Naringenin protects against septic cardiomyopathy in mice by targeting HIF-1α.

Myocardial dysfunction is a prevalent complication of sepsis (septic cardiomyopathy) with a high mortality rate and limited therapeutic options. Naringenin, a natural flavonoid compound with anti-inflammatory and antioxidant properties, holds promise as a potential treatment for sepsis-induced myocardial dysfunction. This study investigated the pharmacological effects of naringenin on septic cardiomyopathy. In vivo and in vitro experiments demonstrated that naringenin improved cardiomyocyte damage. Network pharmacology and database analysis revealed that HIF-1α is a key target protein of naringenin. Elevated expression of HIF-1α was observed in damaged cardiomyocytes, and the HIF-1α inhibitor effectively protected against LPS-induced cardiomyocyte damage. Molecular docking studies confirmed the direct binding between naringenin and HIF-1α protein. Importantly, our findings demonstrated that naringenin did not provide additional attenuation of cardiomyocyte injury on the biases of HIF-1α inhibitor treatment. In conclusion, this study proves that naringenin protects against septic cardiomyopathy through HIF-1α signaling. Naringenin is a promising therapeutic candidate for treating septic cardiomyopathy.

The accelerometer-based navigation system demonstrated superior radiological outcomes in restoring mechanical alignment and component sagittal positioning in total knee arthroplasty.

BACKGROUND: This study aimed to determine whether the accelerometer-based navigation (ABN) could improve the accuracy of restoring mechanical axis (MA), component positioning, and clinical outcomes compared to conventional (CON) total knee arthroplasty (TKA). METHODS: A total of 301 consecutive patients (ABN: 27, CON: 274) were included. A 1:4 propensity score matching (PSM) was performed between the two groups according to preoperative demographic and clinical parameters. The postoperative MA, femoral coronal angle (FCA), femoral sagittal angle (FSA), tibial coronal angle (TCA) and tibial sagittal angle (TSA) were compared. Absolute deviations of aforementioned angles were calculated as the absolute value of difference between the exact and ideal value and defined as norms if within 3°, otherwise regarded as outliers. Additional clinical parameters, including the Knee Society knee and function scores (KSKS and KSFS) and range of motion (ROM), were assessed at final follow-up (FU) (mean FU was 21.88 and 21.56 months respectively for ABN and CON group). A secondary subgroup analysis and comparison on clinical outcomes were conducted between norms and outliers in different radiological parameters. RESULTS: A total of 98 patients/102 knees were analyzed after the PSM (ABN: 21 patients/24 knees, CON: 77 patients/78 knees). In the ABN group, the mean MA, FCA and TSA were significantly improved (p = 0.019, 0.006, < 0.001, respectively). Proportions of TKAs within a ± 3°deviation were significantly improved in all the postoperative radiological variables except for TCA (p = 0.003, 0.021, 0.042, 0.013, respectively for MA, FCA, FSA, and TSA). The absolute deviations of FSA and TSA were also significantly lower in the ABN group (p = 0.020, 0.048, respectively). No significant differences were found in either mean value, absolute deviation or outlier ratio of TCA between two groups. On clinical outcomes, there were no significant differences between two groups, although KSKS, KSFS and ROM (p < 0.01, respectively) dramatically improved compared to baseline. The subgroup analysis also demonstrated no statistical difference on clinical outcomes between the outliers and norms in varied radiological parameters. CONCLUSIONS: The ABN could improve the accuracy and precision of mechanical alignment and component positioning without significant improvement of clinical outcomes. Further high quality studies with long term FU are warranted to comprehensively evaluate the value of the ABN.

The prevalence and economic burden of pain on middle-aged and elderly Chinese people: results from the China health and retirement longitudinal study.

