Dual role of triglyceride structures facilitates anti-tumor drug delivery: Both as a self-assembling module and a responsive module.

Small molecule prodrugs self-assembled nano-delivery systems with tumor responsive linkages are emerging as an effective platform. However, the heterogeneity of tumor microenvironment may limit the anti-tumor effect of prodrug nanomedicines with a single response module. Here, we chose disulfide bond as the response module and branched chain alcohol as the self-assembly modification module to construct a single-responsive prodrug. We also constructed a double-responsive paclitaxel prodrug combining triglyceride and disulfide bond, taking into account of the highly expressed lipase and glutathione levels in tumor cells. The results showed that the anti-tumor effect of single-responsive branched chain alcohol modified prodrug nanoparticles was inferior to triglyceride prodrug nanoparticles with dual response modules. The triglyceride structure can not only serve as a self-assembly modification module, but also serve as a response module for intelligent drug release in tumor. Such dual roles will facilitate the efficient delivery of small molecule self-assembled prodrugs to tumor sites.

Enabling oral novel Taxanes-based Chemotherapy with Lipophilic prodrug Self-nanoemulsifying drug delivery system.

Larotaxel (LTX) and SB-T-1214 (SBT), two new synthetic experimental toxoids, have shown broad-spectrum antitumor activity, especially against tumors that are resistant to other drugs. However, their poor solubility, membrane permeability, and first-pass effect limits their use in oral administration. We designed and synthesized two long-chain triglyceride-mimic prodrugs of LTX (LTXSSTG) and SBT (SBTSSTG), which are bridged by disulfide bonds and efficiently incorporated them into Self-nanoemulsifying drug delivery system (SNEDDS). These prodrugs can bypass hepatic metabolism by entering the blood through intestinal lymphatic transport, following a similar oral absorption pathway to dietary lipids. It was found that LTXSSTG and SBTSSTG significantly improved oral bioavailability (about 4.5-fold for LTX and 3.4-fold for SBT) compared to their solution forms. Moreover, with LTXSSTG and SBTSSTG incorporating reduction stimulus-responsive spacer were much more effective in suppressing tumor growth in vivo with eliminated adverse effects than solution form. To sum up, this strategy provides a new avenue to enhance oral delivery of new toxoids.

Clinical efficacy and kinematic analysis of Chinese knotting technique-assisted posterior cruciate ligament reconstruction: A retrospective analysis.

To investigate the clinical efficacy and knee joint kinematic changes of posterior cruciate ligament (PCL) reconstruction assisted by Chinese knotting technique (CKT). A retrospective analysis was conducted on 88 cases of PCL reconstructive surgery admitted between September 2016 and September 2020. All patients were operated on by the same senior doctor and his team. The patients were divided into 2 groups according to whether the CKT was applied, with 44 cases in each group. Both groups received active rehabilitation treatment after surgery. All patients were followed up for more than 2 years. International knee documentation committee, hospital for special surgery (HSS), and Lysholm scores were used to evaluate the clinical efficacy of the 2 methods at 3, 12, and 24 months after surgery. The motion cycle and kinematic indices of the knee joint were measured by the Opti_Knee three-dimensional motion measurement system before surgery and at 3, 12, and 24 months after surgery. A secondary arthroscopic examination was performed at 12 months after surgery, MAS score was used to evaluate the secondary endoscopic examination of PCL. All the patients had wound healing in stage I without infection. International Knee in both sets Documentation Committee scores, HSS scores and Lysholm scores were gradually improved at all time points (P < .05); compared with the traditional group, the HSS score was higher in the reduction group 12 months after surgery (P < .05), but there was no significant difference at 24 months after surgery. 12 months and 24 months after 3 dimensional motion measurement system using Opti_Knee showed a reduction group before and after displacement and displacement of upper and lower range than the traditional group (P < 0. 05). One year after surgery, the good and good rate of MAS score reduction group was higher than traditional group. CKT assisted PCL reconstruction can improve the subjective function score of the affected knee joint and the results of secondary microscopy. Satisfactory knee kinematic function can be obtained in the early stage, and the anteroposteric relaxation of the knee joint can be reduced.

Endogenous cAMP elevation in Brassica napus causes changes in phytohormone levels.

