Prognostic and immunological role of adaptor related protein complex 3 subunit mu2 in colon cancer.

The expression levels and prognostic role of AP3M2 in colorectal adenocarcinoma (CRAC) have yet to be fully unveiled. Our study comprehensively investigated the clinical significance of AP3M2 in colorectal cancer through an extensive bioinformatics data mining process (TCGA, GEO, GEPIA, Timer, Ualcan, ROCPLOT, and David), followed by experimental validation. We found AP3M2 is a cancer gene, which can be used to distinguish between colorectal cancer and colorectal adenomas, liver metastasis, lung metastasis, colorectal polyp. Higher AP3M2 expression levels were associated with longer overall survival in colon adenocarcinoma. AP3M2 might be the primary biomarker for oxaliplatin in colon cancer and an acquired resistance biomarker for oxaliplatin and 5-fu. AP3M2 was positively associated with CD274, CTLA4. AP3M2 might be associated with T-cell, NF-kappaB transcription factor activity, and response to hypoxia. AP3M2 could predict chemotherapy effectiveness and prognosis for colon cancer patients. AP3M2 might inhibit tumor growth via influencing tumor-infiltrating immune cells in the context of Tumor microenvironment. AP3M2 plays as an oncogene in CRAC and is suggested as a new potential biotarget for therapy.

Copper-Catalyzed Synthesis of Substituted Primary Arylamines from Cyclohexenone Oxime Esters.

A novel protocol has been developed for the Cu-catalyzed synthesis of primary arylamines with meta-substituents using cyclohexenone oxime esters. Mechanistic insights suggest that the reaction proceeds via an intermolecular 1,5-H hydrogen atom transfer of an imine radical intermediate. This approach features high efficiency, a readily available catalyst system, and broad functional group tolerance.

Prognostic and immunological role of acetaldehyde dehydrogenase 1B1 in human tumors: A pan-cancer analysis.

Acetaldehyde dehydrogenases (ALDH) 1B1 is associated with a poor prognosis in pancreatic cancer, colorectal cancer, and osteosarcoma. Overexpression of ALDH also impairs tumor immunity. However, it is unclear how ALDH1B1 is associated with patient prognosis and immune infiltration in different cancer types. This is an original research based on bioinformatics analysis. In this study, we investigated the expression and prognostic value of ALDH1B1 in pan-cancer specimens using several databases, including GEPIA2 and Kaplan-Meier Plotter. The GEPIA2 and TIMER2 databases were used to explore correlations between ALDH1B1 expression and immune infiltration in cancers, especially head and neck squamous cell carcinoma (HNSC) and stomach adenocarcinoma (STAD). Finally, the expression of ALDH1B1 was validated by qPCR and immunohistochemistry. The expression of ALDH1B1 differed in most cancers compared to normal tissue controls. ALDH1B1 has an important impact on the prognosis different cancer types, and the high expression of ALDH1B1 is inversely associated with survival in patients with HNSC. A significant positive correlation was identified between ALDH1B1 expression in HNSC and immune infiltration. The poor prognosis associated with high expression of ALDH1B1 may be related to the promotion of M2 polarization of tumor-associated macrophages. Furthermore, markers of immune cell infiltration, such as exhausted T cells and regulatory T cells showed different patterns of ALDH1B1-associated immune infiltration. ALDH1B1 can serve as a prognostic biomarker in pan-cancer types and is correlated with immune infiltration.

Thrombospondin-2 promotes the proliferation and migration of glioma cells and contributes to the progression of glioma.