BACKGROUND: To estimate the prevalence of pain among people aged 45 years and older in China, to analyze the effect factors of pain and pain related economic burden. METHODS: Nationally representative sample was derived from China Health and Retirement Longitudinal Study (CHARLS). Pain data, medical cost data were obtained, as well as information of demographic characteristics, social structure, social-economic status, other health needs and health behaviors. The prevalence of pain in 2011, 2013, and 2015 was calculated. Univariate analysis and multivariate analysis were used to find the effect factors of pain. An optimization two-part model was used to calculate the range of the direct medical costs caused by pain. RESULTS: The prevalence of pain among people 45 years or older in China was 31.73% in 2011, 37.27% in 2013 and 28.62% in 2015. When evaluating factors lead a higher prevalence of pain, the results of the multi-variable after one-way analysis were older age, female, lower education, rural residents, without insurance status, abstained from alcohol and lower body mass index (BMI). Through the optimization of two-part model, the direct medical costs caused by pain was 898.9-1563.0 yuan in 2011, 2035.8-2568.7 yuan in 2013 and 2628.8-3945.7 yuan in 2015 (129.9US$ - 225.9US$ in 2011, 294.2 US$ - 371.2US$ in 2013 and 379.9US$ - 570.2US$ in 2015, converted to 2010 RMB). CONCLUSION: The prevalence of pain among middle-aged and elderly Chinese is high. Residents with older age, female, lower education, rural residents, without insurance status, abstained from alcohol and lower BMI seem to have a higher pain prevalence. Pain can cause extra direct medical costs and will cause more economic loss with the progress of time. Future research should pay more attention to effective treatment, management and prevention of pain to decrease its burden.

O-Linked ß-N-Acetylglucosamine Modification of A20 Enhances the Inhibition of NF-κB (Nuclear Factor-κB) Activation and Elicits Vascular Protection After Acute Endoluminal Arterial Injury.

OBJECTIVE: Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked ß-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling. However, the specific molecular target for O-GlcNAcylation that is responsible for glucosamine-induced vascular protection remains unclear. In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection. APPROACH AND RESULTS: In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation. Thiamet G treatment did not increase A20 protein expression but did significantly enhance binding to TAX1BP1 (Tax1-binding protein 1), a key regulatory protein for A20 activity. Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity. A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects. In balloon-injured rat carotid arteries, glucosamine treatment markedly inhibited neointimal formation and p65 activation compared with vehicle treatment. Adenoviral delivery of A20 shRNA to the injured arteries dramatically reduced balloon injury-induced A20 expression and inflammatory response compared with scramble shRNA and completely abolished the vascular protection of glucosamine. CONCLUSIONS: These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.

Severe Wear and multiple Pseudotumor formation due to revision for ceramic head breakage after ceramic-on-ceramic Total hip arthroplasty: a case report.

BACKGROUND: Head breakage is a serious complication following total hip arthroplasty when using Ceramic on Ceramic bearings surfaces. There is still in controversy about the selection of bearing surfaces when conducting revision surgery. CASE PRESENTATION: We describe the case of a fifty-year-old man who had undergone right total hip arthroplasty (THA) with ceramic-on-ceramic prostheses in 2011. After a fall 6 years after the primary procedures, radiographs suggested a ceramic head breakage for revision THA with exchange of metal-on-polyethylene bearing. However, 8 months later, severe metallosis and multiple pseudotumor was confirmed in pelvis and surrounding hip after re-revision THA with ceramic-on-polyethylene prostheses. Analysis of the serum metal ion indicated massive wear of the metal head and erosion of the stem neck and taper. CONCLUSIONS: This case vividly demonstrates metal bearings should be avoided and revision with complete synovectomy and thorough debridement should be performed whenever possible for a fractured ceramic bearing.

Triptolide attenuates pressure overload-induced myocardial remodeling in mice via the inhibition of NLRP3 inflammasome expression.

