Combining non-invasive liquid biopsy and a methylation analysis to assess surgical risk for early esophageal cancer.

Background: While the widespread use of endoscopic submucosal dissection (ESD) has significantly reduced the incidence of early esophageal cancer (ESCA), the limited ability of ESD to strip deep infiltrating esophageal lesions results in a considerable risk of intraoperative perforation. Circulating-free DNA (cfDNA) is widely used in modern tumor screening due to its non-invasive detection capabilities. A methylation analysis offers vital insights into the condition and advancement of malignancies due to its unique positioning, such as a marker of cancer. This study investigated the potential of combining a non-invasive liquid biopsy technique, along with a methylation analysis, to assess the surgical perforation risk of ESCA patients. Methods: In this study, we conducted an analysis of gene expression differences between stage I esophageal squamous carcinoma samples and healthy tissue samples using data from The Cancer Genome Atlas (TCGA) database. We also identified the genes associated with progression-free survival (PFS) in esophageal squamous carcinoma. Integrating the framework of the methylation analysis, we explored the methylated sites of these distinct genes. To refine this process, we used the Shiny Methylation Analysis Resource Tool (SMART) to conduct a comprehensive analysis of these sites. We then confirmed the stability of the methylation sites in different lesion conditions using methylation-specific quantitative polymerase chain reaction (MS-qPCR) with paraffin tissue samples collected after ESD. Results: We analyzed RNA-sequencing data from 42 early stage ESCA patients and 17 controls, identifying 1,263 up-regulated and 460 down-regulated genes. Functional analyses revealed involvement in key pathways such as cell cycle regulation and immune responses. Furthermore, we identified 38 differentially expressed genes associated with PFS. Using SMART analysis, we found 217 hyper-methylated regions in 38 genes, suggesting potential early markers for ESCA. Validation experiments confirmed the reliability of 29 hyper-methylated regions in FFPE tissue samples and 6 regions in cfDNA. A LunaCAM model showed high accuracy [area under the curve (AUC) =0.89] in discriminating early ESCA. Integrated assessment of six highly methylated regions significantly improved predictive performance, with 90.56% sensitivity, highlighting the importance of combinatorial biomarker evaluation for early cancer detection. Conclusions: This study established a novel approach that integrates non-invasive testing with a methylation analysis to assess the surgical risk of early ESCA patients. The significance of changes in methylation sites in relation to lesion status should not be underestimated, as they have the potential to offer vital insights for proactive risk assessments before surgery.

Association between quadriceps fat pad edema and patellofemoral osteoarthritis: a quantitative Q-Dixon-based magnetic resonance imaging (MRI) analysis.

