allograft tendon structure and properties, possibly because the breakdown of peracetic acid can lead to an enlargement of the interstitial spaces and an increase in porosity. QUESTIONS/PURPOSES: Using a rabbit Achilles tendon model, we asked: What is the effect of peracetic acid-ethanol combined irradiation on (1) the histopathology and fiber diameter of the allograft tendon, (2) tensile creep and load-to-failure biomechanical properties of allograft tendons, and (3) healing of the treated tendon in vivo compared with fresh-frozen allograft and peracetic acid-ethanol sterilization at 4 and 8 weeks? METHODS: The Achilles tendons used in this study were sourced from euthanized 10-week-old male New Zealand White rabbits previously used for ophthalmic experiments. All allografts were divided into three groups: fresh-frozen group (control group, n = 20), peracetic acid-ethanol sterilization group (n =20), and peracetic acid-ethanol combined irradiation group (n = 20). The sterilization protocols were performed per a predetermined plan. In the peracetic acid-ethanol sterilization group, the tendon tissues were covered with the peracetic acid-ethanol sterilization solution (1% peracetic acid for 30 minutes). In the peracetic acid-ethanol combined irradiation group, the tendon tissues were covered with the peracetic acid-ethanol sterilization solution (0.2% peracetic acid for 30 minutes) and were subjected to 15 kGy gamma irradiation. Thirty 10-week-old male New Zealand White rabbits received bilateral Achilles tendon allografts surgically. Tendon samples from each group were harvested at 4 weeks (n = 30) and 8 weeks (n = 30) postoperatively. For each timepoint, eight tissues were used for histologic staining and electron microscopy, 15 tissues were used for biomechanical testing, and seven tissues were used for hydroxyproline assay and quantitative polymerase chain reaction. Histopathology was determined qualitatively by hematoxylin and eosin and Masson staining, while fiber diameter was measured quantitatively by transmission electron microscopy. Biomechanical properties were measured using cyclic loading tests and load-to-failure tests. The healing outcome was quantitatively judged through healing-related genes and proteins. RESULTS: At 4 weeks and 8 weeks postoperatively, the peracetic acid-ethanol combined irradiation group visually demonstrated the best continuity and minimal peripheral adhesions. Histologic staining showed that tendon fibers in the peracetic acid-ethanol combined irradiation group maintained consistent alignment without notable disruptions or discontinuities, and there was a qualitatively observed increase in the number of infiltrating cells compared with the control group at the 4-week timepoint (444 ± 49 /mm 2 versus 256 ± 43 /mm 2 , mean difference 188 /mm 2 [95% confidence interval 96 to 281]; p < 0.001). At 8 weeks postoperatively, the tendon fiber diameter in the peracetic acid-ethanol combined irradiation groups was similar to that of the control group (0.23 ± 0.04 µm versus 0.21 ± 0.03 µm, mean difference 0.02 µm [95% CI -0.04 to 0.08]; p = 0.56). At 8 weeks postoperatively, the peracetic acid-ethanol combined irradiation group exhibited better properties in terms of both ultimate load (129 ± 15 N versus 89 ± 20 N, mean difference 40 N [95% CI 7 to 73]; p = 0.02) and energy absorption density (17 ± 6 kJ/m 2 versus 8 ± 4 kJ/m 2 , mean difference 8 kJ/m 2 [95% CI 0.7 to 16]; p = 0.004) compared with the control group. Gene expression analysis revealed higher expression levels of COL1A1 (2.1 ± 0.8 versus 1.0 ± 0, mean difference 1.1 [95% CI 0.1 to 2.1]; p = 0.003) and MMP13 (2.0 ± 0.8 versus 1.0 ± 0, mean difference 1.0 [95% CI 0.4 to 1.6]; p = 0.03) in the peracetic acid-ethanol combined irradiation group than in the control group. There was a higher amount of collagen Type I in tendons treated with peracetic acid-ethanol combined irradiation than in the control group (0.36 ± 0.03 versus 0.31 ± 0.04, mean difference 0.05 [95% CI 0.01 to 0.09]; p = 0.02). CONCLUSION: Treatment with peracetic acid-ethanol combined irradiation did not have any discernible adverse effect on the histology, fiber diameter, enzymatic resistance, collagen content, or biomechanical strength of the allograft tendons compared with the control group. Peracetic acid-ethanol combined irradiation treatment had a positive impact on remodeling of the extracellular matrix and realignment of collagen fibers. CLINICAL RELEVANCE: This sterilization method could be helpful to expand the scope and frequency with which allogeneic materials are applied. The long-term healing effect and strength of allograft tendons must be tested before clinical use, and it is necessary to conduct comparative studies on autografts and synthetic materials that are currently widely used clinically.