Triptolide is the predominant active component of the Chinese herb Tripterygium wilfordii Hook F (TwHF) that has been widely used to treat several chronic inflammatory diseases due to its immunosuppressive, anti-inflammatory, and anti-proliferative properties. In the present study, we elucidated the cardioprotective effects of triptolide against cardiac dysfunction and myocardial remodeling in chronic pressure-overloaded hearts. Furthermore, the potential mechanisms of triptolide were investigated. For this purpose, C57/BL6 mice were anesthetized and subjected to transverse aortic constriction (TAC) or sham operation. Six weeks after the operation, all mice were randomly divided into 4 groups: sham-operated with vehicle group, TAC with vehicle group, and TAC with triptolide (20 or 100 µg/kg/day intraperitoneal injection) groups. Our data showed that the levels of NLRP3 inflammasome were significantly increased in the TAC group and were associated with increased inflammatory mediators and profibrotic factor production, resulting in myocardial fibrosis, cardiomyocyte hypertrophy, and impaired cardiac function. Triptolide treatment attenuated TAC-induced myocardial remodeling, improved cardiac diastolic and systolic function, inhibited the NLRP3 inflammasome and downstream inflammatory mediators (IL-1ß, IL-18, MCP-1, VCAM-1), activated the profibrotic TGF-ß1 pathway, and suppressed macrophage infiltration in a dose-dependent manner. Our study demonstrated that the protective effect of triptolide against pressure overload in the heart may act by inhibiting the NLRP3 inflammasome-induced inflammatory response and activating the profibrotic pathway.

The effects of tourniquet use in total knee arthroplasty: a randomized, controlled trial.

PURPOSE: Tourniquets are still widely used in total knee arthroplasty (TKA), although they may be associated with several adverse effects. An observer-blinded, randomized, controlled trial was performed to evaluate the effects of tourniquet use in TKA. METHODS: Fifty participants who underwent staged bilateral TKA were recruited for this study. The first-side TKA was randomly allocated to either long-duration tourniquet use or short-duration tourniquet use followed by a 3-month washout period and crossover to the other tourniquet strategy for the opposite-side TKA. Blood loss was monitored perioperatively. The operating time, allogeneic blood transfusion rate, thigh pain, knee pain, limb swelling, clinical outcome as measured by the Likert-type Western Ontario and McMaster University (WOMAC) score, straight leg raising and knee active range of motion (ROM) were also recorded. RESULTS: The long-duration tourniquet group exhibited reduced total blood loss [-99.1 ml, 95 % confidence interval (CI) -168.1 to -30.1, P = 0.0411] and intraoperative blood loss (-225.2 ml, 95 % CI -369.5 to -80.9, P = 0.0071) compared with the short-duration tourniquet group. However, there were greater postoperative blood loss (69.6 ml, 95 % CI 21.1 to 118.2, P = 0.0282) and hidden blood loss (52.8 ml, 95 % CI 10.5 to 95.1, P = 0.0332) in the long-duration tourniquet group. The short-duration tourniquet group showed better outcomes for thigh and knee pain, limb swelling, WOMAC score at 6-week follow-up, straight leg raising and knee ROM. Similar allogeneic blood transfusion rates were observed for both groups. CONCLUSION: Total and intraoperative blood losses were reduced with the long-duration tourniquet use, whereas the short-duration tourniquet use would reduce postoperative and hidden blood losses without increasing the allogeneic blood transfusion rate. In addition, short-duration tourniquet use would result in faster recovery and less pain during the early rehabilitation period following TKA. LEVEL OF EVIDENCE: I.

Smad3-mSin3A-HDAC1 Complex is Required for TGF-ß1-Induced Transcriptional Inhibition of PPARγ in Mouse Cardiac Fibroblasts.

