Reconstruction Strategy for Upper Extremity Defects After Bone Tumor Resection Based on 3D Customized Bone Cement Mold.

BACKGROUND: Reconstructing bone defects in the upper extremities and restoring their functions poses a significant challenge. In this study, we describe a novel workflow for designing and manufacturing customized bone cement molds using 3D printing technology to reconstruct upper extremity defects after bone tumor resection. METHODS: Computer tomography data was acquired from the unaffected upper extremities to create a detachable mold, which can be customized to fit the joint precisely by shaping the bone cement accordingly. Fourteen patients who underwent reconstructive surgery following bone tumor resection in the proximal humerus (13 cases) or distal radius (1 case) between January 2014 and December 2022 were retrospectively evaluated. The medical records of this case series were reviewed for the demographic, radiological, and operative data. Metastasis, local recurrence, and complication were also reviewed. Additionally, Musculoskeletal Tumor Society Score (MSTS) and Visual Analogue Scale (VAS) were used to assess clinical outcomes. RESULTS: The mean follow-up period was 49.36 ± 15.18 months (range, 27-82 months). At the end of follow-up, there were no cases of metastasis or recurrence, and patients did not experience complications such as infection, dislocation, or implant loosening. Two cases complicated with subluxation (14.3%), and 1 case underwent revision surgery for prosthetic fracture (7.1%). The average MSTS score was 23.2 ± 1.76 (77.4%, range, 66.7%-86.7%), and the postoperative VAS score was 1.86 ± 1.03 (range, 1-4), which was significantly lower than that before surgery (average preoperative VAS score was 5.21 ± 2.00 (range, 2-8)) (P < .001). CONCLUSION: Customized 3D molds can be utilized to shape bone cement prostheses, which may serve as a potential alternative for reconstructing the proximal humerus and distal radius following en bloc resection of bone tumors. This reconstruction strategy offers apparent advantages, including precise matching of articular surfaces and comparatively reduced costs.

YY1-induced lncRNA00511 promotes melanoma progression via the miR-150-5p/ADAM19 axis.

Increasing evidence indicates that long noncoding RNAs (lncRNAs) are therapeutic targets and key regulators of tumors development and progression, including melanoma. Long intergenic non-protein-coding RNA 511 (LINC00511) has been demonstrated as an oncogenic molecule in breast, stomach, colorectal, and lung cancers. However, the precise role and functional mechanisms of LINC00511 in melanoma remain unknown. This study confirmed that LINC00511 was highly expressed in melanoma cells (A375 and SK-Mel-28 cells) and tissues, knockdown of LINC00511 could inhibit melanoma cell migration and invasion, as well as the growth of subcutaneous tumor xenografts in vivo. By using Chromatin immunoprecipitation (ChIP) assay, it was demonstrated that the transcription factor Yin Yang 1 (YY1) is capable of binding to the LINC00511 promoter and enhancing its expression in cis. Further mechanistic investigation showed that LINC00511 was mainly enriched in the cytoplasm of melanoma cells and interacted directly with microRNA-150-5p (miR-150-5p). Consistently, the knockdown of miR-150-5p could recover the effects of LINC00511 knockdown on melanoma cells. Furthermore, ADAM metallopeptidase domain expression 19 (ADAM19) was identified as a downstream target of miR-150-5p, and overexpression of ADAM19 could promote melanoma cell proliferation. Rescue assays indicated that LINC00511 acted as a competing endogenous RNA (ceRNA) to sponge miR-150-5p and increase the expression of ADAM19, thereby activating the PI3K/AKT pathway. In summary, we identified LINC00511 as an oncogenic lncRNA in melanoma and defined the LINC00511/miR-150-5p/ADAM19 axis, which might be considered a potential therapeutic target and novel molecular mechanism the treatment of patients with melanoma.

LS-MolGen: Ligand-and-Structure Dual-Driven Deep Reinforcement Learning for Target-Specific Molecular Generation Improves Binding Affinity and Novelty.