Long-term results of single-stage posterior hemivertebra resection and short segment fusion using pedicle screws fixation in thoracolumbar congenital early-onset scoliosis: an 8.97-year average follow-up study.

BACKGROUND: This study aims to evaluate the long-term outcomes of one-stage posterior hemivertebra resection and short segment fusion with pedicle screw fixation in children with thoracolumbar congenital early-onset scoliosis (TLCEOS). It specifically investigates the durability of spinal correction and the incidence of complications over an average follow-up of 8.97 years. METHODS: A retrospective review was conducted on 32 patients treated at a tertiary scoliosis referral center from April 2003 to December 2019. Inclusion criteria were thoracolumbar hemivertebra (T11-L1), treatment via posterior hemivertebra resection and short segment fusion (≤ 5 segments), age under 10 years at surgery, and a follow-up of at least 5 years. Exclusions included idiopathic, syndromic, or neuromuscular scoliosis. Data on demographics, surgical procedures, and radiographic outcomes were collected, and clinical outcomes were evaluated using the Scoliosis Research Society-22 (SRS-22) questionnaire. Statistical analysis was performed using SPSS and R software. RESULTS: The study included 32 patients (22 males, 10 females) with a mean age of 5.00 ± 2.42 years at surgery and an average follow-up of 8.97 ± 2.81 years. On average, 3.47 ± 1.11 segments were fused. The main curve corrected from 38.64° ± 14.12° preoperatively to 9.06° ± 7.29° postoperatively, with a final correction rate of 61%. Significant improvements were observed in the SRS-22 domains of Appearance and Satisfaction with Treatment. There were 17 complications, including neurological, pulmonary, and mechanical issues, with some cases requiring revision surgery. CONCLUSIONS: One-stage posterior hemivertebra resection and short segment fusion with pedicle screw fixation effectively correct TLCEOS long-term, offering significant improvements in patient appearance and satisfaction, with a manageable complication profile.

Causal inference of the effect of plasma proteins on the incidence of oral cancer: two-sample Mendelian randomization.

OBJECTIVE: This study is aimed to investigate the causal relationship between plasma proteins and oral cancer risk using two-sample MR (Mendelian randomization). METHODS: Summary-level GWAS (genome-wide association study) data on plasma protein levels (4,907 proteins) and oral cancer (6,034 cases, 6,585 controls) of European ancestry were utilized. SNPs (single nucleotide polymorphisms) associated with proteins at genome-wide significance were selected as instrumental variables. Multiple MR methods including IVW (inverse-variance weighted), MR-Egger, weighted median, simple mode and weighted mode were applied to estimate causal effects. Sensitivity analyses were conducted. RESULTS: Eight plasma proteins (CCDC167, MID2, NDRG4, PEAR1, PIAS4, RCAN1, SAMHD1 and TNMD) were identified to have significant causal associations with oral cancer risk. NDRG4, RCAN1, SAMHD1 and TNMD were associated with increased oral cancer risk while PEAR1 was associated with decreased risk. The causal estimates were consistent across different methods. Sensitivity analyses indicated the results were robust without significant heterogeneity or horizontal pleiotropy. Multivariable MR adjusting for smoking, alcohol intake and periodontal disease showed CCDC167, MID2, NDRG4, PEAR1, PIAS4 and SAMHD1 still had direct effects on oral cancer. CONCLUSION: This two-sample MR study provides evidence for potentially causal effects of several plasma proteins on oral cancer risk. The identified proteins may serve as biomarkers and shed light on biological mechanisms underlying oral carcinogenesis. Further research is warranted to validate and extend these findings.

