Ilizarov technique for treating elbow stiffness caused by myositis ossificans: A case report.

BACKGROUND: Myositis ossificans (MO) is a rare disease involving the formation of bone outside the musculoskeletal system. While surgical intervention is the main treatment approach, preventing recurrence and standardized rehabilitation are also crucial. Here, we present a surgical strategy to prevent the recurrence of MO. CASE SUMMARY: A 28-year-old female patient was admitted for the first time for a comminuted fracture of the left olecranon. However, incorrect postoperative rehabilitation resulted in the development of elbow joint stiffness with ectopic ossification, causing a loss of normal range of motion. The patient was diagnosed with MO based on physical examination, X-ray findings, and clinical presentation. We devised a surgical strategy to remove MO, followed by fixation with an Ilizarov frame, and implemented a scientifically reasonable rehabilitation plan. The surgery lasted for 3 h with an estimated blood loss of 45 mL. A drainage tube was placed after surgery, and fluid was aspirated through ultrasound-guided puncture. The patient experienced a significant reduction in joint stiffness after surgery. In the final follow-up at 9 mouths, there was evident improvement in the range of motion of the elbow joint, and no other symptoms were reported. CONCLUSION: The Ilizarov frame is an advantageous surgical technique for facilitating rehabilitation after MO removal. It offers benefits such as passive recovery, individualized treatment, and prompt recovery.

Investigating the Impact of Varied Dietary Protein Levels on Litopenaeus vannamei: An Exploration of the Intestinal Microbiota and Transcriptome Responses.

This study explored the effects of dietary protein levels on Litopenaeus vannamei with its intestinal microbiota and transcriptome responses. Previous studies on the effects of dietary protein levels on L. vannamei have focused on growth performance, antioxidant indices, and digestive enzyme activity, but few studies have been conducted at the microbiological and molecular levels. In this study, five isolipid experimental diets with protein levels of 32% (P32), 36% (P36), 40% (P40), 44% (P44), and 48% (P48) were used in an L. vannamei (0.63 ± 0.02 g) feeding trial for 56 days. At the end of the feeding trial, the growth performance, immunity, intestinal health, and transcriptional responses of L. vannamei were determined. This study demonstrated that higher protein levels (P44) led to superior weight gain and growth rates for L. vannamei, with lower feed conversion ratios (FCR) observed in the P48 and P44 groups compared to the P32 and P36 groups (p ≤ 0.05). The P44 and P48 groups also showed a notably higher protein efficiency ratio (PER) compared to others (p ≤ 0.05), and there was no significant difference between them. Upon Vibrio parahaemolyticus infection, the P48 group exhibited a significantly lower survival rate (SR) within 48 h, while during 72 h of white spot syndrome virus (WSSV) infection, the P44 group had a notably higher survival rate than the P32 group (p ≤ 0.05). Digestive enzyme activity and antioxidant levels in L. vannamei initially increased and then decreased as protein levels increased, usually peaking in the P40 or P44 groups. Lower dietary protein levels significantly reduced the relative abundance of beneficial bacteria and increased the relative abundance of pathogenic bacteria in the intestines of L. vannamei. Transcriptome sequencing analysis revealed that most differentially expressed genes (DEGs) were up-regulated and then down-regulated as dietary protein levels increased. Furthermore, KEGG pathway enrichment analysis indicated that several immune and metabolic pathways, including metabolic pathways, glutathione metabolism, cytochrome P450, and lysosome and pancreatic secretion, were significantly enriched. In summary, the optimal feed protein level for L. vannamei shrimp was 40-44%. Inappropriate feed protein levels reduced antioxidant levels and digestive enzyme activity and promoted pathogen settlement, deceasing factors in various metabolic pathways that respond to microorganisms through transcriptional regulation. This could lead to stunted growth in L. vannamei and compromise their immune function.

Immunosenescence and cancer: Opportunities and challenges.

