Two-year outcomes of anti-reflux mucosectomy in treating gastroesophageal reflux disease: A Chinese prospective cohort study.

OBJECTIVES: Anti-reflux mucosectomy (ARMS) is an emerging and promising endoscopic treatment for gastroesophageal reflux disease (GERD). In the current study we aimed to evaluate the safety and efficacy of ARMS in treating Chinese GERD patients. METHODS: This was a single-center prospective cohort study. ARMS was performed in GERD patients by an experienced endoscopist. The patients were required to undergo symptom assessment as well as endoscopic examination, high-resolution manometry (HRM), and impedance-pH monitoring before and after ARMS. RESULTS: Twelve patients were enrolled. Follow-up was completed by all patients at 3 and 6 months, 11 patients at 1 year, and 8 patients at 2 years after ARMS, respectively. Symptom improvement was achieved in 66.7%, 75.0%, 72.7%, and 50.0% of the patients at 3 months, 6 months, 1 year, and 2 years after ARMS, respectively. Postoperative dysphagia was reported by 25.0%, 25.0%, 27.3%, and 25.0% of patients at 3 months, 6 months, 1 year, and 2 years after surgery, none of whom required additional invasive treatment. All patients with preoperative esophagitis healed after ARMS. For impedance-pH monitoring parameters, number of acidic reflux episodes and the proportion of patients with acid exposure time (AET) >4.0% decreased significantly after ARMS. CONCLUSIONS: ARMS was safe and effective in Chinese GERD patients. The efficacy of ARMS was not short-term and remained evident throughout the 2-year follow-up. Further multicenter studies with larger sample sizes are needed to verify our findings.

Patients at risk for further examination with conventional gastroscopy after undergoing magnetically controlled capsule endoscopy.

OBJECTIVE: In this study we aimed to compare the need for further examination with conventional gastroscopy within 1 year after magnetically assisted capsule endoscopy (MCCE) examination between patients with gastrointestinal (GI) symptoms and asymptomatic individuals. METHODS: After propensity score matching analysis, 372 patients with GI symptoms and 372 asymptomatic individuals who had undergone MCCE at the First Affiliated Hospital of Sun Yat-sen University from January 1, 2019 to December 30, 2020 were retrospectively enrolled. Demographic and clinical characteristics of the participants and their MCCE and gastroscopic findings (performed within 1 year after MCCE) were analyzed. RESULTS: Fifty-one (6.85%) patients underwent further examination with conventional gastroscopy within 1 year after MCCE. Those with GI symptoms were more likely to undergo conventional gastroscopy than those without (9.95% vs 3.76%, P < 0.001). Polyps were the most common finding of MCCE. The rate of conventional gastroscopy in patients with focal lesions was significantly higher than that in those without focal lesions (P < 0.05). However, such rate did not differ in the different age groups (P = 0.106). CONCLUSIONS: MCCE is an optimal alternative for gastric examination, especially for large-scale screening of asymptomatic individuals. Patients with GI symptoms or focal lesions detected by MCCE are more likely to seek further examination with conventional gastroscopy for biopsy or endoscopic treatment than those without.

Patient- and physician-reported satisfaction with gastroesophageal reflux disease (GERD) treatment in Chinese clinical practice.

OBJECTIVE: The aim of this study was to assess the level of satisfaction with currently prescribed medications for gastroesophageal reflux disease (GERD) in patients and physicians in China. METHODS: Physicians across China were invited to complete physician surveys concerning factors affecting the prescription of medication for GERD and their satisfaction through an online questionnaire. The enrolled physicians invited the first five GERD patients who visited them on the same day to complete online patient surveys concerning the satisfaction with medications for GERD and its influencing factors. RESULTS: In total, 334 physician surveys (response rate 36.82%) and 1409 patient surveys (86.07%) were analyzed. Over half (62.57%) the physicians recommended taking a proton pump inhibitor (PPI) twice daily and the majority (88.02%) recommended taking a PPI for 1 week to 3 months. Factors affecting the prescription were how much it could improve quality of life (84.73%), followed by safety, medication compliance, and efficacy. Approximately 30% of patients reported taking a PPI twice daily and 47.20% reported taking a PPI for 1 week to 3 months. Factor affecting patients' adherence to medications was safety (64.30%), followed by medical insurance, efficacy and convenience. Approximately one-third of physicians and patients did not report "satisfied" or "very satisfied" with medications for GERD, including 10.51% of patients and 12.87% of physicians reporting "dissatisfied" or "very dissatisfied." CONCLUSION: One-third of GERD patients and physicians were not satisfied or very satisfied with medications for GERD. Novel medications may help optimize the management of GERD.