BACKGROUND: We have recently demonstrated that activated transforming growth factor-ß (TGF-ß) signaling suppresses myocardial peroxisome proliferator-activated receptor γ (PPARγ) expression in the pressure overloaded heart. In this study, we aim to further define the molecular mechanisms that underlie TGF-ß-induced PPARγ transcriptional inhibition. METHODS: Adult mouse cardiac fibroblasts were isolated and cultured. PPARγ promoter activity was measured by the dual-Luciferase reporter assay. Interactions between transcription factors and the target gene were identified. RESULTS: In cultured cardiac fibroblasts transfected with a plasmid containing a human PPARγ promoter, co-transfection of Smad3 and Smad4, but not Smad2, plasmids significantly enhanced TGF-ß1-induced inhibition of PPARγ promoter activity. Promoter deletion analysis and site-directed mutagenesis assays defined two Smad binding elements on the promoter of the PPARγ gene. Utilizing chromatin immunoprecipitation analysis and DNA-affinity precipitation methods, we demonstrated that the transcriptional regulatory complex consisting of Smad3, mSin3A and HDAC1 bound to the promoter of the PPARγ gene in cardiac fibroblasts in response to TGF-ß1 stimulation. Either silencing endogenous mSin3A expression by Lentivirus-mediated transduction of mSin3A shRNA or pretreatment with the specific HDAC1 inhibitor MS-275 effectively attenuated TGF-ß-induced transcriptional suppression of PPARγ. CONCLUSION: These results suggest that TGF-ß1-induced inhibition of PPARγ transcription depends on formation of a functional transcriptional regulatory complex that includes Smad3, mSin3A and HDAC1 at the PPARγ promoter.

Quercetin blocks t-AUCB-induced autophagy by Hsp27 and Atg7 inhibition in glioblastoma cells in vitro.

We previously demonstrated that the acquired resistance because of Hsp27 activation weakens the cytotoxic effect of t-AUCB on glioblastoma cells. Since autophagy is regarded as a survival mechanism for cells exposed to cytotoxic agents, the aim of this study is to investigate whether t-AUCB induces autophagy and whether Hsp27 and autophagy are interacted with each other. Our data demonstrated that t-AUCB induces autophagy in glioblastoma cells and regulates multiple autophagy related-gene expression. t-AUCB induces overexpression of Atg7, which is downstream of Hsp27 and participates in the resistance of glioblastoma cells to t-AUCB treatment. Hsp27 inhibitor quercetin suppresses Atg7 expression and strengthens t-AUCB-induced cell death by autophagy blockage. We concluded that combination of quercetin and t-AUCB might be a potential strategy for glioblastoma treatment.

[Comparison and estimation of different diagnostic methods in detecting the presence of periprosthetic joint infection].

OBJECTIVE: To compare and estimate the diagnostic value and characteristic of different diagnostic methods (blood laboratory test, histological analysis, synovial fluid cytological test and microbiological examination) in detecting the presence of periprosthetic joint infection. METHODS: Data of 52 patients underwent hip or knee joint revision in Peking University People's Hospital Arthritis Clinic and Research Center between July 2013 and March 2015 were analyzed retrospectively. For each patient, results of blood laboratory tests(peripheral-blood white blood cell, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (Hs-CRP)), histological analysis, synovial fluid white cell count (SWCC), microbiological examinations (synovial fluid, tissue and prosthetic joint sonication fluid) were collected. Data were analyzed by t-test, independent sample median test or χ(2) test, respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy for each method were calculated and compared by receiver operating characteristic curve. RESULTS: There were 30 female and 22 male patients. Twenty-one patients (40.4%) were diagnosed as PJI. The levels of CRP, ESR, IL-6 and Hs-CRP in patients with PJI were higher than that in aseptic failure patients (Z=23.084, 13.499, 5.796, 17.045, all P<0.05). The sensitivities of CRP, ESR, IL-6 and Hs-CRP were 90.5%, 81.0%, 95.0% and 90.0%. The sensitivities of histological analysis and SWCC were 55.0% and 70.6%, while they had high specificity as 89.7% and 85.7%. The sensitivity of sonication fluid culture was 90.0%, which was higher than that of tissue culture (71.4%) and synovial fluid culture (65.0%) (χ(2) = 5.333, 6.400, all P<0.05). CONCLUSIONS: The tests of CRP, ESR, IL-6 and Hs-CRP have good value in detecting PJI preoperatively. Histological analysis and SWCC have high specificity, which could help to exclude PJI. Sonication fluid culture has a higher sensitivity than tissue culture and synovial fluid culture.