BACKGROUND: Gliomas, especially high-grade gliomas, are highly malignant with a poor prognosis. Although existing treatments have improved the survival rate of patients with glioma, the recurrence and mortality rates are still not ideal. The molecular mechanisms involved in the occurrence and development of glioma are still poorly understood. We previously reported that thrombospondin-2 (TSP2) expression was increased in tumor specimens from rat models, promoting excitatory synapse formation. However, little is known about the effect of TSP2 on the biological characteristics of glioma. METHODS: Glioma and cerebral cortex tissues were collected from 33 patients, and the expression of TSP2 in them was analyzed. Next, the proliferation and migration of TSP2 on glioma cells were analyzed in vitro. At last, a glioma transplantation model was constructed to explore the growth of TSP2 on glioma in vivo. RESULTS: The expression of TSP2 in surgical glioma specimens was increased compared to that in the normal cortex. Interestingly, the TSP2 protein level was higher in high-grade glioma (HGG, World Health Organization (WHO) grades 3-4) than in low-grade glioma (LGG, WHO grades 1-2) tissues. Exogenous addition of the TSP2 protein at an appropriate concentration promoted the migration of glioma cells but did not significantly affect their proliferation. Surprisingly, overexpression of TSP2 promoted both the migration and proliferation of cultured glioma cells. Moreover, in vivo experimental data implied that overexpression of TSP2 in C6 cells promoted the malignant growth of gliomas, while knockout of TSP2 slowed glioma growth. CONCLUSIONS: TSP2 promotes the migration and proliferation of glioma cells, which may provide new ideas for blocking glioma progression.

Carnosol Reduced Pathogenic Protein Aggregation and Cognitive Impairment in Neurodegenerative Diseases Models via Improving Proteostasis and Ameliorating Mitochondrial Disorders.

Neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, and Huntington's disease are incurable diseases with progressive loss of neural function and require urgent development of effective treatments. Carnosol (CL) reportedly has a pharmacological effect in the prevention of dementia. Nevertheless, the mechanisms of CL's neuroprotection are not entirely clear. The present study aimed to investigate the effects and mechanisms of CL-mediated neuroprotection through Caenorhabditis elegans models. First, CL restored ND protein homeostasis via inhibiting the IIS pathway, regulating MAPK signaling, and simultaneously activating molecular chaperone, thus inhibiting amyloid peptide (Aß), polyglutamine (polyQ), and α-synuclein (α-syn) deposition and reducing protein disruption-mediated behavioral and cognitive impairments as well as neuronal damages. Furthermore, CL could repair mitochondrial structural damage via improving the mitochondrial membrane protein function and mitochondrial structural homeostasis and improve mitochondrial functional defects via increasing adenosine triphosphate contents, mitochondrial membrane potential, and reactive oxygen species levels, suggesting that CL could improve the ubiquitous mitochondrial defects in NDs. More importantly, we found that CL activated mitochondrial kinetic homeostasis related genes to improve the mitochondrial homeostasis and dysfunction in NDs. Meanwhile, CL up-regulated unc-17, cho-1, and cha-1 genes to alleviate Aß-mediated cholinergic neurological disorders and activated Notch signaling and the Wnt pathway to diminish polyQ- and α-syn-induced ASH neurons as well as dopaminergic neuron damages. Overall, our study clarified the beneficial anti-ND neuroprotective effects of CL in different aspects and provided new insights into developing CL into products with preventive and therapeutic effects on NDs.

Preharvest application of hydrogen nanobubble water enhances strawberry flavor and consumer preferences.

The improvement of fruit flavor is a challenge for producers and breeders. This study investigated the effects and mechanisms of preharvest hydrogen nanobubble water (HNW) application on the flavor of cultivated strawberry (Fragaria × ananassa 'Benihoppe'). Compared with surface water, HNW enhanced the volatile profiles, sugar-acid ratio, and sensory attributes (e.g., aroma, flavor, and overall liking) with/without fertilizer application. Meanwhile, flavor components such as esters (e.g., ethyl hexanoate), acids (e.g., hexanoic acid), and soluble sugars (including glucose, fructose, and sucrose) significantly contributed to increased strawberry flavor achieved with HNW. Importantly, HNW may alleviate the negative effects of fertilizers on strawberry fruit aroma. Further study elucidated that the aroma-related genes (including FaLOX, FaADH, FaAAT, FaQR, FaOMT, and FaNES1) were involved in the accumulation of specific volatiles after HNW treatment. This study provided evidence that the practical application of H2 can improve horticultural product quality at a lower carbon cost.

Packaging with hydrogen gas modified atmosphere can extend chicken egg storage.

