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Background and aimsCurrent treatment guidelines recommend ursodeoxycholic acid (UDCA) as the first-line treatment for new-diagnosed primary biliary cholangitis (PBC) patients. However, up to 40% patients are insensitive to UDCA monotherapy, and evaluation of UDCA response at 12 months may result in long period of ineffective treatment. We aimed to develop a new criterion to reliably identify non-response patients much earlier.MethodsFive hundred sixty-nine patients with an average of 59 months (Median: 53; IQR:32-79) follow-up periods were randomly divided into either the training (70%) or the validation cohort (30%). The efficiency of different combinations of total bilirubin (TBIL), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) threshold values to predict outcomes was assessed at 1, 3 or 6 month after the initiation of UDCA therapy. The endpoints were defined as adverse outcomes, including liver-related death, liver transplantation and complications of cirrhosis. Adverse outcome-free survival was compared using various published criteria and a proposed new criterion.ResultsA new criterion of evaluating UDCA responses at 1 month was established as: ALP ≤ 2.5 × upper limit of normal (ULN) and AST ≤ 2 × ULN, and TBIL ≤ 1 × ULN (Xi'an criterion). The 5 year adverse outcome-free survival rate of UDCA responders, defined by Xi'an criterion, was 97%, which was significantly higher than that of those non-responders (64%). An accurate distinguishing high-risk patients' capacity of Xi'an criterion was confirmed in both early and late-stage PBC.ConclusionsXi'an criterion has a similar or even higher ability to distinguish high-risk PBC patients than other published criteria. Xi'an criterion can facilitate early identification of patients requiring new therapeutic approaches.

Ribonucleotide reductases (RNRs) catalyze the de novo conversion of nucleotides to deoxynucleotides in all organisms, controlling their relative ratios and abundance. In doing so, they play an important role in fidelity of DNA replication and repair. RNRs' central role in nucleic acid metabolism has resulted in five therapeutics that inhibit human RNRs. In this review, we discuss the structural, dynamic, and mechanistic aspects of RNR activity and regulation, primarily for the human and Escherichia coli class Ia enzymes. The unusual radical-based organic chemistry of nucleotide reduction, the inorganic chemistry of the essential metallo-cofactor biosynthesis/maintenance, the transport of a radical over a long distance, and the dynamics of subunit interactions all present distinct entry points toward RNR inhibition that are relevant for drug discovery. We describe the current mechanistic understanding of small molecules that target different elements of RNR function, including downstream pathways that lead to cell cytotoxicity. We conclude by summarizing novel and emergent RNR targeting motifs for cancer and antibiotic therapeutics.

Primary intraosseous malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive neoplasms originating from peripheral nerves. Typically manifesting as soft tissue masses accompanied by pain or functional impairment, these tumors pose significant challenges in management. Surgical intervention remains the cornerstone of treatment for patients with MPNST lacking distant metastasis, with generally modest success rates. In cases of recurrence and metastasis, the pursuit of effective systemic therapies has been a focus of clinical investigation. Herein, we present a case study involving an elderly female patient with refractory MPNST. In light of surgical limitations, a multimodal therapeutic approach combining chemotherapy, denosumab, and subsequent administration of anlotinib was pursued following collaborative consultation. This regimen yielded noteworthy clinical benefits, exemplifying a promising avenue in the management of challenging MPNST cases. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are diverse, membrane-bound vesicles released from cells into the extracellular environment. They originate from either endosomes or the cell membrane and typically include exosomes and microvesicles. These EVs serve as crucial mediators of intercellular communication, carrying a variety of contents such as nucleic acids, proteins, and lipids, which regulate the physiological and pathological processes of target cells. Moreover, the molecular cargo of EVs can reflect critical information about the originating cells, making them potential biomarkers for the diagnosis and prognosis of diseases. Over the past decade, the role of EVs as key communicators between cell types in cardiovascular physiology and pathology has gained increasing recognition. EVs from different cellular sources, or from the same source under different cellular conditions, can have distinct impacts on the management, diagnosis, and prognosis of cardiovascular diseases. Furthermore, it is essential to consider the influence of cardiovascular-derived EVs on the metabolism of peripheral organs. This review aims to summarize recent advancements in the field of cardiovascular research with respect to the roles and implications of EVs. Our goal is to provide new insights and directions for the early prevention and treatment of cardiovascular diseases, with an emphasis on the therapeutic potential and diagnostic value of EVs. [ABSTRACT FROM AUTHOR]