In higher plants, the regulatory roles of cAMP (cyclic adenosine 3',5'-monophosphate) signaling remain elusive until now. Cellular cAMP levels are generally much lower in higher plants than in animals and transiently elevated for triggering downstream signaling events. Moreover, plant adenylate cyclase (AC) activities are found in different moonlighting multifunctional proteins, which may pose additional complications in distinguishing a specific signaling role for cAMP. Here, we have developed rapeseed (Brassica napus L.) transgenic plants that overexpress an inducible plant-origin AC activity for generating high AC levels much like that in animal cells, which served the genetic model disturbing native cAMP signaling as a whole in plants. We found that overexpression of the soluble AC activity had significant impacts on the contents of indole-3-acetic acid (IAA) and stress phytohormones, i.e. jasmonic acid (JA), abscisic acid (ABA), and salicylic acid (SA) in the transgenic plants. Acute induction of the AC activity caused IAA overaccumulation, and upregulation of TAA1 and CYP83B1 in the IAA biosynthesis pathways, but also simultaneously the hyper-induction of PR4 and KIN2 expression indicating activation of JA and ABA signaling pathways. We observed typical overgrowth phenotypes related to IAA excess in the transgenic plants, including significant increases in plant height, internode length, width of leaf blade, petiole length, root length, and fresh shoot biomass, as well as the precocious seed development, as compared to wild-type plants. In addition, we identified a set of 1465 cAMP-responsive genes (CRGs), which are most significantly enriched in plant hormone signal transduction pathway, and function mainly in relevance to hormonal, abiotic and biotic stress responses, as well as growth and development. Collectively, our results support that cAMP elevation impacts phytohormone homeostasis and signaling, and modulates plant growth and development. We proposed that cAMP signaling may be critical in configuring the coordinated regulation of growth and development in higher plants.

Silencing LY6D Expression Inhibits Colon Cancer in Xenograft Mice and Regulates Colon Cancer Stem Cells' Proliferation, Stemness, Invasion, and Apoptosis via the MAPK Pathway.

This study explored the role of lymphocyte antigen 6 family member D (LY6D) in colon cancer stem cells' (CCSCs) proliferation and invasion. LY6D was knocked down using siRNA, and the down-regulation of LY6D was verified using Western blotting. After LY6D knockdown, CCSCs' proliferation, stemness, and invasion were suppressed, whereas apoptosis was increased. Gene Ontology (GO) enrichment analysis revealed that the differentially expressed genes (DEGs) between siLY6D and the negative control groups were significantly enriched in the cell-substrate adherens junction, focal adhesion, and cell-substrate junction terms. Meanwhile, the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the DEGs were significantly enriched in the MAPK pathway. In addition, Western blotting results showed that pBRAF and pERK1/2, cascade kinases of the MAPK pathway, were significantly down-regulated after LY6D knockdown. In addition, nude mice xenograft experiments showed that the siLY6D treatment decreased tumor sizes and weights and improved tumor-bearing mice survival rates compared with the control group. In conclusion, these findings indicate that LY6D, which is highly expressed in CCSCs, is a key factor involved in tumor growth and development and might be a potential cancer marker and therapeutic target for colon cancer.

Effective DBS treatment improves neural information transmission of patients with disorders of consciousness: an fNIRS study.

Objective.Deep brain stimulation (DBS) is a potential treatment that promotes the recovery of patients with disorders of consciousness (DOC). This study quantified the changes in consciousness and the neuromodulation effect of DBS on patients with DOC.Approach.Eleven patients were recruited for this study which consists of three conditions: 'Pre' (two days before DBS surgery), 'Post-On' (one month after surgery with stimulation), and 'Post-Off' (one month after surgery without stimulation). Functional near-infrared spectroscopy (fNIRS) was recorded from the frontal lobe, parietal lobe, and occipital lobe of patients during the experiment of auditory stimuli paradigm, in parallel with the coma recovery scale-revised (CRS-R) assessment. The brain hemodynamic states were defined and state transition acceleration was taken to quantify the information transmission strength of the brain network. Linear regression analysis was conducted between the changes in regional and global indicators and the changes in the CRS-R index.Main results.Significant correlation was observed between the changes in the global transition acceleration indicator and the changes in the CRS-R index (slope = 55.910,p< 0.001,R2= 0.732). For the regional indicators, similar correlations were found between the changes in the frontal lobe and parietal lobe indicators and the changes in the CRS-R index (slope = 46.612,p< 0.01,R2= 0.694; slope = 47.491,p< 0.01,R2= 0.676).Significance.Our study suggests that fNIRS-based brain hemodynamics transition analysis can signify the neuromodulation effect of DBS treatment on patients with DOC, and the transition acceleration indicator is a promising brain functional marker for DOC.