Phosphorylation of AKT induced by phosphorylated Hsp27 confers the apoptosis-resistance in t-AUCB-treated glioblastoma cells in vitro.

The aim of this study is to determine whether phosphorylation of AKT could be effected by t-AUCB-induced p-Hsp27 and whether p-AKT inhibition sensitizes glioblastoma cells to t-AUCB, and to evaluate the effects of simultaneous inhibition of p-Hsp27 and p-AKT on t-AUCB treated glioblastoma cells. Cell growth was detected using CCK-8 assay; Caspase-3 activity assay kits and flow cytometry were used in apoptosis analysis; Western blot analysis was used to detect p-Hsp27 and p-AKT levels; RNA interference using the siRNA oligos of Hsp27 was performed to knockdown gene expression of Hsp27. All data were analyzed by the Student-Newman-Keul's test. We demonstrated that t-AUCB treatment induces AKT phosphorylation by activating Hsp27 in U251 and LN443 cell lines. Inhibition of AKT phosphorylation by AKT inhibitor IV sensitizes glioblastoma cells to t-AUCB, strengthens t-AUCB suppressing cell growth and inducing cell apoptosis. We also found inhibiting both p-Hsp27 and p-AKT synergistically strengthen t-AUCB suppressing cell growth. Thus, p-AKT induced by p-Hsp27 confers the apoptosis-resistance in t-AUCB-treated glioblastoma cells. Targeting p-Hsp27 and/or p-AKT may be a potential effective strategy for the treatment of glioblastoma.

Reverse apolipoprotein A-I mimetic peptide R-D4F inhibits neointimal formation following carotid artery ligation in mice.

The ApoA-I mimetic peptide D-4F has demonstrated potent atheroprotective actions in vivo and in vitro. We investigated the effect of R-D4F (ie, the D-4F peptide with reverse order of amino acids) on intimal hyperplasia after vascular injury in a mouse model of carotid artery ligation. Adult male C57BL/6J mice were pretreated intraperitoneally with vehicle, D-4F (1 mg/kg), or R-D4F (1 mg/kg or 5 mg/kg) daily for 3 days; the mice were then subjected to left carotid artery ligation. All treatments were continued for 28 days after surgery. Neither D-4F nor R-D4F treatment affected serum lipid levels. Morphometric analysis showed that the occluded vessels had significant neointimal formation, compared with the uninjured arteries in vehicle-treated mice. Like the D-4F treatment, R-D4F treatment significantly (P < 0.05) inhibited intimal hyperplasia (-42%), local neutrophil and macrophage infiltration, and mRNA expression of the proinflammatory mediator monocyte chemotactic protein 1 (-55%) and vascular cell adhesion protein 1 (-53%), compared with vehicle. Furthermore, the vasoprotective effect of high-dose R-D4F was significantly enhanced, compared with the low dose. In cultured mouse RAW 264.7 macrophages, pretreatment with R-D4F also effectively inhibited lipopolysaccharide-induced leukocyte integrin CD11b expression, a key molecule for leukocyte infiltration. Taken together, these results suggest that R-D4F has significant anti-inflammatory features and facilitates prevention of neointimal formation after vascular injury in mice.

The temozolomide derivative 2T-P400 inhibits glioma growth via administration route of intravenous injection.