LncRNA TUG1 compromised neuronal mitophagy in cerebral ischemia/reperfusion injury by targeting sirtuin 1.

BACKGROUND: Mitophagy protects against cerebral ischemia/reperfusion (CI/R)-induced neuronal apoptosis via mitochondrial clearance. Although taurine-upregulated gene 1 (lncRNA TUG1) has been proposed to be involved in the neuronal apoptosis evoked by CI/R, its specific role in mitophagy during the progression of CI/R injury remains unknown. METHODS: The CI/R rat model was established using middle cerebral artery occlusion/reperfusion (MCAO/R). Human neuroblastoma cell line SH-SY5Y was subjected to oxygen-glucose deprivation and reoxygenation (OGD/R). Ubiquitination assay, co-immunoprecipitation assay, RNA pull-down, and RNA immunoprecipitation were used to determine the interplay among TUG1, sirtuin 1 (SIRT1), and F-box and WD repeat domain-containing 7 (FBXW7). RESULTS: The upregulation of the TUG1 level and downregulation of the mitophagy were observed in both MCAO/R-treated rats and OGD/R-treated cells. The administration of si-TUG1 (a siRNA directed against TUG1) potentiated mitophagy and suppressed neuronal apoptosis in OGD/R-treated cells. However, the neuroprotective effect of si-TUG1 was reversed by mitophagy inhibitor or SIRT1 knockdown in vitro. Functionally, TUG1 enhanced FBXW7-mediated SIRT1 ubiquitination by upregulating FBXW7 expression. The overexpression of FBXW7 abrogated the si-TUG1-reinforced mitophagy by decreasing SIRT1 expression, thus aggravating neuronal apoptosis in the OGD/R+si-TUG1-treated cells. In rats with MCAO/R, the interference of TUG1 clearly decreased neuronal apoptosis, lessened the infarct volume, and relieved the neurological deficits. CONCLUSION: TUG1 knockdown promotes SIRT1-induced mitophagy by suppressing FBXW7-mediated SIRT1 degradation, thus relieving the neuronal apoptosis induced by CI/R injury. LncRNA TUG1 promotes neuronal apoptosis through inhibition of mitophagy. TUG1 decreased SIRT1 expression by promoting FBXW7-mediated SIRT1 ubiquitination. FBXW7/SIRT1 axis mediated the effect of TUG1 on OGD/R-induced neuronal apoptosis by regulating mitophagy.

Ineffective esophageal motility in Chicago Classification version 4.0 better predicts abnormal acid exposure.