Multitarget Protective Effects of JUB on Aß-Induced Neurotoxicity and the Mechanism Predication Using Network Pharmacology Analysis.

Amyloid-ß (Aß) is one of the core factors in the pathogenesis of Alzheimer's disease (AD), and the accumulation of its aggregates in the brain can form age-related plaques, leading to brain cell damage and intellectual decline, which may be the common intersection of all causes of neurotoxicity. Jujuboside B (JUB) has many characteristics such as hypnosis, sedation, antianxiety, and antioxidant stress. However, it is still unclear whether JuB can alleviate the neurotoxicity caused by Aß. Our study demonstrates that JUB improves learning and memory deficits in the nematode model. At the same time, JUB increases the antioxidant activity, prevents excessive accumulation of lipid synthesis, and resists endogenous lipofuscin deposition, thereby inhibiting the toxic effect of Aß. In vitro, JUB can improve Aß1-42-induced neuronal apoptosis level through the Bax/Bcl-2/caspase-3 signaling pathway and restore mitochondrial function in SH-SY5Y cells. The network pharmacology has been used to predict the potential neuroprotective mechanism of JUB. In summary, JUB exhibits neuroprotective properties employing both a neural cell and a nematode, which provides a basis for screening candidate ingredients for preventing AD.

Study of a Multiple Responses, High Deformation, and Programmable PLA-PPC/PVA-PDA Actuator.

The intelligent response actuators based on bilayer polymer can deform under the stimulation of temperature, humidity, light, and other external environment, which is the focus of research. However, achieving multiple responses, high deformation, and programmability is still one of the challenges for these actuators. Herein, a nondetachable bilayer structure, polylactic acid-polypropylene carbonate/polyvinyl alcohol-polydopamine (PLA-PPC/PVA-PDA) multiresponse programmable actuator is prepared by a simple scraping film method. Using PLA-PPC as the solvent-driven response layer, the effects of length, thickness, shape, and solvent vapor on the deformation of PLA-PPC/PVA-PDA actuators are studied. Among them, the high curvature of the film stimulated by ethyl acetate (EA) solution is 29.85 cm-1 . Using PVA-PDA as the response layer to water molecules and infrared (IR) light, the bilayer film shows excellent curling performance. Moreover, the dynamic processes of human clothing and biomimetic squid under solvent stimulation, the picture rolling motion under water molecule stimulation, the biomimetic flower blooming and merging under the synergistic of water molecules and IR light, and the deformation process of biomimetic mimosa under the competition between water molecules and IR light are simulated, which broadens the road for the development of intelligent driving materials.

[Establishment of anterior cruciate ligament reconstruction model in cynomolgus monkey with autogenous hamstring tendon transplantation].

Objective: To investigate the feasibility of establishing an anterior cruciate ligament (ACL) reconstruction model using hamstring tendon autograft in cynomolgus monkeys. Methods: Twelve healthy adult male cynomolgus monkeys, weighing 8-13 kg, were randomly divided into two groups ( n=6). In the experimental group, the ACL reconstruction model of the right lower limb was prepared by using a single bundle of hamstring tendon, and the ACL of the right lower limb was only cut off in the control group. The survival of animals in the two groups was observed after operation. Before operation and at 3, 6, and 12 months after operation, the knee range of motion, thigh circumference, and calf circumference of the two groups were measured; the anterior tibial translation D-value (ATTD) was measured by Ligs joint ligament digital body examination instrument under the loads of 13-20 N, respectively. At the same time, the experimental group underwent MRI examination to observe the graft morphology and the signal/ noise quotient (SNQ) was caculated. Results: All animals survived to the end of the experiment. In the experimental group, the knee range of motion, thigh circumference, and calf circumference decreased first and then gradually increased after operation; the above indexes were significantly lower at 3 and 6 months after operation than before operation ( P<0.05), and no significant difference was found between pre-operation and 12 months after operation ( P>0.05). In the control group, there was no significant change in knee range of motion after operation, showing no significant difference between pre- and post-operation ( P>0.05), but the thigh circumference and calf circumference gradually significantly decreased with time ( P<0.05), and the difference was significant when compared with those before operation ( P<0.05). At 6 and 12 months after operation, the thigh circumference and calf circumference were significantly larger in the experimental group than in the control group ( P<0.05). At 3 and 6 months after operation, the knee range of motion was significantly smaller in the experimental group than in the control group ( P<0.05). Under the loading condition of 13-20 N, the ATTD in the experimental group increased first and then decreased after operation; and the ATTD significantly increased at 3, 6 months after operation when compared with the value before operation ( P<0.05). But there was no significant difference between the pre-operation and 12 months after operation ( P>0.05). There was no significant change in ATTD in the control group at 3, 6, and 12 months after operation ( P>0.05), and which were significantly higher than those before operation ( P<0.05). At each time point after operation, the ATTD was significantly smaller in the experimental group than in the control group under the same load ( P<0.05). The MRI examination of the experimental group showed that the ACL boundary gradually became clear after reconstruction and was covered by the synovial membrane. The SNQ at each time point after operation was significantly higher than that before operation, but gradually decreased with time, and the differences between time points were significant ( P<0.05). Conclusion: The ACL reconstruction model in cynomolgus monkey with autogenous hamstring tendon transplantation was successfully established.

