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The South China Sea (SCS) is the largest semi-enclosed marginal sea in the western Pacific. The alternation of East Asian monsoon causes a significant seasonal pattern of chlorophyll, primary productivity, and export flux of sinking particles. However, the source and sink of dissolved organic carbon (DOC) pools with different bioavailability are less studied. Here we evaluated the seasonal production of DOC in labile, semi-labile and refractory forms using a coupled physical-biogeochemical model. This study aims to understand the dynamics and budgets of organic matters in the SCS. Model results show that the production of labile, semi-labile and refractory DOC is highly correlated with the net primary productivity (NPP) which is higher in winter and lower in summer, reflecting a dependence of DOC on the NPP. The seasonal variation in Pearl River discharge dominates the DOC production in the northern coastal region. In the northeast, the Kuroshio intrusion associated frontal system is attributed to cause high winter production. The DOC production in the southwest is controlled by both winter mixing and summer upwelling. The production of refractory DOC with the least bioavailability favors carbon sequestration. Its annual mean production is 1.8±0.5 mg C m−2 d−1, equivalent to 26% of the export flux of particulate organic carbon at 1000 m.

Understanding the influence of fine atmospheric particles (PM2.5) on cellular biophysical properties is an integral part for comprehending the mechanisms underlying PM2.5-induced diseases because they are closely related to the behaviors and functions of cells. However, hitherto little work has been done in this area. In the present work, we aimed to interrogate the influence of the PM2.5 water-soluble compound (PM2.5-WSC) on the biophysical performance of a human lung carcinoma epithelial cell line (A549) by exploring the cellular morphological and mechanical changes using atomic force microscopy (AFM)-based imaging and nanomechanics. AFM imaging showed that PM2.5-WSC treated cells exhibited evidently reduced lamellipodia and an increased height when compared to the control group. AFM nanomechanical measurements indicated that the treated cells had higher elastic energy and lower adhesion work than the control group. Our western blot assay and transmission electron microscopy (TEM) results revealed that after PM2.5-WSC treatment, the contents of cytoskeletal components (β-actin and β-tubulin) increased, but the abundance of cell surface microvilli decreased. The biophysical changes of PM2.5-WSC-treated cells measured by AFM can be well correlated to the alterations of the cytoskeleton and surface microvilli identified by the western blot assay and TEM imaging. The above findings confirm that the adverse risks of PM2.5 on cells can be reliably assessed biophysically by characterizing the cellular morphology and nanomechanics. The demonstrated technique can be used to diminish the gap of our understanding between PM2.5 and its harmful effects on cellular functions.

Background The purpose of the study was to investigate whether pelvic incidence (PI) will affect the occurrence of PJK in Lenke 5 AIS patients after correction surgery and try to explore a better surgical scheme based on PI. Methods Lenke 5C AIS patients that underwent correction surgery with a minimum of a 2-year follow-up were identified. Demographic and radiographic data were collected preoperatively, postoperatively, and at the final follow-up. The comparison between the PJK and the Non-PJK group was conducted and the subgroup analysis was performed based on the preoperative value of PI to investigate the potential mechanism of PJK. Clinical assessments were performed using the Scoliosis Research Society (SRS)-22 questionnaire. Results The mean preoperative Cobb angle of the TL/L curve was 53.4°±8.6. At the final follow-up, the mean TL/L Cobb angle was drastically decreased to 7.3°±6.8 (P 2 = 0.425, P = 0.514). For low PI patients, there is no significant difference where the UIV is located with regards to the TK apex between the PJK and Non-PJK subgroups (χ2 = 1.103, P = 0.401). For high PI patients, PJK was more likely to occur when UIV was cephalad to than caudal to the TK apex (31.25 % vs. 4.7 %, P = 0.038). There was no significant difference in the selection of LIV between the two groups. Conclusions There is no difference in the incidence of PJK between the Lenke 5 AIS patients with low PI (< 45°) and high PI (≥45°), but the main risk factor of PJK should be different. For patients with low PI, overcorrection of LL should be strictly avoided during surgery. For patients with high PI, the selection of UIV should not be at or cephalad to the apex of thoracic kyphosis to retain more mobile thoracic segments.

BACKGROUND CONTEXT Tranexamic acid (TXA) is widely used in surgery for adolescent idiopathic scoliosis (AIS) and has been proved to be efficacious in reducing intraoperative blood loss (IBL) and the transfusion rate. However, the routine TXA regimen was intraoperative administration alone, in which the concentration of TXA could not cover the whole process of hyperfibrinolysis. And, its ability to control the massive postoperative blood loss (PBL) may be insufficient. Thus, we promoted a multiple-dose regimen of TXA for patients with AIS who underwent surgical correction. PURPOSE The primary aims were (1) to determine whether the multiple-dose regimen of TXA could reduce PBL and the postoperative transfusion rate, and (2) to compare the efficacy of oral administration with intravenous administration. The secondary aims were (3) to evaluate whether this regimen could alleviate inflammatory response, and (4) to assess the occurrence of drug-related side effects. STUDY DESIGN Prospective, double-blinded, randomized controlled trial. PATIENT SAMPLE A total of 108 patients with AIS who underwent posterior scoliosis correction and spinal fusion (PSS) were enrolled in this study. OUTCOME MEASURES The primary parameters were PBL and postoperative transfusion rate. Other parameters such as total blood loss (TBL), maximum hemoglobin (Hb) decrease, volume of drainage, inflammation markers (interleukin-6 [IL-6] and C-reactive protein [CRP]), and occurrence of complications were also collected and compared. Multiple regression analysis was used to examine the variables that affected PBL. METHODS Patients were randomized into three groups. All patients received intravenous TXA 50 mg/kg loading dose and 10 mg/kg/h maintenance dose during surgery. Group A received 1 g oral TXA at 4 hours, 10 hours, and 16 hours postoperatively; group B received 0.5 g intravenous TXA at 6 hours, 12 hours, and 18 hours postoperatively; group C received placebo. RESULTS The mean PBL and postoperative transfusion rate in group A (957.8±378.9 mL, 13.89%) and B (980.3±491.8 mL, 11.11%) were significantly lower than those in group C [1,495.9±449.6 mL, mean differences=538.1 mL, 95% confidence interval (CI), 290.1-786.1 mL, p

T7 peptide is considered as an antiangiogenic polypeptide. The presents study aimed to further detect the antiangiogenic mechanisms of T7 peptide and determine whether combining T7 peptide and meloxicam (COX-2/PGE2 specific inhibitor) could offer a better therapy to combat hepatocellular carcinoma (HCC). T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3β1 and αvβ3 pathways. Cell proliferation, migration, apoptosis, or tube formation ability were detected, and the expression of integrin-associated regulatory proteins was detected. The anti-tumor activity of T7 peptide, meloxicam, and their combination were evaluated in HCC tumor models established in mice. T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3β1 and αvβ3 pathways. Meloxicam enhanced the activity of T7 peptide under hypoxic condition. T7 peptide partly inhibited COX-2 expression via integrin α3β1 not αvβ3-dependent pathways under hypoxic condition. T7 peptide regulated apoptosis associated protein through MAPK-dependent and -independent pathways under hypoxic condition. The MAPK pathway was activated by the COX-2/PGE2 axis under hypoxic condition. The combination of T7 and meloxicam showed a stronger anti-tumor effect against HCC tumors in mice. The data highlight that meloxicam enhanced the antiangiogenic activity of T7 peptide in vitro and in vivo.