As individuals age, cancer becomes increasingly common. This continually rising risk can be attributed to various interconnected factors that influence the body's susceptibility to cancer. Among these factors, the accumulation of senescent cells in tissues and the subsequent decline in immune cell function and proliferative potential are collectively referred to as immunosenescence. Reduced T-cell production, changes in secretory phenotypes, increased glycolysis, and the generation of reactive oxygen species are characteristics of immunosenescence that contribute to cancer susceptibility. In the tumor microenvironment, senescent immune cells may promote the growth and spread of tumors through multiple pathways, thereby affecting the effectiveness of immunotherapy. In recent years, immunosenescence has gained increasing attention due to its critical role in tumor development. However, our understanding of how immunosenescence specifically impacts cancer immunotherapy remains limited, primarily due to the underrepresentation of elderly patients in clinical trials. Furthermore, there are several age-related intervention methods, including metformin and rapamycin, which involve genetic and pharmaceutical approaches. This article aims to elucidate the defining characteristics of immunosenescence and its impact on malignant tumors and immunotherapy. We particularly focus on the future directions of cancer treatment, exploring the complex interplay between immunosenescence, cancer, and potential interventions.

PS-Net: A Learning Strategy for Accurately Exposing the Professional Photoshop Inpainting.

Restoring missing areas without leaving visible traces has become a trivial task with Photoshop inpainting tools. However, such tools have potentially illegal or unethical uses, such as removing specific objects in images to deceive the public. Despite the emergence of many forensics methods of image inpainting, their detection ability is still insufficient when attending to professional Photoshop inpainting. Motivated by this, we propose a novel method termed primary-secondary network (PS-Net) to localize the Photoshop inpainted regions in images. To the best of our knowledge, this is the first forensic method devoted specifically to Photoshop inpainting. The PS-Net is designed to deal with the problems of delicate and professional inpainted images. It consists of two subnetworks: the primary network (P-Net) and the secondary network (S-Net). The P-Net aims at mining the frequency clues of subtle inpainting features through the convolutional network and further identifying the tampered region. The S-Net enables the model to mitigate compression and noise attacks to some extent by increasing the co-occurring feature weights and providing features that are not captured by the P-Net. Furthermore, the dense connection, Ghost modules, and channel attention blocks (C-A blocks) are adopted to further strengthen the localization ability of PS-Net. Extensive experimental results illustrate that PS-Net can successfully distinguish forged regions in elaborate inpainted images, outperforming several state-of-the-art solutions. The proposed PS-Net is also robust against some postprocessing operations commonly used in Photoshop.

PBRM1 Deficiency Sensitizes Renal Cancer Cells to DNMT Inhibitor 5-Fluoro-2'-Deoxycytidine.

PBRM1 is a tumor suppressor frequently mutated in clear cell renal cell carcinoma. However, no effective targeted therapies exist for ccRCC with PBRM1 loss. To identify novel therapeutic approaches to targeting PBRM1-deficient renal cancers, we employed a synthetic lethality compound screening in isogenic PBRM1+/+ and PBRM1-/- 786-O renal tumor cells and found that a DNMT inhibitor 5-Fluoro-2'-deoxycytidine (Fdcyd) selectively inhibit PBRM1-deficient tumor growth. RCC cells lacking PBRM1 show enhanced DNA damage response, which leads to sensitivity to DNA toxic drugs. Fdcyd treatment not only induces DNA damage, but also re-activated a pro-apoptotic factor XAF1 and further promotes the genotoxic stress-induced PBRM1-deficient cell death. This study shows a novel synthetic lethality interaction between PBRM1 loss and Fdcyd treatment and indicates that DNMT inhibitor represents a novel strategy for treating ccRCC with PBRM1 loss-of-function mutations.

Identification and Verification of m7G Modification Patterns and Characterization of Tumor Microenvironment Infiltration via Multi-Omics Analysis in Clear Cell Renal Cell Carcinoma.

The epigenetic modification of tumorigenesis and progression in neoplasm has been demonstrated in recent studies. Nevertheless, the underlying association of N7-methylguanosine (m7G) regulation with molecular heterogeneity and tumor microenvironment (TME) in clear cell renal cell carcinoma (ccRCC) remains unknown. We explored the expression profiles and genetic variation features of m7G regulators and identified their correlations with patient outcomes in pan-cancer. Three distinct m7G modification patterns, including MGCS1, MGCS2, and MGCS3, were further determined and systematically characterized via multi-omics data in ccRCC. Compared with the other two subtypes, patients in MGCS3 exhibited a lower clinical stage/grade and better prognosis. MGCS1 showed the lowest enrichment of metabolic activities. MGCS2 was characterized by the suppression of immunity. We then established and validated a scoring tool named m7Sig, which could predict the prognosis of ccRCC patients. This study revealed that m7G modification played a vital role in the formation of the tumor microenvironment in ccRCC. Evaluating the m7G modification landscape helps us to raise awareness and strengthen the understanding of ccRCC's characterization and, furthermore, to guide future clinical decision making.