Background: Anterior knee pain (AKP) is a common symptom of patellofemoral osteoarthritis (PFOA). There is limited prospective evidence supporting the relationships between patellofemoral maltracking parameters, AKP, and PFOA. Thus, this prospective cross-sectional study aimed to determine the association between quadriceps fat pad (QFP) edema and patellofemoral maltracking in patients with chronic AKP and to evaluate the feasibility and diagnostic performance of a PFOA assessment using fat fraction (FF) and T2* based on Q-Dixon. Methods: This was a cross-sectional study with prospective data collection. Patients with chronic AKP were recruited from an orthopedic outpatient magnetic resonance imaging (MRI) waiting room at Shanghai Tongren Hospital between November 1, 2022, and April, 30, 2023. Exclusion criteria included age of <18 years, knee trauma, major internal derangement, prior surgery/arthroscopy, pre-existing joint diseases, and contraindications to MRI. MRI was performed using a 3.0-T instrument, and patellofemoral maltracking parameters were measured. Patellofemoral feature-relevant items, including patellar cartilage defects, patellar bone marrow lesions (BMLs), patellar osteophytes, anterior femoral osteophytes, Hoffa synovitis, and synovitis-effusion, from the semi-quantitative MRI Osteoarthritis Knee Score (MOAKS) were measured. The Anterior Knee Pain Scale (AKPS) was used to assess pain and function. FF/T2* measurement differences between groups and their associations with maltracking metrics, osteoarthritis grading based on the Iwano grading system, MOAKS, and AKPS, were investigated. Based on Iwano grading, the participants were categorized as having no-PFOA (n=40), mild PFOA (n=40), and advanced PFOA (n=40). Chi-squared and one-way analysis of variance were used to assess potential differences between the groups. Spearman's correlation test was used to analyze the correlation between the morphological parameters, AKPS, Iwano grade, MOAKS, and MRI quantitative values. Receiver operating characteristic (ROC) curves assessed the area under the curve (AUC), sensitivity, and specificity of quantitative values for distinguishing PFOA from no-PFOA. Results: Among the 120 included patients, those in the mild (86.2±8.5) and advanced (83.9±9.5) PFOA groups had significantly lower AKPS scores than those in the no-PFOA group (88.8±7.3) (P=0.03). The mean FF and T2* values of the QFP were significantly higher in the no-PFOA group than those in the mild and advanced PFOA groups (P<0.001 for FF and P=0.02 for T2*). Quantitative data on the QFP and patellofemoral maltracking parameters showed no association. FF (r=-0.686, P<0.001) and T2* (r=-0.314, P=0.008) showed a negative correlation with the Iwano grade. The AUCs for PFOA diagnosis were 0.906 [95% confidence interval (CI), 0.853-0.960] (FF) and 0.744 (95% CI, 0.657-0.831) (T2*). Conclusions: QFP FF and T2* were not associated with patellofemoral maltracking parameters but with increased PFOA in patients with AKP, suggesting that QFP abnormalities play a role in PFOA. Therefore, a quantitative QFP assessment (FF and T2*) based on Q-Dixon technology could be a convenient and reliable new imaging biomarker for PFOA severity during clinical diagnosis, treatment, and follow-up.

Analgesic efficacy of an opioid-free postoperative pain management strategy versus a conventional opioid-based strategy following laparoscopic radical gastrectomy: an open-label, randomized, controlled, non-inferiority trial.

OBJECTIVE: In patients undergoing laparoscopic radical gastrectomy, the use of subcostal transversus abdominis plane block (STAPB) for completely opioid-free postoperative pain management lacks convincing clinical evidence. METHODS: This study included 112 patients who underwent laparoscopic radical gastrectomy at the 900TH Hospital of the Joint Logistics Support Force from October 2020 to March 2022. Patients were randomly divided into (1:1) continuous opioid-free STAPB (C-STAPB) group and conventional group. In the C-STAPB group, 0.2% ropivacaine (bilateral, 20 ml per side) was injected intermittently every 12 h through a catheter placed on the transverse abdominis plane for postoperative pain management. The conventional group was treated with a conventional intravenous opioid pump (2.5 µg/kg sufentanil and 10 mg tropisetron, diluted to 100 ml with 0.9% NS). The primary outcomes were the accumulative area under the curve of the numeric rating scale (NRS) score at 24 and 48 h postoperatively at rest and during movement. The secondary outcomes were postoperative recovery outcomes, postoperative daily food intake, and postoperative complications. RESULTS: After exclusion (n = 16), a total of 96 patients (C-STAPB group, n = 46; conventional group, n = 49) were included. We found there were no significant differences in the cumulative AUC of NRS score PACU-24 h and PACU-48 h between the C-STAPB group and conventional group at rest [(mean difference, 1.38; 95% CI, - 2.21 to 4.98, P = 0.447), (mean difference, 1.22; 95% CI, - 6.20 to 8.65, P = 0.744)] and at movement [(mean difference, 2.90; 95% CI, - 3.65 to 9.46; P = 0.382), (mean difference, 4.32; 95% CI, - 4.46 to 13.1; P = 0.331)]. The 95% CI upper bound of the difference between rest and movement in the C-STAPB group was less than the inferior margin value (9.5 and 14 points), indicating the non-inferiority of the analgesic effect of C-STPAB. The C-STAPB group had faster postoperative recovery profiles including earlier bowel movement, defecation, more volume of food intake postoperative, and lower postoperative nausea and vomiting compared to conventional groups (P < 0.001). CONCLUSIONS: After laparoscopic radical gastrectomy, the analgesic effect of C-STAPBP is not inferior to the traditional opioid-based pain management model. TRIAL REGISTRATION: ChiCTR2100051784.

Enhancing the SCC Resistance of the Anchor Steel with Microalloying in a Simulated Mine Environment.