Deep learning-based molecular generative models have garnered considerable interest in the field of de novo drug design. However, most extant models focus on either ligand-based or structure-based strategies, thereby failing to effectively harness the combined knowledge derived from both ligands and the structure of the binding target. In this article, we introduce LS-MolGen, a novel ligand and structure-integrated molecular generative model. This model synergistically combines representation learning, transfer learning, and reinforcement learning. The targeted knowledge assimilation from transfer learning, coupled with an advanced exploration strategy in reinforcement learning, empowers LS-MolGen to efficiently generate novel and high-affinity molecules efficiently. The comparable performance of our model is affirmed through multiple evaluations, including EGFR, DRD3, CDK2, AA2AR, ADRB2, and a dedicated case study of inhibitor design for SARS-CoV-2 Mpro. The results indicate that LS-MolGen performs better than other ligand-based or structure-based generative models in de novo designing promising compounds with novel scaffolds and high binding affinity. This proof-of-concept study signifies the potential of our ligand- and structure-based generative model, LS-MolGen, as a promising new tool for target-specific molecular generation and drug design.

Are there correlations between facet joint parameters and lumbar disk herniation laterality in young adults?

OBJECTIVE: We aimed to determine whether there is an association, in young adults, between the occurrence of lumbar disk herniation (LDH) at a given segment and the segment's facet joint parameters [facet orientation (FO) and tropism (FT)]. In addition, associations between facet joint parameters in the corresponding segment and LDH laterality were also investigated. METHODS: We retrospectively analyzed data from 529 patients who were between 18 and 35 years old, who had experienced single-level LDH (L4-5 or L5-S1) between June 2017 and December 2019, and with<2 years of clinical history. We included an additional 122 patients with no history of LDH as an age-matched control group. LDH were classified by laterality (left-sided, right-sided, or central herniation). At each level, we investigated the relationship between facet joint parameters and herniation laterality. RESULTS: FOA values at the L4-L5 level and the L5-S1 level were significantly lower and FT was higher for the LDH group compared with those for the control group. The level at which LDH occurred, FOL, FOR, and FT differed significantly among the three groups. There was a significant association between herniationlaterality and FO at the L4-L5 level but not at the L5-S1 level. CONCLUSIONS: Abnormal facet joint parameters are significantly associated with LDH. Young adults with higher FT should be paid more attention, to prevent the occurrence of LDH. Compared with L5-S1 level, intervertebral disk herniation at the L4-L5 level tended to occur ipsilateral to the side with a lower facet joint angle when FT was present.

A Morphometric Study of the Distal Femoral Resected Surface In Osteoarthritis Knees of the Patients in Southwest China and a Comparison with Femoral Components in Six Total Knee Arthroplasty Systems.

OBJECTIVE: Mismatch between the femoral component and the resected surface is related to the postoperative clinical outcome. This study aimed to measure the morphometric features of the distal femoral resected surfaces in patients with osteoarthritis in southwestern China and to compare the measured morphometric data with six commonly used total knee arthroplasty (TKA) femoral components in China. METHOD: The computer tomography (CT) images of a total of 406 knees from 203 osteoarthritis patients who underwent TKA from January 2018 to December 2021 were imported into Mimics 21.0 software to reconstruct the three-dimensional (3D) model of the femur. Morphometric data of the distal femoral resected surfaces were measured after the completion of simulated bone resection in the software. The data included the medial-lateral (ML) dimension, anterior-posterior (AP) dimension, and the aspect ratio (AR) (AR = ML/AP), which were compared between genders with independent sample t-tests. In addition, we plotted the scatter diagram of those morphometric data in Origin software, and the linear fits of ML versus AP and AR versus AP were performed and compared for the six femoral components commonly used in enrolled patients in China. RESULTS: The mean ML dimension, the mean AP dimension, and the mean AR value measured for Chinese knees were 66.62 ± 4.57 mm, 58.10 ± 3.74 mm, and 1.15 ± 0.06 respectively. All dimensions were significantly larger in males than in females, including the calculated values for AR (P < 0.05). The fitted lines for males showed that the ML dimensions tended to be wider compared to femoral components of a given AP dimension. Females tended to have wider ML dimensions compared to small femoral components and, on the other hand, narrower ML dimensions compared to large femoral components. CONCLUSION: The femoral component of the current commonly used TKA prosthesis in China may not be perfectly matched to the distal femoral resected surface of patients in southwestern China. Male patients tended to underhang in all dimensions of the ML dimension. Female patients with shorter AP lengths are more likely to experience underhang, whereas those with longer AP lengths are more likely to develop overhangs. Therefore, we recommend multiple ML width options for a given AP length to more appropriately match the Chinese femoral anatomy.