BACKGROUND: Although hydrogen gas (H2 ) has been widely used in industry and gradually used in medicine, it is less applied to agriculture, especially in modified atmosphere packing (MAP). RESULTS: During chicken egg storage, H2 MAP not only slowed down or delayed the reduction in antioxidant capacities, but also alleviated the deterioration of egg quality. The extent of micro-cracks in the eggshell was also negatively influenced by H2 , which might result in eggs being less vulnerable to microbes. The earlier results demonstrated that the H2 MAP-extended shelf life of chicken eggs might be caused by the responses of eggshell and re-establishment of redox homeostasis. According to the data collected from different provinces of China, cost-economics analysis further suggested that the increase in the extra cost caused by H2 was trivial compared with the original price of eggs. CONCLUSION: Together, H2 MAP can prolong the shelf life of chicken eggs with the prospect of wider application. © 2021 Society of Chemical Industry.

A Novel Mechanism of the c-Myc/NEAT1 Axis Mediating Colorectal Cancer Cell Response to Photodynamic Therapy Treatment.

Photodynamic therapy (PDT) is considered a potential treatment regimen for colorectal cancer cases (CRC). p53 signaling and the miR-124/iASPP axis play an essential role in the PDT resistance of CRC cells. PDT treatment downregulated NEAT1 expression in p53wt HCT116 and RKO cells. In these two cell lines, NEAT1 silencing enhanced the suppressive effects of PDT on cell viability and apoptosis. Within the subcutaneously implanted tumor model, NEAT1 silencing enhanced PDT-induced suppression on tumor growth. Regarding p53-deleted HCT116 cells, PDT only moderately affected cell proliferation but induced downregulation of NEAT1. NEAT1 directly targeted miR-124, acting as a ceRNA, competing with iASPP for miR-124 binding, and counteracting miR-124-mediated repression on iASPP under PDT treatment. NEAT1 silencing was enhanced, whereas miR-124 inhibition attenuated PDT effects on CRC cells; miR-124 inhibition significantly reversed the roles of NEAT1 silencing in PDT-treated CRC cells. miR-124 negatively correlated with NEAT1 and iASPP, respectively, whereas NEAT1 and iASPP positively correlated with each other. PDT downregulated c-Myc in CRC cells, and c-Myc activated the transcription of NEAT1 through the targeting of its promoter region. Within p53mut SW480 cells, PDT failed to alter cell viability and apoptosis but still downregulated c-Myc, NEAT1, and iASPP and upregulated miR-124. In p53 mutant high-abundant CRC tissues, c-Myc and NEAT1 were up-regulated, and miR-124 was downregulated. In c-Myc high-abundant CRC tissues, NEAT1 and iASPP were up-regulated, and miR-124 was downregulated. The critical role of the c-Myc/NEAT1 axis in mediating CRC response to PDT treatment via the miR-124/iASPP/p53 feedback loop was conclusively demonstrated.

Molecular Hydrogen Maintains the Storage Quality of Chinese Chive through Improving Antioxidant Capacity.

Chinese chive usually becomes decayed after a short storage time, which was closely observed with the redox imbalance. To cope with this practical problem, in this report, molecular hydrogen (H2) was used to evaluate its influence in maintaining storage quality of Chinese chive, and the changes in antioxidant capacity were also analyzed. Chives were treated with 1%, 2%, or 3% H2, and with air as the control, and then were stored at 4 ± 1 °C. We observed that, compared with other treatment groups, the application of 3% H2 could significantly prolong the shelf life of Chinese chive, which was also confirmed by the obvious mitigation of decreased decay index, the loss ratio of weight, and the reduction in soluble protein content. Meanwhile, the decreasing tendency in total phenolic, flavonoid, and vitamin C contents was obviously impaired or slowed down by H2. Results of antioxidant capacity revealed that the accumulation of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) was differentially alleviated, which positively matched with 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and the improved activities of antioxidant enzymes, including superoxide dismutase (SOD), guaiacol peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX). Above results clearly suggest that postharvest molecular hydrogen application might be a potential useful approach to improve the storage quality of Chinese chive, which is partially achieved through the alleviation of oxidative damage happening during the storage periods. These findings also provide potential theoretical and practical significance for transportation and consumption of perishable vegetables.

Inhibitor of apoptosis-stimulating p53 protein protects against inflammatory bowel disease in mice models by inhibiting the nuclear factor kappa B signaling.