The aim of this study is to investigate the inhibitory effects of 2T-P400, a derivative of temozolomide (TMZ), on glioma growth. SHG-44 and U373 human glioblastoma cell lines and SHG-44 cell subcutaneous and intracranial xenograft mouse models were used as the model system for these studies. Cell growth was analyzed using MTT assay. For intracranial glioma xenograft model, mouse brains were obtained and made as paraffin section for immunohistochemical staining. Tumor volume was calculated with this formula: tumor volume = length × width2/ 2. The results showed that 2T-P400 or TMZ significantly inhibits cell growth in a concentration dependent manner with the IC50 values of 12.90 ± 1.05 or 9.73 ± 2.12 µg/ml on SHG-44 cell line and 13.12 ± 0.86 or 10.13 ± 1.02 µg/ml on U373 cell line respectively. In SHG-44 cell subcutaneous xenograft model, the tumor volume of 2T-P400 or TMZ treated group was 1,062.12 ± 204.76 or 803.59 ± 110.32 mm3 respectively, which was significantly smaller than that in physiological saline (with volume of 1,968.85 ± 348.37 mm3) treated group. In intracranial xenograft model, the tumor volume of 2T-P400 or TMZ group was 6.12 ± 1.69 or 5.58 ± 1.45 mm3 respectively, significantly smaller than that in physiological saline group of 33.08 ± 6.88 mm3. Moreover, polyethylene glycol 400 (PEG400) exhibited no significant tumor growth inhibition. Our results indicated that 2T-P400 posses the same growth inhibitory effect as TMZ on glioblastoma cell lines and the subcutaneously and intracranially transplanted gliomas in xenograft mouse models. It may be a suitable alternate of TMZ for the treatment of glioma via intravenous administration route.

Quercetin sensitizes human glioblastoma cells to temozolomide in vitro via inhibition of Hsp27.

AIM: Quercetin is an effective Hsp27 inhibitor and has been reported to facilitate tumor cell apoptosis. The aim of this study was to investigate whether quercetin could sensitize human glioblastoma cells to temozolomide (TMZ) in vitro. METHODS: Both U251 and U87 human glioblastoma cells were treated with quercetin and/or TMZ for 48 h. Cell viability was detected using the MTT assay. Cell apoptosis was analyzed with caspase-3 activity kits and flow cytometry. Hsp27 expression and phosphorylation were examined using Western blot analysis. RNA interference using Hsp27 siRNA oligos was performed to knock down the gene expression of Hsp27. RESULTS: TMZ (200 or 400 µmol/L) alone effectively inhibited the viability of U251 and U87 cells. When combined with quercetin (30 µmol/L), TMZ (100 µmol/L) significantly inhibited the cell viability, and the inhibition of TMZ (200 and 400 µmol/L) was enhanced. TMZ or quercetin anole did not affect caspase-3 activity and cell apoptosis, while TMZ combined with quercetin significantly increased caspase-3 activity and induced cell apoptosis. TMZ anole significantly increased Hsp27 phosphorylation in U251 and U87 cells, while quercetin or Hsp27 siRNA oligos combined with TMZ attenuated TMZ-induced Hsp27 phosphorylation and significantly inhibited Hsp27 expression. CONCLUSION: Combined treatment with TMZ and quercetin efficiently suppressed human glioblastoma cell survival in vitro.

γ-secretase inhibitor DAPT sensitizes t-AUCB-induced apoptosis of human glioblastoma cells in vitro via blocking the p38 MAPK/MAPKAPK2/Hsp27 pathway.

AIM: Trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB) is a soluble epoxide hydrolase inhibitor that suppresses glioblastoma cell growth in vitro. The aim of this study was to examine whether the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) could sensitize glioma cells to t-AUCB-induced apoptosis. METHODS: Both U251 and U87 human glioblastoma cell lines were tested. Cell growth was assessed using the cell counting kit-8. Cell apoptosis was detected with caspase-3 activity assay kits and flow cytometry. The protein levels in the p38 MAPK/MAPKAPK2/Hsp27 pathway in the cells were analyzed using Western blots. RESULTS: Pretreatment with DAPT (2 µmol/L) substantially potentiated the growth inhibition caused by t-AUCB (200 µmol/L) in U251 and U87 cells. Furthermore, pretreatment with DAPT markedly increased t-AUCB-induced apoptosis of U251 and U87 cells. T-AUCB alone did not significant affect caspase-3 activity in the cells, but t-AUCB plus DAPT pretreatment caused significant increase of caspase-3 activity. Furthermore, pretreatment with DAPT completely blocked t-AUCB-induced phosphorylation of p38 MAPK, MAPKAPK2 and Hsp27 in the cells. CONCLUSION: The γ-secretase inhibitor DAPT sensitizes t-AUCB-induced apoptosis of human glioblastoma cells in vitro via blocking the p38 MAPK/MAPKAPK2/Hsp27 pathway, suggesting that the combination of t-AUCB and DAPT may be a potentially effective strategy for the treatment of glioblastoma.

