Novel prediction model combining PET/CT metabolic parameters, inflammation markers, and TNM stage: prospects for personalizing prognosis in nasopharyngeal carcinoma.

PURPOSE: This study aims to develop a novel prediction model and risk stratification system that could accurately predict progression-free survival (PFS) in patients with nasopharyngeal carcinoma (NPC). METHODS: Herein, we included 106 individuals diagnosed with NPC, who underwent 18F-FDG PET/CT scanning before treatment. They were divided into training (n = 76) and validation (n = 30) sets. The prediction model was constructed based on multivariate Cox regression analysis results and its predictive performance was evaluated. Risk factor stratification was performed based on the nomogram scores of each case, and Kaplan-Meier curves were used to evaluate the model's discriminative ability for high- and low-risk groups. RESULTS: Multivariate Cox regression analysis showed that N stage, M stage, SUVmax, MTV, HI, and SIRI were independent factors affecting the prognosis of patients with NPC. In the training set, the model considerably outperformed the TNM stage in predicting PFS (AUCs of 0.931 vs. 0.841, 0.892 vs. 0.785, and 0.892 vs. 0.804 at 1-3 years, respectively). The calibration plots showed good agreement between actual observations and model predictions. The DCA curves further justified the effectiveness of the model in clinical practice. Between high- and low-risk group, 3-year PFS rates were significantly different (high- vs. low-risk group: 62.8% vs. 9.8%, p < 0.001). Adjuvant chemotherapy was also effective for prolonging survival in high-risk patients (p = 0.009). CONCLUSION: Herein, a novel prediction model was successfully developed and validated to improve the accuracy of prognostic prediction for patients with NPC, with the aim of facilitating personalized treatment.

FMOD Alleviates Depression-Like Behaviors by Targeting the PI3K/AKT/mTOR Signaling After Traumatic Brain Injury.

Depression frequently occurs following traumatic brain injury (TBI). However, the role of Fibromodulin (FMOD) in TBI-related depression is not yet clear. Previous studies have suggested FMOD as a potential key factor in TBI, yet its association with depression post-TBI and underlying mechanisms are not well understood. Serum levels of FMOD were measured in patients with traumatic brain injury using qPCR. The severity of depression was assessed using the self-depression scale (SDS). Neurological function, depressive state, and cognitive function in mice were assessed using the modified Neurological Severity Score (mNSS), forced swimming test (FST), tail suspension test (TST), Sucrose Preference Test (SPT), and morris water maze (MWM). The morphological features of mouse hippocampal synapses and neuronal dendritic spines were revealed through immunofluorescence, transmission electron microscopy, and Golgi-Cox staining. The protein expression levels of FMOD, MAP2, SYP, and PSD95, as well as the phosphorylation levels of the PI3K/AKT/mTOR signaling pathway, were detected through Western blotting. FMOD levels were decreased in TBI patients' serum. Overexpression of FMOD preserved neuronal function and alleviated depression-like behaviour, increased synaptic protein expression, and induced ultrastructural changes in hippocampal neurons. The increased phosphorylation of PI3K, AKT, and mTOR suggested the involvement of the PI3K/AKT/mTOR signaling pathway in FMOD's protective effects. FMOD exhibits potential as a therapeutic target for depression related to TBI, with its protective effects potentially mediated through the PI3K/AKT/mTOR signaling pathway.

Recent advances in the role of miRNAs in post-traumatic stress disorder and traumatic brain injury.

Post-traumatic stress disorder (PTSD) is usually considered a psychiatric disorder upon emotional trauma. However, with the rising number of conflicts and traffic accidents around the world, the incidence of PTSD has skyrocketed along with traumatic brain injury (TBI), a complex neuropathological disease due to external physical force and is also the most common concurrent disease of PTSD. Recently, the overlap between PTSD and TBI is increasingly attracting attention, as it has the potential to stimulate the emergence of novel treatments for both conditions. Of note, treatments exploiting the microRNAs (miRNAs), a well-known class of small non-coding RNAs (ncRNAs), have rapidly gained momentum in many nervous system disorders, given the miRNAs' multitudinous and key regulatory role in various biological processes, including neural development and normal functioning of the nervous system. Currently, a wealth of studies has elucidated the similarities of PTSD and TBI in pathophysiology and symptoms; however, there is a dearth of discussion with respect to miRNAs in both PTSD and TBI. In this review, we summarize the recent available studies of miRNAs in PTSD and TBI and discuss and highlight promising miRNAs therapeutics for both conditions in the future.

Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis.

