The study aimed to observe the therapeutic effect of static progressive stretching (SPS) combined with extracorporeal shock wave therapy (ESWT) on extension knee joint contracture in rats and the effect on the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway in the development of joint capsule fibrosis. Thirty-six Sprague Dawley rats were randomly divided into blank control group, immobilization model group, natural recovery group, ESWT intervention group, SPS intervention group, and SPS combined with ESWT intervention group. The left knee joints of the rats, except for the control group, were fixed with an external fixation brace for four weeks at full extension to form joint contracture. The therapeutic effect of each intervention was assessed by evaluating total and arthrogenic contracture, the number of total cells and collagen deposition in the anterior joint capsule, the protein levels of TGF-β1, FGF-2, and ERK2 in the anterior joint capsule, the mean optical density of upstream RAS and downstream ERK2 positive expression in the MAPK/ERK pathway. SPS in combination with ESWT was more effective in relieving joint contracture, improving the histopathological changes in the anterior joint capsule, and suppressing the high expression of target proteins and the overactivated MAPK/ERK pathway. The overactivated MAPK/ERK pathway was involved in the formation of extension knee joint contracture in rats. SPS in combination with ESWT was effective in relieving joint contracture and fibrosis of joint capsule. Moreover, the inhibition of the overactivated MAPK/ERK pathway may be the potential molecular mechanism for its therapeutic effect.

Dementia is a syndrome characterized by multidomain acquired chronic cognitive impairment that has a profound impact on daily life. Neurogenerative diseases such as Alzheimer’s disease or nondegenerative diseases such as vascular dementia are considered to cause dementia. The need for further diagnostic improvement originates from the prevalence of these conditions, especially in developed countries with a predominance of the elderly population. Today, the diagnosis and follow-up of all neurodegenerative diseases cannot be performed without radiological imaging, primarily magnetic resonance imaging (MRI). The introduction of 3T MRI and its modern techniques, such as arterial spin labeling, has enabled better visualization of morphologic changes in dementia. For better diagnosis and follow-up in patients with dementia, various semiquantitative scales have been designed to improve the accuracy of assessment and decrease interobserver variability. Moreover, there is a growing need for MRI in the assessment of novel therapies and their side effects. To better apply MRI findings in the diagnosis of both already developed dementia and its early stages, the aim of this paper is to review the available literature and summarize the specific MRI changes.

Interleukin 35 (IL-35) mediates immunosuppression of T cells in autoimmune diseases. T cells play an important role in primary biliary cholangitis (PBC) with incompletely elucidated pathogenesis. Thus, we aimed to investigate the role of IL-35 regulation on T cells in PBC patients. Fifty-one PBC patients and 28 controls were enrolled in this study. Plasma IL-35 level was measured. Purified peripheral CD4+ and CD8+ T cells were stimulated with exogenous IL-35 to investigate their functional phenotypes. IL-35-treated CD8+ T cells were cultured with human intrahepatic biliary epithelial cell line to determine the cytotoxicity of CD8+ T cells from PBC patients. Plasma IL-35 concentration was lower in PBC patients and negatively correlated with alkaline phosphatase. CD4+ T cells from PBC patients exhibited elevated transcription factor expressions and cytokine secretion, whereas CD8+ T cells produced increased cytotoxic molecules and cytokines. In vitro IL-35 stimulation suppressed the production of IL-17 and IL-22 by CD4+ T cells from PBC patients. CD8+ T cells treated with IL-35 mediated reduced target cell death in the direct contact co-culture system in PBC patients. This process was accompanied by reduced production of cytotoxic molecules and cytokines and increased expressions of immune checkpoint receptors in CD8+ T cells. Reduced circulating IL-35 might be insufficient to suppress T cell function, leading to the immune dysregulation in PBC patients.

Although obesity is a preventable disease, maintaining a normal body weight can be very challenging and difficult, which has led to a significant increase in the demand for surgical subcutaneous fat removal (SSFR) to improve physical appearance. The need for SSFR is further exacerbated because of the global rise in the number of bariatric surgeries, which is currently the single most durable intervention for mitigating obesity. Fat tissue is now recognized as a vital endocrine organ that produces several bioactive proteins. Thus, SSFR-mediated weight (fat) loss can potentially have significant metabolic effects; however, currently, there is no consensus on this issue. This review focuses on the metabolic sequelae after SSFR interventions for dealing with cosmetic body appearance. Data were extracted from existing systematic reviews and the diversity of possible metabolic changes after SSFR are reported along with gaps in the knowledge and future directions for research and practice. We conclude that there is a potential for metabolic sequelae after SSFR interventions and their clinical implications for the safety of the procedures as well as for our understanding of subcutaneous adipose tissue biology and insulin resistance are discussed.