The Preparation of Superhydrophobic Polylactic Acid Membrane with Adjustable Pore Size by Freeze Solidification Phase Separation Method for Oil-Water Separation.

An environmentally friendly pore size-controlled, superhydrophobic polylactic acid (PLA) membrane was successfully prepared by a simpler freeze solidification phase separation method (FSPS) and solution impregnation, which has application prospects in the field of oil-water separation. The pore size and structure of the membrane were adjusted by different solvent ratios and solution impregnation ratios. The PLA-FSPS membrane after solution impregnation (S-PLA-FSPS) had the characteristics of uniform pore size, superhydrophobicity and super lipophilicity, its surface roughness Ra was 338 nm, and the contact angle to water was 151°. The S-PLA-FSPS membrane was used for the oil-water separation. The membrane oil flux reached 16,084 L·m-2·h-1, and the water separation efficiency was 99.7%, which was much higher than that of other oil-water separation materials. In addition, the S-PLA-FSPS membrane could also be applied for the adsorption and removal of oil slicks and underwater heavy oil. The S-PLA-FSPS membrane has great application potential in the field of oil-water separation.

Construction of a ratiometric fluorescent sensing platform based on near-infrared carbon dots for organophosphorus pesticides detection.

In this work, a convenient ratiometric fluorescent platform was designed to measure organophosphorus pesticides (OPs) based on acetylcholinesterase (AChE), acetylthiocholine (ATCh), manganese dioxide nanosheets (MnO2), near-infrared carbon dots (RCDs) and o-phenylenediamine (OPD). In this platform, a direct oxidation of OPD by MnO2 generated the luminescent product 2,3-diaminophenolazine (DAP) through intrinsic oxidase activity, while RCDs served as a fluorescent reference indicator. In the presence of AChE and ATCh, the enzymatic hydrolysate thiocholine (TCh) would reduce MnO2 nanosheets to Mn2+, leading to the quenching of DAP fluorescence. On the other hand, OPs can inhibit the catabolism of ATCh by AChE thus acting as a recognizer of OPs. According to these reactions, OPs were quantitatively analyzed by the intensity ratio of fluorescence emitted from RCDs and DAP (F560/F676). The constructed platform can detect OPs with the range of 0.2-0.6 µM with a detection limit of 4.3 nM. Figure A ratiometric fluorescent probe based on carbon dots was obtained and using it to determine the concentration of organophosphorus pesticides.

fNIRS-based functional connectivity signifies recovery in patients with disorders of consciousness after DBS treatment.