Crosstalk between heat shock factor 1 and signal transducer and activator of transcription 3 mediated by interleukin-8 autocrine signaling maintains the cancer stem cell phenotype in liver cancer.

BACKGROUND AND AIM: Liver cancer stem cells (LCSCs) cause therapeutic refractoriness and relapse in hepatocellular carcinoma. Heat shock factor 1 (HSF1) plays versatile roles in multiple cancers. However, the role of HSF1 in LCSCs is not well understood. This study investigated the function and signal mechanisms of HSF1 in maintaining LCSC phenotypes. METHODS: We established two LCSC lines, HepG2-R and HuH-7-R. Constitutive activation of HSF1 was observed in these LCSCs. Specific short hairpin RNAs (shRNAs) and chemical inhibitors were used to identify the relationship between HSF1 expression and LCSCs phenotypes. RESULTS: We revealed a concomitant activation modality involving HSF1 and STAT3 in LCSCs and liver cancer tissues. We also found that liver cancer patients whose HSF1 and STAT3 mRNA expression levels were high presented with unfavorable clinicopathological characteristics. Moreover, the secretion of interleukin-8 (IL-8) was elevated in the LCSC medium and was directly regulated by HSF1 at the transcriptional level. In turn, IL-8 activated HSF1 and STAT3 signaling, and a neutralizing IL-8 antibody inhibited HSF1 and STAT3 activity, reduced cancer stem cell marker expression, and decreased LCSC microsphere formation. Simultaneous intervention with HSF1 and STAT3 led to synergistically suppressed stemness acquisition and growth suppression in the LCSCs in vivo and in vitro. CONCLUSIONS: Our study indicates that IL-8 mediates the crosstalk between the HSF1 and Stat3 signaling pathways in LCSCs and that the combined targeting of HSF1 and STAT3 is a promising treatment strategy for patients with advanced liver cancer.

Ten-year trends in surgical management of 1207 congenital scoliosis.

PURPOSE: To report and analyze development trends in the surgical treatment of congenital scoliosis (CS) in a large CS cohort over a 10-year period. METHODS: We retrospectively searched and extracted medical records of CS inpatients receiving posterior instrumented fusion surgery at our institute from January 2010 to December 2019. We analyzed information on demographics and surgical information, including the surgical approach, number of fused segments, use of osteotomy and titanium cage implantation, length of stay, intraoperative blood loss, and rates of complications and readmission. RESULTS: 1207 CS inpatients were included. In the past decade, the proportion of patients younger than 5 years increased from 15.5 to 26.9%. The average number of fused segments decreased from 9.24 to 7.48, and the proportion of patients treated with short-segment fusion increased from 13.4 to 30.3%. The proportion of patients treated with osteotomy and titanium cage implantation increased from 55.65% and 12.03% to 76.5% and 40.22%. The average length of stay and blood loss decreased from 16.5 days and 816.1 ml to 13.5 days and 501.7 ml. The complication and readmission rates also decreased during these ten years. CONCLUSION: During this ten-year period, the surgical treatment of CS at our institute showed trends toward a younger age at fusion, lower number of fused segments, higher rate of osteotomy and titanium cage implantation, reduced blood loss, shorter length of stay and lower rate complications and readmission. These results suggest performing osteotomy combined with titanium cage implantation at an earlier age can achieve fewer fused segments and complications.

The incidence and interrelationship of hemivertebra and concomitant cardiac abnormalities in congenital scoliosis.