Traumatic brain injury (TBI) is the leading cause of disability and mortality globally. Melatonin (Mel) is a neuroendocrine hormone synthesized from the pineal gland that protects against TBI. Yet, the precise mechanism of action is not fully understood. In this study, we examined the protective effect and regulatory pathways of melatonin in the TBI mice model using transcriptomics and bioinformatics analysis. The expression profiles of mRNA, long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA) were constructed using the whole transcriptomes sequencing technique. In total, 93 differentially expressed (DE) mRNAs (DEmRNAs), 48 lncRNAs (DElncRNAs), 59 miRNAs (DEmiRNAs), and 59 circRNAs (DEcircRNAs) were identified by the TBI mice with Mel treatment compared to the group without drug intervention. The randomly selected coding RNAs and non-coding RNAs (ncRNAs) were identified by quantitative real-time polymerase chain reaction (qRT-PCR). To further detect the biological functions and potential pathways of those differentially expressed RNAs, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were executed. In our research, the regulatory network was constructed to show the relationship of lncRNA-RBPs. The lncRNA-mRNA co-expression network was established based on the Pearson coefficient to indicate the expression correlations. Moreover, the DEcircRNA-DEmiRNA-DEmRNA and DElncRNA-DEmiRNA-DEmRNA regulatory networks were constructed to demonstrate the regulatory relationship between ncRNAs and mRNA. Finally, to further verify our predicted results, cytoHubba was used to find the hub gene in the synaptic vesicle cycle pathway, and the expression level of SNAP-25 and VAMP-2 after melatonin treatment were detected by Western blotting and immunofluorescence. To sum up, these data offer a new insight regarding the molecular effect of melatonin treatment after TBI and suggest that the high-throughput sequencing and analysis of transcriptomes are useful for studying the drug mechanisms in treatment after TBI.

A novel circular RNA, circIgfbp2, links neural plasticity and anxiety through targeting mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after traumatic brain injury.

Traumatic brain injury (TBI) can lead to different neurological and psychiatric disorders. Circular RNAs (circRNAs) are highly expressed in the nervous system and enriched in synapses; yet, the underlying role and mechanisms of circRNAs in neurological impairment and dysfunction are still not fully understood. In this study, we investigated the expression of circRNAs and their relation with neurological dysfunction after TBI. RNA-Seq was used to detect differentially expressed circRNAs in injured brain tissue, revealing that circIgfbp2 was significantly increased. Up-regulated hsa_circ_0058195, which was highly homologous to circIgfbp2, was further confirmed in the cerebral cortex specimens and serum samples of patients after TBI. Moreover, correlation analysis showed a positive correlation between hsa_circ_0058195 levels and the Self-Rating Anxiety Scale scores in these subjects. Furthermore, knockdown of circIgfbp2 in mice relieved anxiety-like behaviors and sleep disturbances induced by TBI. Knockdown of circIgfbp2 in H2O2 treated HT22 cells alleviated mitochondrial dysfunction, while its overexpression reversed the process. Mechanistically, we discovered that circIgfbp2 targets miR-370-3p to regulate BACH1, and down-regulating BACH1 alleviated mitochondrial dysfunction and oxidative stress-induced synapse dysfunction. In conclusion, inhibition of circIgfbp2 alleviated mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after TBI through the miR-370-3p/BACH1/HO-1 axis. Thus, circIgfbp2 might be a novel therapeutic target for anxiety and sleep disorders after TBI.

CircLphn3 protects the blood-brain barrier in traumatic brain injury.

Circular RNAs (circRNAs) are a new and large group of non-coding RNA molecules that are abundantly expressed in the central nervous system. However, very little is known about their roles in traumatic brain injury. In this study, we firstly screened differentially expressed circRNAs in normal and injured brain tissues of mice after traumatic brain injury. We found that the expression of circLphn3 was substantially decreased in mouse models of traumatic brain injury and in hemin-treated bEnd.3 (mouse brain cell line) cells. After overexpressing circLphn3 in bEnd.3 cells, the expression of the tight junction proteins, ZO-1, ZO-2, and occludin, was upregulated, and the expression of miR-185-5p was decreased. In bEnd.3 cells transfected with miR-185-5p mimics, the expression of ZO-1 was decreased. Dual-luciferase reporter assays showed that circLphn3 bound to miR-185-5p, and that miR-185-5p bound to ZO-1. Additionally, circLphn3 overexpression attenuated the hemin-induced high permeability of the in vitro bEnd.3 cell model of the blood-brain barrier, while miR-185-5p transfection increased the permeability. These findings suggest that circLphn3, as a molecular sponge of miR-185-5p, regulates tight junction proteins' expression after traumatic brain injury, and it thereby improves the permeability of the blood-brain barrier. This study was approved by the Animal Care and Use Committee of Chongqing Medical University of China (approval No. 2021-177) on March 22, 2021.