Since its discovery in 1978, cisplatin‐based chemotherapy regimens have served a pivotal role in human cancer treatment, saving millions of lives. However, its high risk still poses a significant challenge for cisplatin‐induced acute kidney injury (AKI), which occurs in 30% of cisplatin‐treated patients. Unfortunately, no effective solution for preventing or managing this severe complication, which greatly impacts its clinical administration. Kidney is the main organ injured by cisplatin, and the injury is related to cisplatin‐induced cell apoptosis and DNA injury. Therefore, to achieve the safe use of cisplatin in tumour treatment, the key lies in identifying a kidney treatment that can effectively minimize cisplatin nephrotoxicity. Here, we successfully synthesized and applied a DNA‐nanostructure complex, named TFG, which contains tetrahedral framework nucleic acids (tFNAs) and FG‐4592, a novel Hif‐1α inducer. As cargo, TFG is composed entirely of DNA strands. It possesses low nephrotoxicity and renal aggregation properties while FG‐4592 is able to relieve renal injury by downregulating the apoptosis signal pathways. And it can relieve cisplatin‐induced renal injury when taken cisplatin treatment. This work aims to enhance chemotherapy protection in tumour patients by using TFG, a DNA‐based nanomedicines to kidney. This work has the potential to revolutionize the treatment of renal diseases, particularly drug‐induced kidney injury, leading to improved clinical outcomes. [ABSTRACT FROM AUTHOR]

As an important part of a bridge, bearings are vulnerable to damage when exposed to various loading and environmental changes during their lifetime, resulting in the necessitating repair or replacement operations. The investigation and maintenance of bearings' diseases are helpful to prolong their durability. Compared with laboratory research, the field investigation of bearing diseases is more representative due to the realistic working environment. In this paper, the defects of 10,486 bearings in 19 expressway bridges and 8,862 bearings in 5 high-speed railway (HSR) bridges in Eastern China are inspected through manual on-site visual observation and parameter measurement, followed by a large amount of bearing diseases data obtained to perform a statistical analysis for evaluating many aspects, including the classification and the potential causes of the bearing diseases, the service status. Finally, a three-level maintenance strategy for bearings is developed and applied to the replacement of 1,166 bearings in eight expressway bridges and 15 bearings in seven girders of HSR bridges. The results show that most diseases of elastomeric bearings are caused by design defects but for pot or spherical by the problems remaining from bearings installation, and the proposed bridge jacking scheme and bearing replacement technologies are efficient, labour- and material-saving. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence reveals that SARS-CoV-2 possesses the capability to disrupt the gastrointestinal (GI) homeostasis, resulting in the longterm symptoms such as loss of appetite, diarrhea, gastroesophageal reflux, and nausea. In the current review, we summarized recent reports regarding the long-term effects of COVID-19 (long COVID) on the gastrointestine. Objective: To provide a narrative review of abundant clinical evidence regarding the development and management of long-term GI symptoms in COVID19 patients. Results: Long-term persistent digestive symptoms are exhibited in a majority of long-COVID patients. SARS-CoV-2 infection of intestinal epithelial cells, cytokine storm, gut dysbiosis, therapeutic drugs, psychological factors and exacerbation of primary underlying diseases lead to long-term GI symptoms in COVID-19 patients. Interventions like probiotics, prebiotics, fecal microbiota transplantation, and antibiotics are proved to be beneficial in preserving intestinal microecological homeostasis and alleviating GI symptoms. Conclusion: Timely diagnosis and treatment of GI symptoms in long-COVID patients hold great significance as they may contribute to the mitigation of severe conditions and ultimately lead to the improvement of outcomes of the patients. [ABSTRACT FROM AUTHOR]