BACKGROUND: Congenital scoliosis(CS) is associated with multiple organs defect, and cardiac abnormalities have been reported commonly associated with CS. Hemivertebra is caused by the failure of vertebral formation, which is a major constitute of CS. Till now, few studies focus on the incidence and interrelationship of hemivertebra and concomitant cardiac abnormalities in congenital scoliosis. We aimed to analyze the cardiac defect in CS patients with or without hemivertebra, and further explore the incidence of cardiac defect between different types of hemivertebra. METHODS: The ultrasonic cardiography (UCG) results of surgically treated congenital scoliosis (CS) patients between 2015 and 2018 were retrospectively analyzed. Patients were divided into hemivertebra group and non-hemivertebra group according to preoperative CT. Patients with hemivertebra was further divided into sub-group by single/multiple or fully/partially/mixed segmented hemivertebra. Demographic information, radiographic data and cardiac abnormalities were statistically compared between groups. RESULTS: A total of 329 patients were analyzed, including 216 patients with hemivertebra and 113 patients without hemivertebra. UCG results were abnormal in 89 cases (27.1%), including 41 males(12.5%) and 48 females(14.6%). Hemivertebra group had comparable incidence of cardiac abnormalities with non-hemivertebra group (p = 0.517). No significant difference in the incidence of UCG abnormalities between single and multiple hemivertebra group (P = 0.246). Binary logistic regression analysis showed that female sex with multiple hemivertebra was a risk factor for abnormal UCG (P = 0.009, OR = 3.449). Cardiac abnormalities was comparable among fully, partially and mixed segmented hemivertebra group(P = 0.264). In abnormal UCG, 33 patients with hemivertebra had non-valvular abnormalities, and 48.5% (16/33) were septal defects. 28 patients had valvular abnormalities, most of them were mitral valve abnormalities, especially mitral valve redundancy, prolapse and insufficiency(82.1%, 23/28). No significant difference between the incidence of non-valvular and valvular abnormalities in patients with hemivertebra (P = 0.581). CONCLUSIONS: The incidence of abnormal UCG results was approximately 28.2% in CS patients with hemivertebra. Female patients with multiple hemivertebra had a higher risk of UCG abnormalities. Mitral valve abnormalities were the most common abnormality of UCG found in CS patients with hemivertebra. TRIAL REGISTRATION: retrospectively registered.

Necessity of routinely performing foraminoplasty during percutaneous endoscopic transforaminal discectomy (PETD) for lumbar disc herniation.

OBJECTIVE: To assess the role of foraminoplasty during percutaneous endoscopic transforaminal discectomy (PETD) and compared the 2-year clinical results of patients underwent PETD w/o foraminoplasty. METHODS: A total of 412 patients, who underwent PETD at L3-S1 by the same surgical group, were enrolled in this study. The MRI was used to determine the height (H1) and width (W1) of the intervertebral foramen of L3-S1, the distance between the exiting nerve root and the upper edge of the lower vertebral pedicle (H2), and the distance (W2) between the point with 3 mm to the ventral side of the intervertebral space and superior articular process. The intervertebral foramen widths in the flexion (W3) and extension positions (W4) were also measured. A VAS of low back pain (LBP) and leg pain, ODI and JOA scores of LBP were used to assess the clinical results. RESULTS: Intraoperative verification showed that 347 cases (group A) did not need foraminoplasty, while the other 65 patients (group B) needed foraminoplasty, including 31 at L4-5 and 34 at L5-S1. The H1 and H2 of L3-S1 were reduced gradually without significant difference between two groups. The W1, W2, W3 and W4 were higher in group A (p < 0.05). The W3 was higher than W4 in both groups (p < 0.05). At 2-year follow-up, there was no significant difference of ODI and JOA score between two groups (p > 0.05). The VAS score of LBP was better in group A (p < 0.05). CONCLUSIONS: Most of PETD procedure at L3-S1 levels could reach the therapeutic target without foraminoplasty. Due to anatomic characteristics of L5-S1, the foraminoplasty rate was much higher at L5-S1.

Uterine CD56+ cell density and euploid miscarriage in women with a history of recurrent miscarriage: A clinical descriptive study.

In women with a history of recurrent miscarriage, the uterine CD56+ cell density in subjects with subsequent euploid miscarriage was significantly higher than those with subsequent aneuploid miscarriage. Both endometrial and embryonic factors should be investigated when interpreting uterine CD56+ cell density results relating to recurrent miscarriage.

Bacillus amyloliquefaciens ameliorates high-carbohydrate diet-induced metabolic phenotypes by restoration of intestinal acetate-producing bacteria in Nile Tilapia.