This work explored a new idea for enhancing the resistance to stress corrosion cracking (SCC) of mining anchor steel through microalloying. Microalloyed anchor steels with Nb, Cu, Ni, Sb, and C were prepared through vacuum smelting and hot rolling. Electrochemical measurements, slow strain rate tensile (SSRT) tests, and fracture morphology observations were used to study the electrochemical and SCC behavior in the simulated mine environment. The results proved that the microstructure of microalloyed steels varies slightly. Adding Ni, Cu, and Sb can improve the mechanical properties of the anchor steel, while reducing C content decreases tensile strength as a result of loss of the solution-strengthening effect. The addition of Sb, Cu, Ni, and reducing the content of C enhances the resistance to corrosion and SCC by mitigating anodic dissolution (AD), while adding Nb improves SCC resistance by inhibiting hydrogen embrittlement (HE). The combined addition of 1% Ni, 0.5% Cu, 0.05% Nb, 0.1% Sb, and 0.5% C presented the highest SCC resistance, which is a promising prospect for the development of high-performance, low-alloy anchor steels. The combined addition of 1% Ni, 0.5% Cu, 0.05% Nb, and 0.1% Sb resulted in the inhibition of electrochemical reactions and corrosion. As a result of the synergistic effect of the microalloy, both AD and HE mechanisms were simultaneously inhibited, which greatly enhanced SCC resistance.

Association among peripatellar fat pad edema and related patellofemoral maltracking parameters: a case-control magnetic resonance imaging study.

BACKGROUND: The peripatellar fat pads are critical for protective cushioning during movement, and their endocrine function has been shown to affect osteoarthritis. Magnetic resonance imaging (MRI) is frequently used to visualize edema of the peripatellar fat pads due to injury. In this study, we aimed to assess the relationship between peripatellar fat pad edema and patellofemoral maltracking MRI parameters and investigate the association among cases of peripatellar fat pad edema. METHODS: Age- and sex-matched peripatellar fat pad edema cases were identified and divided into superolateral Hoffa, quadriceps, and prefemoral groups. Images were assessed according to tibial tuberosity lateralization, trochlear dysplasia, patellar alta, patellar tilt, and bisect offset. McNemar's test or paired t-tests and Spearman's correlation were used for statistical analysis. Interobserver agreement was assessed with the intraclass correlation coefficient. RESULTS: Of 1210 MRI scans, 50, 68, and 42 cases were in the superolateral Hoffa, quadriceps, and prefemoral groups, respectively. Subjects with superolateral Hoffa fat pad edema had a lower lateral trochlear inclination (p = 0.028), higher Insall-Salvati (p < 0.001) and modified Insall-Salvati (p = 0.021) ratios, and lower patellotrochlear index (p < 0.001) than controls. The prefemoral group had a lower lateral trochlear inclination (p = 0.014) and higher Insall-Salvati (p < 0.001) and modified Insall-Salvati (p = 0.004) ratios compared with the control group. In contrast, the patellotrochlear index (p = 0.001) was lower. Mean patellar tilt angle (p = 0.019) and mean bisect offset (p = 0.005) were significantly different between cases and controls. The quadriceps group showed no association. Superolateral Hoffa was positively correlated with prefemoral (p < 0.001, r = 0.408) and negatively correlated with quadriceps (p < 0.001, r = -0.500) fat pad edema. CONCLUSIONS: Superolateral Hoffa and prefemoral fat pad edemas were associated with patellar maltracking parameters. Quadriceps fat pad edema and maltracking parameters were not associated. Superolateral Hoffa fat pad edema was positively correlated with prefemoral and negatively correlated with quadriceps fat pad edema.

Design, synthesis and evaluation of novel pyrimidinylaminothiophene derivatives as FGFR1 inhibitors against human glioblastoma multiforme.