Drugs and therapies available for the treatment of inflammatory bowel disease (IBD) are not satisfactory. Our previous study has established the inhibitor of apoptosis-stimulating p53 protein (iASPP) as an oncogenic regulator in colorectal cancer by forming a regulatory axis or feedback loop with miR-124, p53, or p63. As iASPP could target and inhibit nuclear factor kappa B (NF-κB) activation, in this study the role and mechanism of iASPP in IBD was investigated. The aberrant up-regulation of iASPP in IBD was subsequently confirmed, based on online data sets, clinical sample examinations and 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced colitis mice models. TNBS or DSS stimulation successfully induced colon shortness, body weight loss, mice colon oxidative stress and inflammation. In both types of colitis mice models, iASPP over-expression improved, whereas iASPP knockdown aggravated TNBS or DSS stimulation-caused colon shortness, body weight loss and mice colon oxidative stress and inflammation. Meanwhile, in both types of colitis mice models, iASPP over-expression inhibited p65 phosphorylation and decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, C-X-C motif chemokine ligand (CXCL)1 and CXCL2 in mice colons, whereas iASPP knockdown exerted opposite effects.

Glioma-Derived TSP2 Promotes Excitatory Synapse Formation and Results in Hyperexcitability in the Peritumoral Cortex of Glioma.

Seizures are common in patients with glioma, especially low-grade glioma (LGG). However, the epileptogenic mechanisms are poorly understood. Recent evidence has indicated that abnormal excitatory synaptogenesis plays an important role in epileptogenesis. The thrombospondin (TSP) family is a key regulator of synaptogenesis. Thus, this study aimed to elucidate the role of TSP2 in epileptogenesis in glioma-related epilepsy. The expression of TSP2 was increased in tumor tissue specimens from LGG patients, and this increase may have contributed to an increase in the density of spines and excitatory synapses in the peritumoral area. A glioma cell-implanted rat model was established by stereotactic implantation of wild-type TSP2-expressing, TSP2-overexpressing or TSP2-knockout C6 cells into the neocortex. Similarly, an increase in the density of excitatory synapses was also observed in the peritumoral area of the implanted tumor. In addition, epileptiform discharges occurred in the peritumoral cortex and were positively correlated with the TSP2 level in glioma tissues. Moreover, α2δ1/Rac1 signaling was enhanced in the peritumoral region, and treatment with the α2δ1 antagonist gabapentin inhibited epileptiform discharges in the peritumoral cortex. In conclusion, glioma-derived TSP2 promotes excitatory synapse formation, probably via the α2δ1/Rac1 signaling pathway, resulting in hyperexcitability in the peritumoral cortical networks, which may provide new insight into the epileptogenic mechanisms underlying glioma-related epilepsy.

Diagnostic value of NSE factor combined with ultrasound hemodynamic indexes in cervical lymph node metastasis of lung cancer.

Value of neuron-specific enolase (NSE) factor combined with ultrasound hemodynamic parameters in the diagnosis of cervical lymph node metastasis of lung cancer was explored. The clinical data of 85 patients with lung cancer, admitted to Qingdao Municipal Hospital (Group) from January 2015 to December 2016, were retrospectively analyzed. According to the results of pathological examination, 47 patients with cervical lymph node metastasis were enrolled in the metastatic group and 38 patients without lymph node metastasis were enrolled in the non-metastatic group. The expression level of NSE in serum and the hemodynamic indicators of blood flow resistance index (RI) and pulsatility index (PI) were compared between the two groups. ROC curve analysis was used to analyze the diagnostic efficacy of NSE, RI, PI, and their combination in lymph node metastasis of lung cancer. The NSE, RI and PI indexes in the metastatic group were significantly higher than those in the non-metastatic group (P<0.05). The sensitivity and specificity of NSE in the diagnosis of cervical lymph node metastasis of lung cancer were 73.68 and 72.34%, respectively; the sensitivity and specificity of RI were 78.95 and 80.85%, respectively; the sensitivity and specificity of PI were 81.58 and 68.09%, respectively. Also, the sensitivity and specificity of NSE combined with RI were 89.47 and 61.70%, respectively, and the diagnostic AUC was 0.881. The sensitivity and specificity of NSE combined with PI were 92.11 and 74.47%, respectively, and the diagnostic AUC was 0.905. NSE, RI, and PI have certain diagnostic value for cervical lymph node metastasis of lung cancer, however, the combined diagnosis is more valuable, and can be used as the auxiliary diagnosis of cervical lymph node metastasis of lung cancer.

