Study on the Effect of Laser Marker in the Treatment of Osteoarthritis of the Knee Joint and the Accuracy of Reconstruction of Lower Extremity Alignment.

Objective: Knee osteoarthritis (KOA) is a prevalent joint disease characterized by cartilage degradation and periarticular bone hyperplasia. Accurate assessment of knee alignment is fundamental for effective treatment, as it directly influences surgical planning and postoperative outcomes. This study assesses the effectiveness of laser marker technology in KOA treatment and its precision in reconstructing lower extremity alignment. Methods: Sixty KOA patients admitted to our orthopedics department from March 2020 to December 2021 were randomized into two groups via random number table method, with 30 patients in each. All patients underwent knee replacement surgery. The experiment group received laser marker assessments, while the control group had X-ray examinations. Postoperative Hospital for Special Surgery (HSS) scores and knee mobility of the patients were compared. Results: At 6 weeks, 3 months, and 6 months postoperatively, the experimental group exhibited significnatly higher HSS scores (89.75±3.81, 91.78±2.15, and 91.84±1.79) than the control group (84.28±2.56, 87.15±1.98, and 88.02±1.21) (P < .05). Better knee mobility (111.17±4.94) was observed in the experimental group versus the control group (108.07±3.08) at 6 months postoperatively (P < .05). Conclusion: Laser marker technology provides a clear visualization of lower extremity structures, offering a comprehensive assessment of KOA deformities. This could potentially lead to improved diagnostic precision and enhanced surgical outcomes. The study encourages further research into the broader application of laser marker technology in knee osteoarthritis treatment, such as the evaluation of its cost-effectiveness versus traditional methods.

Comparison of Therapeutic Effects Between Arthroscopic Debridement and Olecranon Fossa Augmentation Plasty for Elbow Osteoarthritis.

Aim: To compare the efficacy of arthroscopic debridement and olecranon fossa augmentation plasty in patients with elbow osteoarthritis. Methods: Eighty-four patients with elbow osteoarthritis admitted to our hospital were randomly divided into two groups with 42 cases in each group. Patients in the control group received expanded olecranon fossa plasty, while those in the observation group underwent arthroscopic debridement. Then the elbow joint function, VAS score, stress level, and incidence of complications were compared between the two groups. Results: The MEPS score, ROM level, and VAS score, as well as the expression of TNF-α, IL-6, and ACTH between the two groups, were significantly different before and after surgery (P < .05). Moreover, compared to patients in the control group, the MEPS score and ROM level of patients in the observation group were higher than those in the control group after six months since surgery, while VAS score, the levels of TNF-α, IL-6, and ACTH were lower on the second day after surgery (P < .05). Conclusion: Arthroscopic cleaning is more helpful in improving elbow joint function and alleviating pain in patients with osteoarthritis of the elbow compared to olecranon fossa augmentation and reconstruction surgery.

Iron quantitative analysis of motor combined with bulbar region in M1 cortex may improve diagnosis performance in ALS.

OBJECTIVES: To explore whether the combined analysis of motor and bulbar region of M1 on susceptibility-weighted imaging (SWI) can be a valid biomarker for amyotrophic lateral sclerosis (ALS). METHODS: Thirty-two non-demented ALS patients and 35 age- and gender-matched healthy controls (HC) were retrospectively recruited. SWI and 3D-T1-MPRAGE images were obtained from all individuals using a 3.0-T MRI scan. The bilateral posterior band of M1 was manually delineated by three neuroradiologists on phase images and subdivided into the motor and bulbar regions. We compared the phase values in two groups and performed a stratification analysis (ALSFRS-R score, duration, disease progression rate, and onset). Receiver operating characteristic (ROC) curves were also constructed. RESULTS: ALS group showed significantly increased phase values in M1 and the two subregions than the HC group, on the all and elderly level (p < 0.001, respectively). On all-age level comparison, negative correlations were found between phase values of M1 and clinical score and duration (p < 0.05, respectively). Similar associations were found in the motor region (p < 0.05, respectively). On both the total (p < 0.01) and elderly (p < 0.05) levels, there were positive relationships between disease progression rate and M1 phase values. In comparing ROC curves, the entire M1 showed the best diagnostic performance. CONCLUSIONS: Combining motor and bulbar analyses as an integral M1 region on SWI can improve ALS diagnosis performance, especially in the elderly. The phase value could be a valuable biomarker for ALS evaluation. KEY POINTS: • Integrated analysis of the motor and bulbar as an entire M1 region on SWI can improve the diagnosis performance in ALS. • Quantitative analysis of iron deposition by SWI measurement helps the clinical evaluation, especially for the elderly patients. • Phase value, when combined with the disease progression rate, could be a valuable biomarker for ALS.

α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer.