Titanium mini-plate has been used in unilateral open-door laminoplasty to maintain the open angle of laminae. Previously, both all-level fixation (C3-C7) and alternative-level (C3, C5, C7) unilateral open-door laminoplasty have been proven to have satisfactory clinical outcomes. However, whether they could achieve similar long-term clinical and radiographic efficacy is still questionable.To compare the long-term clinical and radiological outcomes between alternative-level and all-level fixation unilateral open-door laminoplasty with a mini-plate fixation system.Retrospective comparative study.Ninety-one patients who underwent unilateral open-door laminoplasty.Clinical results including Japanese Orthopedic Association score, Visual Analogue Score, Neck Dysfunction Index score. Radiographic results including cervical curvature index, cervical range of motion, and the spinal canal expansive parameters, including anteroposterior diameter, Pavlov's ratio, and open angle.Between April 2007 and June 2011, 91 patients with minimum 7-year postoperative follow-up were included. Thirty-eight underwent alternative-level fixation (group A) and 53 underwent all-level fixation (group B). Demographic data, including age, gender, operative time, blood loss, and cost, were collected and compared between the two groups. Clinical and radiographic data were obtained preoperatively, at 3 and 6 months and 1 and 3 years postoperatively, as well as at final follow-up. The difference between the two groups and between different time points within one group was compared.Both groups obtained satisfactory clinical outcomes till the final follow-up. No statistic difference was found in Japanese Orthopedic Association, Visual Analogue Score, and Neck Dysfunction Index between the two groups throughout the whole follow-up. Both groups maintained APD and Pavlov's ratio well till follow-up. However, statistic difference was found in the open angle between two groups at final follow-up (34.17±2.75° vs. 36.19±1.80°, p.05). When we subdivided the cervical segments in group A, we found the mini-plate segments showed maintenance in open angle but a 4.52° decrease in suture segments. The mean cost in group B (17,669.82±1,157.65 $) was significantly higher than in group A (11,452.19±871.07 $; p.05).Despite a difference in the maintenance of open angle, both fixation methods achieved satisfactory clinical outcomes. We believe alternative-level fixation is also a safe, effective, and economical fixation method.

Background The optimal management of lumbar synovial cysts (LSCs) has always been controversial. Open or minimally invasive partial hemilaminotomy as a direct decompression approach has been widely studied, whereas to our knowledge, there has been no report of an indirect decompression method for LSC. Case Description A 60-year-old male complained of chronic low back pain for 2 years. He reported that the pain had been getting worse and started radiating to the bilateral posterior thighs and right lateral calf for 6 months. An ovoid lesion with a hyperintense center attached to the medial side of the right facet joint at the L4-5 level, as well as L4-5 dynamic instability, were found with magnetic resonance imaging and lumbar x-ray examinations, respectively. L4-5 oblique lumbar interbody fusion combined with anterior fixation was performed. After surgery, the patient felt distinct pain relief and was discharged on the third day postoperatively. Three months later, lumbar magnetic resonance imaging and 3-dimensional computed tomography were performed again. The L4-5 disk height and foraminal height recovered from 7.1–12.3 mm and 14.8–18.5 mm, respectively. No evidence of a cyst was disclosed. The patient did not complain of any low back pain or radicular pain during the 12-month follow-up. Conclusions Indirect decompression surgery may be a new option for the management of LSC, especially in those with lumbar instability and that communicate with the facet joint. Further research with a larger and more comprehensive sample population is required.

Nanoparticles (NPs) enter a cell primarily via endocytosis, during which they are engulfed by the cell and reside in lipid vesicles named endosomes. Apart from when an endosome is pinched off the plasma membrane, structural integrity of its lipid membrane is usually well maintained. Under certain circumstances, however, such structural integrity can be considerably perturbed by a nanoparticle. For instance, recent experiments [Chu et al., Sci. Rep., 2014, 4, 4495] indicate that nanodiamonds with sharp corners can escape from an endosome by piercing its lipid membrane. Nonetheless, the energetics of this behavior and how it may be controlled by membrane adhesion and NP morphology remain unclear. In this work, we employ continuum modeling to investigate membrane pore formation induced by the spontaneous binding of a sharp nanoparticle. Based on two axial-symmetric NP models, we characterize the indispensable role played by curvature heterogeneity, membrane adhesion, and the sharpness as well as the size of a nanoparticle in 'breaking' a lipid membrane. Apart from revealing a general mechanism of NP binding-induced membrane pore formation, our results provide the reference for improving the endosomal escape of nanoparticles through manipulating their morphology, a direction that can be explored either independently or combined with existing strategies targeting NP surface chemistry.

Maintaining an effective drug concentration in the nidus during the early stage is essential for the surgical treatment of osteoarticular tuberculosis (TB) and the prevention of internal infection. In this study, an implantable composite scaffold, denoted as n-HP@ICG, was synthesized by attaching isoniazid (INH) to chitosan followed by crosslinking via glutaraldehyde to porous nanohydroxyapatite/polyamide 66 (n-HA/PA66). Drug release and biocompatibility experiments showed that INH could be effectively released from the composite scaffold for approximately 15 days in vitro and 28 days in vivo with no obvious cytotoxicity or harm to liver or kidney function. The anti-TB test indicated that n-HP@ICG had satisfactory anti-TB effects, including the inhibition of Mycobacterium tuberculosis activity, proliferation and adhesion. The rabbit femoral condyle defect repair experiment showed that the composite scaffold had satisfactory osteoconduction and osseointegration. These results demonstrate that the n-HP@ICG composite scaffold can simultaneously provide relatively long-term drug release, biosafety, and anti-TB and bone regeneration activity and is thus promising for treating osteoarticular TB.

Background: Assessing the relation between arthritis and cognitive impairment could expand the understanding of health consequences of arthritis. The aim was to prospectively examine the association between arthritis and cognitive functions among middle-aged and elderly Chinese.Methods: Our analyses were based on data from the nationwide China Health and Retirement Longitudinal Study (2011–2016). Arthritis was ascertained by self-reported doctor diagnosis during the baseline survey. Cognitive functions were evaluated in three domains including episodic memory, mental status, and global cognition. Linear mixed models were employed to assess the association between baseline arthritis and cognition functions.Results: Of 7,529 Chinese adults, 49.79% were men, and mean age was 57.53 years. During a follow-up of 4 years, participants with baseline arthritis showed lower scores of episodic memory [β = −0.08; 95% confidence interval (CI): −0.14, −0.03], mental status (β = −0.14; 95% CI: −0.22, −0.05), and global cognition (β = −0.22; 95% CI: −0.34, −0.11), compared to those without arthritis. In addition, participants with arthritis showed increased rates of decline in mental status and global cognition by 0.04 (95% CI: 0.01, 0.08) and 0.05 (95% CI: 0.01, 0.09) units per year, respectively.Conclusion: Arthritis was associated with subsequent risk of poorer cognitive functions and slightly faster declines in cognitive functions among Chinese middle-aged and elderly adults. Our findings should be confirmed in future large prospective studies in Chinese and other populations.

The subarctic Pacific is one of the major high-nitrate, low-chlorophyll (HNLC) regions where marine productivity is greatly limited by the supply of iron (Fe) in the region. There is a distinct seasonal difference in the chlorophyll concentrations of the east and west sides of the subarctic Pacific because of the differences in their driving mechanisms. In the western subarctic Pacific, two chlorophyll concentration peaks occur: the peak in spring and early summer is dominated by diatoms, while the peak in late summer and autumn is dominated by small phytoplankton. In the eastern subarctic Pacific, a single chlorophyll concentration peak occurs in late summer, while small phytoplankton dominate throughout the year. In this study, two one-dimensional (1D) physical–biological models with Fe cycles were applied to Ocean Station K2 (Stn. K2) in the western subarctic Pacific and Ocean Station Papa (Stn. Papa) in the eastern subarctic Pacific. These models were used to study the role of Fe limitation in regulating the seasonal differences in phytoplankton populations by reproducing the seasonal variability in ocean properties in each region. The results were reasonably comparable with observational data, i.e., cruise and Biogeochemical-Argo data, showing that the difference in bioavailable Fe (BFe) between Stn. K2 and Stn. Papa played a dominant role in controlling the respective seasonal variabilities of diatom and small phytoplankton growth. At Stn. Papa, there was less BFe, and the Fe limitation of diatom growth was two times as strong as that at Stn. K2; however, the difference in the Fe limitation of small phytoplankton growth between these two regions was relatively small. At Stn. K2, the decrease in BFe during summer reduced the growth rate of diatoms, which led to a rapid reduction in diatom biomass. Simultaneously, the decrease in BFe had little impact on small phytoplankton growth, which helped maintain the relatively high small phytoplankton biomass until autumn. The experiments that stimulated a further increase in atmospheric Fe deposition also showed that the responses of phytoplankton primary production in the eastern subarctic Pacific were stronger than those in the western subarctic Pacific but contributed little to primary production, as the Fe limitation of phytoplankton growth was replaced by macronutrient limitation.