Totally Robotic Distal Gastrectomy: A Safe and Feasible Minimally Invasive Technique for Gastric Cancer Patients Who Undergo Distal Gastrectomy.

PURPOSES: To explore the safety and feasibility of totally robotic distal gastrectomy (TRDG) for gastric cancer patients who undergo distal gastrectomy. METHODS: Consecutive patients with gastric cancer who underwent TRDG (TRDG group) and robotic-assisted distal gastrectomy (RADG) (RADG group) were systematically reviewed at the Second Xiangya Hospital of Central South University from October 2015 to August 2018. Data were collected and statistically analyzed. RESULTS: A total of 161 consecutive patients were included in this study: 84 cases in the TRDG group and 77 in the RADG group. Clinical characteristics and pathological results were mostly similar in both groups. The TRDG group had a significantly longer anastomotic time (20.6 ± 3.3 vs. 17.5 ± 4.0 min, p ˂ 0.001) but showed no difference in total operating time (167.0 ± 18.0 vs. 162.9 ± 17.6 min, p = 0.159). The postoperative hospitalization in the TRDG group was shorter than that in the RADG group (6.7 ± 1.2 vs. 7.2 ± 1.7 days, p = 0.019). Conversion rate, estimated blood loss, and postoperative complications were similar in both groups. There were no statistical differences in the estimated 2-year disease-free survival and overall survival rate between both groups. CONCLUSIONS: Although our current results need to be verified in further studies, TRDG represents a safe and feasible approach to distal gastrectomy and embodies the theory of minimally invasive surgery.

Anti-fat effect and mechanism of polysaccharide-enriched extract from Cyclocarya paliurus (Batal.) Iljinskaja in Caenorhabditis elegans.

Obesity is a global epidemic. Recent studies have shown that Cyclocarya paliurus (C. paliurus) leaves have the potential to alleviate fat deposits. However, the fat-reducing mechanism of it remains unclear. Using Caenorhabditis elegans (C. elegans) as a model, we found that C. paliurus polysaccharide (CPP) significantly decreased fat storage in both normal and high-fat worms without affecting the movement. Moreover, the size and number of lipid droplets were reduced in CPP-treated ZXW618 worms. In energy metabolism, CPP decreased Escherichia coli (E. coli) OP50 growth and pharyngeal pumping and increased the expression of vit-2. In lipid metabolism, CPP down-regulated the expression of the sbp-1 and nhr-49 genes by modulating mdt-15 to prevent the expression of the Δ9-desaturase genes (fat-5, fat-6 and fat-7). Meanwhile, the expression of the acs-2 genes, the downstream of nhr-49, was suppressed by CPP. These findings provided insights into the CPP-induced anti-fat mechanisms, which contributed to the application of CPP in anti-obesity drugs.

Effects of an Informational Video About Anesthesia on Pre- and Post-Elective Cesarean Section Anxiety and Recovery: A Randomized Controlled Trial.

BACKGROUND Showing an informational anesthesia video can reduce the preoperative anxiety of parturients undergoing elective cesarean section (CS). However, the best method for presenting such videos remains unclear, and whether such videos can reduce the anxiety level of women during the entire perioperative period for CS (including preoperative and postoperative) has not been studied yet. MATERIAL AND METHODS This study was a single-center prospective randomized trial. We randomly divided 121 pregnant women who were scheduled to undergo elective cesarean section (CS) into 2 groups: one group was shown an informational video (video group) and another group was not (control group). Spielberger's state-trait anxiety inventory was used to evaluate the perioperative anxiety level of parturient women at 3 time points: 1 day before CS, after video education, and 2 days after CS. Salivary cortisol level was evaluated to assess the patients' anxiety level at these 3 time points. Finally, the maternal satisfaction scale for CS and an obstetric quality-of-recovery score (OBsQoR-11) were used to evaluate the satisfaction and recovery of the parturient women 2 days after CS. RESULTS Watching a video about anesthesia significantly reduced the anxiety level of the parturient women during the perioperative period (1 day before CS: p=1.00, p=0.96; after video education: p<0.01, p=0.004; 2 days after CS: p=0.01, p=0.01). The postoperative satisfaction scores were significantly improved in the video group (p=0.007). OBsQoR-11 scores in the video group and control group were not significantly different (p=0.48). Maternal anxiety level was moderately positively correlated with cortisol hormone level. CONCLUSIONS Showing an informational video about anesthesia (video+education) can significantly reduce perioperative anxiety and improve satisfaction after CS. Although it did not improve the postoperative recovery, it was still significant for anesthesia.