SAM-DTA: a sequence-agnostic model for drug-target binding affinity prediction.

Drug-target binding affinity prediction is a fundamental task for drug discovery and has been studied for decades. Most methods follow the canonical paradigm that processes the inputs of the protein (target) and the ligand (drug) separately and then combines them together. In this study we demonstrate, surprisingly, that a model is able to achieve even superior performance without access to any protein-sequence-related information. Instead, a protein is characterized completely by the ligands that it interacts. Specifically, we treat different proteins separately, which are jointly trained in a multi-head manner, so as to learn a robust and universal representation of ligands that is generalizable across proteins. Empirical evidences show that the novel paradigm outperforms its competitive sequence-based counterpart, with the Mean Squared Error (MSE) of 0.4261 versus 0.7612 and the R-Square of 0.7984 versus 0.6570 compared with DeepAffinity. We also investigate the transfer learning scenario where unseen proteins are encountered after the initial training, and the cross-dataset evaluation for prospective studies. The results reveals the robustness of the proposed model in generalizing to unseen proteins as well as in predicting future data. Source codes and data are available at https://github.com/huzqatpku/SAM-DTA.

The principles of health, illness and treatment - The key concepts from "The Yellow Emperor's Classic of Internal Medicine".

The Yellow Emperor's Classic of Internal Medicine is an important book in the study of Traditional Chinese Medicine (TCM) with the text presenting an integration of the essential TCM practices and philosophy in the use and application of Chinese medicine for healthcare. Within the Chinese Health System, TCM provides a balancing and integrating approach to health and the prevention of disease. The book provides the story of human existence, of our relationship to the environment and how 'balance' provides us with health and wellbeing in our daily lives. The role of the TCM practitioner is to look for wellness as a way of preventing disease. This paper discusses the key terms of the 'Dao', 'Qi', 'Yin' and 'Yang', 'Ben' and 'Biao' and the essence and role of the elements of fire, water, wood, metal and earth in health and disease prevention. TCM is an integrative approach to health and has many lessons for global health systems.

Mechanism study of platelet derived growth factor receptor alpha on the bidirectional differentiation regulation of glioma-associated oncogene homolog 1-positive mesenchymal stem cells in mice / 中华口腔医学杂志