A Nomogram for Predicting Overall Survival of Patients With Primary Spinal Cord Glioblastoma.

OBJECTIVE: Primary spinal cord glioblastoma (PSCGBM) is a rare malignancy with a poor prognosis. To date, no prognostic nomogram for this rare disease was established. Hence, we aimed to develop a nomogram to predict overall survival (OS) of PSCGBM. METHODS: Clinical data of patients with PSCGBM was retrospectively collected from the neurosurgery department of Soochow University Affiliated Second Hospital and the Surveillance Epidemiology and End Results database. Information including age, sex, race, tumor extension, extent of resection, adjuvant treatment, marital status, income, year of diagnosis and months from diagnosis to treatment were recorded. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors for PSCGBM. A nomogram was constructed to predict 1-year, 1.5-year, and 2-year OS of PSCGBM. RESULTS: A total of 132 patients were included. The 1-year, 1.5-year, and 2-year OS were 45.5%, 29.5%, and 18.9%, respectively. Four variables: age groups, tumor extension, extent of resection, and adjuvant therapy, were identified as independent prognostic factors. The nomogram showed robust discrimination with a C-index value for the prediction of 1-year OS, 1.5-year OS, and 2-year of 0.71 (95% confidence interval [CI], 0.61-0.70), 0.72 (95% CI, 0.62-0.70), and 0.70 (95% CI, 0.61-0.70), respectively. The calibration curves exhibited high consistencies between the predicted and observed survival probability in this cohort. CONCLUSION: We have developed and internally validated a nomogram for predicting the survival outcome of PSCGBM for the first time. The nomogram has the potential to assist clinicians in making individualized predictions of survival outcome of PSCGBM.

Droplet-based mechanical transducers modulated by the symmetry of wettability patterns.

Asymmetric mechanical transducers have important applications in energy harvesting, signal transmission, and micro-mechanics. To achieve asymmetric transformation of mechanical motion or energy, active robotic metamaterials, as well as materials with asymmetric microstructures or internal orientation, are usually employed. However, these strategies usually require continuous energy supplement and laborious fabrication, and limited transformation modes are achieved. Herein, utilizing wettability patterned surfaces for precise control of the droplet contact line and inner flow, we demonstrate a droplet-based mechanical transducer system, and achieve multimodal responses to specific vibrations. By virtue of the synergistic effect of surface tension and solid-liquid adhesion on the liquid dynamics, the droplet on the patterned substrate can exhibit symmetric/asymmetric vibration transformation when the substrate vibrates horizontally. Based on this, we construct arrayed patterns with distinct arrangements on the substrate, and employ the swarm effect of the arrayed droplets to achieve three-dimensional and multimodal actuation of the target plate under a fixed input vibration. Further, we demonstrate the utilization of the mechanical transducers for vibration management, object transport, and laser modulation. These findings provide a simple yet efficient strategy to realize a multimodal mechanical transducer, which shows significant potential for aseismic design, optical molding, as well as micro-electromechanical systems (MEMS).

Selenium and Zinc Intakes of Staple Grains and Their Correlation with Urine Selenium and Zinc in the Tibetan Rural Residents along the Yarlung Zangbo River.