[Comparison of multi-mode and single-mode intraoperative neurophysiological monitoring in the treatment of severe ossification of the cervical posterior longitudinal ligament with anterior cervical corpectomy with fusion].

OBJECTIVE: To compare the application of multi-mode and single-mode intraoperative neurophysiological monitoring in the treatment of severe ossification of posterior longitudinal ligament of cervical spine with anterior cervical corpectomy with fusion. METHODS: From April 2015 to June 2018, 32 patients with severe ossification of the posterior longitudinal ligament were treated in the Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. There were 21 males and 11 females, aged 45 to 73 years old, with a mean age of 59 years old. The duration of the disease ranged from 6 to 72 months, with a mean of 39 months. The main manifestations were numbness, numbness and weakness of limbs, cotton feeling of foot stepping on lower limbs, instability of standing and walking. With the gradual aggravation of symptoms, quadriplegia, dysfunction of urine and defecation may occur. Patients with ossification of posterior longitudinal ligament of cervical spine were monitored by somatosensory evoked potentials, motor evoked potentials and electromyogram patterns. RESULTS: During the operation, 8 patients had abnormal amplitude of somatosensory evoked potential(SEP); 5 of them had bleeding during anterior cervical decompression procedure and were placed with too much hemostatic cotton, which caused compression of spinal cord and resulted in abnormal SEP waveform. After removal of the hemostatic cotton, SEP waveform returned ot normal; 3 patients had abnormal SEP waveform due to decreased systolic pressure, which was corrected by increased systolic pressure. Twelve patients had abnormal amplitude of motor evoked potential during monitoring, 9 of which were caused by intraoperative mis-contact with nerve root, and turned to normal after timely adjustment of position, 3 of which were caused by intraoperative inhalation of muscle relaxant during surgery. Among 11 patients with abnormal EMG waveform, 9 patients recovered to normal waveform after adjusting operation, 2 patients recovered to normal waveform after short observation, and all patients recovered to normal waveform of motor evoked potential after operation(P<0.05). There were 2 cases of cerebrospinal fluid leakage after operation, which healed spontaneously 7 days after operation, and no complications of spinal cord and nerve occurred in all patients after operation. CONCLUSIONS: In anterior cervical corpectomy with fusion operation for the treatment of severe cervical ossification of posterior longitudinal ligament, various modes of intraoperative neurophysiological monitoring can real-time understand spinal cord and nerve function status, significantly reduce the incidence of spinal cord and nerve injury during operation, and effectively improve the safety of operation.

The chromogranin A-derived antifungal peptide CGA-N9 induces apoptosis in Candida tropicalis.

CGA-N9, a peptide derived from human chromogranin A (CGA), was found to have antimicrobial activity in our previous investigation, but its mechanism of action remains unclear. Herein, the mechanism of action of CGA-N9 was investigated. We found that CGA-N9 induced the depolarization of the cell membrane and uptake of calcium ions into the cytosol and mitochondria. With the disruption of the mitochondrial membrane potential, the generation of intracellular reactive oxygen species (ROS) increased. Accordingly, we assessed apoptotic processes in Candida tropicalis cells post-treatment with CGA-N9 and found cytochrome c leakage, chromatin condensation and DNA degradation. The interaction of CGA-N9 with DNA in vitro showed that CGA-N9 did not degrade DNA but bound to DNA via an electrostatic interaction. In conclusion, CGA-N9 exhibits antifungal activity by inducing apoptosis in C. tropicalis.

Finite element analysis of the effect of sagittal angle on ankle joint stability in posterior malleolus fracture: A cohort study.