OBJECTIVE: While deep brain stimulation (DBS) has proved effective for certain patients with disorders of consciousness (DOC), the working neural mechanism is not clear, the response varies for patients, and the assessment is inadequate. This paper aims to quantify the DBS-induced changes of consciousness in DOC patients at the neural functional level. METHODS: Ten DOC patients were included for DBS surgery. The DBS target was the right centromedian-parafascicular (CM-pf) nuclei for four patients and the bilateral CM-pf nuclei for six patients. Functional near-infrared spectroscopy (fNIRS) was taken to measure the neural activation of patients, in parallel with Coma Recovery Scale-Revised (CRS-R), before the DBS surgery and one month after. The fNIRS signals were recorded from the frontal, parietal, and occipital lobes. Functional connectivity analysis quantified the communication between brain regions, area communication strength, and global communication efficiency. Linear regression analysis was conducted between the changes of indices based on functional connectivity analysis and the changes of the CRS-R index. RESULTS: Patients with trauma (n = 4) exhibited a greater increase of CRS-R scores after DBS treatment compared with patients with hemorrhage (n = 4) and brainstem infarction (n = 2). Global communication efficiency changed consistently with the CRS-R index (slope = 57.384, p < 0.05, R2=0.483). No significant relationship was found between the changes of area communication strength of six brain lobes and the changes of the CRS-R index. CONCLUSIONS: The cause of DOC is essential for the outcome of DBS treatment, and brain communication efficiency is a promising functional marker for DOC recovery. SIGNIFICANCE: fNIRS-based functional connectivity analysis on brain network signifies changes of consciousness in DOC patients after DBS treatment.

Establishing a glutamine metabolism-based model for predicting the prognosis of low-grade glioma.

Background: The natural history of patients with low-grade glioma (LGG) varies widely, but most patients eventually deteriorate, leading to poor prognostic outcomes. We aim to develop biological models that can accurately predict the outcome of LGG prognosis. Methods: Prognostic genes for glutamine metabolism were searched by univariate Cox regression, and molecular typing was constructed. Functional enrichment analysis was done to evaluate potential prognostic-related pathways by analyzing differential genes in different subtypes. Enrichment scores of specific gene sets in different subtypes were measured by gene set enrichment analysis. Different immune infiltration levels among subtypes were calculated using algorithms such as CIBERSORT and ESTIMATE. Gene expression levels of prognostic-related gene signatures of glutamine metabolism phenotypes were used to construct a RiskScore model. Receiver operating characteristic curve, decision curve and calibration curve analyses were used to evaluate the reliability and validity of the risk model. The decision tree model was used to determine the best predictor variable ultimately. Results: We found that C1 had the worst prognosis and the highest level of immune infiltration, among which the highest macrophage infiltration can be found in the M2 stage. Moreover, most of the pathways associated with tumor development, such as MYC_TARGETS_V1 and EPITHELIAL_MESENCHYMAL_TRANSITION, were significantly enriched in C1. The wild-type IDH and MGMT hypermethylation were the most abundant in C1. A five-gene risk model related to glutamine metabolism phenotype was established with good performance in both training and validation datasets. The final decision tree demonstrated the RiskScore model as the most significant predictor of prognostic outcomes in individuals with LGG. Conclusion: The RiskScore model related to glutamine metabolism can be an exceedingly accurate predictor for LGG patients, providing valuable suggestions for personalized treatment.

Ultrasonic-assisted extraction of swertisin from sour Jujube seed and comprehensive revelation of its antioxidant activity.

As a typical flavonoid glycoside, swertisin mainly exists in sour Jujube seed. In this study, swertisin was extracted by ultrasound-assisted extraction method optimized with Box-Behnken design and response surface methodology. The antioxidant effect of swertisin was determined in vitro and in Caenorhabditis elegans (C. elegans). Furthermore, the potential mechanisms of its antioxidant stress were comprehensively evaluated and explored with network pharmacology and molecular docking technology. The results showed obvious scavenging ability of swertisin on free radical and swertisin (50, 250, and 500 µmol/L) significantly enhanced antioxidative enzymes activity (GST-4, SOD-3, and GSH-PX ) and reduced the reactive oxygen species and malondialdehyde accumulation in C. elegans, thereby protecting them from oxidative stress (heat stress and hydrogen peroxide). A total of 139 antioxidant targets of swertisin were screened and 70 signal pathways were enriched, including cancer-related pathways, lipid metabolism, liver injury-related pathways, acute lung injury, nervous system diseases, etc. This study provides the basis for further investigation on the antioxidant stress mechanism and contributes to the development of relevant drugs from natural products. PRACTICAL APPLICATIONS: The imbalance between the antioxidant defense system and reactive oxygen species is one of the main causes of neurodegenerative diseases, cardiovascular diseases, cancer, and aging. Therefore, alleviating oxidative stress injury has become a common strategy, which is helpful for the multi-target treatment of related diseases. The flavonoid of sour Jujube seed possesses potential antioxidant activity with multiple food health effects. From this study results, we optimized ultrasound-assisted extraction method for extracting the swertisin from sour Jujube seed and supported the use of C. elegans as an in vivo experimental model. We can recommend that the swertisin as a natural ingredient has a positive effect on antioxidation, which provided a scientific basis for treating related diseases through relevant pharmacological mechanisms and making antiaging functional food formula.