Vascular endothelial growth factor receptors (VEGFRs) have emerged as the most promising anti-angiogenic therapeutic targets for the treatment of recurrent glioblastomas (GBM). However, anti-VEGF treatments led to the high proportion of non-responder patients or non lasting clinical response and the tumor progression to the greater malignant stage. To overcome these problems, there is an utmost need to develop innovative anti-angiogenic therapies. In this study, we report the development of a series of new FGFR1 inhibitors. Among them, compound 4i was able to potently inhibit FGFR1 kinase activities both in vitro and in vivo. This compound displayed strong anti-angiogenic activity in HUVECs and anti-tumor growth and anti-invasion effects in U-87MG cell line. These results emphasize the importance of FGFR1-mediated signaling pathways in GBM and reveal that pharmacological inhibition of FGFR1 can enhance the anti-tumoral, anti-angiogenic and anti-metastatic efficiency against GBM. These data support targeting of FGFR1 as a novel anti-angiogenic strategy and highlight the potential of compound 4i as a promising anti-angiogenic and anti-metastatic candidate for GBM therapy.

Gene Therapy with p14/tBID Induces Selective and Synergistic Apoptosis in Mutant Ras and Mutant p53 Cancer Cells In Vitro and In Vivo.

Any gene therapy for cancer will be predicated upon its selectivity against cancer cells and non-toxicity to normal cells. Therefore, safeguards are needed to prevent its activation in normal cells. We designed a minimal p14ARF promoter with upstream Ap1 and E2F enhancer elements and a downstream MDR1 inhibitory element, TATA box, and a transcription initiation site (hereafter p14ARFmin). The modified p14ARFmin promoter was linked to bicistronic P14 and truncated BID (tBID) genes, which led to synergistic apoptosis via the intrinsic and extrinsic pathways of apoptosis when expressed. The promoter was designed to be preferentially activated by mutant Ras and completely inhibited by wild-type p53 so that only cells with both mutant Ras and mutant p53 would activate the construct. In comparison to most p53 gene therapies, this construct has selective advantages: (1) p53-based gene therapies with a constitutive CMV promoter cannot differentiate between normal cells and cancer cells, and can be toxic to normal cells; (2) our construct does not induce p21WAF/CIPI in contrast to other p53-based gene therapies, which can induce cell cycle arrest leading to increased chemotherapy resistance; (3) the modified construct (p14ARFmin-p14-tBID) demonstrates bidirectional control of its promoter, which is completely repressed by wild-type p53 and activated only in cells with both RAS and P53 mutations; and (4) a novel combination of genes (p14 and tBID) can synergistically induce potent intrinsic and extrinsic apoptosis in cancer cells.

C-Terminal p53 Palindromic Tetrapeptide Restores Full Apoptotic Function to Mutant p53 Cancer Cells In Vitro and In Vivo.

We previously demonstrated that a synthetic monomer peptide derived from the C-terminus of p53 (aa 361−382) induced preferential apoptosis in mutant p53 malignant cells, but not normal cells. The major problem with the peptide was its short half-life (half-life < 10 min.) due to a random coil topology found in 3D proton NMR spectroscopy studies. To induce secondary/tertiary structures to produce more stability, we developed a peptide modelled after the tetrameric structure of p53 essential for activation of target genes. Starting with the above monomer peptide (aa 361−382), we added the nuclear localization sequence of p53 (aa 353−360) and the end of the C-terminal sequence (aa 383−393), resulting in a monomer spanning aa 353−393. Four monomers were linked by glycine to maximize flexibility and in a palindromic order that mimics p53 tetramer formation with four orthogonal alpha helices, which is required for p53 transactivation of target genes. This is now known as the 4 repeat-palindromic-p53 peptide or (4R-Pal-p53p). We explored two methods for testing the activity of the palindromic tetrapeptide: (1) exogenous peptide with a truncated antennapedia carrier (Ant) and (2) a doxycycline (Dox) inducer for endogenous expression. The exogenous peptide, 4R-Pal-p53p-Ant, contained a His tag at the N-terminal and a truncated 17aa Ant at the C-terminal. Exposure of human breast cancer MB-468 cells and human skin squamous cell cancer cells (both with mutant p53, 273 Arg->His) with purified peptide at 7 µM and 15 µM produced 52% and 75%, cell death, respectively. Comparatively, the monomeric p53 C-terminal peptide-Ant (aa 361−382, termed p53p-Ant), at 15 µM and 30 µM induced 15% and 24% cell death, respectively. Compared to the p53p-Ant, the exogenous 4R-pal-p53p-Ant was over five-fold more potent for inducing apoptosis at an equimolar concentration (15 µM). Endogenous 4R-Pal-p53p expression (without Ant), induced by Dox, resulted in 43% cell death in an engineered MB468 breast cancer stable cell line, while endogenous p53 C-terminal monomeric peptide expression produced no cell death due to rapid peptide degradation. The mechanism of apoptosis from 4R-Pal-p53p involved the extrinsic and intrinsic pathways (FAS, caspase-8, Bax, PUMA) for apoptosis, as well as increasing reactive oxygen species (ROS). All three death pathways were induced from transcriptional/translational activation of pro-apoptotic genes. Additionally, mRNA of p53 target genes (Bax and Fas) increased 14-fold and 18-fold, respectively, implying that the 4R-Pal-p53p restored full apoptotic potential to mutant p53. Monomeric p53p only increased Fas expression without a transcriptional or translational increase in Fas, and other genes and human marrow stem cell studies revealed no toxicity to normal stem cells for granulocytes, erythrocytes, monocytes, and macrophages (CFU-GEMM). Additionally, the peptide specifically targeted pre-malignant and malignant cells with mutant p53 and was not toxic to normal cells with basal levels of WT p53.