Objective: To investigate the role of platelet derived growth factor receptor alpha (PDGFRα) on bidirectional differentiation of glioma-associated oncogene homolog 1-positive mesenchymal stem cells (Gli1+-MSC). Methods: Breeding double reporter transgenic mice ROSAmT/mG/Gli1-CreERt2/PDGFRαfl (Experimental group) and ROSAmT/mG/Gli1-CreERt2 (Control group), 20 mice in each of the two groups at four weeks of age were selected, MSC were isolated from the mouse aortic epithelium. After tamoxifen inducement, the two groups of Gli1+-MSC were screened by green fluorescent protein (GFP) labeling and flow cytometry sorting. PDGFRα was conditionally knocked out in the experimental group, and the control group Gli1+-MSC expressed PDGFRα normally. The two groups of Gli1+-MSC were subjected to adipogenic induction and fibrogenic induction, the Western blotting was performed to detect PDGFRα, adipocyte markers [perilipin and CCAAT/enhancer binding protein alpha (C/EBPα)] and fibrogenic markers [alpha smooth muscle actin (α-SMA) and fibroblast-specific protein 1 (FSP-1)] and semi-quantitative analysis was performed. The degree of cellular adipose differentiation after bidirectional induction of Gli1+-MSC in both groups was observed by oil red O staining and analyzed semi-quantitatively. Results: After tamoxifen induction, Gli1+-MSC could be accurately isolated from flow cytometry by GFP labeling. Via adipogenic differentiation, the expression of PDGFRα in the experimental group (0.017±0.002) was significantly lower than that in the control group (0.184±0.012) (t=25.48，P=0.002). The protein expressions of perilipin (3.138±0.414) and C/EBPα (3.565±0.289) were significantly higher than those in the control group (2.312±0.218 and 2.179±0.103, respectively) (t=6.21，P=0.025；t=6.69，P=0.022). Thus, the knock-out of PDGFRα enhanced the adipogenic differentiation ability of Gli1+-MSC. After fibrogenesis induction, the protein expressions of PDGFRα, α-SMA and FSP-1 in the experimental group (0.030±0.001, 0.932±0.177 and 0.276±0.020, respectively) were significantly lower than those in the control group (0.439±0.006, 1.352±0.170 and 0.835±0.097, respectively) (t=149.40, P<0.001; t=66.38,P<0.001; t=11.41,P<0.08). This suggested that the knock-out of PDGFRα significantly inhibited Gli1+-MSC differentiation toward fibroblasts. After bidirectional induction, significantly less adipocyte formation was seen in the control group and more in the experimental group. Quantitative analysis showed that the amount of oil red O staining in the experimental group (0.461±0.042) was significantly higher than that in the control group (0.017±0.007) after bidirectional induction (t=23.20, P<0.01). Conclusions: PDGFRα plays an important role in the regulation of bidirectional differentiation of vascular adventitial Gli1+-MSC.

Education level has an effect on the recovery of total knee arthroplasty: a retrospective study.

OBJECTIVE: This study aimed to observe the relationship between education level and outcomes after total knee arthroplasty (TKA). METHODS: One thousand two hundred sixty four patients after TKA in our hospital from April 2016 to April 2020 were reviewed. These patients were divided into 4 groups (A who were illiterate, B who had elementary school degree, C who had junior high school degree, D who had senior high school degree or higher) by the educational level, which was blinded to the observers. The postoperative outcomes of KSS score, pain, joint extension and flexion function were observed 1 year after discharged from hospital. RESULTS: Among 1253 patients met the inclusion criteria, the average age was 68.63 years, the average body mass was 57.73 kg. There are no distinctions among 4 groups one day after the surgery. However, the outcomes of the follow up were that, the KSS score was: 77.84 ± 10.635; 80.70 ± 8.956; 87.92 ± 8.123;91.27 ± 8.262, with significant differences (P < 0.05). The mean VAS scores were: 1.97 ± 1.60; 2.07 ± 1.66; 1.197 ± 1.5265, 1.044 ± 1.4662. Patients in Group C and D had significantly less pain than that in Group A and B (P < 0.05). The knee flexion range of motion (ROM) was: 91.21 ± 11.69°; 91.77 ± 11.95°; 102.12 ± 11.38°; 109.96 ± 10.64°, Group D performed best, with significant differences (P < 0.05). The knee extension ROM were: - 2.41 ± 4.49°; - 0.91 ± 2.82°; - 0.83 ± 2.87°; - 0.35 ± 1.60°, with significant difference between Group D and the others (P < 0.05). CONCLUSION: Education level affects the outcomes such as VAS score, KSS score, the extension and flexion ROM of the knee after TKA. The patients with higher education level have better outcomes.

The Antibacterial Activity Comparison between Novel Carbon-Based Nanofilm Coated Titanium Alloy and Co-Cr-Mo Alloy.