BACKGROUND: The updated Chicago Classification version 4.0 (CCv4.0) establishes a more stringent criteria to diagnose ineffective esophageal motility (IEM). This study aims to investigate the clinical significance of IEM in CCv4.0 in the context of gastroesophageal reflux disease (GERD). METHODS: A retrospective study was conducted among suspected GERD patients who had heartburn and/or regurgitation as their chief complaints and completed esophageal function tests in our center from 2017 to 2019. Patients were further grouped as "CCv3.0 IEM" and normal motility according to Chicago Classification version 3.0 (CCv3.0), and as "CCv4.0 IEM" and normal motility according to CCv4.0. The clinical characteristics, high-resolution manometry, esophageal reflux monitoring, and proton pump inhibitor (PPI) efficacy were compared between different groups. Multivariate analyses were performed to identify esophageal motility parameters associated with reflux burden and symptom outcome. RESULTS: Of 172 subjects included, 93 patients were identified as CCv3.0 IEM, 69 as CCv4.0 IEM. IEM in either version was concomitant with elevated acid burden and impaired esophageal clearance as compared to normal motility in corresponding diagnostic criteria, while the only presence of IEM in CCv4.0 was predictive to abnormal acid exposure (AET > 6%: OR = 2.66, 95% CI [1.27-5.56], p < 0.01). The presence of "CCv3.0 IEM" and low EGJ-CI (EGJ-CI < 39.1 mmHg·cm) had no added value in predicting increased reflux burden. No interaction effect was found between the presence of IEM and a weakened EGJ. None of the manometric variables was capable of predicting PPI response. CONCLUSIONS: Stringent criteria of IEM in CCv4.0 can better predict abnormal acid exposure as compared to CCv3.0.

P2RY2 Alleviates Cerebral Ischemia-Reperfusion Injury by Inhibiting YAP Phosphorylation and Reducing Mitochondrial Fission.

P2Y purinoceptor 2 (P2RY2) is involved in the regulation of cell proliferation and apoptosis. The aim of this study was to explore the effects of P2RY2 on cerebral ischemia/reperfusion (I/R) injury and its molecular mechanism. Middle cerebral artery occlusion (MCAO) model in rats and OXYGEN and oxygen-glucose deprivation/reoxygenation (OGD/R) model in PC12 cells were established. P2RY2 expressions in I/R injury model in vitro and in vivo were up-regulated. In the OGD/R group, ROS level, cyto-CytC and mitochondrial fission factors expressions and cell apoptosis were increased, while SOD activity, mito-CytC and mitochondrial fusion factors expressions were decreased. P2RY2 overexpression could reverse these results. Up-regulated P2RY2 expression decreased Yes-associated protein (YAP) phosphorylation level, promote the nuclear translocation of YAP, and inhibit cell apoptosis, which can be reversed by YAP inhibitor verteporfin. The addition of PI3K/AKT inhibitor LY294002 could reverse the decrease of YAP phosphorylation level and cell apoptosis, and the increase of nuclear translocation caused by P2RY2 overexpression. Further in vivo studies validated that interference with P2RY2 increased the cerebral infarction area, decreased AKT expression, enhanced YAP phosphorylation, and inhibited the nuclear translocation of YAP. In conclusion, P2RY2 can alleviate cerebral I/R injury by inhibiting YAP phosphorylation and reducing mitochondrial fission.

Identification of mitochondrial RNA polymerase as a potential therapeutic target of osteosarcoma.

POLRMT (RNA polymerase mitochondrial) is essential for transcription of mitochondrial genome encoding components of oxidative phosphorylation process. The current study tested POLRMT expression and its potential function in osteosarcoma (OS). The Cancer Genome Atlas (TCGA) cohorts and Gene Expression Profiling Interactive Analysis (GEPIA) database both show that POLRMT transcripts are elevated in OS tissues. In addition, POLRMT mRNA and protein levels were upregulated in local OS tissues as well as in established and primary human OS cells. In different OS cells, shRNA-induced stable knockdown of POLRMT decreased cell viability, proliferation, migration, and invasion, whiling inducing apoptosis activation. CRISPR/Cas9-induced POLRMT knockout induced potent anti-OS cell activity as well. Conversely, in primary OS cells ectopic POLRMT overexpression accelerated cell proliferation and migration. In vivo, intratumoral injection of adeno-associated virus-packed POLRMT shRNA potently inhibited U2OS xenograft growth in nude mice. Importantly, levels of mitochondrial DNA, mitochondrial transcripts and expression of respiratory chain complex subunits were significantly decreased in U2OS xenografts with POLRMT shRNA virus injection. Together, POLRMT is overexpressed in human OS, promoting cell growth in vitro and in vivo. POLRMT could be a novel therapeutic target for OS.