A novel mechanism linking ferroptosis and endoplasmic reticulum stress via the circPtpn14/miR-351-5p/5-LOX signaling in melatonin-mediated treatment of traumatic brain injury.

Traumatic brain injury (TBI) can lead to disability or devastating consequences with few established treatments. Although ferroptosis has been shown to be involved in TBI, the underlying mechanism was rarely known. Melatonin has been indicated to exhibit neuroprotective activities. However, the anti-ferroptotic effects of melatonin on TBI have not yet to be elucidated. We aimed to investigate whether ferroptosis was induced in humans after TBI and whether ferroptosis inhibition by melatonin could protect against blood-brain barrier (BBB) damage after TBI in vivo and in vitro. Circular RNAs (circRNAs) are highly expressed in the brain. For the first time, differentially expressed circRNA after melatonin treatment for TBI were detected by RNA sequencing. We found that lipid peroxidation was induced in humans after TBI, while melatonin significantly improved brain function of mice after TBI and alleviated ferroptosis and endoplasmic reticulum (ER) stress in vivo and in vitro. A total of 1826 differentially expressed circRNAs were found (fold change >2, Q < 0.01), including 921 down-regulated and 905 up-regulated circRNAs in the injured brain tissues of TBI mice receiving melatonin treatment. Mechanistically, melatonin administration reduced the level of circPtpn14 (mmu_circ_0000130), which functioned by acting as a miR-351-5p sponge to positively regulate the expression of the ferroptosis-related 5-lipoxygenase (5-LOX). Moreover, circPtpn14 overexpression partly abolished the inhibitory effects of melatonin on ferroptosis. Collectively, our findings provide the first evidence that melatonin could exert anti-ferroptotic and anti-ER stress effects in brain injury by alleviating lipid peroxidation via the circPtpn14/miR-351-5p/5-LOX signaling.

Mindfulness meditation alters neural activity underpinning working memory during tactile distraction.

Evidence suggests that mindfulness meditation (MM) improves selective attention and reduces distractibility by enhancing top-down neural modulation. Altered P300 and alpha neural activity from MM have been identified and may reflect the neural changes that underpin these improvements. Given the proposed role of alpha activity in supressing processing of task-irrelevant information, it is theorised that altered alpha activity may underlie increased availability of neural resources in meditators. The present study investigated attentional function in meditators using a cross-modal study design, examining the P300 during working memory (WM) and alpha activity during concurrent distracting tactile stimuli. Thirty-three meditators and 27 healthy controls participated in the study. Meditators showed a more frontal distribution of P300 neural activity following WM stimuli (p = 0.005, η2 = 0.060) and more modulation of alpha activity at parietal-occipital regions between single (tactile stimulation only) and dual task demands (tactile stimulation plus WM task) (p < 0.001, η2 = 0.065). Additionally, meditators performed more accurately than controls (p = 0.038, η2 = 0.067). The altered distribution of neural activity concurrent with improved WM performance suggests greater attentional resources dedicated to task related functions, such as WM in meditators. Thus, meditation-related neural changes are likely multifaceted, involving both altered distribution and also amplitudes of brain activity, thereby enhancing attentional processes depending on task requirements.

Hsp27 regulates epithelial mesenchymal transition, metastasis and proliferation in colorectal carcinoma.

The primary factor associated with poor survival rate in patients with colorectal carcinoma (CRC) is the presence of metastasis. The underlying molecular mechanisms of CRC metastasis are yet to be fully elucidated. The present study investigated the function of heat shock protein 27 (Hsp27) on the invasion and proliferation of CRC cells. The clinical significance of Hsp27 was evaluated using tissue microarray analysis (n=81). Invasion and metastasis assays were used to determine the function of Hsp27 in CRC metastasis in vitro and in vivo using RNA interference and the ectopic expression of Hsp27. The upregulation of Hsp27 has been frequently identified in CRC tissues. Patients with CRC and a high expression level of Hsp27 have a reduced overall survival rate. Silencing Hsp27 inhibited the growth and invasion of CRC cells in vitro and in vivo, whereas ectopic overexpression of Hsp27 promoted the proliferation and invasion of CRC cells in vitro. Furthermore, depletion of Hsp27 expression inhibited the epithelial-to-mesenchymal transition (EMT), whilst ectopic overexpression of Hsp27 induced EMT. The results of the present study indicated that Hsp27 serves an important function in the aggressiveness of CRC through inducing EMT. Hsp27 suppression may represent a potential therapeutic option for the suppression of CRC progression.