Objective: The purpose of this study was to reveal the antibacterial activity of carbon-based nanofilm titanium alloy. Methods: The experiments were performed both in vitro and in vivo of animals using two circular-piece test specimens of the same specification, which were made from carbon-based nanofilm coated titanium alloy and commonly used in artificial joints Co-Cr-Mo alloy, respectively. In the in vitro experiments, the two test specimens were cocultured with standard strains of Staphylococcus aureus and Escherichia coli, and the antibacterial properties of the two test specimens were evaluated via inhibition zone size, scanning electron microscopy, fluorescence staining, colony forming unit count, and others; the cytotoxicities of the two test specimens were evaluated by coculturing and them with rabbit bone marrow mesenchymal stem cells (BMSCs). In the in vivo experiments, the two test specimens were implanted in the muscle tissue of experimental rabbits to evaluate their histocompatibilities. Results: Both in vitro cocultures of the carbon-based nanofilm titanium alloy and the Co-Cr-Mo alloy with Staphylococcus aureus and Escherichia coli failed to form inhibition zone. However, some biofilms were observed on the surface of the Co-Cr-Mo alloy. Fewer bacteria adhered to the carbon-based nanofilm titanium alloy can be observed via scanning electron microscopy and fluorescence staining techniques. Meanwhile, the colony forming counts showed that, compared with the Co-Cr-Mo alloy, the carbon-based nanofilm titanium alloy had fewer bacteria adhered (P < 0.05). After coculture of the two test specimens with rabbit BMSCs, there was no significant difference in cell count, and both cell counts showed no cytotoxicity. In the in vivo experiment of animals, there are relatively fewer giant cells and better histocompatibility in tissues near the carbon-based nanofilm titanium alloy. Conclusion: Compared with Co-Cr-Mo alloy, the novel carbon-based nanofilm titanium alloy enjoys stronger in vitro antibacterial activity and better in vivo histocompatibility.

A Strong Correlation Between the Severity of Flatfoot and Symptoms of Knee Osteoarthritis in 95 Patients.

Objective: The purpose of this study is to assess the association between the presence and severity of flatfoot and symptoms of knee OA. Methods: 95 participants with knee OA were recruited from a patient cohort at a regional hospital. Symptoms of knee OA, including knee degeneration, femorotibial alignment, pain, stiffness and dysfunction were assessed using the Kellgren-Lawrence (K-L) grading system, femoral-tibial angle (FTA), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Participants were divided into groups with flatfoot (mild, moderate and severe) and without flatfoot based on the Clarke's angle. Linear regression and ordinal logistic regression were used for statistical analysis, as appropriate. Results: Having flatfoot was associated with a significantly increased risk of having a higher K-L grade (OR: 20.03; 95% CI, 5.88, 68.27; p < 0.001), smaller FTA (Beta: -2.96; 95% CI, -4.41, -1.50; p < 0.001), higher pain score (Beta: 0.47; 95% CI, 0.24, 0.69; p < 0.001) and greater loss of function (Beta: 0.25; 95% CI, 0.02, 0.48; p = 0.03). Severe grades of flat feet were associated with a higher K-L grade (OR: 0.19; 95% CI, 0.08, 0.44; p < 0.001), smaller FTA (Beta: 1.51; 95% CI, 0.66, 2.35; p = 0.001), higher pain score (Beta: -0.25; 95% CI, -0.39, -0.11; p = 0.001), greater stiffness (Beta: -0.24; 95% CI, -0.38, -0.09; p = 0.002) and greater loss of function (Beta: -0.27; 95% CI, -0.41, -0.14; p < 0.001). Conclusion: The results indicated that the severity of flattening is significantly associated with symptoms of knee OA. For the conservative management of knee OA, both flatfoot and its severity should be carefully considered.

Saccharina japonica fucan suppresses high fat diet-induced obesity and enriches fucoidan-degrading gut bacteria.

Low molecular weight seaweed polysaccharides exhibit promising potential as novel therapeutics for the prevention of obesity and gut microbiota dysbiosis. The interplay between polysaccharides and gut microbiota may play crucial roles in their anti-obesity effects, but is largely unknown, including the impact of polysaccharides on the composition of the gut microbiota with polysaccharide-degrading capacity. The primary structure of a 5.1 kDa fucan (J2H) from Saccharina japonica was characterized and oral administration of J2H effectively suppressed high-fat diet-induced obesity, blood glucose metabolic dysfunction, dyslipidemia, and gut microbiota dysbiosis. Furthermore, the Jensen-Shannon divergence analysis demonstrated that J2H enriched at least four gut bacterial species with fucoidan-degrading potential, including Bacteroides sartorii and Bacteroides acidifaciens. Our findings suggest that the low molecular weight S. japonica fucan, J2H, is a promising potential agent for obesity prevention and its enrichment of gut bacteria with fucoidan-degrading potential may play a vital role in the anti-obesity effects.