Poor utilisation efficiency of carbohydrate always leads to metabolic phenotypes in fish. The intestinal microbiota plays an important role in carbohydrate degradation. Whether the intestinal bacteria could alleviate high-carbohydrate diet (HCD)-induced metabolic phenotypes in fish remains unknown. Here, a strain affiliated to Bacillus amyloliquefaciens was isolated from the intestine of Nile tilapia. A basal diet (CON), HCD or HCD supplemented with B. amy SS1 (HCB) was used to feed fish for 10 weeks. The beneficial effects of B. amy SS1 on weight gain and protein accumulation were observed. Fasting glucose and lipid deposition were decreased in the HCB group compared with the HCD group. High-throughput sequencing showed that the abundance of acetate-producing bacteria was increased in the HCB group relative to the HCD group. Gas chromatographic analysis indicated that the concentration of intestinal acetate was increased dramatically in the HCB group compared with that in the HCD group. Glucagon-like peptide-1 was also increased in the intestine and serum of the HCB group. Thus, fish were fed with HCD, HCD supplemented with sodium acetate at 900 mg/kg (HLA), 1800 mg/kg (HMA) or 3600 mg/kg (HHA) diet for 8 weeks, and the HMA and HHA groups mirrored the effects of B. amy SS1. This study revealed that B. amy SS1 could alleviate the metabolic phenotypes caused by HCD by enriching acetate-producing bacteria in fish intestines. Regulating the intestinal microbiota and their metabolites might represent a powerful strategy for fish nutrition modulation and health maintenance in future.

"High-risk" host cell proteins (HCPs): A multi-company collaborative view.

Host cell proteins (HCPs) are process-related impurities that may copurify with biopharmaceutical drug products. Within this class of impurities there are some that are more problematic. These problematic HCPs can be considered high-risk and can include those that are immunogenic, biologically active, or enzymatically active with the potential to degrade either product molecules or excipients used in formulation. Some have been shown to be difficult to remove by purification. Why should the biopharmaceutical industry worry about these high-risk HCPs? What approach could be taken to understand the origin of its copurification and address these high-risk HCPs? To answer these questions, the BioPhorum Development Group HCP Workstream initiated a collaboration among its 26-company team with the goal of industry alignment around high-risk HCPs. The information gathered through literature searches, company experiences, and surveys were used to compile a list of frequently seen problematic/high-risk HCPs. These high-risk HCPs were further classified based on their potential impact into different risk categories. A step-by-step recommendation is provided for establishing a comprehensive control strategy based on risk assessments for monitoring and/or eliminating the known impurity from the process that would be beneficial to the biopharmaceutical industry.

Xinmai 'an extract enhances the efficacy of sildenafil in the treatment of pulmonary arterial hypertension via inhibiting MAPK signalling pathway.

CONTEXT: Xinmai 'an tablet has been used to improve myocardial blood supply. Recently, some compounds from its formula have shown that they can treat pulmonary arterial hypertension (PAH). OBJECTIVE: This study investigates the effects of Xinmai 'an extract (XMA) on PAH and further tests the co-therapeutic enhancement with sildenafil (SIL). MATERIALS AND METHODS: Pulmonary artery smooth muscle cells were subjected to stimulation with SIL (12.5 µM) and XMA (250 µg/mL) for 48 h. Sprague-Dawley rats were randomly grouped into eight groups (n = 8 per group): (I) control group received saline; (II) MCT group received MCT (60 mg/kg); (III) SIL-Low group received MCT + SIL at 10 mg/kg/day; (IV) SIL-high group received MCT + SIL at 30 mg/kg/day; (V) XMA-High group received MCT + XMA at 251.6 mg/kg/day; (VI) SIL (Low)+XMA (Low) group received SIL (10 mg/kg) + XMA at 62.9 mg/kg/day; (VII) SIL (Low)+XMA (Medium) group received SIL (10 mg/kg) + XMA at 125.8 mg/kg/day; (VIII) SIL (Low)+XMA (High) group received SIL (10 mg/kg) + XMA at 251.6 mg/kg/day. Both XMA and SIL were given by gavage and were maintained daily for 2 weeks. RESULTS: XMA could improve SIL's efficacy in the treatment of PAH by decreasing cell viability more effectively at non-cytotoxic concentrations (250 µg/mL) and reducing Right Ventricular Systolic Pressure (RVSP) in PAH rat. Potential mechanisms might at least in part be through activating the MAPK signalling pathway. DISCUSSION AND CONCLUSIONS: The combination of XMA and SIL can improve the efficacy of pulmonary hypertension and reduce the dosage of SIL.