Magnetic sphincter augmentation in treating refractory gastroesophageal reflux disease: A systematic review and meta-analysis.

OBJECTIVE: In this systematic review and meta-analysis we aimed to determine the efficacy and safety of magnetic sphincter augmentation (MSA) in the management of refractory gastroesophageal reflux disease (rGERD). METHODS: Literature search was conducted in PubMed, the Cochrane Library, EMBASE, Web of Science, OpenGrey and ClincalTrials.gov for single-arm studies evaluating the efficacy and safety of MSA in rGERD or comparative studies with proton pump inhibitor (PPI) or laparoscopic Nissen fundoplication (LNF) serving as the control published until April 2020. Primary outcome was the rate of postoperative PPI use, and secondary outcomes included postoperative GERD-health-related quality of life (GERD-HRQL), normalization of acid exposure time (AET) and incidence of procedure-related adverse events (AE). RESULTS: Ten single-arm studies, one randomized controlled trial and three cohort studies involving 1138 participants were included. Post-MSA PPI withdrawal, significant GERD-HRQL improvement and AET normalization were achieved in 87.0%, 88.0% and 75.0% of the patients, respectively. The incidence of postoperative dysphagia was 29% and endoscopic dilation was required in 7.4% of patients undergoing MSA. MSA showed a better efficacy in symptom control than PPI (PPI cessation: 91% vs 0%; GERD-HRQL improvement: 81% vs 8%) and similar effectiveness but a lower risk of gas-bloat syndrome (risk ratio [RR] 0.69, 95% confidence interval [CI] 0.51-0.93, P = 0.01) and better reserved ability to belch (RR 1.48, 95% CI 0.76-2.86, P = 0.25) compared with LNF. CONCLUSIONS: MSA was an effective and safe therapy for rGERD. Well-designed randomized trials that compare the efficacy of MSA with other therapies are needed.

White-light endoscopy is insufficient to distinguish between types of esophageal white lesions.

OBJECTIVE: Esophageal white lesions (EWL) are commonly observed under upper endoscopy, while their clinical significance remains undetermined. The aim of this study was to identify the endoscopic characteristics of EWL and distinguish between different types of EWL. METHODS: Consecutive patients with upper gastrointestinal complaints and participants admitted for health check-up who underwent esophagogastroduodenoscopy from October 2018 to August 2019 in a tertiary hospital were prospectively screened. EWL were detected under endoscopy and biopsy was performed for histological analysis. Participants' characteristics, lifestyle, esophageal motility and reflux monitoring variables were analyzed. RESULTS: Of the 3641 consecutive participants screened, 303 of them aged 56.12 ± 10.95 years were found to have EWL (detection rate of 8.3%). More than one-third of them preferred hot drinks, eating pickled or spicy food, smoking and alcohol consumption and 5.3% had current or former upper gastrointestinal or head and neck cancers. The common endoscopic appearance of the EWL (2.9 mm ± 1.2 mm in diameter) included slightly elevated plaque, translucent white in color, with a clear border, round or oval in shape, and a scaly, rough or smooth surface. Histology showed low-grade intraepithelial dysplasia in 13 cases, leukoplakia in 10 and intestinal metaplasia in one. No significant differences were found between the histological findings and endoscopic manifestations of EWL. CONCLUSIONS: EWL are not uncommon in daily endoscopic examination, with some of them being precancerous lesions. Conventional white-light endoscopy is insufficient to identify EWL, while histological assessment is important. Further studies using advanced endoscopic techniques with long-term follow-up are needed.

Transcranial direct-current stimulation protects against cerebral ischemia-reperfusion injury through regulating Cezanne-dependent signaling.