WRQ-2, a gemcitabine prodrug, reverses gemcitabine resistance caused by hENT1 inhibition.

Gemcitabine is widely used in the clinic as a first-line antitumor agent. However, intrinsic and acquired resistance hinders its wide clinical application. In this study, a gemcitabine prodrug nominated as WRQ-2 was designed and synthesized by conjugating gemcitabine with the indole-3-methanol analogue OSU-A9 through a carbamate linkage. WRQ-2 exhibited high cytotoxicity against six cancer cell lines (HeLa, A549, MDA-MB-231, HuH-7, MGC-803, and HCT-116) with IC50 values in low micromolar range. WRQ-2 reversed the resistance of HeLa cells to gemcitabine caused by hENT1 inhibition. Compared to gemcitabine, WRQ-2 induced a higher degree of DNA damage and apoptosis in the presence of hENT1 inhibitor. Our study suggests that compound WRQ-2 is a potential gemcitabine prodrug and worth of further antitumor activity investigation.

Thoracic Jia-Ji electro-acupuncture mitigates low skeletal muscle atrophy and improves motor function recovery following thoracic spinal cord injury in rats.

OBJECTIVES: The goal of this study was to determine whether electro-acupuncture (EA) stimulation might protect the motor endplate, minimize muscle atrophy in the hind limbs, and enhance functional recovery of rats with spinal cord injury (SCI). METHODS: Sprague-Dawley adult female rats (n = 30) were randomly assigned into Sham, SCI, and EA + SCI groups (n = 10 each). Rats in the Sham and SCI groups were bound in prone position only for 30 min, and rats in the EA + SCI group were treated with electro-acupuncture. The EA was conducted from the first day after surgery, lasted for 30 mins, once every day for 28 consecutive days. RESULTS: EA significantly prevented motor endplate degeneration, improved electrophysiological function, and ameliorated hindlimb muscle atrophy after SCI. Meanwhile, EA upregulated Tuj-1 expression, downregulated GFAP expression, and reduced glial scar formation. Additionally, after 4 weeks of EA treatment, the serum of SCI rats exhibited a reduced inflammatory response. CONCLUSION: These findings suggest that EA can preserve the motor endplate and reduce muscular atrophy. In addition, EA has been shown to improve the function of upper and lower neurons, reduce glial scar formation, suppress systemic inflammation, and improve axon regeneration.

18F-PSMA-1007 PET/CT-derived semi-quantitative parameters for risk stratification of newly diagnosed prostate cancer.