Aims To prospectively examine the association between arthritis and type 2 diabetes (T2D) in the Chinese population and confirm this association through a comprehensive meta-analysis of cohort studies. Meterials and methods Data were from the China Health and Retirement Longitudinal Study which was started in 2011-2013 and followed up in 2013-2014 and 2015-2016. Arthritis was defined as self-reported physician diagnosis at baseline, and incident T2D was determined by self-reported physician diagnosis, fasting blood glucose ≥7.0 mmol/L or glycosylated haemoglobin ≥6.5% during the follow-ups. Cox proportional hazards regression models were used to assess the association between arthritis and risk for T2D. A meta-analysis was conducted to pool our effect estimate and those from other cohort studies using a random-effects model. Results Eleven thousand four hundred and eight participants (47.9% men; mean age: 59.3 years) were included in final analyses. During a 4-year follow-up, 981 participants reported incident T2D. Compared with individuals without arthritis, those with arthritis at baseline had an 18% higher risk for incident T2D (multivariable-adjusted hazard ratio: 1.18; 95% confidence interval: 1.04, 1.34). In the meta-analysis of 13 cohort studies including ours, a total of 2,473,514 participants were included with 121,851 incident diabetes. The pooling HR was 1.32 (95% CI: 1.21, 1.44) for the association between arthritis and diabetes. Conclusion Arthritis was associated with an increased risk of incident diabetes in Chinese adults, and the positive association was confirmed in the meta-analysis of cohort studies. Our work can inform clinical trials to assess the effectiveness of arthritis treatments in reducing risk of diabetes.

Background Litter size affects fetal development but its relation to diet-induced fatty liver later in life is unknown. Objectives This aim of this study was to test the hypothesis that litter size influences postweaning fatty liver development in response to soybean oil-supplemented diet. Methods Weanling twin (TW) or triplet (TP) male lambs (n = 16) were fed a control diet or 2% soybean oil-supplemented diet (SO) for 90 d. Liver tissue morphology, biochemical parameters, and lipid metabolic enzymes were determined. Hepatic gene expression was analyzed by RNA sequencing (n = 3), followed by enrichment analysis according to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Differentially expressed genes involved in lipid metabolism were further verified by quantitative reverse transcriptase-polymerase chain reaction (n = 4). All data were analyzed by a 2-factor ANOVA, apart from differentially expressed genes, which were identified by the Benjamini-Hochberg approach (q value ≤0.05). Results SO increased liver triglyceride (by 55%) and nonesterified fatty acid (by 54%) concentrations in TPs (P ≤ 0.05) but not in TWs (P > 0.05). SO also induced a 2.3- and 2.1-fold increase in the liver steatosis score of TPs and TWs, respectively (P ≤ 0.05). Moreover, SO reduced the activity of lipolytic enzymes including hepatic lipase and total lipase in TPs by 47% and 25%, respectively (P ≤ 0.05). In contrast, activities of lipogenic enzymes, including malic enzyme and acetyl coenzyme A carboxylase, were significantly higher in TPs (P ≤ 0.05). Moreover, TPs had higher expression of lipogenic genes, such as FASN (by 45%) and APOB (by 72%), and lower expression of lipolytic genes, such as PRKAA2 (by 28%) and CPT1A (by 43%), compared with TWs (P ≤ 0.05). Conclusions TPs have a gene expression profile that is more susceptible to SO-induced fatty liver than that of TWs, which indicates that insufficient maternal nutrient supply at fetal and neonatal stages may increase the risk of nonalcoholic fatty liver disease.

Background Spinal tuberculosis accounts for more than 50% of bone tuberculosis cases. This study compared clinical, radiological and functional outcomes between anterior and posterior approaches for treatment of middle or lower thoracic spinal tuberculosis in elderly patients. Methods We retrospectively examined middle or lower thoracic spinal tuberculosis (T5–T12) in patients over 65 years. All procedures included debridement, decompression, autologous bone graft and fixation. Surgical procedure, surgical duration, estimated blood loss during surgery and laboratory results were recorded. Pleural effusion volume, thoracic cavity volume, Oswestry Disability Index score, neurological status, radiological parameters and complication rate were evaluated. Results No significant difference was found in surgical duration, blood loss, kyphosis angle correction, loss of correction, thoracic cavity volume, or complication rate between the two groups (P > 0.05). Average postoperative pleural effusion volumes were 605.9 ± 209.5 mL (377–1074 mL) and 262.9 ± 228.1 mL (0–702.4 mL) in the anterior and posterior groups, respectively (P = 0.004). Average hospitalization durations were 26.4 ± 10.5 days (17–53 days) and 19.2 ± 5.0 days (14–30 days) (P = 0.04). Average postoperative serum albumin levels were 24.19 ± 3.84 g/L (19–29.5 g/L) and 28.24 ± 2.52 g/L (24.4–31.6 g/L) (P = 0.01). No relapse or reinfection was observed in either group at the final follow-up. Surgical revision was not required in either group. Conclusions Both anterior and posterior surgeries can be used to treat middle or lower thoracic spinal (T5-T12) tuberculosis in elderly patients. In general, the posterior approach might be superior, especially for patients with poor general health.

Objective To build a model for proximal junctional kyphosis (PJK) prognostication in Lenke 5 adolescent idiopathic scoliosis (AIS) patients undergoing long posterior instrumentation and fusion surgery by machine learning and analyze the risk factors for PJK. Materials and methods In total, 44 AIS patients (female/male: 34/10; PJK/non-PJK: 34/10) who met the inclusion criteria between January 2013 and December 2018 were retrospectively recruited from West China Hospital. Thirty-seven clinical and radiological features were acquired by two independent investigators. Univariate analyses between PJK and non-PJK groups were carried out. Twelve models were built by using four types of machine learning algorithms in conjunction with two oversampling methods [the synthetic minority technique (SMOTE) and random oversampling]. Area under the receiver operating characteristic curve (AUC) was used for model discrimination, and the clinical utility was evaluated by using F1 score and accuracy. The risk factors were simultaneously analyzed by a Cox regression and machine learning. Results Statistical differences between PJK and non-PJK groups were as follows: gender (p = 0.001), preoperative factors [thoracic kyphosis (p = 0.03), T1 slope angle (T1S, p = 0.078)], and postoperative factors [T1S (p = 0.097), proximal junctional angle (p = 0.003), upper instrumented vertebra (UIV) - UIV + 1 (p = 0.001)]. Random forest using SMOTE achieved the best prediction performance with AUC = 0.944, accuracy = 0.909, and F1 score = 0.667 on independent testing dataset. Cox model revealed that male gender and larger preoperative T1S were independent prognostic factors of PJK (odds ratio = 10.701 and 57.074, respectively). Gender was also at the first place in the importance ranking of the model with best performance. Conclusion The random forest using SMOTE model has the great value for predicting the individual risk of developing PJK after long instrumentation and fusion surgery in Lenke 5 AIS patients. Moreover, the combination of the outcomes of a Cox model and the feature ranking extracted by machine learning is more valuable than any one alone, especially in the interpretation of risk factors.