Preparation and evaluation of experimental animal models of ischemic brain injury / 中国药理学通报

Aim Ischemic brain injury ( IBI) is one of the main causes of death and disability worldwide.Faced with this serious disease, human beings still laek effective treatment methods.With the advancement of science and the improvement of medi¬cal standards, the basic and clinieal research of cerebrovaseular diseases continues to develop to a higher and more in-depth lev¬el.Due to the limitations of clinical researeh, animal models of eerebral ischemia have beeome an indispensable tool for studying the mechanism of cerebrovascular disease damage and prevention and treatment measures.It is necessary to construct scientific, standard and standardized experimental methods and proee- dures..Methods This artiele combines our laboratory s long-tenn praetieal experienee in preparing animal models of cerebral is¬chemia.comprehensive literature data, comparison and evalua¬tion of the characteristics of commonly used animal models.Re¬sults Standardized preparation methods and discusses the com¬mon criteria for preparing experimental animal models of cerebral Ischemia, which is the occurrence of cerebral ischemia injury.Conclusions 'Hie researeh of mechanism and the researeh and de¬velopment of prevention and treatment drugs provide reliable ex¬perimental animal models.

Relieved Low Back Pain after Total Hip Arthroplasty in Patients with Both Hip Osteoarthritis and Lumbar Degenerative Disease.

OBJECTIVE: To investigate the relief of low back pain after hip arthroplasty in patients with hip joint and spinal degenerative diseases, and to discuss the effects of unilateral and bilateral hip surgery on the relief of low back pain. METHODS: In this retrospective study, we followed 153 patients (69 males and 84 females, age: 43-88 years) who had undergone total hip arthroplasty (THA) via a posterolateral approach and also suffered from lumbar degenerative diseases in the period of 2009 to 2019. The inclusion criteria were: (i) patients who had been diagnosed with severe hip degenerative disease and also been diagnosed with lumbar degenerative disease; (ii) patients who had undergone THA surgery; and (iii) patients who were retrospectively recruited. The exclusion criteria were: (i) patients who had undergone lumbar fusion or internal fixation surgery; or (ii) patients who had vascular claudication, history of major trauma, diabetic polyneuropathy, lumbar and pelvic infections, tumor diseases; (iii) or patients who had undergone THA because of femoral neck fracture or ankylosing spondylitis. The improvement of hip joint function and the relief of low back pain (LBP) were studied, and the effect of unilateral and bilateral THA on the relief of LBP were discussed. Hip pain and function were evaluated by the Harris Hip Score (HHS), LBP was evaluated by Visual Analog Scale (VAS), and lumbar function was evaluated by the Japanese Orthopaedic Association (JOA) scoring system. RESULTS: The average follow-up time was 44.3 months (24-108 months). All patients recovered smoothly without complications. The LBP VAS of 153 patients decreased from 4.13 ± 1.37 preoperatively to 1.90 ± 1.44 postoperatively. The average HHS increased from 45.33 ± 13.23 preoperatively to 86.44 ± 7.59 postoperatively at the latest follow-up. According to Japanese Orthopaedic Association scoring system, the proportion of patients with good response to treatment in these 153 patients reached 93.46%. LBP VAS decreased from 4.18 ± 1.38 preoperatively to 1.95 ± 1.49 postoperatively in unilateral group and from 3.94 ± 1.32 preoperatively to 1.73 ± 1.23 postoperatively in bilateral group, respectively. There were only nine patients with persistent or aggravated LBP after operation. Among them, six patients underwent subsequent lumbar surgery (five patients had pain relieved after reoperation and one patient had not) and the other three patients chose conservative treatment for pain. CONCLUSION: THA can relieve LBP while relieving hip pain and restoring hip function in patients with both hip and lumbar degenerative disease, thus possibly avoiding further spinal surgery.

Inflammation-Immunity-Nutrition Score: A Novel Prognostic Score for Patients with Resectable Colorectal Cancer.