OBJECTIVE: Aim of this study was to establish three-dimensional finite element model of the posterolateral-oblique type of posterior malleolus fracture with different sagittal angle and to explore the effect of sagittal angle on ankle joint stability. METHODS: CT data of ankle were collected from a normal male volunteer.Established finite element model of the normal ankle and verified its reliability. Five posterior malleolus fracture models with different sagittal angles were established. Finite element analysis(FEA)was carried out to simulate the conditions of vertical loading in neutral position with a total weight of 600 N.Recorded the data and did statistical analyses. RESULTS: (1) The contact area was 483.55 mm2 and the maximum contact stress was 3.793 MPa in the model of the normal ankle joint. (2) There was a positive correlation between the sagittal angle(SA)and the contact area(CA)(r = 0.925,P < 0.05). Regression equation was CA = 316.755 + 1.749* SA. The correlation between the sagittal angle and the maximum contact stress(MCS)was negative (r = -0.988,P < 0.01). Regression equation was MCS = 5.214-0.018*SA. There was a negative correlation between the sagittal angle of fracture and relative displacement(RD)(r = -0.950,P < 0.05). Regression equation was RD = 1.388-0.009*SA. CONCLUSION: The greater the sagittal angle of fracture was, The more stable the ankle joint was. The sagittal angle of fracture could be used as a relative index to reflect ankle stability for posterior malleolus fracture.

Effects on longevity extension and mechanism of action of carnosic acid in Caenorhabditis elegans.

The beneficial effects of carnosic acid (CA) on health in terms of antioxidative, anti-inflammatory, antibacterial, anti-cancer and neuroprotective properties have long been recognized. However, the role of CA in aging remains unknown. In the present study, we examined the effects on longevity extension, as well as the mechanism of action, of CA in Caenorhabditis elegans (C. elegans). The results suggest that CA increased the lifespan of C. elegans. Meanwhile, CA was absorbed by the worms and promoted the healthspan of C. elegans by improving the mobility, reducing the accumulation of age pigment, delaying Aß-induced and polyQ-dependent paralysis and increasing the resistance to heat and oxidative stress. In terms of the mechanism underlying the longevity extension induced by CA, the beneficial effects were associated with the increased expression of SOD-3 but not with ROS scavenging activity. The CA-mediated longevity extension involved the upregulating of the expression of the skn-1, sek-1, sod-5, hsf-1, hsp-16.1 and hsp-16.2 genes but acted independently of the insulin/insulin-like growth factor signaling (IIS) pathway. Furthermore, CA treatment had no impact on the lifespan of skn-1 and hsf-1 mutants, confirming that mitogen-activated protein kinase (MAPK) and heat-shock transcription factor-1 (HSF-1) pathways were associated with the longevity mechanism of CA. These findings contribute to our knowledge of the lifespan extension and underlying mechanism of action of CA in C. elegans.

Downregulation of miRNA-15a and miRNA-16 promote tumor proliferation in multiple myeloma by increasing CABIN1 expression.

Multiple myeloma (MM) is a malignant disorder characterized by the neoplastic growth of plasma cells in the bone marrow. MicroRNAs (miRNAs/miRs) modulate key regulatory cell pathways via their influence on target genes, and may serve a crucial function in tumorigenesis. Previous studies have indicated that the downregulation of miR-15a and miR-16 contributes to MM pathogenesis. However, the functional mechanisms of miR-15a and miR-16 in MM remain unclear. In the present study, potential target sites for miR-15a and miR-16 were identified on the calcineurin-binding protein 1 (CABIN1) mRNA sequence from analyses of previously published crosslinking, ligation and sequencing of hybrids data. Again-of-function study was also performed, which determined that miR-15a/16 directly targeted CABIN1 mRNA and negatively regulated the expression of CABIN1 at the mRNA and protein level in MM cells. A cell proliferation assay demonstrated that the upregulation of miR-15a and miR-16 inhibited the proliferation of MM cells via targeting CABIN1. miR-15a and miR-16 were significantly decreased in MM specimens, compared with in normal specimens, whereas CABIN1 mRNA levels were significantly higher in MM samples compared with in normal samples. CABIN1 mRNA levels were negatively correlated with miR-15a and miR-16 expression levels in MM tissues, as determined using Pearson's correlation coefficient analysis. The results of the present study indicate that the downregulation of miR-15a and miR-16 promotes tumor proliferation in MM by increasing CABIN1 expression. The present study may aid elucidation of the functions of miR-15a and miR-16 and their function in MM carcinogenesis.