Integrated Proteomics and Metabolomics Reveal the Mechanism of Nephrotoxicity Induced by Triptolide.

Triptolide (TP), the main active ingredient of Tripterygium wilfordii Hook F., has great potential in the treatment of autoimmune diseases. However, it has been found that the side effects of TP involve multiple organs and systems, of which the most serious side effects relate to the kidney. The mechanism of nephrotoxicity caused by TP requires further investigation. In the present study, we integrated proteomic and metabolomic methods to identify proteins and small molecule metabolites associated with TP-induced nephrotoxicity. There was a significant difference (p value <0.05) in the expression changes of 357 proteins for quantitative proteomics. In addition, high resolution metabolomic data showed significant changes in the levels of 9 metabolites, including hypoxanthine, PC(22:0/18:4), sphingosine, phenylalanine, etc. Finally, based on the Kyoto Encyclopaedia of Genes and Genomes (KEGG) database for network analysis, it was determined that the 7 differentially expressed proteins were highly correlated with these 9 metabolites. Enrichment analysis revealed that the metabolic pathways involved purine and pyrimidine metabolism, glycerol and phospholipid metabolism, sphingolipid metabolism, and amino acid metabolism. The key target proteins were verified by Western blot technology, and the mechanism of TP-induced nephrotoxicity was further elucidated to provide a basis for safe and rational application.

Diagnostic value and clinical significance of magnetic resonance imaging with the FS-PD-TSE sequence in diagnosing lumbar cartilaginous endplate failure.

PURPOSE: The aims were to use magnetic resonance imaging (MRI) to compare the efficacy of fat-suppressed proton-density turbo-spin-echo (FS-PD-TSE) images and T1-weighted (T1WIs) and T2-weighted images (T2WIs) in identifying cartilaginous endplate failure (CEF), and to propose a modified Rajasekaran classification based on the FS-PD-TSE sequence. METHODS: Thirty-one lumbar disc herniation (LDH) cases were enrolled. Totally, 155 discs and 310 endplates were evaluated by MRI with T1W, T2W, and FS-PD-TSE sequences. Disc degeneration (DD), LDH grades, and the total endplate score (TEPS) of CEF were evaluated. Chi-square, Spearman rank correlation analysis, and multiclass logistic regression were used to compared the sensitivity in diagnosing CEF. A modified Rajasekaran classification based on FS-PD-TSE sequence was established to diagnose CEF. The multiclass logistic regression model was used to analyse the relationship between modified Rajasekaran classification and DD and LDH. RESULTS: There were 117 (75.5%) segments with CEF in T1WIs, 115 (74.2%) in T2WIs, and 127 (81.9%) in FS-PD-TSE, respectively. Chi-square test showed FS-PD-TSE images were more sensitive than T1WIs and T2WIs (P < 0.05). Spearman rank correlation analysis revealed a significant correlation between TEPS and LDH and DD in T1WIs, T2WIs, and FS-PD-TSE images (P < 0.05). A multiclass logistic regression model showed that the incidence of DD and LDH significantly increased accordingly with increases in modified Rajasekaran classification (P < 0.05). CONCLUSION: The FS-PD-TSE sequence has high diagnostic value for lumbar CEF. CEF is a risk factor for LDH. The new classification for lumbar CEF based on the FS-PD-TSE sequence has good predictive ability for LDH and DD. These slides can be retrieved under Electronic Supplementary Material.

Modified mini-open SRS-Schwab grade 4 osteotomy combined with percutaneous pedicle screws fixation in post-traumatic thoracolumbar kyphosis.