Columbianetin alleviates lipopolysaccharides (LPS)-induced inflammation and apoptosis in chondrocyte through activation of autophagy by inhibiting serum and glucocorticoid-induced protein kinase 1 (SGK1) expression.

Osteoarthritis (OA) is a degenerative disease of articular cartilage involving the entire joint tissue. Columbianetin (CBT) is a major active compound of radix angelicae pubescentis, which is used in the treatment of OA. This paper attempts to explore the role of CBT in OA. Lipopolysaccharides (LPS) was used to induce mouse chondrocytes ATDC5. The effect of CBT on cell viability in ATDC5 cells with or without LPS induction was determined by CCK-8 and LDH kits. The inflammatory response was evaluated using ELISA kits. Apoptosis in LPS-induced ATDC5 cells were examined by TUNEL staining. The expression of apoptosis and autophagy-related proteins was tested with Western blot. The relationship between CBT and serum and glucocorticoid-induced protein kinase 1 (SGK1) was examined by RT-qPCR, Western blot, and molecular docking. After SGK1 overexpression or addition of the autophagy inhibitor 3-methyladenine (3 MA), the above experiments were done again. Results revealed that CBT increased LPS-induced decrease in ATDC5 cell viability. CBT inhibited inflammation triggered by LPS, evidenced by reduced levels of TNF-α, IL-6 and IL-1ß. Cell apoptosis was attenuated following CBT adding in ATDC5 cells exposed to LPS, accompanied by upregulated Bcl-2 expression and downregulated Bax and cleaved caspase 3 expression. In addition, CBT elevated Beclin1 and LC3II/LC3I expression but decreased p62 expression. Additionally, CBT inhibited SGK1 expression. However, SGK1 overexpression or 3 MA reversed the effects of CBT on LPS-induced loss of ATDC5 cell viability, inflammation, apoptosis and autophagy. Collectively, CBT could improve OA through the activation of chondrocyte autophagy by suppressing SGK1 expression.

Cytokine release syndrome induced by pembrolizumab: A case report.

RATIONALE: Cytokine release syndrome (CRS) is an immune hyperactivation phenomenon in immunotherapy and, unlike other immune-related adverse events, only a few case reports have documented CRS due to the use of immune checkpoint inhibitors. In this article, we report a case of 2 episodes of CRS and delirium caused by pembrolizumab in a short period of time. This helps clinicians to understand CRS and to improve the diagnosis and treatment of immune-related adverse events. PATIENT CONCERNS: A 67-year-old patient with lung cancer developed fever, delirium, acute renal insufficiency, and acute cardiac insufficiency after 9 cycles of pablizumab therapy, and reappeared with these symptoms 1 week after improvement with glucocorticoid therapy. DIAGNOSES: The patient presented with concomitant cardiac insufficiency, hepatic and renal failure, delirium with high C-reactive protein levels and the patient's response to glucocorticoids, and exclusion of cerebrovascular accident and severe infection, resulting in a final diagnosis of CRS. INTERVENTIONS: Glucocorticoid therapy and symptomatic support treatment. OUTCOMES: After 2 hospitalizations, the patient did not develop CRS. LESSONS: To our knowledge, this is the first case of delirium and CRS that occurred twice in a short period of time. This patient had no immune-related adverse reactions during the previous 9 immunotherapy sessions. This adverse reaction occurred after the inflammation of the wisdom teeth and was presumed to be related to an overstimulation of the immune response due to infection. Premature discontinuation of hormones for the patient's 1st treatment of CRS may be the reason for the 2nd occurrence of CRS. Therefore, timely and full course of glucocorticosteroids is a key therapeutic measure to cause CRS after the use of immune checkpoint inhibitors.

Methyltransferase-like 14 suppresses growth and metastasis of renal cell carcinoma by decreasing long noncoding RNA NEAT1.