Transcranial direct-current stimulation (tDCS) is proved safe and shows therapeutic effect in cerebral ischemic stroke in clinical trials. But the underlying molecular mechanisms remain unclear. Here we show that tDCS treatment reduces the infarct volume after rat cerebral ischemia-reperfusion (I/R) injury and results in functional improvement of stroke animals. At the cellular and molecular level, tDCS suppresses I/R-induced upregulation of Cezanne in the ischemic neurons. Cezanne inhibition confers neuroprotection after rat I/R and oxygen glucose deprivation (OGD) in the cortical neuronal cultures. Inhibiting Cezanne increases the level of SIRT6 that is downregulated in the ischemic neurons. Suppressing SIRT6 blocks Cezanne inhibition-induced neuroprotective effect and overexpressing SIRT6 attenuates OGD-induced neuronal death. We further show that downregulating Cezanne reduces DNA double-strand break (DSB) through upregulation of SIRT6 in OGD-insulted neurons. Together, this study suggests that Cezanne-dependent SIRT6-DNA DSB signaling pathway may mediate the neuroprotective effect of tDCS in ischemic neurons.

Melatonin: Effects on Cartilage Homeostasis and Therapeutic Prospects in Cartilage-related Diseases.

Cartilage is a relatively simple connective tissue that plays a variety of roles in the human body, including joint support and protection, load bearing of the intervertebral discs, joint lubrication, formation of the external structure of the ears and nose and support of the trachea. The maintenance of cartilage homeostasis is therefore crucial. Cartilage-related diseases are difficult to diagnose and treat because their molecular and pathological mechanisms are not fully understood. Melatonin, which has a wide range of physiological effects, is an endocrine hormone mainly secreted by the pineal gland. Its biological effects include its antioxidant, antiaging, analgesic, and hypnotic effects and its ability to stabilize the circadian rhythm. In recent years, research on cartilage homeostasis and melatonin has been increasing, and melatonin has gradually been used in the treatment of cartilage-related diseases. Therefore, this article will briefly review the role of melatonin in cartilage homeostasis, including its anti-inflammatory effects and effects in protecting cartilage from damage by other factors and promoting chondrocyte growth and the expression of cartilage-related genes. Based on the above, the current status and future developmental direction of melatonin in the treatment of cartilage-related diseases are also discussed, demonstrating the broad prospects of melatonin in maintaining cartilage homeostasis and treating cartilage injury-related diseases.

Arginine is neuroprotective through suppressing HIF-1α/LDHA-mediated inflammatory response after cerebral ischemia/reperfusion injury.

Neuroinflammation is a secondary response following ischemia stroke. Arginine is a non-essential amino acid that has been shown to inhibit acute inflammatory reaction. In this study we show that arginine treatment decreases neuronal death after rat cerebral ischemia/reperfusion (I/R) injury and improves functional recovery of stroke animals. We also show that arginine suppresses inflammatory response in the ischemic brain tissue and in the cultured microglia after OGD insult. We further provide evidence that the levels of HIF-1α and LDHA are increased after rat I/R injury and that arginine treatment prevents the elevation of HIF-1α and LDHA after I/R injury. Arginine inhibits inflammatory response through suppression of HIF-1α and LDHA in the rat ischemic brain tissue and in the cultured microglia following OGD insult, and protects against ischemic neuron death after rat I/R injury by attenuating HIF-1α/LDHA-mediated inflammatory response. Together, these results indicate a possibility that arginine-induced neuroprotective effect may be through the suppression of HIF-1α/LDHA-mediated inflammatory response in microglia after cerebral ischemia injury.

l-lysine confers neuroprotection by suppressing inflammatory response via microRNA-575/PTEN signaling after mouse intracerebral hemorrhage injury.