BACKGROUND: We aimed to analyze the clinical results of Schwab grade 4 osteotomy combined with percutaneous pedicle screws (PPS) fixation for treatment of post-traumatic thoracolumbar kyphosis (PTK). METHODS: Thirty four patients with PTK (group A) were included in our study. The average age was 54.9 ± 3.3 years. All patients had severe back pain with 8.6 ± 1.3 VAS scores. The affected level was T12 in 16 patients and L1 in 18 patients. The average preoperative regional kyphosis angle (RKA) was 30.7 ± 6.00. Three patients had neurological dysfunction with ASIA grade D. All patients underwent Schwab grade 4 osteotomy combined with PPS fixation. The control group (Group B) were 26 PTK patients treated with Schwab grade 4 osteotomy and open pedicle screws fixation in our institution. RESULTS: Operation time in groups A and B was 280 ± 50 min and 210 ± 30 min, respectively (P < 0.05). Estimated blood loss in groups A and B was 310 ± 70 ml and 630 ± 40 ml, respectively (P < 0.05). No cerebral spinal fluid leakage, segmental nerve function damage, and other complications observed during and after the operations in both groups. RKA, SVA, and LL improved significantly after surgery in both groups (P < 0.05). The average correction rate in groups A and B was 64.5 and 66.3% (P > 0.05). CT showed that the misplacement rate in groups A and B was 5.5 and 6.6% (P > 0.05). The average follow-up in groups A and B was 25.2 ± 7.6 months and 30.6 ± 2.7 months. No fracture and other complications were observed in both groups. Solid bone fusion was showed in all cases at 6 months follow-up. In groups A and B, all patients with preoperative neurological dysfunction recovered to ASIA grade E at the last follow-up. The VAS score of back pain improved significantly from 8.6 ± 1.3 to 1.6 ± 1.0 at the last follow-up in group A (P < 0.05), while it improved significantly from 8.3 ± 1.2 to 3.0 ± 1.1 at the last follow-up in group B (P < 0.05). VAS of back pain was better in group A than that in group B. CONCLUSION: Schwab grade 4 osteotomy combined with percutaneous pedicle screws fixation is a minimally invasive, safe and effective method for PTK treatment.

Association between chronic endometritis and uterine natural killer cell density in women with recurrent miscarriage: clinical implications.

AIM: This aim of this study was to determine the association between uterine natural killer (uNK) cell density and chronic endometritis (CE). METHODS: Endometrial biopsies from 135 women with recurrent miscarriage were obtained precisely 7 days after luteinizing hormone surge in natural cycles. Endometrial sections were immunostained for CD56 for uNK cells and CD138 for plasma cells, respectively. Uterine NK cell counting was performed according to a standardized protocol and results were expressed as percentage of CD56+ cells/ total stromal cells. High uNK cell density was defined as >4.5% and CE was diagnosed when the plasma cell density > 5.15 cells/ 10 mm2 . RESULTS: The uNK cells density in women with CE (median, 5.1%; range, 3.4-8.8%) was significantly (P < 0.05) higher than that of those without CE (median, 3.8%; range, 1.2%-7.3%). The prevalence of high uNK cell density in women with CE (11/29, 37.9%) was significantly (P < 0.05) higher than that of women without CE (8/106, 7.5%). CONCLUSION: To conclude, there was a significant association between high uNK cell density and CE. In women with high uNK cell density, plasma cell should be examined to determine if the underlying cause is associated with CE.

Influence of contoured versus straight rod on clinical outcomes and sagittal parameters in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) at L4/5 level-more than 5 years follow-up.

BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is among the most commonly performed surgical procedure to treat lumbar degenerative disorders. In open TLIF procedure, usually rods were contoured to restore normal lumbar sagittal alignment. However, in MIS-TLIF procedure, contoured rods sometimes were easier to rotate and harder to be locked at the satisfactory position due to instrumentation design and limited exposure. Thus, straight rods had been used in single-level MIS-TLIF in our institution. However, the effect of rod contouring on sagittal parameters and clinical outcomes remains unclear. In the present study, we aim to evaluate the effects of single-segment MIS-TLIF with contoured versus straight rods on sagittal parameters and clinical outcomes. METHODS: A retrospective review of MIS-TLIF at L4/5 was performed between 2009 and 2013 in our hospital. Seventy-six cases were divided into contoured rod group (CR group, n = 35) and straight rod group (SR group, n = 41). Clinical outcomes and radiographic measurements at five years' follow-up were evaluated by visual analog score (VAS), Oswestry disability index (ODI) and Japanese Orthopaedic Association (JOA) score, spino-pelvic parameters, disc height and fused segment angle. Fusion rate and cage subsidence were also measured. RESULTS: Preoperative VAS, JOA, ODI and radiographic parameters were comparable between two groups. The average follow-up was 63.72 ± 3.86 months. VAS, JOA and ODI were significantly improved at 5-year follow-up in both groups, and there were no significant differences between two groups(P > 0.05). Fused segment angle (FSA) was greater in CR group than SR group (P = 0.024), while the other radiographic parameters were not significantly different(P > 0.05). Rod process, fusion rate and cage subsidence were not risk factors of post-surgical malalignment, patients with pre-surgical sagittal imbalance was more prone to show post-surgical malalignment (P < 0.05). CONCLUSIONS: Both CR and SR groups acquired satisfactory clinical results. Although contoured rods had better fused segment angle, contoured or straight rods at single L4/5 level had little effect on global spino-pelvic parameters and clinical outcomes in a 5-year follow-up.

Gas Sensors Based on Nano/Microstructured Organic Field-Effect Transistors.

Benefiting from the advantages of organic field-effect transistors (OFETs), including synthetic versatility of organic molecular design and environmental sensitivity, gas sensors based on OFETs have drawn much attention in recent years. Potential applications focus on the detection of specific gas species such as explosive, toxic gases, or volatile organic compounds (VOCs) that play vital roles in environmental monitoring, industrial manufacturing, smart health care, food security, and national defense. To achieve high sensitivity, selectivity, and ambient stability with rapid response and recovery speed, the regulation and adjustment of the nano/microstructure of the organic semiconductor (OSC) layer has proven to be an effective strategy. Here, the progress of OFET gas sensors with nano/microstructure is selectively presented. Devices based on OSC films one dimensional (1D) single crystal nanowires, nanorods, and nanofibers are introduced. Then, devices based on two dimensional (2D) and ultrathin OSC films, fabricated by methods such as thermal evaporation, dip-coating, spin-coating, and solution-shearing methods are presented, followed by an introduction of porous OFET sensors. Additionally, the applications of nanostructured receptors in OFET sensors are given. Finally, an outlook in view of the current research state is presented and eight further challenges for gas sensors based on OFETs are suggested.

Light-Stimulated Synaptic Transistors Fabricated by a Facile Solution Process Based on Inorganic Perovskite Quantum Dots and Organic Semiconductors.

Implementation of artificial intelligent systems with light-stimulated synaptic emulators may enhance computational speed by providing devices with high bandwidth, low power computation requirements, and low crosstalk. One of the key challenges is to develop light-stimulated devices that can response to light signals in a neuron-/synapse-like fashion. A simple and effective solution process to fabricate light-stimulated synaptic transistors (LSSTs) based on inorganic halide perovskite quantum dots (IHP QDs) and organic semiconductors (OSCs) is reported. Blending IHP QDs and OSCs not only improves the charge separation efficiency of the photoexcited charges, but also induces delayed decay of the photocurrent in the IHP QDs/OSCs hybrid film. The enhanced charge separation efficiency results in high photoresponsivity, while the induced delayed decay of the photocurrent is critical to achieving light-stimulating devices with a memory effect, which are important for achieving high synaptic performance. The LSSTs can respond to light signals in a highly neuron-/synapse-like fashion. Both short-term and long-term synaptic behaviors have been realized, which may lay the foundation for the future implementation of artificial intelligent systems that are enabled by light signals. More significantly, LSSTs are fabricated by a facile solution process which can be easily applied to large-scale samples.