The Treatment of Cesarean Scar Pregnancy with Uterine Artery Embolization and Curettage as Compared to Transvaginal Hysterotomy.

OBJECTIVES: To investigate the outcome and menstrual status in patients after treatment of cesarean scar pregnancy (CSP) by transvaginal hysterotomy or uterine artery embolization combined with uterine curettage. STUDY DESIGN: A retrospective cohort study. An analysis of CSP patients was performed using records from Shanghai First Maternity & Infant Hospital affiliated with Tongji University for the period between July 16, 2014 and January 22, 2016. Twenty-seven patients were treated with transvaginal hysterotomy and in this group, 49 patients received uterine curettage after UAE. The clinical information on these patients and clinical outcomes especially the status of menstruation were reviewed. RESULTS: There was only one complication in transvaginal hysterotomy group, while 3 cases of villus residue occurred in UAE group. Nineteen patients (70.4%) in transvaginal hysterotomy group self-assessed their menstrual volumes, which had no remarkable changes; 6 patients (22.2%) felt that their menstrual volumes had decreased. Thirty-five patients in UAE group (71.4%) reported that their menstrual volumes decreased (P<0.05). The range of pictorial blood loss score was 55-82 in transvaginal hysterotomy group and 9-74 in UAE group, and the mean pictorial blood loss score was decreased from 68.4 to 65.8 in transvaginal hysterotomy group (a 3.2±4.4% reduction) and from 66.4 to 38.8 in UAE group (a 41.7±26.4% reduction) (P<0.05). CONCLUSIONS: Transvaginal hysterotomy appears to be more advantageous than UAE combined with uterine curettage. The menstrual interval and duration changed significantly in UAE group.

Defect width: the prognostic index for vaginal repair of cesarean section diverticula.

PURPOSE: To evaluate the clinical parameter associated with cesarean section diverticula anatomic healing via vaginal repair management. METHODS: Observational cohort study. From Jul 2014 to Dec 2015, 143 women with CSD underwent vaginal repair surgery in Shanghai First Maternity and Infant Hospital, and 137(95.80%) were diagnosed using both transvaginal ultrasound and MRI. A total of 124 patients (86.71%) who were followed-up for more than 6 months after surgery were enrolled in this study. Excision and suture of CSD was performed through the vaginal approach. The defect sizes of the width, length, depth and TRM before or after repair were evaluated. RESULTS: The mean preoperative duration of menstruation was 14.47 ± 3.30 days and the thickness of the remaining muscular layer was 2.65 ± 1.13 mm before surgery. The study revealed that the healing effects of CSD repair stabilized 3 months after surgery. At the median follow-up time (11.28 months), CSD disappeared after surgery in 64.52% of patients (80/124), and 60.0% of patients (48/80) reached ≤7 days of menstruation. Meanwhile, for 35.48% of patients (44/124), CSD persisted at the median follow-up after surgery, and 31.82% (14/44) of these patients reached ≤7 days of menstruation(P < 0.05). TRM at a median follow-up time after vaginal repair >7.88 mm, 92.11% (70/76) of CSD disappeared. Moreover, when preoperative CSD width ≤18.85 mm indicates that only 18.75% (12/64) of patients will present with CSD after vaginal repair, as determined by MRI (95% CI 0.515-0.737). CONCLUSION: The defect width of the preoperative CSD was the prognostic index of CSD anatomical repair effect. When the preoperative CSD width >18.85 mm, we should pay more attention to the edge of the defect during vaginal repairing.

Vaginal Repair of Cesarean Section Scar Diverticula that Resulted in Improved Postoperative Menstruation.