Genetic-driven deregulation of the Wnt pathway is crucial but not sufficient for colorectal cancer (CRC) tumourigenesis. Here, we show that environmental glutamine restriction further augments Wnt signaling in APC mutant intestinal organoids to promote stemness and leads to adenocarcinoma formation in vivo via decreasing intracellular alpha-ketoglutarate (aKG) levels. aKG supplementation is sufficient to rescue low-glutamine induced stemness and Wnt hyperactivation. Mechanistically, we found that aKG promotes hypomethylation of DNA and histone H3K4me3, leading to an upregulation of differentiation-associated genes and downregulation of Wnt target genes, respectively. Using CRC patient-derived organoids and several in vivo CRC tumour models, we show that aKG supplementation suppresses Wnt signaling and promotes cellular differentiation, thereby significantly restricting tumour growth and extending survival. Together, our results reveal how metabolic microenvironment impacts Wnt signaling and identify aKG as a potent antineoplastic metabolite for potential differentiation therapy for CRC patients.

Dietary glutamine supplementation suppresses epigenetically-activated oncogenic pathways to inhibit melanoma tumour growth.

Tumour cells adapt to nutrient deprivation in vivo, yet strategies targeting the nutrient poor microenvironment remain unexplored. In melanoma, tumour cells often experience low glutamine levels, which promote cell dedifferentiation. Here, we show that dietary glutamine supplementation significantly inhibits melanoma tumour growth, prolongs survival in a transgenic melanoma mouse model, and increases sensitivity to a BRAF inhibitor. Metabolomic analysis reveals that dietary uptake of glutamine effectively increases the concentration of glutamine in tumours and its downstream metabolite, αKG, without increasing biosynthetic intermediates necessary for cell proliferation. Mechanistically, we find that glutamine supplementation uniformly alters the transcriptome in tumours. Our data further demonstrate that increase in intra-tumoural αKG concentration drives hypomethylation of H3K4me3, thereby suppressing epigenetically-activated oncogenic pathways in melanoma. Therefore, our findings provide evidence that glutamine supplementation can serve as a potential dietary intervention to block melanoma tumour growth and sensitize tumours to targeted therapy via epigenetic reprogramming.

A novel multi-target regression framework for time-series prediction of drug efficacy.

Excavating from small samples is a challenging pharmacokinetic problem, where statistical methods can be applied. Pharmacokinetic data is special due to the small samples of high dimensionality, which makes it difficult to adopt conventional methods to predict the efficacy of traditional Chinese medicine (TCM) prescription. The main purpose of our study is to obtain some knowledge of the correlation in TCM prescription. Here, a novel method named Multi-target Regression Framework to deal with the problem of efficacy prediction is proposed. We employ the correlation between the values of different time sequences and add predictive targets of previous time as features to predict the value of current time. Several experiments are conducted to test the validity of our method and the results of leave-one-out cross-validation clearly manifest the competitiveness of our framework. Compared with linear regression, artificial neural networks, and partial least squares, support vector regression combined with our framework demonstrates the best performance, and appears to be more suitable for this task.

Synthesis and biological evaluation of a series of liver-selective phosphonic acid thyroid hormone receptor agonists and their prodrugs.

Phosphonic acid (PA) thyroid hormone receptor (TR) agonists were synthesized to exploit the poor distribution of PA-based drugs to extrahepatic tissues and thereby to improve the therapeutic index. Nine PAs showed excellent TR binding affinities (TRbeta(1), K(i) < 10 nM), and most of them demonstrated significant cholesterol lowering effects in a cholesterol-fed rat (CFR) model. Unlike the corresponding carboxylic acid analogue and T(3), PA 22c demonstrated liver-selective effects by inducing maximal mitochondrial glycerol-3-phosphate dehydrogenase activity in rat liver while having no effect in the heart. Because of the low oral bioavailability of PA 22c, a series of prodrugs was synthesized and screened for oral efficacy in the CFR assay. The liver-activated cyclic 1-(3-chlorophenyl)-1,3-propanyl prodrug (MB07811) showed potent lipid lowering activity in the CFR (ED(50) 0.4 mg/kg, po) and good oral bioavailability (40%, rat) and was selected for development for the treatment of hypercholesterolemia.

Thalidomide analogues as anticancer drugs.

The evolution of thalidomide as an effective treatment in several neoplasms has led to the search for compounds with increased antiangiogenic and anti-tumor effects, but decreased side-effects. The development of thalidomide analogues which retain the immunomodulatory effects of the parent compound, while minimizing the adverse reactions, brought about a class of agents termed the Immunomodulatory drugs (IMiDs). The IMiDs have undergone significant advances in recent years as evidenced by the recent FDA-approvals of one of the lead compounds, CC-5013 (lenalidomide), for 5q-myelodysplasia and for multiple myeloma (MM). Actimid (CC-4047), another IMiD lead compound, has also undergone clinical testing in MM. Apart from hematologic malignancies, these drugs are actively under investigation in solid tumor malignancies including prostate cancer, melanoma, and gliomas, in which potent activity has been demonstrated. The preclinical and clinical data relating to these analogues, as well as ENMD-0995, are reviewed herein. Encouraging results with these thalidomide analogues brought forth synthesis and screening of additional novel thalidomide analogues in the N-substituted and tetrafluorinated classes, including CPS11 and CPS49. This review also discusses the patents and preclinical findings for these agents.