Some patients with microsatellite instability-high colorectal cancer (MSI-H CRC) have shown a poor response to immunotherapy in clinical trials. We investigated the intrinsic resistance to and efficacy of immunotherapy in patients with MSI-H CRC. The PubMed and Web of Science databases were searched using keywords such as “colorectal cancer,” “immunotherapy,” and “clinical experiment.” Random-effects models were used to generate the combined complete response, partial response, stable disease, progressive disease, objective response rate (ORR), disease control rate (DCR), and incidence of adverse events. We then performed a subgroup analysis based on the ORR and incidence of intrinsic resistance. The meta-analysis included seven clinical trials. The incidences of complete response, partial response, stable disease, and progressive disease summarized by the random-effects model were 8%, 37%, 26%, and 25%, respectively. The ORR and DCR were 45% and 71%, respectively. The ORRs of programmed cell death protein 1 inhibitor (anti-PD-1), programmed death ligand 1 inhibitor (anti-PD-L1), and anti-PD-1 combined with cytotoxic T lymphocyte-associated antigen 4 inhibitor (anti-CTLA-4) immunotherapy were 38%, 54%, and 57%, respectively. The ORR of immune checkpoint inhibitors for first- and third-line therapy was 56% and 32%, respectively. Dual-drug immunotherapy significantly reduced the incidence of intrinsic resistance to immunotherapy (12% vs 31%). The incidences of intrinsic resistance to first-line therapy and second-line and later therapy were 29% and 26%, respectively. Approximately 25% of patients with MSI-H CRC had intrinsic resistance to immunotherapy. Anti-PD-1 combined with anti-CTLA-4 significantly increased the ORR, thereby reducing the incidence of intrinsic resistance. Moving immunotherapy into earlier lines of therapy, although not reducing the incidence of intrinsic resistance, can improve the ORR in patients with MSI-H CRC.

Obesity is a serious metabolic disease that significantly increases cardiovascular risks and other health complications. Sarcopenia is an independent risk factor for morbidity and mortality in patients suffering from obesity that increases the health risks and is associated with cardiac, respiratory, and other diseases. Bariatric and metabolic surgery (BMS) leads to significant changes in body composition. Our pilot study showed that bariatric patients are at risk of sarcopenia after BMS. This finding resulted in a hypothesis that an exercise plan in the experimental group will lead to postural stabilization and a lower decline in muscle homotopy, further leading to a greater reduction in fat mass and a positive effect of exercise on skeletal muscle volume and strength and endocrine-metabolic function. The aim of the present study is to determine the effect of programmed aerobic and strength training on muscle function, volume, and morphology in patients after BMS. The study is a single-center, randomized clinical trial after sleeve gastrectomy focused on muscle tissue. The experimental group will perform targeted physical activity once a week for 12 months and the training plan will include anaerobic and aerobic components. Magnetic resonance imaging of skeletal muscles will be correlated with the values of densitometry examination and changes in body composition, certain blood parameters of myokines, biomechanical analysis of movement abnormalities, and behavioral and dietary counseling. This study will address the research questions about the effect of programmed training on muscle tissue and muscular functions after BMS.

Renal biopsy pathology is an essential gold standard for the diagnosis of most kidney diseases. With the increase in the incidence rate of kidney diseases, the lack of renal pathologists, and an imbalance in their distribution, there is an urgent need for a new renal pathological diagnosis model. Advances in artificial intelligence (AI) along with the growing digitization of pathology slides for diagnosis are promising approach to meet the demand for more accurate detection, classification, and prediction of the outcome of renal pathology. AI has contributed substantially to a variety of clinical applications, including renal pathology. Deep learning, a subfield of AI that is highly flexible and supports automatic feature extraction, is increasingly being used in multiple areas of pathology. In this narrative review, we first provide a general description of AI methods, and then discuss the current and prospective applications of AI in the field of renal pathology. Both diagnostic and predictive prognostic applications are covered, emphasizing AI in renal pathology images, predictive models, and 3D in renal pathology. Finally, we outline the challenges associated with the implementation of AI platforms in renal pathology and provide our perspective on how these platforms might change in this field.

Alteration of urokinase plasminogen activator receptor (uPAR) in neoplasms is a pre-requisite for invasiveness and metastatic ability. In the present study, we aimed to evaluate the relationship of pre-chemotherapy soluble uPAR (suPAR) with the odds for metastasis, lack of disease control, and its predictive ability for progression-free survival (PFS). Baseline plasma suPAR levels were measured by ELISA in 89 patients with various cancers prior to initiation of systemic treatment. Patients were followed prospectively until metastatic progression or death. TCGA Pan-Cancer dataset was mined for available RNAseq expression data of the PLAUR gene in patients with breast, colon, and lung cancer, and the relevant genomic and clinical data were extracted for further analysis. Pre-chemotherapy suPAR levels were significantly associated with white blood cell counts and fibrinogen and were significantly elevated both in patients with metastatic disease and in patients with progression. Increasing suPAR was significantly associated with odds for progression in the prespecified multivariate analysis (odds ratio 2.47, 95% confidence interval 1.3–5.11). In univariate Cox regression, suPAR was predictive of shortened PFS (hazard ratio 1.065, 95% confidence interval 1.002–1.13; p = 0.041). There was a trend toward shortened PFS in patients with higher baseline suPAR levels (cutoff 8.1 ng/mL). In the TCGA lung cancer cohort, PLAUR mRNA expression was significantly associated with shortened PFS in both univariate and multivariate analyses. High PLAUR gene expression conferred significant survival disadvantage only in patients with colon and lung cancer. SuPAR may bear predictive potential for adverse outcomes in cancer, but its utility as a biomarker seems to be more pronounced in cancers with associated inflammatory state.