Growing evidence supports that N6-methyladenosine (m6A) modification acts as a critical regulator involved in tumorigenesis at the mRNA level. However, the role of m6A modification at the noncoding RNA level remains largely unknown. We found that methyltransferase-like 14 (METTL14) was significantly downregulated in renal cell carcinoma (RCC) tissues (n = 580). Gain-of-function and loss-of-function experiments revealed that METTL14 attenuated the proliferation and migration ability of RCC cells in vivo and in vitro. The methylated RNA immunoprecipitation experiments identified that METTL14 decreased the expression of long noncoding RNA nuclear enriched abundant transcript 1_1 (NEAT1_1) in an m6A-dependent manner. Mechanistically, RNA pull-down assay and RNA immunoprecipitation identified NEAT1_1 directly bound to m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Notably, YTHDF2 accelerated the degradation of NEAT1_1 by selectively recognizing METTL14-mediated m6A marks on NEAT1_1. Multivariate analysis suggested that METTL14 downregulation was associated with malignant characteristics and predicted poor prognosis in RCC patients. In conclusion, our results uncover a newly identified METTL14-YTHDF2-NEAT1_1 signaling axis, which facilitates RCC growth and metastasis and provides fresh insight into RCC therapy.

Integrated traditional Chinese medicine alleviates sciatica while regulating gene expression in peripheral blood.

BACKGROUND: Although integrated traditional Chinese medicine (TCM) has long been indicated to be effective in the treatment of sciatica and is widely used in the management of this condition, the mechanism by which integrated TCM alleviates sciatica has not yet been fully defined, and the effect of integrated TCM on gene expression in the peripheral blood of patients with sciatica is still unknown. We performed this study to investigate the effect of integrated TCM on peripheral blood gene expression in patients with sciatica and to explore new clues for studying the mechanism of integrated TCM in alleviating sciatica. METHODS: We used a microarray to identify differentially expressed genes (DEGs) in the peripheral blood of patients with sciatica and healthy controls (DEGs-baseline), bioinformatic analysis to reveal the characteristics of DEGs-baseline, and the key genes that contribute to the gene dysregulation. A microarray was also used to identify DEGs in the peripheral blood of patients with sciatica after integrated TCM treatment compared with those at baseline, and the expression levels of DEGs were validated by qRT-PCR. RESULTS: We identified 153 DEGs-baseline, which included 131 upregulated genes and 22 downregulated genes. Bioinformatic analysis revealed that most of the DEGs-baseline were related to immunity and the inflammatory response and that TLR4, MMP9, MPO, CAMP, RETN, TLR5, and IL1RN were key genes involved in the dysregulation of genes in the peripheral blood of patients with sciatica. The expression levels of TLR5, IL1RN, SLC8A1, RBM20, GPER1, IL27, SOCS1, and GRTP1-AS1 were decreased in the peripheral blood of patients after integrated TCM treatment compared with that at baseline, which was accompanied by relief of pain. CONCLUSION: Integrated TCM treatment relieved pain while regulating the gene expression of TLR5, IL1RN, SLC8A1, RBM20, GPER1, IL27, SOCS1, and GRTP1-AS1 in the peripheral blood of patients with sciatica. Our study provides new clues for studying the mechanism of TCM in treating sciatica.

Integrated Analysis of mRNA-Seq and MiRNA-Seq Reveals the Molecular Mechanism of the Intestinal Immune Response in Marsupenaeus japonicus Under Decapod Iridescent Virus 1 Infection.