l-lysine is a basic amino acid that has been shown to exert neuroprotective effect. However, the underlying mechanism remains to be elucidated. In this study, we investigate how l-lysine exerts its neuroprotective effect in hemin-insulted mouse cortical neurons in vitro and the mouse model of intracerebral hemorrhage (ICH) in vivo. We demonstrate that l-lysine treatment promotes M2 microglial polarization and reduces inflammatory response both in vitro and in vivo, suggesting that l-lysine may play a neuroprotective role in ICH injury. Indeed, we show that l-lysine treatment reduces cortical neuronal death after hemin insult in vitro and decrease the number of degenerating neurons after ICH in vivo. l-lysine also improves the functional recovery of ICH animals in neurobehavioral tests. Consistent with the role of PTEN in regulating inflammatory response, we find that PTEN inhibition promotes M2 microglial polarization and suppresses pro-inflammatory response in mouse ICH injury, which contribute to the neuroprotective effect of l-lysine. Moreover, our results reveal that microRNA-575 directly suppressed PTEN to promote M2 microglial polarization and mediate the neuroprotective effect of l-lysine in ICH injury. Together, our results suggest that l-lysine confers neuroprotection after ICH injury through enhancing M2 microglial polarization and reducing inflammatory response, which is mediated by microRNA-575 upregulation and subsequent PTEN downregulation.

PTEN Inhibition Protects Against Experimental Intracerebral Hemorrhage-Induced Brain Injury Through PTEN/E2F1/ß-Catenin Pathway.

Intracerebral hemorrhage (ICH) is a subtype of stroke with highest mortality and morbidity. We have previously demonstrated that dipotassium bisperoxo (picolinato) oxovanadate (V), (bpV[pic]) inhibits phosphatase and tensin homolog (PTEN) and activates extracellular signal-regulated kinase (ERK)1/2. In this study, we examined the effect of bpV[pic] in the rat ICH model in vivo and the hemin-induced injury model in rat cortical cultures. The rat model of ICH was created by injecting autologous blood into the striatum, and bpV[pic] was intraperitoneally injected. The effects of bpV[pic] were evaluated by neurological tests, Fluoro-Jade C (FJC) staining, and Nissl staining. We demonstrate that bpV[pic] attenuates ICH-induced brain injury in vivo and hemin-induced neuron injury in vitro. The expression of E2F1 was increased, but ß-catenin expression was decreased after ICH, and the altered expressions of E2F1 and ß-catenin after ICH were blocked by bpV[pic] treatment. Our results further show that bpV[pic] increases ß-catenin expression through downregulating E2F1 in cortical neurons and prevents hemin-induced neuronal damage through E2F1 downregulation and subsequent upregulation of ß-catenin. By testing the effect of PTEN-siRNA, PTEN cDNA, or combined use of ERK1/2 inhibitor and bpV[pic] in cultured cortical neurons after hemin-induced injury, we provide evidence suggesting that PTEN inhibition by bpV[pic] confers neuroprotection through E2F1 and ß-catenin pathway, but the neuroprotective role of ERK1/2 activation by bpV[pic] cannot be excluded.

The neuroprotective effect of bisperoxovandium (pyridin-2-squaramide) in intracerebral hemorrhage.

Background: The authors have recently designed a new compound bisperoxovandium (pyridin-2-squaramide) [bpV(pis)] and verified that bpV(pis) confers neuroprotection through suppressing PTEN and activating ERK1/2, respectively. Intracerebral hemorrhage (ICH) is the second most common cause of stroke and has severe clinical outcome. In this study, we investigate the effect of bpV(pis) in ICH model both in vivo and in vitro. Materials and methods: The novel drug bpV(pis) was synthesized in the Faculty of Pharmacy, Wuhan University School of Medicine. An ICH model was generated on both SD rats and cells. bpV(pis) was injected into intracerebroventricular or culture media. Western blotting was applied to test the signal pathway. To determine the effect of bpV(pis) on PTEN inhibition and ERK1/2 activation, we measured the phosphorylation level of AKT (a direct downstream target of PTEN that negatively regulates AKT) and ERK1/2. FJC, MTT, and LDH were applied to measure the cell viability. Neurobehavioral tests were performed to measure the effect of bpV(pis). Results: The in vivo results showed that intracerebroventricular administration of bpV(pis) significantly alleviates hematoma, the damage of brain-blood barrier and brain edema. The in vitro results demonstrated that bpV(pis) treatment reduces ICH-induced neuronal injury. Western blotting results identified that bpV(pis) exerts a neuroprotective effect by significantly increasing the phosphorylation level of AKT and ERK1/2 after experimental ICH. Neurobehavioral tests indicate that bpV(pis) promotes functional recovery in ICH animals. Conclusion: This study provides first and direct evidence for a potential role of bpV(pis) in ICH therapy.