Background Previous studies have reported the progression of deformity in patients with adolescent idiopathic scoliosis after implant removal. However, for patients with congenital scoliosis, few studies have investigated the prognosis after implant removal. Methods We observed 24 patients with congenital scoliosis, who underwent implant removal, for at least 3 years. Radiographic parameters and demographic data were compared to evaluate whether implant removal would lead to deformity progression. Results Four of the 24 patients (16.7%) suffered correction loss and underwent revision surgery (RS). All correction losses occurred within 12 months of implant removal. The average curve of fixed segments (9.84° ± 7.22° to 16.42° ± 16.79°; P = 0.017) and kyphosis of fixed segments (10.46° ± 13.42° to 18.98° ± 25.99°; P = 0.03) increased significantly throughout the follow-up. After excluding patients who underwent RS, the changes in curve of fixed segments (9.10°–11.58°) and kyphosis of fixed segments (8.50°–9.24°) were all within the measurement error. The coronal and sagittal balance maintained during the follow-up. Through comparison, we thought that the younger age and lower Risser’s grade with larger scoliosis might be risk factors for correction loss. Conclusions Implant removal after fusion surgery for congenital scoliosis may present loss of correction and require RS, thus preserving implants is recommended. When removal of instrumentation is inevitable, parents and patients should be counseled for potential loss of correction and RS, and patients should be monitored for the progression of deformity.

Hepatocellular carcinoma (HCC) is one of the most common and most lethal malignant tumors in the world. Microvascular invasion (MVI) is a major risk factor for survival outcomes and intrahepatic metastasis after resection in patients with HCC. Relevant English literatures retrieved using PubMed on the research progress of MVI in patients with HCC were reviewed. For HCC patients, especially those with MVI, it is very important to develop a comprehensive and sequential treatment plan to support the long-term survival of patients. This manuscript reviewed and analyzed the risk factors for MVI; the preoperative prediction of MVI, which informs the selection of surgical strategies; and the current situation and future direction of comprehensive postoperative treatment strategies; to provide a basis for the comprehensive treatment of HCC patients with MVI. For HCC patients with MVI, the preoperative prediction of MVI may play a certain guiding role in planning procedures, and the comprehensive sequential postoperative pathological detection of HCC MVI may provide a basis for treatment decisions.

3D-printed titanium alloy orthopedic implants combine the dual advantages of 3D printing and titanium alloys implants, which not only have complex structures that cannot be manufactured by traditional techniques, but also inherit the excellent physical and chemical properties of titanium and its alloys, so they are widely used in the field of orthopedics in recent years. The inherent porous structure of 3D-printed implants and the original modification processes of titanium alloys provide the conditions for the functionalization of implants. To meet the needs of orthopedic surgeons and patients, functionalized implants with the ability of long-term stability promotion, anti-infection or anti-tumor have been developed, in which various methods of functionalization deserve to be summarized, compared and analyzed. Therefore, in this review, we will collect the existing knowledge on functionalization of 3D-printed titanium alloy orthopedic implants and give our own opinion.

The predecessor of endoscopic surgery, arthroscopic microdiscectomy (AMD) was first introduced to China in the 1990s after its introduction in Japan, Germany and the United States in the 1980s (1-3).

Hepatocellular carcinoma (HCC) is regarded as a leading cause of cancer-related deaths, and its progression is associated with hypoxia and the induction of hypoxia-inducible factor (HIF). Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, induces cell death in various malignancies. However, the underlying mechanism remains to be elucidated in HCC, especially under hypoxic conditions. The alteration of COX-2 and HIF-1α oncogenicity was evaluated in HCC specimens by tissue microarray. Cell viability, angiogenesis assays, and xenografted nude mice were used to evaluate the effects of meloxicam, along with flow cytometry to detect the cell cycle, apoptosis, and mitochondrial membrane potential (ΔΨm) of HCC. qRT-PCR, Western blotting, immunofluorescence, immunohistochemistry, luciferase assay, and RNAi were carried out to determine the HIF-1α signaling affected by meloxicam. In this study, we showed that meloxicam exerts antiproliferative and antiangiogenesis efficacy in vitro and in vivo and causes disruption of mitochondrial membrane potential (ΔΨm), thus leading to caspase-dependent apoptosis under hypoxic environments. Exposure to meloxicam significantly reduced HIF-1α transcriptional activation and expression through sequestering it in the cytoplasm and accelerating degradation via increasing the von Hippel-Lindau tumor suppressor protein (pVHL) in HCC. These data demonstrated that inhibition of HIF-1α by meloxicam could suppress angiogenesis and enhance apoptosis of HCC cells. This discovery highlights that COX-2 specific inhibitors may be a promising therapy in the treatment of HCC.

MAO-treated porous Ti6Al4V holds enormous potential for use in orthopedic implants due to their excellent biocompatibility and favourable mechanical strength. However, the effects on the V ion accumulation and release following the MAO-treated Ti6Al4V remain undetermined. The aim of the present study was to assess the effects of Vanadium on biocompatibility. In this study, the surface features and chemical compositions were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectrometry (EDS) and X-ray photoelectron spectroscopy (XPS). The ion release of Ti, Al and V was quantitatively measured by inductively-coupled plasma mass spectroscopy (ICP-MS) after immersion in Hanks' solution. To probe the mechanism of V release, the corrosion resistance of porous Ti6Al4V before and after the MAO process was evaluated by electrochemical tests. Thereafter, the effects on the biocompatibility were tested in vitro by cell culture assays and then in vivo by subcutaneous embedment. Finally, the bone tissue response and in vivo release profile of V ions were characterized by intra-osseous implantation. Therefore, this study suggests that the effect of V released from MAO-treated porous Ti6Al4V on biocompatibility and application safety is small and preventable.

Purpose: Systemic therapy has often been used for patients with advanced hepatocellular carcinoma (HCC). However, due to drug resistance, the use of cytotoxic chemotherapy in the treatment of patients with advanced HCC has typically demonstrated low response rates. Secretory clusterin (sCLU) is expressed in aggressive late-stage tumors and associated with resistance to chemotherapy, including that in HCC cases. The present research aimed to investigate the biological role of sCLU in HCC. Methods: sCLU expression in HCC and normal tissues was examined using immunohistochemical staining, followed by analysis of the correlation between sCLU expression and clinical indicators. In addition, the role and internal mechanism of sCLU in cell proliferation and apoptosis were investigated in HCC cells. Results: sCLU expression was significantly upregulated in HCC tissues; and was associated with histological grade and poor overall survival. The levels of sCLU were significantly increased in Bel7402, SMMC7721 and resistant HCC cells (Bel7404-OR). Inhibiting the activity of sCLU enhanced the chemosensitivity of Bel7402 and SMMC7721 cells. Downregulation of sCLU could increase the expression of Gadd45a in HCC cells. Overexpression of sCLU contributed to drug resistance in Bel7402, SMMC7721 and Bel7404-OR cells; whereas, overexpression of Gadd45a alone overcame drug resistance in the cells above. No significant expression changes of sCLU and Gadd45a were observed in HCC cells after the interference of a selective inhibitor of the PI3K/Akt signaling pathway. However, regulation of the expression of Gadd45a could influence the phosphorylation level of Akt; and further regulate the expression of Bcl-2 and Bax proteins involved in the mitochondrial apoptosis pathways. Conclusions: The results demonstrate that sCLU/Gadd45a/PI3K/Akt signaling represents a novel pathway that could regulate drug resistance in a one-way manner in HCC cells.