Grains account for a large proportion of the diet of rural residents in Tibet. The lack of selenium (Se) and zinc (Zn) threatens the population's nutrition and health. However, the intakes of selenium and zinc in grains remains unclear. To clarify the nutritional status of selenium and zinc consumed from staple grains of residents along the Yarlung Zangbo River in Tibet, 341 grain samples and 242 urine samples were collected, and 244 food frequency questionnaires were completed along the Yarlung Zangbo River in 2020-2021. The results showed that the selenium concentrations of 88.5% of self-produced tsampa and 80.8% of self-produced flour were lower than the grain selenium threshold (<25 µg·kg-1). The intake of selenium and zinc from staple grains (tsampa, flour, and rice) contributed 15.0% and 43.5% to the recommended nutrient intake (RNI) on average, respectively. A geographical detector model analyzed factors affecting urinary selenium and zinc levels. Selenium and zinc intakes in rice and flour, and dietary diversity score (DDS) were the main factors affecting urinary selenium and zinc (p < 0.01). Their interaction effects on urinary selenium and zinc were greater than those of a single factor. The staple grains of rural residents along the Yarlung Zangbo River were in a state of selenium deficiency. The zinc content of the staple grain purchased was lower than that of the main grain produced by rural residents. Changing the grain consumption pattern and adjusting the proportion of exogenous grains can improve selenium and zinc nutrition in residents.

Establish a new parameter "horizontal view-axial angle" and explore its role in the treatment of atlantoaxial instability diseases.

Objective: The objective of the study is to establish a new parameter that can be clearly measured on x-ray images to complement the description of the sagittal alignment of the craniocervical junction. The authors anticipate that this new parameter will enhance surgeons' understanding of the sagittal alignment of the craniocervical junction and play a positive role in the guidance of intraoperative reduction and in the evaluation of postoperative outcomes of patients with atlantoaxial instability. Methods: From November 2018 to June 2020, a total of 159 asymptomatic subjects who underwent frontal and lateral cervical x-ray examination in the Second Affiliated Hospital of Soochow University were included in the study. Age, gender, previous spinal trauma, and disease history of each subject were recorded. After screening, 127 effective samples were finally obtained. When taking lateral cervical radiographs, all subjects placed their neck in a neutral position and looked straight ahead with both eyes. On the obtained lateral x-ray images, a straight line was drawn from the radix to the anterior clinoid process; another line was made along the posterior edge of the C2 vertebral body; and the angle between the two lines was measured, which was defined as the "horizontal view-axial angle." The angle formed by the tangent of the posterior edge of the C2 vertebra and C7 vertebral body is the "C2-C7 angle," which was used to describe the curvature of the lower cervical vertebra. The normal range of horizontal view-axial angle and its relationship with C2-7 angle were evaluated. Results: The average C2-C7 angle of male subjects was (14.0° ± 7.4°), while that of female subjects was (11.09° ± 7.36°). The average horizontal view-axial angle of male subjects was (92.79° ± 4.52°), and that of female subjects was (94.29° ± 4.50°). Pearson correlation test showed that there was a significant negative correlation between horizontal view-axis angle and C2-C7 angle. Conclusions: For patients with atlantoaxial instability diseases, the horizontal view-axis angle is expected to be a sagittal parameter to guide the intraoperative reduction and evaluate postoperative outcomes.

Catastrophic Periprosthetic Osteolysis in Total Hip Arthroplasty at 20 Years: A Case Report and Literature Review.

BACKGROUND: Periprosthetic osteolysis is a serious complication following total hip arthroplasty (THA). However, most orthopedic surgeons only focus on bone loss and hip reconstruction. Thus, it was required to understand the treatment algorithm for periprosthetic osteolysis integrally. CASE PRESENTATION: A 52-year-old Asian male presented with chronic hip pain. A mass appeared on the medial side of the proximal left thigh at more than 20 years after bilateral THA. Radiographs revealed catastrophic periprosthetic osteolysis, especially on the acetabular side. Large amounts of necrotic tissue and bloody fluids were thoroughly debrided during revision THA. A modular hemipelvic prosthesis was used for revision of the left hip. Four years later, the patient presented with right hip pain, where a mass appeared on the medial side of the proximal right thigh. A primary acetabular implant with augment was used for revision of the right hip. Laboratory evaluation of bloody fluid retrieved from surgery revealed elevated levels of inflammatory markers. CONCLUSION: Inflammatory responses to polyethylene wear debris can lead to severe bone resorption and aseptic loosening in the long-term following THA. Therefore, in spite of revision THA, interrupting the cascade inflammatory might be the treatment principle for periprosthetic osteolysis.