PURPOSE: This study was designed to investigate the prognostic value of the combination of high-sensitivity C-reactive protein, lymphocyte, and albumin in patients with resectable colorectal cancer. PATIENTS AND METHODS: Seven-hundred-and-nineteen patients who underwent colorectal cancer resection in Hubei Cancer Hospital were included. Inflammation-Immunity-Nutrition score (0-6) was constructed based on preoperative high-sensitivity C-reactive protein, lymphocyte, and albumin. Time-dependent receiver operating characteristic curve, decision curve, Kaplan-Meier survival curve, Cox regression, and C-index were conducted to detect the prognostic values of inflammation-immunity-nutrition score. The prognostic values of inflammation-immunity-nutrition score in different subgroups by sex, location of tumor, pathologic stage, and KRAS mutation were also explored. The prognostic performance of inflammation-immunity-nutrition score was further compared with that of other traditional prognostic indicators. RESULTS: The median follow-up time was 40 months. High inflammation-immunity-nutrition score (>2 scores) presented worse survival, with the adjusted hazard ratios (95% confidence intervals) of 3.106 (2.202-4.380) for overall survival and 2.105 (1.604-2.764) for disease-free survival. Besides, the associations of high inflammation-immunity-nutrition score with overall survival were even stronger in cases with wild type KRAS, with the adjusted hazard ratios (95% confidence intervals) of 4.018 (2.355-6.854). Considering the AUCs, C-indices, and hazard ratios estimates, inflammation-immunity-nutrition score presented better prognostic performance than high-sensitivity modified Glasgow prognostic score, high-sensitivity C-reactive protein to albumin ratio, prognostic nutrition index, carcinoembryonic antigen, and carbohydrate antigen 19-9 for overall survival. CONCLUSION: Inflammation-immunity-nutrition score might serve as a powerful prognostic score in patients with colorectal cancer for overall survival, particularly in patients with wild type KRAS.

Novel parameter based on lipid indicators ratio improves prognostic value of plasma lipid levels in resectable colorectal cancer patients.

BACKGROUND: At present, the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited. AIM: To evaluate the value of a novel parameter for colorectal cancer (CRC) prognosis scoring based on preoperative serum lipid levels. METHODS: Four key serum lipid factors, namely, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), were detected. Two representative ratios, HDL-C-LDL-C ratio (HLR) and ApoA1-ApoB ratio (ABR) were calculated. The relationship of these parameters with the prognosis of CRC patients including progression-free survival (PFS) and overall survival (OS) was analyzed by Kaplan-Meier plot and Cox proportional hazards regression. A novel lipoprotein cholesterol-apolipoprotein (LA) score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored. RESULTS: Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C, ApoA1, HLR, and ABR were positively associated with the prognosis of CRC patients. LA score was independently associated with a good prognosis in resectable CRC patients. Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores. CONCLUSION: The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.

Comparative Study of Sargassum fusiforme Polysaccharides in Regulating Cecal and Fecal Microbiota of High-Fat Diet-Fed Mice.

Seaweed polysaccharides represent a kind of novel gut microbiota regulator. The advantages and disadvantages of using cecal and fecal microbiota to represent gut microbiota have been discussed, but the regulatory effects of seaweed polysaccharides on cecal and fecal microbiota, which would benefit the study of seaweed polysaccharide-based gut microbiota regulator, have not been compared. Here, the effects of two Sargassum fusiforme polysaccharides prepared by water extraction (SfW) and acid extraction (SfA) on the cecal and fecal microbiota of high-fat diet (HFD) fed mice were investigated by 16S rRNA gene sequencing. The results indicated that 16 weeks of HFD dramatically impaired the homeostasis of both the cecal and fecal microbiota, including the dominant phyla Bacteroidetes and Actinobacteria, and genera Coriobacteriaceae, S24-7, and Ruminococcus, but did not affect the relative abundance of Firmicutes, Clostridiales, Oscillospira, and Ruminococcaceae in cecal microbiota and the Simpson's index of fecal microbiota. Co-treatments with SfW and SfA exacerbated body weight gain and partially reversed HFD-induced alterations of Clostridiales and Ruminococcaceae. Moreover, the administration of SfW and SfA also altered the abundance of genes encoding monosaccharide-transporting ATPase, α-galactosidase, ß-fructofuranosidase, and ß-glucosidase with the latter showing more significant potency. Our findings revealed the difference of cecal and fecal microbiota in HFD-fed mice and demonstrated that SfW and SfA could more significantly regulate the cecal microbiota and lay important foundations for the study of seaweed polysaccharide-based gut microbiota regulators.