BpV(pic) confers neuroprotection by inhibiting M1 microglial polarization and MCP-1 expression in rat traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of motor and cognitive impairment in young adults. It is associated with high mortality rates and very few effective treatment options. Bisperoxovanadium (pyridine-2-carboxyl) [bpV(pic)] is an commercially available inhibitor of Phosphatase and tensin homolog (PTEN). Previous studies have shown that bpV(pic) has protective effects in central nervous system. However, the role of bpV(pic) in TBI is unclear. In this study we aimed to investigate the neuroprotective role of bpV(pic) in rat TBI model. We found that injection of bpV(pic) significantly reduces brain edema and neurological dysfunction after TBI and this is mediated by AKT pathway. TBI is known to promote the M1 pro-inflammatory phenotype of microglial polarization and this effect is inhibited by bpV(pic) treatment which, instead promotes M2 microglial polarization in vivo and in vitro. We also found evidence of bpV(pic)-regulated neuroinflammation mediated by AKT activation and NF-κB p65 inhibition. BpV(pic) treatment also suppressed microglia in the peri-TBI region. MCP-1 is known to recruit monocytes and macrophages to promote inflammation, we show that bpV(pic) can inhibit TBI-induced up-regulation of MCP-1 via the AKT/NF-κB p65 signaling pathway. Taken together, our findings demonstrate that bpV(pic) plays a neuroprotective role in rat TBI, which may be achieved by inhibiting M1 microglia polarization and MCP-1 expression by modulating AKT/NF-κB p65 signaling pathway.

Intracranial Mirror Aneurysm: Epidemiology, Rupture Risk, New Imaging, Controversies, and Treatment Strategies.

There are some controversies about the surgical treatment strategy of mirror aneurysms. Whether to choose 1-stage or 2-stage surgery, bilateral or unilateral craniotomy, or surgical or interventional treatment are the main points in dispute. In this review, the different surgery strategies faced by patients are discussed. Different surgical methods are adopted based on the patient's individual state and the location and size of the aneurysm. A new imaging method is introduced using 3D Slicer, which clearly recognizes the relationship among aneurysm, brain tissue, skull, and nerve. The 3D Slicer can help surgeons undertake adequate preoperative preparation. In addition, we also introduce some ruptured factors (e.g., age, gender, hypertension, morphologic, and hemodynamic) concerning mirror aneurysm. Systematic discussion of the controversies and methods in surgical treatment of mirror aneurysms may provide new perspectives in future research for the prevention and treatment of mirror aneurysms.

Application of Finite Element Analysis for Investigation of Intervertebral Disc Degeneration: from Laboratory to Clinic.

Due to the ethical concern and inability to detect inner stress distributions of intervertebral disc (IVD), traditional methods for investigation of intervertebral disc degeneration (IVDD) have significant limitations. Many researchers have demonstrated that finite element analysis (FEA) is an effective tool for the research of IVDD. However, the specific application of FEA for investigation of IVDD has not been systematically elucidated before. In the present review, we summarize the current finite element models (FEM) used for the investigation of IVDD, including the poroelastic nonlinear FEM, diffusive-reactive theory model and cell-activity coupled mechano-electrochemical theory model. We further elaborate the use of FEA for the research of IVDD pathogenesis especially for nutrition and biomechanics associated etiology, and the biological, biomechanical and clinical influences of IVDD. In addition, the application of FEA for evaluation and exploration of various treatments for IVDD is also elucidated. We conclude that FEA is an excellent technique for research of IVDD, which could be used to explore the etiology, biology and biomechanics of IVDD. In the future, FEA may help us to achieve the goal of individualized precision therapy.