Purpose: This study aimed to assess the value of 18F-PSMA-1007 positron emission tomography/computed tomography (PET/CT)-derived semi-quantitative parameters of primary tumor for risk stratification of newly diagnosed prostate cancer (PCa). Methods: Sixty patients referred for 18F-PSMA-1007 PET/CT imaging for primary PCa were retrospectively analyzed and classified into the low-intermediate-risk (LIR) or high-risk (HR) group. The maximum standardized uptake value (SUVmax) of primary tumor, prostate total lesion PSMA (TL-PSMAp), and prostate PSMA-tumor volume (PSMA-TVp) were measured, and group differences were evaluated using the Mann-Whitney U test. Spearman's correlation was performed to assess the correlation between the above parameters with prostate-specific antigen (PSA) levels and Gleason score (GS). Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for SUVmax, TL-PSMAp, and PSMA-TVp to identify high-risk PCa and compare diagnostic efficacy. Results: Among 60 patients, 46 were assigned to the HR group and 16 to the LIR group. In all patients, SUVmax, TL-PSMAp, and PSMA-TVp were moderately correlated with pre-treatment PSA values (r = 0.411, p = 0.001; r = 0.663, p < 0.001; and r = 0.549, p < 0.001, respectively). SUVmax and TL-PSMAp were moderately correlated with GS (r = 0.457 and r = 0.448, respectively; p < 0.001), while PSMA-TVp was weakly correlated with GS (r = 0.285, p = 0.027). In the ROC curve analysis, the optimal cut-off values of SUVmax, TL-PSMAp, and PSMA-TVp for identifying high-risk PCa were 9.61, 59.62, and 10.27, respectively, and the areas under the operating curve were 0.828, 0.901, and 0.809, respectively. The sensitivities of SUVmax, TL-PSMAp, and PSMA-TVp were 91.03%, 71.74%, and 63.04%, respectively, and the specificities were 71.43%, 100.00%, and 92.86%, respectively. Conclusions: TL-PSMAp had a superior ability to identify high-risk PCa. The semi-quantitative parameters of primary tumor on 18F-PSMA-1007 PET/CT imaging can be an objective imaging reference index to determine PCa risk stratification.

Genome-wide identification, new classification, expression analysis and screening of drought & heat resistance related candidates in the RING zinc finger gene family of bread wheat (Triticum aestivum L.).

BACKGROUND: RING (Really Interesting New Gene) zinc finger (RING-zf) proteins belong to an important subclass of zinc fingers superfamily, which play versatile roles during various developmental stages and in abiotic stress responses. Based on the conserved cysteine and histidine residues, the RING-zf domains are classified into RING-HC (C3HC4), RING-H2 (C3H2C3), RING-v, RING-D, RING-S/T, RING-G, and RING-C2. However, little is known about the function of the RING-zfs of wheat. RESULTS: In this study, 129 (93.5%) of 138 members were found in nucleus, indicating TaRING-zf were primarily engaged in the degradation of transcription factors and other nuclear-localized proteins. 138 TaRING-zf domains can be divided into four canonical or modified types (RING-H2, RING-HC, RING-D, and RING-M). The RING-M was newly identified in T. aestivum, and might represent the intermediate other states between RING-zf domain and other modified domains. The consensus sequence of the RING-M domain can be described as M-X2-R-X14-Cys-X1-H-X2-Cys-X2-Cys-X10-Cys-X2-Cys. Further interspecies collinearity analyses showed that TaRING-zfs were more closely related to the genes in Poaceae. According to the public transcriptome data, most of the TaRING-zfs were expressed at different 15 stages of plant growth, development, and some of them exhibited specific responses to drought/heat stress. Moreover, 4 RING-HC (TraesCS2A02G526800.1, TraesCS4A02G290600.1, TraesCS4B02G023600.1 and TraesCS4D02G021200.1) and 2 RING-H2 (TraesCS3A02G288900.1 and TraesCS4A02G174600.1) were significantly expressed at different development stages and under drought stress. These findings provide valuable reference data for further study of their physiological functions in wheat varieties. CONCLUSIONS: Taken together, the characterization and classifications of the TaRING-zf family were extensively studied and some new features about it were revealed. This study could provide some valuable targets for further studies on their functions in growth and development, and abiotic stress responses in wheat.

Design, synthesis and antitumor activity study of a gemcitabine prodrug conjugated with a HDAC6 inhibitor.

Gemcitabine, as a first-line antitumor drug, has attracted extensive attention. However the occurrence of drug resistance limits its clinical utilization. In this paper, a gemcitabine prodrug GZ was designed and synthesized by conjugation of gemcitabine with a newly reported HDAC6 selective inhibitor pentadecanoic acid. GZ displayed high cytotoxicity to nine cancer cell lines with IC50 values in the low micromolar range. In vivo, GZ displayed superior antitumor activity to gemcitabine in a 4T1 tumor xenograft model without obvious pathological damage to important organs of mice. Our study showed that compound GZ is a potential gemcitabine prodrug, which is worthy of further antitumor activity exploration.