The biomechanical influence of facet joint parameters on corresponding segment in the lumbar spine: a new visualization method.

BACKGROUND CONTEXT: Facet joints have been discussed as influential factors in the development of lumbar degeneration, which includes disc herniation and degenerative lumbar spondylolisthesis. Facet orientation (FO) and facet tropism (FT) are two important structural parameters of the lumbar facet joints. Many previous studies have focused on single parameter analysis of the lumbar spine. Owing to the correlation between independent variables, single-factor analysis cannot reflect the interaction between variables; however, there has been no corresponding biomechanical method developed to address this problem. PURPOSE: To investigate the complex biomechanical influences on the lumbar spine when vertebral FO and FT are varied using finite element analysis (FEA) and contour maps visualization, and analyze the biomechanical role of facet joint structural parameters in the process of lumbar degenerative diseases. STUDY DESIGN: A biomechanical modelling, analysis, and verification study was performed. METHODS: A three-dimensional non-linear FEA model of 3 denucleated intervertebral discs (L2-3, L3-4, L4-5) with adjacent vertebral bodies (L2-L5) was created. Previously performed in vitro experiments provided experimental data for the range of motion in each load direction that was used for calibration. For 12 lumbar models, different facet joint angles relative to the sagittal plane at both L3-4 facet joints were simulated for 35°≤FO≤50° and 0°≤FT≤15°. By modifying different values of FO and FT, FEA simulation of different lumbar spine models was performed. Contour maps were used to visualize the FO- and FT-relevant data. RESULTS: Under flexion, extension, and torsion moments, facet joint contact force and intradiscal stress increased with increasing FT. In the condition where FT remained 0° and increasing FO values, facet joint contact force and intradiscal stress remained low with no apparent increasing or decreasing trend when the model was under flexion, extension, and torsion moments. In the condition where FO and the FT values were varied at the same time, the highest force and stress regions in the contour maps were observed when all three types of moments were applied. Stress distributions of the L3-4 disc with different FT and FO values showed disc stress increased significantly with increases of FT and was concentrated on the ipsilateral region of the facet joint with the more sagittal orientation. CONCLUSIONS: The combination of FO and FT has an important impact on the corresponding disc and facet joints, but FT played a more significant role. Moreover, disc stress was concentrated on the ipsilateral region of facet joint with greater sagittal orientation when FT existed. FT with high sagittal orientation may increase risk of recurrent LDH due to increase ipsilateral disc pressure. CLINICAL SIGNIFICANCE: These biomechanical findings may help clinicians to understand the prognosis of some lumbar degenerative conditions.

WIPI1 promotes osteosarcoma cell proliferation by inhibiting CDKN1A.

Detection of TCGA data revealed that WIPI1 is highly expressed in osteosarcoma cells. So we explore the mechanisms of WIPI1 affecting the proliferation of osteosarcoma cells through Affymetrix microarray analysis. Functional analysis of differentially expressed genes shows that the classical signaling pathways affecting tumor formation and development have changed significantly. By fitting analysis, it is speculated that the WIPI1 may function in the direction of osteosarcoma by regulating the expression of multiple cell cycle-related genes such as CDKN1A, CDK4 and CCND1. Therefore, the key genes are selected for RT-PCR and Western-blot verification. Combined with flow and other means, WIPI1 may affect the cell cycle and the osteosarcoma by regulating the expression of CDKN1A, CDK4 and CCND1. To verify the results, the effect of WIPI1 on cell proliferation was quantified by MTT, cell counts and nude mouse tumorigenicity assay. The results showed that WIPI1 promotes osteosarcoma cell proliferation.