This study shows that the response of satellite-observed chlorophyll (CHL) to eddy motion varies seasonally in the South China Sea (SCS). The spatial pattern of the CHL anomaly composite for eddies is a dipole in summer and a monopole in winter, indicating that sea surface CHL is largely regulated by the horizontal rotational velocity of the eddy in summer and by eddy pumping and trapping in winter. The dipole pattern for anticyclonic eddies was confirmed by in situ observations, which also show that the dipole pattern is mainly restricted to the mixed layer. The underlying mechanism was further investigated with a coupled physical–biogeochemical model. The key driver leading to the seasonal variation of the eddy effect is found to be the seasonal variation of the mixed layer depth. In summer when the mixed layer is shallow, the monopole nutrient change induced by eddy is restricted to the subsurface. The sea surface CHL distribution is thus mostly affected by eddy advection. In winter, the deepening of the mixed layer mixes the nutrients from subsurface where eddy significantly changes the nutrient levels, allowing the monopole pattern to be observed in the sea surface CHL anomaly.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. The Yes-associated protein-1 (YAP) plays a critical role in cell proliferation, apoptosis and angiogenesis. Verteporfin is a photosensitizer used in photodynamic therapy and also a small molecular inhibitor of the Hippo-YAP pathway. However, little is known about whether verteporfin could inhibit YAP activity in PDAC cells. Our present results showed that verteporfin suppressed the proliferation of human PDAC PANC-1 and SW1990 cells by arresting cells at the G1 phase, and inducing apoptosis in dose- and time-dependent manners. Verteporfin also inhibited the tumor growth on the PDAC xenograft model. Treatment with verteporfin led to downregulation of cyclinD1 and cyclinE1, modulation of Bcl-2 family proteins and activation of PARP. In addition, verteporfin exhibited an inhibitory effect on angiogenesis and vasculogenic mimicry via suppressing Ang2, MMP2, VE-cadherin, and α-SMA expression in vitro and in vivo. Mechanism studies demonstrated that verteporfin impaired YAP and TEAD interaction to suppress the expression of targeted genes. Our results provide a foundation for repurposing verteporfin as a promising anti-tumor drug in the treatment of pancreatic cancer by targeting the Hippo pathway.

The P18 peptide is a functional fragment of pigment epithelial-derived factor (PEDF), which is an endogenic angiogenesis inhibitor. This study sought to determine the anti-angiogenic bioactivity of the P18 peptide in hepatocellular carcinoma (HCC) and to elucidate the underlying mechanism. Xenograft tumour growth assays demonstrated the P18 peptide suppressed angiogenesis of HCC in vivo. Wound healing, Transwell and Matrigel-culture assays indicated that the P18 peptide inhibited the cell migration and tube formation of endothelial cells (ECs) in vitro. Cell viability and apoptosis assessed by Cell Counting Kit-8 (CCK-8) and flow cytometry assays suggested that the P18 peptide inhibited angiogenesis by inducing apoptosis of ECs. Angiogenesis- and signal transduction-associated molecules analysed by western blot demonstrated that the P18 peptide targets vascular endothelial cell growth factor receptor 2 (VEGFR2) on ECs. In conclusion, by inhibiting the phosphorylation of VEGFR2, the P18 peptide modulates signalling transduction between VEGF/VEGFR2 and suppresses activation of the PI3K/Akt cascades, leading to an increase in mitochondrial-mediated apoptosis and anti-angiogenic activity. This bioactivity of the P18 peptide may represent a novel therapeutic strategy for the treatment of HCC.

New mechanical biomarkers were discovered and used to investigate drug effects on HeLa cells. HeLa cells were measured using advanced atomic force microscopy (AFM) techniques before and after treatment with an anticancer drug (docetaxel, a microtubule polymerizer) and the biomechanical properties of cells were analyzed using theoretical models. The biomechanical results show that the length of the surface brush, the factor of viscosity, and the adhesion work of untreated HeLa cells reduced from 920 nm, 0.72 and 4.12 × 10−16 N m to 673 nm, 0.52 and 5.37 × 10−17 N m for treated cells, respectively. In order to reveal the underlying mechanisms of these changes, transmission electron microscopy (TEM) and western blotting assays were employed to characterize structural changes of the cells. Compared to the untreated cells, TEM images confirmed a thinner brush layer on the surface of treated cells while the western blotting of tubulin extracted from the cells indicated an increased microtubule concentration for the treated cells. These changes are consistent with previous studies on the influence of docetaxel on cells. Based on the above results, we conclude that docetaxel can lead to an increased microtubule network in HeLa cells, a thinner brush layer on HeLa cell surfaces and that the length of surface brush, the factor of viscosity, and the adhesion work can be exploited as effective mechanical biomarkers to evaluate drug effects on HeLa cells. This work demonstrates a new AFM-based technique that can be exploited to assess drug action on cells and is promising for the application of drug screening.

Objective The purposes of the present study were to introduce an indirect decompression using oblique lateral lumbar interbody fusion combined with anterolateral screw fixation (OLIF-AF) for the treatment of lumbar degenerative disc disease and examine the clinical efficacy and radiographic outcomes. Methods A total of 65 patients had undergone single-level OLIF-AF at L2–L5 from December 2017 to August 2018. The cross-sectional area of the thecal sac was evaluated using magnetic resonance imaging. The disk height, foraminal height (FH), and degree of upper vertebral slippage were evaluated using computed tomography. The visual analog scale score and Oswestry disability index were recorded pre- and postoperatively. Results The visual analog scale scores and Oswestry disability index had significantly improved after surgery (P 0.05). Adverse events were observed in 15 patients (23.1%) patients and included pain at the iliac bone donor site in 1 (1.5%), left thigh pain/numbness in 2 (3.1%), quadriceps weakness in 2 (3.1%), psoas weakness in 3 (4.6%), intraoperative endplate injury in 2 (3.1%) and cage subsidence in 5 (7.7%). Conclusions Our results have shown that OLIF-AF surgery is a relatively safe and effective surgical option for LDDD at L2–L5. Cage subsidence was the most common operative complication.

Dysphagia is a common postoperative complication in patients undergoing occipitocervical fusion (OCF). Previous studies had proposed the use of two measures-the occipital to C2 angle (O-C2a) and the occipital and external acoustic meatus to axis angle (O-EAa)-to predict postoperative dysphagia after OCF. However, these studies had small sample sizes and the predictive abilities of both measures are still not clear.To evaluate the predictive ability of O-EAa and O-C2a for dysphagia after OCF.A retrospective clinical study.A total of 109 consecutive patients who had undergone OCF.Presence of postoperative dysphagia, O-C2a, C2 tilting angle (C2Ta), O-EAa, and the narrowest oropharyngeal airway space (nPAS).Between April 2010 and June 2018, 109 consecutive patients who had undergone OCF were reviewed. Patients were divided into two groups according to the presence of postoperative dysphagia. Radiographic measurements, including O-C2a, C2Ta, O-EAa, and nPAS, were evaluated at preoperative and 1 month postoperative and the findings were compared. Simple linear regression was used to measure the correlations between the parameters and the presence of dysphagia, and the correlations within the parameters. Multiple regression analysis was used to examine the variables that affected the change of nPAS (dnPAS%). Sensitivity and specificity analyses were used to evaluate the effectiveness of the previously proposed measures ("O-C2a change≤-5°" and "postoperative O-EAa100°") for prediction of post-OCF dysphagia.The incidence of dysphagia after OCF was 26.6% (29/109). Preoperative values for the radiographic parameters were similar between patients with and without dysphagia. In the dysphagia group, both O-C2a and O-EAa values showed a dramatic decrease after surgery, which was accompanied by a decrease in nPAS. Postoperative O-C2a, O-EAa, and nPAS in the dysphagia group were significantly smaller than those in the nondysphagia group (p.05). The changes in O-EAa, O-C2a, and nPAS showed a linear correlation with the presence of dysphagia (p.05). In addition, linear correlations were found between two of the three parameters. Multiple regression showed the change of O-C2a and O-EAa were significant predictors for dnPAS% (β=0.200, p=.022 and β=0.549, p=.000). The sensitivity and specificity of "O-C2a change≤-5°" in predicting dysphagia were 75.9% and 80.0% respectively, and those of "postoperative O-EAa100°" were 75.9% and 62.5%, respectively. However, the sensitivity of the combination of these two values in predicting postoperative dysphagia was as high as 96.6%.Both O-EAa and O-C2a could be critical predictors for postoperative dysphagia. During surgery, ensuring that the O-EAa exceeds 100° and simultaneously avoiding an O-C2a reduction greater than 5° could effectively avert postoperative dysphagia.