The NLRP3 inflammasome is a crucial constituent of the body’s innate immune system, and a multiprotein platform which is initiated by pattern recognition receptors (PRRs). Its activation leads to caspase-1 maturation and release of inflammatory cytokines, interleukin-1β (IL-1β) and IL-18, and subsequently causes pyroptosis. Recently, the excess activation of NLRP3 inflammasome has been confirmed to mediate inflammatory responses and to participate in genesis and development of atherosclerosis. Therefore, the progress on the discovery of specific inhibitors against the NLRP3 inflammasome and the upstream and downstream inflammatory factors has become potential targets for clinical treatment. Here we review the recently described mechanisms about the NLRP3 inflammasome activation, and discuss emphatically the pharmacological interventions using statins and natural medication for atherosclerosis associated with NLRP3 inflammasome.

Chemical modifications of RNA molecules regulate both RNA metabolism and fate. The deposition and function of these modifications are mediated by the actions of writer, reader, and eraser proteins. At the cellular level, RNA modifications regulate several cellular processes including cell death, proliferation, senescence, differentiation, migration, metabolism, autophagy, the DNA damage response, and liquid-liquid phase separation. Emerging evidence demonstrates that RNA modifications play active roles in the physiology and etiology of multiple diseases due to their pervasive roles in cellular functions. Here, we will summarize recent advances in the regulatory and functional role of RNA modifications in these cellular functions, emphasizing the context-specific roles of RNA modifications in mammalian systems. As m6A is the best studied RNA modification in biological processes, this review will summarize the emerging advances on the diverse roles of m6A in cellular functions. In addition, we will also provide an overview for the cellular functions of other RNA modifications, including m5C and m1A. Furthermore, we will also discuss the roles of RNA modifications within the context of disease etiologies and highlight recent advances in the development of therapeutics that target RNA modifications. Elucidating these context-specific functions will increase our understanding of how these modifications become dysregulated during disease pathogenesis and may provide new opportunities for improving disease prevention and therapy by targeting these pathways.

Introduction: The correlation between diabetes and stroke has been studied extensively in epidemiological research. Here, we used bibliometric software to visualize and analyze the literature related to diabetic stroke to provide an overview of the current state of research, hotspots, and future trends in the field. Methods: Based on the Web of Science Core Collection (WoSCC) database, we collected studies related to diabetic stroke from 2007 to December 2022. We used CiteSpace (version 6.1.R5), VOSviewer, and Scimago Graphica to create knowledge maps and conduct visual analyses on authors, countries, institutions, cited references, and keywords, and Origin for statistical analysis. Results: We included a total of 5,171 papers on diabetic stroke from the WoSCC database. Overall, there was a steady increase in the number of publications, with a high number of emerging scientists. The USA was the most productive and influential country, which dominated national collaborations. The most common subject category was "neurology." In total, 12 major clusters were generated from the cited references. Keyword analysis showed that keywords related to poststroke injury and treatment are those with the highest burst intensity and latest burst time. Conclusions: Individual disease treatment remains a hot topic, and how to balance acute stroke treatment and glycemic control is currently a difficult clinical problem. At the same time, the mechanism of their interaction and the prevention and treatment of related causative factors remain a hot topic of current and future research. [ABSTRACT FROM AUTHOR]

Context: Cabozantinib combined with immune checkpoint inhibitors (ICIs) has brought a new therapeutic effect for the medical treatment of renal cell carcinoma (RCC). Objectives: We performed a meta-analysis of randomized controlled trials and single-arm trials to evaluate the efficacy and safety of cabozantinib plus ICIs in RCC. Methods: We extracted data from PubMed, Cochrane, Medline and Embase databases, and rated literature quality through Cochrane risk of bias tool and MINORS. RevMan5.3 software was used to analyze the results of randomized controlled trials and single-arm trials. Results: A total of 7 studies were included. Treatment with cabozantinib plus ICIs improved PFS [HR 0.75, (95%CI: 0.52, 1.08), p = 0.12] and the OS [HR 0.80, (95%CI: 0.60, 1.07), p = 0.13] in randomized controlled trials. Meanwhile, the result of the ORR inrandomized controlled trialswas [risk ratio (RR) 1.37, (95%CI: 1.21, 1.54), p < 0.00001] and in single-arm trials was [risk difference (RD) 0.49, (95%CI: 0.26, 0.71), p < 0.0001]. Conclusion: Cabozantinib plus ICIs prolonged the PFS and OS, and improved ORR in patients with RCC. Our recommendation is to use cabozantinib plus ICIs to treat advanced RCC, and to continuous monitor and manage the drug-related adverse events. [ABSTRACT FROM AUTHOR]