Corrigendum: DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production.

[This corrects the article DOI: 10.3389/fonc.2021.629974.].

Case Report: 18F-PSMA-1007 PET/CT Avid Solitary Penile Metastasis of Castration-Resistant Prostate Cancer With a PSA of 0.072 ng/ml.

Penile metastasis of prostate cancer is rare, with a poor prognosis, and only a limited number of relevant cases have been reported so far. With the application of 18F-PSMA-1007 PET/CT, the biochemical recurrence of prostate cancer can be detected at an early stage for providing important evidence, facilitating clinical decision-making. Here, we have reported a case of solitary penile metastatic recurrence in the context of mild PSA progression (PSA: 0.072 ng/ml). This case highlights the preferable sensitivity of 18F-PSMA-1007 PET/CT imaging in prostate cancer.

Endoscopic tightening of the cardia mucosa in gastroesophageal reflux disease: A case series of 120 patients up to 1-year follow-up.

Background and Aim: A technique of endoscopic tightening of the cardia mucosa for the treatment of gastroesophageal reflux disease (GERD) was developed and its clinical efficacy was observed. Methods: 120 patients with GERD who underwent endoscopic tightening surgery from December 2017 to December 2019 were included in this study. GERD-Q score and constitution type of patients were evaluated preoperatively and at 1 month, 3 months, 6 months, and 1 year after surgery. In addition, effectiveness and side effects of the procedure were graded based on gastroesophageal flap valve (GEFV) function. Results: GERD-Q score of 1 month, 3 months, 6 months, and 1 year after surgery were significantly decreased (P<0.01) compared with preoperative score. There were no significant differences between GERD-Q score of 1 month, 3 months, 6 months, and 1 year after surgery. The surgery proves to be effective in all GEFV grades, especially in Hill-III. Conclusion: Endoscopic tightening is an effective method for the treatment of patients with GERD, especially of Hill-III patients. Attention should be paid to cardia width, ligation ring depth, and ring number during operation. Relevance for Patients: ETCM is a safe endoscopic procedure with minimal trauma, which has been proved effective for patients who are diagnosed with GERD.

Endoscopic tightening of the cardia mucosa in gastroesophageal reflux disease: A case series of 120 patients up to 1-year follow-up.

Background and Aim: A technique of endoscopic tightening of the cardia mucosa for the treatment of gastroesophageal reflux disease (GERD) was developed and its clinical efficacy was observed. Methods: 120 patients with GERD who underwent endoscopic tightening surgery from December 2017 to December 2019 were included in this study. GERD-Q score and constitution type of patients were evaluated preoperatively and at 1 month, 3 months, 6 months, and 1 year after surgery. In addition, effectiveness and side effects of the procedure were graded based on gastroesophageal flap valve (GEFV) function. Results: GERD-Q score of 1 month, 3 months, 6 months, and 1 year after surgery were significantly decreased (P<0.01) compared with preoperative score. There were no significant differences between GERD-Q score of 1 month, 3 months, 6 months, and 1 year after surgery. The surgery proves to be effective in all GEFV grades, especially in Hill-III. Conclusion: Endoscopic tightening is an effective method for the treatment of patients with GERD, especially of Hill-III patients. Attention should be paid to cardia width, ligation ring depth, and ring number during operation. Relevance for Patients: ETCM is a safe endoscopic procedure with minimal trauma, which has been proved effective for patients who are diagnosed with GERD.

Efficacy of Adjuvant Transarterial Chemoembolization after Radical Hepatectomy in Solitary Hepatocellular Carcinoma Patients: A Retrospective Study.