Objective This study aimed to present a new endoscopic technique for osteoid osteoma (OO) of the lumbar spine and sacrum and to evaluate its safety and effectiveness. Methods Eleven consecutive patients with spinal OO underwent percutaneous endoscopic excision and ablation (PEEA) between March 2014 and May 2018. A cannula 0.7 cm in diameter was used for the procedure. According to the size of the nidus, whole-piece removal and piecemeal intralesional resection were used. Afterward, ablation was performed using an endoscopic radiofrequency electrode in the residual osteoma cavities. Clinical outcomes were assessed by Visual Analog Scale (VAS) scores. The efficacy of this technique was assessed using relevant clinical data and postoperative radiographs. Results The niduses of the 11 patients were all located in the posterior element of the lumbar spine and sacrum (10 in the lumbar spine and 1 in the sacrum). The preoperative VAS score was 7.18 (range, 6–9), the score on postoperative day 1 was 1 (range, 0–2), and the last follow-up VAS score was 0.27 (range, 0–1). All patients were discharged within 24 hours after surgery. The mean follow-up period was 21.8 months (range, 12–36 months). No serious complications were observed during the follow-up period. Conclusions PEEA is a safe and effective technique for OO in the lumbar spine and sacrum in which the nidus is located in the posterior element. However, it has a steep learning curve. Further research with a larger and more comprehensive sample population is warranted.

Recurrence and metastasis are the two leading causes of poor prognosis of hepatocellular carcinoma (HCC) patients. Cyclooxygenase (COX)-2 is overexpressed in many types of cancers including HCC and promotes its metastasis. Meloxicam is a selective COX-2 inhibitor that has been reported to exert an anti-proliferation and invasion/migration response in various tumors. In this study, we examined the role of meloxicam on HCC cell proliferation and migration and explored the molecular mechanisms underlying this effect. We found that meloxicam inhibited HCC cell proliferation and had a cell cycle arrest effect in human HCC cells. Furthermore, meloxicam suppressed the ability of HCC cells expressing higher levels of COX-2 and prostaglandin E2 (PGE2) to migration via potentiating expression of E-cadherin and alleviating expression of matrix metalloproteinase (MMP)-2 and -9. COX-2/PGE2 has been considered to activate the β-catenin signaling pathway which promotes cancer cell migration. We found that treatment with PGE2 significantly enhanced nuclear accumulation of β-catenin and the activation of GSK3β which could be reversed by meloxicam in HCC cells. We also observed that HCC cell migration and upregulation of the level of MMP-2/9 and downregulation of E-cadherin induced by PGE2 were suppressed by FH535, an inhibitor of β-catenin. Taken together, these findings provide a new treatment strategy against HCC proliferation and migration.

Hepatocellular carcinoma (HCC) is a highly malignant disease with a poor prognosis and high mortality due to a low early diagnosis rate, resistance to systemic treatments and progression to late-stage liver disease. Owing to limitations in the detection of HCC and the lack of awareness of healthcare systems, fewer than 40% of HCC patients are eligible for surgery due to advanced stages of the disease at the time of diagnosis and the occurrence of multiple lesions in the cirrhotic or fibrotic liver. At present, the updated American Association for the Study of Liver Disease (AASLD) guidelines no longer recommend alpha-fetoprotein (AFP) testing as a part of diagnostic evaluation. Thus, it is imperative to establish a novel diagnostic strategy with high sensitivity and reliability to monitor risk factors to detect HCC at an early stage. In recent years, “liquid biopsy,” (including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)), has emerged as a technique for the characterization of circulating cells, providing a strong basis for the individualized treatment of patients. As a noninvasive detection method, liquid biopsy is expected to play an important role in the early diagnosis, dynamic monitoring of cancer patients and drug screening. In this review, we will focus on the clinical applications, recent studies and future prospects of liquid biopsy, particularly focusing on HCC.

The resistance to sorafenib highly affects its clinical benefits for treating hepatocellular carcinoma (HCC). Sodium orthovanadate (SOV) is a phosphate analog that displays anti-cancer activities against various types of malignancies including HCC. The present study has demonstrated that SOV is able to overcome sorafenib resistance and strengthens sorafenib in suppressing sorafenib-resistant HCC cells in vitro and in animal models. Similar to its action on parental HCC cells, SOV induced cell cycle arrest at G2/M phases by regulating cyclin B1 and cyclin-dependent kinase 1, and apoptosis by reducing mitochondrial membrane potential, in sorafenib-resistant HCC cells. More importantly, SOV inhibited ATPase activity, which was significantly elevated in sorafenib-resistant HCC cells. SOV also reduced the expression of HIF-1α and HIF-2α and their nuclear translocation, resulting in downregulation of their downstream factors including vascular endothelial growth factor, lactate dehydrogenase-A and glucose transporter 1. Its ability to inhibit ATPase activity and hypoxia-inducible pathways enabled SOV to efficiently suppress both normoxic and hypoxic cells, which compose cancer cell populations inside sorafenib-resistant HCC tumors. The present results indicate that SOV may be a potent candidate drug for overcoming the resistance to sorafenib in treating HCC.

Study design An imaging anatomical measurement. Objective To investigate the anatomical feasibility of percutaneous kyphoplasty for lumbar osteoporotic vertebral compression fractures via a unilateral transverse process-pedicle approach (TPA). Summary of background data Kyphoplasty via a unilateral approach has been reported and good clinical results have been achieved. However, because of the lack of an anatomical study, these approaches have yet to be popularized. Methods A total of 150 lumbar vertebral bodies of 30 patients were simulated kyphoplasty on the computed tomographic scans through conventional transpedicle approach (CTA) and the TPA, respectively. Anatomical parameters including the distance between the entry point and the midline of the vertebral body, the puncture inclination angle, and the success rate of puncture were measured and compared. Results The distance between the entry point and the midline from L1 to L5 lumbar levels varied from 20.6 ± 2.2 mm to 28.6 ± 2.9 mm in the CTA group and from 23.6 ± 2.2 mm to 33.6 ± 2.9 mm in the TPA group. The entry point from L1 to L5 in the TPA group was 3.0 ± 2.1 mm to 5.1 ± 2.7 mm more lateral than that in the CTA group. The medial inclination angles from L1 to L5 were 30.2° ± 6.4° to 47.7° ± 5.4° in the TPA and 15.3° ± 6.0° to 22.8° ± 8.7° in the CTA group. The inclination angles in the TPA group were greater than that in the CTA group and the safe range of the puncture angles was also wider. The success rate was 51.7% in the CTA group and 87.7% in the TPA group. Conclusion The entry point through a TPA was localized at the midline of the transverse process, 3.0 to 5.1 mm outside the lateral margin of the pedicle projection. Compared with CTA, the puncture inclination angle in the TPA approach was much larger with a wider safe puncture range. The TPA approach allowed an easy puncture to meet or surpass the midline of the lumbar vertebral body. Level of evidence N/A.

The purpose of this study was to investigate whether the therapeutic activity of gemcitabine (GCB) in hepatocellular carcinoma (HCC) could be increased by the down-regulation of secretory clusterin (sCLU), a glycoprotein that is considered to play a cytoprotective role in the resistance to chemotherapy. The expression of sCLU was detected in HCC tumor tissues and cell lines. A cell viability and apoptosis assay were performed in parental HCC cells or the same cells transfected with sCLU shRNA and treated with or without GCB. The potential downstream pathways were investigated using the Human Apoptosis RT2 Profiler™ PCR Array. The expression levels of sCLU in HCC tissues were significantly higher than in adjacent non-tumor liver tissues and were associated with the histological grade and transarterial chemoembolization. sCLU overexpression was also found in three HCC cell lines and hepatocytes. The depletion of sCLU synergistically increased GCB sensitivity in Bel7402 and SMMC7721 cells and induced cell apoptosis. Based on the PCR array analysis, sCLU depletion also resulted in the up-regulation of BNIP1, GADD45A, TNFRSF10A, and TRADD and down-regulation of AKT1 in Bel7402 and SMMC7721 cells compared with the parental controls. These results were further supported by a Western blot analysis, which showed increased GADD45a protein expression and the decreased expression of phosphorylated AKT. GADD45a overexpression also increased the sensitivity to GCB in the Bel7402 and SMMC7721 cells. Targeting sCLU may be a useful method to enhance the cytotoxic effect of GCB in hepatocellular carcinoma.