Background: Clinically, patients with myasthenia gravis are generally treated with drugs to improve their physical condition, and poor medication adherence can hinder their recovery. Many studies have shown the importance of medication adherence for effective treatment. Various factors may affect a patient's medication adherence; however, studies concerning medication adherence in patients with myasthenia gravis are rare. Objectives: This study aimed to identify the factors related to medication adherence in patients with myasthenia gravis, and determine the possibility of predicting medication adherence. Methods: This cross-sectional observational study was conducted among inpatients and outpatients with myasthenia gravis of the First Affiliated Hospital of Guangzhou University of Chinese Medicine in China. Data on patient demographics, disease-related characteristics, and medical treatment were collected. We evaluated medication adherence of the patients using the Morisky Medication Adherence Scale-8, Beliefs about Medicines Questionnaire, and the Self-efficacy for Appropriate Medication Use Scale. Results: We distributed 200 questionnaires and finally retrieved 198 valid questionnaires. A total of 139 (70.2%) women participated in this study, and 81 (40.9%) among the 198 participants were aged 40–59 years. In total, 103 (52.0%) participants exhibited bad adherence to pharmacological treatment, and factors such as taking medication irregularly [odds ratio (OR) = 0.242, 95% CI = 0.093–0.627], the necessity of taking medicine (OR = 1.286, 95% CI = 1.142–1.449), the concerns of taking medicine (OR = 0.890, 95% CI = 0.801–0.988), and the self-efficacy for taking medications under difficult circumstances (OR = 1.194, 95% CI = 1.026–1.389) had statistically significant impacts on medication adherence. Conclusion: Our study shows that taking medication irregularly and concerns of taking medicine are the risk factors for medication adherence. Meanwhile, the necessity of talking medicine and self-efficacy for taking medications under difficult circumstances are the protective factors for medication adherence. Our findings can help medical staff to enhance patients' medication adherence by informing patients necessary medical knowledge, emphasizing the necessity for medication, relieving patients' concerns regarding medication, and improving the self-efficacy for taking medications under difficult circumstances. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM), characterized by β-cell dysfunction and insulin resistance (IR), presents considerable treatment challenges. Apelin is an adipocyte-derived factor that shows promise in improving IR; however, it is limited by poor targeting and a short half-life. In the present study, engineered small extracellular vesicles (sEVs) derived from Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) loaded with apelin were used to address the limitations of the therapeutic application of apelin. Methods: WJ-MSCs were transduced to obtain engineered sEVs loaded with overexpressed apelin (apelin-MSC-sEVs) and the control sEVs (MSC-sEVs). T2DM mice were injected with apelin-MSC-sEVs and MSC-sEVs, and blood glucose monitoring, glucose and insulin tolerance tests, confocal microscopy, and immunocytochemical analysis were performed. IR models of 3T3-L1 adipocytes were employed to detect GLUT4 expression in each group using western blotting; the affected pathways were determined by measuring the changes in Akt and AMPK signaling and phosphorylation. Results: Upon successful engineering, WJ-MSCs demonstrated significant overexpression of apelin. The genetic modification did not adversely impact the characteristics of sEVs, ranging from surface protein markers, morphology, to particle size, but generated apelin-overexpressed sEVs. Apelin-MSC-sEVs treatment resulted in notable enhancement of Akt and AMPK pathway activities within 3T3-L1 adipocytes and adipose tissues of T2DM mice. Furthermore, the apelin-loaded sEVs significantly reduced plasma glucose levels, increased pancreatic β-cell proliferation, improved insulin and glucose tolerance, and modulated pro-inflammatory cytokine profiles, compared to mice treated with the control sEVs. Conclusion: Our study developed novel genetically engineered apelin-loaded sEVs derived from WJ-MSCs, and demonstrated their potent role in augmenting insulin sensitivity and regulating inflammatory responses, highlighting their therapeutic promise in T2DM management. The findings open new avenues for the development of clinically viable treatments for T2DM in humans using the apelin-loaded sEVs. [ABSTRACT FROM AUTHOR]