The intestine is not only an important digestive organ but also an important immune organ for shrimp; it plays a key role in maintaining homeostasis. Decapod iridescent virus 1 (DIV1) is a new type of shrimp-lethal virus that has received extensive attention in recent years. To date, most studies of the shrimp intestinal immune response under viral infections have relied on single omics analyses; there is a lack of systematic multi-omics research. In the current study, intestinal mRNA-seq and microRNA (miRNA)-seq analyses of Marsupenaeus japonicus under DIV1 infection were performed. A total of 1,976 differentially expressed genes (DEGs) and 32 differentially expressed miRNAs (DEMs) were identified. Among them, 21 DEMs were negatively correlated with 194 DEGs from a total of 223 correlations. Functional annotation analysis revealed that M. japonicus can regulate glycosaminoglycan biosynthesis (chondroitin sulfate, dermatan sulfate, and keratan sulfate), vitamin metabolism (retinol metabolism and ascorbate and aldarate metabolism), immune pathway activation (Toll and IMD signaling pathways, Wnt signaling pathway, IL-17 signaling pathway, and Hippo signaling pathway), immunity enzyme activity promotion (triose-phosphate isomerase), antimicrobial peptide (AMP) expression, reactive oxygen species (ROS) production, and cell apoptosis through miRNAs to participate in the host's antiviral immune response, while DIV1 can influence Warburg effect-related pathways (pyruvate metabolism, glycolysis/gluconeogenesis, and citrate cycle), glycosphingolipid biosynthesis-related pathways (glycosphingolipid biosynthesis-globo and isoglobo series and glycosphingolipid biosynthesis-lacto and neolacto series), and the tight junction and adhesion junction of the intestinal mucosal epithelium through the host's miRNAs and mRNA to promote its own invasion and replication. These results indicate that intestinal miRNAs play important roles in the shrimp immune response against DIV1 infection. This study provides a basis for further study of the shrimp intestinal antiviral immune response and for the formulation of effective new strategies for the prevention and treatment of DIV1 infection.

The predictive value of plasminogen activator inhibitor-1, fibrinogen, and D-dimer for deep venous thrombosis following surgery for traumatic lower limb fracture.

BACKGROUND: Deep venous thrombosis (DVT) is a common postoperative complication in patients with lower limb fractures. This study aims to investigate the predictive value of plasminogen activator inhibitor-1 (PAI-1), fibrinogen (FIB), and D-dimer (D-D) for DVT following lower limb traumatic fracture surgery and to investigate risk factors for DVT. METHODS: Clinical data of 63 patients who underwent lower limb traumatic fracture surgery in our hospital from September 2018 to March 2019 were retrospectively analyzed. Patients were divided into a DVT group and a non-DVT group. The differences in the levels of plasminogen activator inhibitor-1 (PAI-1), fibrinogen (FIB), and D-dimer (D-D) were compared, and a receiver operating characteristic (ROC) curve was used to analyze their predictive value for DVT following surgery for lower limb traumatic fracture. Multiple logistic regression analysis was used to analyze the risk factors of DVT. RESULTS: The levels of PAI-1, FIB, and D-D in the DVT group were higher on the third day after surgery compared to the pre-surgical levels, and were also higher than those in the non-DVT group (P<0.05). The area under the ROC curve indicated that the predictive values of PAI-1, FIB, D-D, and the combination of these three indicators for DVT were 0.792, 0.429, 0.966, and 0.992, respectively. Patients with preexisting factors including a BMI ≥24 kg/m2 , a history of diabetes, postoperative infection, an abnormal white blood cell count, an abnormal average thrombocytocrit, and abnormal levels of PAI-1, FIB, and D-D had a higher incidence of DVT following surgery compared to patients without these factors (P<0.05). The results of the multivariate logistic regression model analysis showed that the presence of postoperative infection, abnormal white blood cell count, abnormal mean platelet volume, and abnormal levels of PAI-1, FIB, and D-D were independent risk factors affecting postoperative DVT in patients with lower limb fractures (P<0.05). CONCLUSIONS: The levels of PAI-1, FIB, and D-D were significantly increased in patients with DVT following surgery for lower limb fractures. Therefore, early monitoring of PAI-1, FIB, and D-D levels, and coagulation function is a good predictive indicator of postoperative thrombosis.

[Long non-coding RNA for metabolism of bone tissue].

The mechanism of metabolism of bone and cartilage are one of focus of orthopedic knowledge, and its clinical and basic study plays an important role in preventing and treating osteoporosis, degeneration of bone and joint, bone tumor. At present, the mechanism of metabolism of bone and cartilage studied from protein, signal pathway to mRNA transcription factor regulation. As a new regulatory factor for non-coding proteins, long non-coding RNA(LncRNA) participates in physiological and pathological process. In recent years, a large number of researche showed that LncRNA plays an important role in metabolism of bone and cartilage, and proved LncRNA participates in development and conversion of bone metabolism. With the exposure of function chennel and target of LncRNA, the key role of LncRNA in bone metabolism were proved constantly. The paper concluded biological characteristics of LncRNA, function and target spot of LncRNA in bone and cratilage metabolism, and in further state gene regulatory mechanism of bone and cartilage metabolism, explore diagnosis and treatment, provide new thought and treatment target for bone metabolism.