Understanding how nanomaterials interact with cell membranes is related to how they cause cytotoxicity and is therefore critical for designing safer biomedical applications. Recently, graphene (a two-dimensional nanomaterial) was shown to have antibacterial activity on Escherichia coli, but its underlying molecular mechanisms remain unknown. Here we show experimentally and theoretically that pristine graphene and graphene oxide nanosheets can induce the degradation of the inner and outer cell membranes of Escherichia coli, and reduce their viability. Transmission electron microscopy shows three rough stages, and molecular dynamics simulations reveal the atomic details of the process. Graphene nanosheets can penetrate into and extract large amounts of phospholipids from the cell membranes because of the strong dispersion interactions between graphene and lipid molecules. This destructive extraction offers a novel mechanism for the molecular basis of graphene's cytotoxicity and antibacterial activity.

Study Design. A retrospective study. Objective. To evaluate the radiological and clinical results of simultaneous surgery with preservation of the posterior vertebral wall for rigid post-traumatic kyphosis in the thoracolumbar spine. Summary of Background Data. Management of rigid post-traumatic kyphosis has been a challenge for surgeons. Current widely used posterior osteotomy procedures have the disadvantages of significant invasiveness, spinal column shortening, and instrumentation-related complications. Methods. From 2004 to 2009, 21 patients with rigid post-traumatic kyphosis in the thoracolumbar spine (T11–L2) were managed in our hospital. Average kyphotic angle was 45.2° ± 11.2° (range, 31°–67°). The surgical technique used was posterior and anterior circumferential release and anterior corpectomy with posterior vertebral wall preservation and short segmental instrumentation. Preoperative and postoperative kyphotic angle was measured to assess the degree of kyphosis correction and maintenance. Changes in low back pain were assessed by Japanese Orthopaedic Association scores. Results. All patients were successfully managed with this procedure without major complications. Most patients (19 of 21) were instrumented with anterior-only fixation, while posterior interspinal wire was added in 2 patients with osteoporosis. The mean blood loss was 470 mL (range, 300–700 mL). Patients were followed for an average of 32 months (range, 6–70 mo) postoperatively. Back pain was relieved to some degree in all patients and the improvement in Japanese Orthopaedic Association scores was 76.9% ± 7.9. Average kyphotic angle was 6.0° ± 5.7° (range, −2 to 17) immediately after surgery and 7.2° ± 5.8° (range, −3 to 17) at final follow-up. Average of 1° of correction loss was documented and all patients obtained solid fusion uneventfully. Conclusion. This technique is indicated for most patients with rigid post-traumatic kyphosis in the thoracolumbar spine and can yield satisfactory clinical results not only in terms of pain relief, kyphosis correction, vertebral height restoration, and spinal canal integrity preservation, but also in reducing the risk of excessive bleeding and spinal cord injury.

Sorafenib (SOR) is a promising treatment for advanced hepatocellular carcinoma (HCC). However, the precise mechanisms of toxicity and drug resistance have not been fully explored and new strategies are urgently needed for HCC therapy. Meloxicam (MEL) is a selective cyclooxygenase-2 (COX-2) inhibitor which elicits antitumor effects in human HCC cells. In the present study, we investigated the interaction between MEL and SOR in human SMMC‑7721 cells and the role endoplasmic reticulum (ER) stress exerts in the combination of SOR with MEL treatment-induced cytotoxicity. Our results revealed that the combination treatment synergistically inhibited cell proliferation and enhanced apoptosis. Furthermore, the combination treatment enhanced ER stress-related molecules which involved in SMMC-7721 cell apoptosis. GRP78 knockdown by siRNA or co-treatment with MG132 significantly increased this combination treatment-induced apoptosis. In addition, we found that the combination treatment suppressed tumor growth by way of activation of ER stress in in vivo models. We concluded that the combination of SOR with MEL treatment-induced ER stress, and eventually apoptosis in human SMMC-7721 cells. Knockdown of GRP78 using siRNA or proteosome inhibitor enhanced the cytotoxicity of the combination of SOR with MEL-treatment in SMMC-7721 cells. These findings provided a new potential treatment strategy against HCC.

Objectives Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated to exert anti-tumour effects against various malignancies. However, up to now, mechanisms involved in meloxicam anti-hepatocellular carcinoma effects have remained unclear. Materials and methods Cell viability and apoptosis were assessed by CCK-8 and flow cytometry. Endoplasmic reticulum (ER) stress and autophagy-associated molecules were analysed by western blotting and immunofluorescence assay. GRP78 and Atg5 knock-down by siRNA or chemical inhibition was used to investigate cytotoxic effects of meloxicam treatment on HCC cells. Results We found that meloxicam led to apoptosis and autophagy in HepG2 and Bel-7402 cells via a mechanism that involved ER stress. Up-regulation of GRP78 signalling pathway from meloxicam-induced ER stress was critical for activation of autophagy. Furthermore, autophagy activation attenuated ER stress-related cell death. Blocking autophagy by 3-methyladenine (3-MA) or Atg5 siRNA knock-down enhanced meloxicam lethality for HCC by activation of ER stress-related apoptosis. In addition, GRP78 seemed to lead to autophagic activation via the AMPK–mTOR signalling pathway. Blocking AMPK with a chemical inhibitor inhibited autophagy suggesting that meloxicam-regulated autophagy requires activation of AMPK. Conclusions Our results revealed that both ER stress and autophagy were involved in cell death evoked by meloxicam in HCC cells. This inhibition of autophagy to enhance meloxicam lethality, suggests a novel therapeutic strategy against HCC.

Liver cancer, a large proportion of which is hepatocellular carcinoma (HCC), is diagnosed in more than 700000 people each year worldwide. Liver cancer is particularly prevalent in Asia, Sub-Saharan Africa and the South Pacific, where hepatitis B and hepatitis C infection rates are very high. However, due to resistance to chemotherapy, patients with intermediate and advanced-stage disease cannot benefit from this treatment. Clusterin, which is overexpressed in many different cancers, is a stress-induced cytoprotective protein that confers treatment resistance. Custirsen (OGX-011) is a novel 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide that targets secretory clusterin protein expression and is currently in clinical trials for patients with different cancers. In recent years, a number of different clinical trials have been performed, and two phase III clinical trials of custirsen evaluating combinations with chemotherapy in patients with metastatic castration-resistant prostate cancer and metastatic non-small cell lung cancer are currently in progress. The aims of this review are to summarize the current state of research on clusterin, predict future research directions and analyze the potential of the clinical application of custirsen in HCC.

Sorafenib is a type of multikinase inhibitor that exhibits antiangiogenic and antiproliferative effects; in addition, sorafenib is a unique first-line drug recommended for the treatment of advanced hepatocellular carcinoma (HCC). However, the effectiveness of HCC treatment remains poor due to acquired drug resistance. It has been suggested that hypoxia, induced as a results of the antiangiogenic effects of sustained sorafenib treatment, may be an important factor in sorafenib resistance. The transcription factor hypoxia-inducible factor (HIF)-2α has been reported to be associated with cell proliferation under hypoxic conditions; therefore, it was hypothesized that hypoxia may enhance tumor cell proliferation via this mechanism. The present study aimed to evaluate whether the knock-down of HIF-2α was able to enhance the therapeutic efficacy of sorafenib in order to effectively treat HCC. The results demonstrated that hypoxia protected HCC cells against sorafenib; however, short hairpin RNA-HIF-2α transfection in combination with sorafenib treatment exhibited a significantly synergistic effect against HCC cell proliferation. In addition, HCC cells acquired increased β-catenin/C-Myc expression, which enhanced proliferation under hypoxic conditions; however, targeted knock-down of HIF-2α or C-Myc markedly decreased cell proliferation in HCC cells. In conclusion, the results of the present study indicated that the targeted knock-down of HIF-2α in combination with sorafenib may be a promising strategy for the treatment of HCC.