Background: More and more studies have suggested that hepatocellular carcinoma (HCC) patients with high-risk recurrence factors can benefit the most from postoperative adjuvant transarterial chemoembolization (PA-TACE) for its potential effect in delaying cancer recurrence. However, it remains unclear if solitary HCC (SHCC) patients particularly those without high-risk recurrence factors should also receive PA-TACE. This study aimed to analyze the efficacy of PA-TACE in them. Methods: Retrospectively, we enrolled 123 SHCC patients who either received radical hepatectomy alone (No TACE group, n = 39) or followed by PA-TACE (PA-TACE group, n = 84) in our institution. Prognostic risk factors, disease-free survival (DFS), and overall survival (OS) were analyzed using the Cox proportional hazard regression model, the Kaplan-Meier method, and the log-rank test. Results: Liver cirrhosis was the only independent risk factor for SHCC patients. Overall, the PA-TACE group had no improved OS (P = 0.977) but worse DFS compared with the No TACE group (P = 0.045). Consistently, in subgroup analysis, SHCC patients with negative microvascular invasion (MVI), tumor size ≤ 5 cm and preoperative alpha-fetoprotein (AFP) < 400 ng/ml had similar OS (P = 0.466, P = 0.864, P = 0.488, respectively) but even worse DFS (P = 0.035, P = 0.040, P = 0.019, respectively) than those in the No TACE group. Besides, there was no significant difference in DFS and OS between the two groups of SHCC patients with liver cirrhosis (P = 0.342, P = 0.941, respectively). Conclusions: PA-TACE may not improve the long-term survival of SHCC patients, but may even potentially promote their postoperative tumor recurrence, especially for those with MVI-negative, tumor size ≤ 5 cm, and preoperative AFP < 400 ng/ml.

Impact of polyphenols extracted from Tricholoma matsutake on UVB-induced photoaging in mouse skin.

BACKGROUND: Despite Tricholoma matsutake has been used as natural health products with multiple medicinal properties, detailed information about its polyphenolic composition as sources of anti-photoaging agents remains to be determined. OBJECTIVE: To investigate the impact of polyphenols extracted from Tricholoma matsutake (TME) on Ultraviolet B (UVB)-induced skin photoaging. MATERIALS AND METHODS: Various factors of oxidative stress and inflammation as well as histological and immunohistochemical analysis in the mouse dorsal skin were determined after UVB radiation. RESULTS: Topical administration with TME suppressed the UVB-induced skin thickness, wrinkles and erythema, and increased skin collagen content. Furthermore, TME decreased reactive oxygen species (ROS) level, upregulated glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and glucose-6-phosphate dehydrogenase (G6PDH) activities and inhibited the expression of IL-1, IL-6, IL-8, and TNF-α in mice irradiated with UVB. TME could reduce UVB-induced p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation and effectively inhibited the activity of the transcriptional factor nuclear factor-kappa B (NF-κB), thereby reducing the cyclooxygenase-2 (COX-2) expression, which is an important mediator of inflammatory cascade leading to the inflammatory response. CONCLUSION: Our data demonstrated that TME had various beneficial effects on UVB-induced skin photoaging due to its antioxidant and anti-inflammatory activities, and it might be exploited as a promising natural product in skin care, anti-photoaging and the therapeutic intervention of skin disorders related to both oxidative stress and inflammation.

Stigmasterol inhibits the progression of lung cancer by regulating retinoic acid-related orphan receptor C.

OBJECTIVE: This study aims to investigate the role of stigmasterol in lung cancer. The study aims to investigate the role of stigmasterol in lung cancer and further explore its possible mechanisms. METHODS: Cell Counting Kit-8 assay, 5-ethynyl-2-deoxyuridine (EdU), TUNEL and Flow cytometry were conducted to detect the proliferation and apoptosis of lung cancer cell lines. qRT-PCR and western blot were conducted to detect mRNA and protein levels of caspase-3 and caspase-9. In addition, Gene Ontology, STRING, SWISSMODEL, cellular thermal shift assay (CETSA) and Swiss Target Prediction were used to predict the targets of stigmasterol. RESULTS: Behavioral studies showed that stigmasterol inhibited the proliferation and promoted the apoptosis of lung cancer cells. Further research revealed that retinoic acid-related orphan receptor C (RORC) directly targeted stigmasterol in lung cancer. Interestingly, rescue experiments indicated that RORC overexpression reversed the inhibitory effect of stigmasterol on lung cancer. CONCLUSION: In our study, we confirmed the functional role of the stigmasterol-RORC axis in lung cancer progression, which provides a latent target for lung cancer treatment.