Synthetic MRI, multiplexed sensitivity encoding, and BI-RADS for benign and malignant breast cancer discrimination.

Objective: To assess the diagnostic value of predictive models based on synthetic magnetic resonance imaging (syMRI), multiplexed sensitivity encoding (MUSE) sequences, and Breast Imaging Reporting and Data System (BI-RADS) in the differentiation of benign and malignant breast lesions. Methods: Clinical and MRI data of 158 patients with breast lesions who underwent dynamic contrast-enhanced MRI (DCE-MRI), syMRI, and MUSE sequences between September 2019 and December 2020 were retrospectively collected. The apparent diffusion coefficient (ADC) values of MUSE and quantitative relaxation parameters (longitudinal and transverse relaxation times [T1, T2], and proton density [PD] values) of syMRI were measured, and the parameter variation values and change in their ratios were calculated. The patients were randomly divided into training (n = 111) and validation (n = 47) groups at a ratio of 7:3. A nomogram was built based on univariate and multivariate logistic regression analyses in the training group and was verified in the validation group. The discriminatory and predictive capacities of the nomogram were assessed by the receiver operating characteristic curve and area under the curve (AUC). The AUC was compared by DeLong test. Results: In the training group, univariate analysis showed that age, lesion diameter, menopausal status, ADC, T2pre, PDpre, PDGd, T2Delta, and T2ratio were significantly different between benign and malignant breast lesions (P < 0.05). Multivariate logistic regression analysis showed that ADC and T2pre were significant variables (all P < 0.05) in breast cancer diagnosis. The quantitative model (model A: ADC, T2pre), BI-RADS model (model B), and multi-parameter model (model C: ADC, T2pre, BI-RADS) were established by combining the above independent variables, among which model C had the highest diagnostic performance, with AUC of 0.965 and 0.986 in the training and validation groups, respectively. Conclusions: The prediction model established based on syMRI, MUSE sequence, and BI-RADS is helpful for clinical differentiation of breast tumors and provides more accurate information for individualized diagnosis.

Molecular Targets and Biological Functions of cAMP Signaling in Arabidopsis.

Cyclic AMP (cAMP) is a pivotal signaling molecule existing in almost all living organisms. However, the mechanism of cAMP signaling in plants remains very poorly understood. Here, we employ the engineered activity of soluble adenylate cyclase to induce cellular cAMP elevation in Arabidopsis thaliana plants and identify 427 cAMP-responsive genes (CRGs) through RNA-seq analysis. Induction of cellular cAMP elevation inhibits seed germination, disturbs phytohormone contents, promotes leaf senescence, impairs ethylene response, and compromises salt stress tolerance and pathogen resistance. A set of 62 transcription factors are among the CRGs, supporting a prominent role of cAMP in transcriptional regulation. The CRGs are significantly overrepresented in the pathways of plant hormone signal transduction, MAPK signaling, and diterpenoid biosynthesis, but they are also implicated in lipid, sugar, K+, nitrate signaling, and beyond. Our results provide a basic framework of cAMP signaling for the community to explore. The regulatory roles of cAMP signaling in plant plasticity are discussed.

[Application of modified anterolateral supra-fibular-head approach in treatment of tibial plateau fractures involving posterolateral column].