Angiogenesis is required for the invasion, metastasis and chemoresistance of tumor cells. In addition to vascular endothelial cell growth factor (VEGF), angiopoietin-2 (Ang2) is considered to be a promising target for anti-angiogenic therapy. The T7 peptide, an active fragment of full-length tumstatin [the noncollagenous 1 domain of the type IV collagen α3 chain, α3(IV)NC1], has equivalent anti-angiogenic activity to that of full-length tumstatin. This study aimed to explore the mechanisms of the T7 peptide in the regulation of Ang2 expression in endothelial cells (ECs) as well as inhibition of angiogenesis and invasion of hepatocellular carcinoma cells. We also examined the role of autophagy in angiogenesis. Human umbilical vein endothelial cells (HUVECs) were incubated with endothelial cell medium (ECM)-2 in a hypoxia chamber to mimic hypoxic conditions. The recombinant T7 peptide inhibited the cell viability, tube formation and induced apoptosis of the HUVECs. The T7 peptide downregulated the protein expression of Ang2 by inhibiting phosphorylation of AKT under hypoxic conditions. The migration of HUVECs and invasion of HepG2 cells were inhibited by the T7 peptide via inhibition of Ang2 expression. EC autophagy was induced by the T7 peptide. Inhibition of autophagy enhanced the anti‑angiogenic activity of the T7 peptide by increasing EC apoptosis. In vivo, immunohistochemistry of VE-cadherin and CD31 showed that angiogenesis was decreased significantly by the T7 peptide in a nude mouse xenogeneic tumor model. In conclusion, the T7 peptide inhibited angiogenesis and exerted its antitumor effects by inhibition of Ang2, phosphorylation of AKT and matrix metalloproteinase-2 (MMP-2) regulated by Ang2. Furthermore, inhibition of autophagy may significantly enhance the anti-angiogenic activity of the T7 peptide.

Congenital C2–3 fusion (C2–3CF) is often involved in patients with atlantoaxial dislocation, and posterior occipitocervical fixation surgery is usually required. Hypoplasia of C2 pedicle is common in such patients, making C2 pedicle screws (PS) instrumentation inapplicable. Because of congenital fusion, C3PS instrumentation would be an ideal alternative for it will not sacrifice an additional motion segment; however, the morphological and clinical feasibility has not been previously reported. We included 42 C2–3CF patients to this study and evaluated pedicle trajectories of C2 and C3 using a three-dimensional CT. Clinical applications of C3PS instrumentation were evaluated and followed. Among the 42 patients, 23 (54.8 %) and 8 (19.0 %) had C2 and C3 pedicle trajectory diameters

The cysteine protease cathepsin B (Cat B) is important in the progression of tumor cells, however, the function and molecular mechanisms of Cat B in hepatocellular carcinoma (HCC) remain to be elucidated. Our previous study demonstrated that integrin αvβ3 regulated the biological behavior of HCC. The present study demonstrated that Cat B was also important in cell proliferation and apoptosis in HCC. Notably, Cat B was observed to activate the phosphoinositide 3‑kinase (PI3K)/Akt signaling pathway to promote HCC proliferation. Furthermore, inhibition of integrin αvβ3 significantly prevented Cat B‑induced activation of PI3K/Akt and the progression of HCC. Thus, the results of the present study suggested the presence of a Cat B/integrin αvβ3/PI3K/Akt axis in the regulation of the progression of HCC.

Aim. To investigate the role of vitamin A in liver damage induced by bile duct ligation (BDL) in rats.Methods. Thirty male Wistar rats were randomly divided into three groups: SHAM group, BDL group, and BDL + VitA group . The concentrations of retinol and retinyl palmitate in the liver were analyzed using HPLC, and liver function was evaluated by the level of TBIL, ALT, AST, and ALP in serum. Hepatic oxidative status was estimated by measuring T-SOD, CAT, GSH, MDA, and AOPP. Nrf2 expression was assessed using immunohistochemistry and western blotting, and EMSA was performed to determine Nrf2 DNA-binding activity. The expression of the downstream factors such as Ho1 and Nqo1 was also examined using immunohistochemistry and western blotting assays.Results. Vitamin A treatment restored levels of retinoids in liver, improved liver function, alleviated oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the experimental obstructive jaundice. Vitamin A was also found to increase the expression of Nrf2 downstream proteins such as Ho1 and Nqo1.Conclusion. Vitamin A was here found to ameliorate cholestatic liver injury. This effect may be related to the activation of Nrf2/ARE pathway in bile duct ligation rats.

Study Design. A morphologic study of manubrium sterni using 3-dimensional computed tomography (3D-CT). Objective. To investigate the anatomic features of adult manubrium as a source of bone graft and to measure the sizes and available cancellous bone volume of manubrium. Summary of Background Data. Manubrium bone graft has been reported as a potential ideal material in anterior cervical fusion surgery, whereas the related applied anatomy is lacking in the literature. Methods. One hundred twenty adult manubria from 68 male and 52 female patients were scanned and reformatted with 3D-CT. Configurations of manubrium was observed on 3D volume–rendered images. The breadths, height, medullar thickness, and thickness distribution of manubrium were evaluated. A safe area for procurement of graft was proposed and the available cancellous bone volume of manubrium was measured. Results. Frontal manubrium bears a prominent pentagonal area, which was a bare area without muscle attachments. The breadths, height, and thickness of male manubrium were significantly larger than those of female manubrium. Maximal medullar thickness for male patient was 10.4 ± 1.1 (range, 8.8–12.8) mm, and for female patient it was 9.4 ± 1.4 (range, 6.6–11.9) mm. Minimal medullar thickness for male was 6.8 ± 1.1 (range, 4.9–9.4) mm, and for female it was 5.8 ± 0.9 (range, 4.2–7.4) mm. The thickest region of manubrium located at the level of lower clavicular notches, whereas the thinnest region located at the junction between upper two-thirds and lower third of manubrium. Available volume of cancellous bone was 10.1 ± 2.2 (range, 6.6–15.6) cm3 in male and 7.7 ± 2.5 (range, 3.6–12) cm3 in female. Conclusion. The size of male manubrium is significantly larger than that of female manubrium. Manubrium bone is far more sufficient for most adult anterior cervical fusion surgeries. Safe area for procurement of graft is defined as the upper two-thirds of manubrium, and the optimal site to access medullar cavity is suggested at bare area. However, because considerable variability of manubrium size exists, preoperative evaluation of manubrium is suggested to avoid pitfalls, especially when manubrium graft is intended in a female patient.

The prevalence of cardiac abnormalities in patients with adolescent idiopathic scoliosis in an Asian population has not been reported. A retrospective study was conducted to evaluate the incidence of cardiac abnormalities in these patients. From January 2007 to April 2009, echocardiography and pulmonary function tests were performed in 80 adolescent idiopathic scoliosis patients who required surgical intervention. A thorough analysis of cardiopulmonary functions and cardiac structures was performed. The risk factors, types of cardiac abnormalities, and associations between severity of scoliosis or pulmonary function and cardiac abnormalities were assessed. Cardiac abnormalities were detected by echocardiogram in 25 patients, including 14 with structural abnormalities and 11 with functional abnormalities. The most common functional abnormality was tricuspid regurgitation (9 of 80; 11.3%), whereas atrial septal defect was the most common structural abnormality (7 of 80). Altered hemodynamics occurred in 5 patients, including 3 with ventricular septal defect and 2 with mitral valve dysplasia. Abnormal electrocardiographic findings presented in only 9 of the 25 patients with cardiac abnormalities. No significant associations were found between severity of scoliosis or pulmonary function and cardiac abnormalities. A high incidence of cardiac abnormality exists in patients with adolescent idiopathic scoliosis in this region. Although most patients tolerated surgery, some patients were at risk of decompensation postoperatively. Electrocardiography is of limited value for detecting cardiac problems in patients with adolescent idiopathic scoliosis, we recommend echocardiography as a routine modality in the preoperative evaluation of patients with adolescent idiopathic scoliosis.