STUDY OBJECTIVE: Owing to the increase in cesarean sections (C-sections) worldwide, long-term complications such as postmenstrual spotting, chronic pelvic pain, and C-section scar ectopic pregnancies have created a new medical era of gynecologic disease. A new type of vaginal repair is evaluated to repair C-section diverticulum (CSD) and rebuild the muscular layer to improve symptoms of abnormal uterine bleeding and decrease the risk of uterine rupture. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: A total of 121 patients with CSD diagnoses by transvaginal ultrasound (TVU) presented with postmenstrual spotting between June 2012 and March 2015. All patients had undergone at least 1 C-section delivery and had no history of postmenstrual spotting before undergoing C-section. INTERVENTION: Vaginal excision and suture of CSD. MEASUREMENT AND MAIN RESULTS: The mean duration of menstruation was 14.87 ± 3.46 days preoperatively and decreased to 8.22 ± 2.73 days at 1 month after surgery, 8.89 ± 2.67 days at 3 months after surgery, and 9.02 ± 2.47 days at 6 months after surgery (p < .01). The length, width, depth, and thickness of the remaining muscular layer (TRM) at 1 month, 3 months, and 6 months assessed by TVU also improved significantly after surgery (p < .05). However, postoperative menstruation and imaging data did not differ markedly between 3 months and 6 months, suggesting that follow-up at 3 months represents an adequate endpoint for evaluating the effectiveness of surgery. At 6 months, 80.3% of patients (94 of 117) reached ≤10 days of menstruation. Further study revealed that a TRM at 6 months of ≥8.5 mm measured by TVU (relative risk [RR], 6.418; 95% confidence interval [CI], 1.478-28.443) and an interval between CS and vaginal repair of ≤2.5 years (RR, 12.0; 95% CI, 1.541- 93.454) were good prognostic factors associated with surgery. CONCLUSION: Vaginal repair of CSD improved the symptoms of postmenstrual spotting and anatomically corrected the scars. An interval between C-section and a surgery of ≤2.5 years was optimal for vaginal repair, and a TRM at 6 months of ≥8.5 mm represented the standard healing of CSD.

Coaxial electrospun aligned tussah silk fibroin nanostructured fiber scaffolds embedded with hydroxyapatite-tussah silk fibroin nanoparticles for bone tissue engineering.

The bone is a composite of inorganic and organic materials and possesses a complex hierarchical architecture consisting of mineralized fibrils formed by collagen molecules and coated with oriented hydroxyapatite. To regenerate bone tissue, it is necessary to provide a scaffold that mimics the architecture of the extracellular matrix in native bone. Here, we describe one such scaffold, a nanostructured composite with a core made of a composite of hydroxyapatite and tussah silk fibroin. The core is encased in a shell of tussah silk fibroin. The composite fibers were fabricated by coaxial electrospinning using green water solvent and were characterized using different techniques. In comparison to nanofibers of pure tussah silk, composite notably improved mechanical properties, with 90-fold and 2-fold higher initial modulus and breaking stress, respectively, obtained. Osteoblast-like MG-63 cells were cultivated on the composite to assess its suitability as a scaffold for bone tissue engineering. We found that the fiber scaffold supported cell adhesion and proliferation and functionally promoted alkaline phosphatase and mineral deposition relevant for biomineralization. In addition, the composite were more biocompatible than pure tussah silk fibroin or cover slip. Thus, the nanostructured composite has excellent biomimetic and mechanical properties and is a potential biocompatible scaffold for bone tissue engineering.

The use of a modified, oscillating positive expiratory pressure device reduced fever and length of hospital stay in patients after thoracic and upper abdominal surgery: a randomised trial.

QUESTION: Does the use of an oscillating positive expiratory pressure (PEP) device reduce postoperative pulmonary complications in thoracic and upper abdominal surgical patients? DESIGN: A multi-centre, parallel-group, randomised controlled trial with intention-to-treat analysis, blinding of some outcomes, and concealed allocation. PARTICIPANTS: A total of 203 adults after thoracic or upper abdominal surgery with general anaesthesia. INTERVENTION: Participants in the experimental group used an oscillating PEP device, thrice daily for 5 postoperative days. Both the experimental and control groups received standard medical postoperative management and early mobilisation. OUTCOME MEASURES: Fever, days of antibiotic therapy, length of hospital stay, white blood cell count, and possible adverse events were recorded for 28 days or until hospital discharge. RESULTS: The 99 participants in the experimental group and 104 in the control group were well matched at baseline and there was no loss to follow-up. Fever affected a significantly lower percentage of the experimental group (22%) than the control group (42%), with a RR of 0.56 (95% CI 0.36 to 0.87, NNT 6). Similarly, length of hospital stay was significantly shorter in the experimental group, at 10.7 days (SD 8.1), than in the control group, at 13.3 days (SD 11.1); the mean difference was 2.6 days (95% CI 0.4 to 4.8). The groups did not differ significantly in the need for antibiotic therapy, white blood cell count or total expense of treatment. CONCLUSION: In adults undergoing thoracic and upper abdominal surgery, postoperative use of an oscillating PEP device resulted in fewer cases of fever and shorter hospital stay. However, antibiotic therapy and total hospital expenses were not significantly reduced by this intervention. TRIAL REGISTRATION: NCT00816881.