OBJECTIVE: To explore effectiveness of reduction and internal fixation via modified anterolateral supra-fibular-head approach in treatment of tibial plateau fractures involving posterolateral column. METHODS: Between January 2016 and September 2018, 19 patients diagnosed as tibial plateau fractures involving posterolateral column were treated with reduction and internal fixation via modified anterolateral supra-fibular-head approach. There were 11 males and 8 females with an average age of 43.2 years (range, 28-65 years). The causes of tibial fracture were traffic accident (12 patients), falling injury (5 patients), and falling from height (2 patients). According to the Schatzker typing, the tibial fractures were rated as type Ⅱ in 9 cases, type Ⅲ in 4 cases, type Ⅴ in 4 cases, and type Ⅵ in 2 cases. The time from injury to operation was 5-13 days (mean, 8.5 days). There were 2 patients with osteoporosis. The operation time, intraoperative blood loss, and postoperative complications were recorded. The knee X-ray film was reviewed regularly to observe the fracture healing. At last follow-up, the fracture reductions were evaluated by Rasmussen radiological score. The knee joint function was evaluated by Hospital for Special Surgery (HSS) score system. RESULTS: The average operation time was 95 minutes (range, 65-130 minutes). The average intraoperative blood loss was 220 mL (range, 150-350 mL). All incisions healed by first intention. No complications such as infection or deep venous thrombosis occurred. All patients were followed up 12-20 months (mean, 15.4 months). X-ray films showed that the fractures healed with the healing time of 12-20 weeks (mean, 14.5 weeks). No complications such as loosening or breakage of internal fixation occurred. At last follow-up, according to the Rasmussen radiological score, the fracture reductions were evaluated as excellent in 13 cases, good in 4 cases, fair in 1 case, and poor in 1 case. HSS scores of knee joint function were excellent in 14 cases, good in 3 cases, fair in 1 case, and poor in 1 case. The knee joint range of motion was 90°-135°, with an average of 113.4°. CONCLUSION: Application of modified anterolateral supra-fibular-head approach in reduction and internal fixation for tibial plateau fractures involving posterolateral column has the advantages of full exposure, less trauma, safety, and reliable reduction and fixation.

Insulin-like growth factor 1/insulin-like growth factor 1 receptor signaling protects against cell apoptosis through the PI3K/AKT pathway in glioblastoma cells.

Glioblastoma multiforme (GBM) is a malignant tumor caused by complex pathological mechanisms, and is characterized by a high rate of cancer-related mortality and poor patient prognosis. Overgrowth of cancer cells, which results from the inhibition of cell apoptosis and/or the promotion of cell proliferation, leads to the progression of GBM. Therefore, studies into the regulatory mechanisms of cancer cell growth in GBM are required to identify potential therapeutic targets and improve treatment for GBM. In the present study, the role of insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1R) signaling in the survival of GBM cells was evaluated. It was observed that IGF1 significantly inhibited the intrinsic and extrinsic pathways of apoptosis (P<0.05), and overexpression of IGF1R significantly promoted the survival of GBM cells (P<0.05). Moreover, both exogenous IGF1 and overexpression of IGF1R promoted the phosphorylation of protein kinase B (AKT), and inhibition of the phosphoinositide 3-kinase (PI3K)/AKT pathway significantly attenuated the inhibitory effects of IGF1/IGF1R on GBM apoptosis (P<0.05). Collectively, these findings indicate that IGF1/IGF1R promotes the survival of GBM cells through activation of the PI3K/AKT pathway. Therefore, inhibition of IGF1/IGF1R may be a viable therapeutic strategy to suppress the progression of GBM.

Clinical significance of novel biomarker NGAL in early diagnosis of acute renal injury.

The present study investigated the clinical significance of the novel biomarker neutrophil gelatinase-associated lipocalin (NGAL) for the early diagnosis of acute renal injury (AKI). Thirty-eight critically ill patients with acute renal injury treated at Zhengzhou No. 7 People's Hospital between December 2015 and November 2016 served as the AKI group (observation group). At the same time, 38 critically ill patients without acute renal injury were also selected as the non-AKI group (control group). Serum NGAL and creatinine (SCr) levels were measured by enzyme-linked immunosorbent assay (ELISA) at 2, 8, 12 and 24 h post-operation, whereas particle-enhanced turbidimetric immunoassay (PETIA) was used to quantify the levels of cysteine protease inhibitor cystatin C (CysC) in serum at 2, 8, 12 and 24 h post-operation. The correlations between indicators were also analyzed, with ROC curves used to evaluate the diagnostic values of NGAL, SCr and CysC in AKI. No significant differences in SCr levels were found between the two groups at different time-points after operation (P>0.05), but NGAL and CysC levels in the observation group were significantly higher than in the control group (P<0.05). Pearson correlation coefficient analysis showed NGAL and CysC were positively correlated with Scr levels. For NGAL in early diagnosis, the area under the AKI curve was 0.904, the sensitivity was 90.2% and the specificity was 89.5%; for CysC in early diagnosis, the area under the AKI curve was 0.806, the sensitivity was 79.2% and the specificity was 78.5%; for SCr in early diagnosis, the area under the AKI curve was 0.634, the sensitivity was 64.2% and the specificity was 62.5%. Therefore, NGAL demonstrated a satisfactory early predictive value for AKI and can be used as a biomarker for early AKI diagnosis.