Salivary extracellular vesicles (EVs) have emerged as key tools for non-invasive diagnostics, playing a crucial role in the early detection and monitoring of diseases. These EVs surpass whole saliva in biomarker detection due to their enhanced stability, which minimizes contamination and enzymatic degradation. The review comprehensively discusses methods for isolating, enriching, quantifying, and characterizing salivary EVs. It highlights their importance as biomarkers in oral diseases like periodontitis and oral cancer, and underscores their potential in monitoring systemic conditions. Furthermore, the review explores the therapeutic possibilities of salivary EVs, particularly in personalized medicine through engineered EVs for targeted drug delivery. The discussion also covers the current challenges and future prospects in the field, emphasizing the potential of salivary EVs in advancing clinical practice and disease management. [ABSTRACT FROM AUTHOR]

Extracting and digitizing drug attributes from medical literature is the first step to build a knowledge computing system for precision disease treatment. In order to build a cardiovascular drug knowledge base, this paper proposes a multi-label text classification method for cardiovascular drug attributes from the Chinese drug guideline. The drug attributes are characterized by a BERT pre-trained model, and a dual-feature extraction structure is proposed based on the BiGRU neural network to capture high-level semantic information. Label categorization of cardiovascular drug attributes, such as indications and mode of administration, is accomplished. The F1 score of 0.8431 was obtained using 5-fold cross-validation. Comparing KNN and Naïve bayes, and conducting CNN and BiGRU control experiments on the basis of Word2Vec characterization of medication guidelines, the proposed multi-label text classification method is effective and the F1 value is significantly improved. Proved by analysis of ablation and crossover experiments, the proposed method can achieve a high accuracy rate averaged at 0.8339. [ABSTRACT FROM AUTHOR]

B/T mixed phenotype acute leukemia (MPAL), which represents only 2–3% of all MPAL cases, is classified as a high-risk leukemia subtype. Adults diagnosed with B/T MPAL have a notably low 3-year survival rate, estimated at 20–40%. The rarity and undercharacterization of B/T MPAL present substantial challenges in identifying an optimal treatment protocol. This report aims to shed light on this issue by presenting a case in which a patient with a complex karyotype was treated using a combination of venetoclax, azacitidine, and blinatumomab. This novel, chemo-free regimen resulted in the patient achieving both hematologic and molecular complete remission, with no severe organ or hematological toxicity observed. Notably, the patient continued to maintain molecular remission for 1 year following the transplantation. Based on these findings, the combination of venetoclax, azacitidine, and blinatumomab could be considered a potential therapeutic approach for B/T MPAL patients, meriting further investigation. [ABSTRACT FROM AUTHOR]

This study aimed to systematically evaluate the clinical efficacy of Chinese herbal medicine combined with negative pressure wound therapy (NPWT) in the treatment of diabetic foot ulcers (DFU). Computerised searches of the China National Knowledge Infrastructure, Wanfang, Chinese BioMedical Literature Database, PubMed, Cochrane Library and Embase databases were conducted for randomised controlled trials on the use of Chinese herbal medicines combined with NPWT for the treatment of DFU. The search period ranged from the time of establishment of each database to July 2023. Literature screening and data extraction were performed independently by two investigators, and the quality of the included studies was assessed. The meta‐analysis was performed using Review Manager 5.4 software. A total of 25 studies were analysed, including 1777 DFUs, with 890 and 887 patients in the experimental and control groups, respectively. The results showed that the treatment of DFUs with a Chinese herbal medicine in combination with NPWT increased the overall effectiveness (odds ratio [OR] = 4.32, 95% confidence interval [CI]: 2.96–6.30, p < 0.001), wound healing rate (mean difference [MD] = 18.35, 95% CI: 13.07–23.64, p < 0.001) and ankle brachial index (MD = 0.10, 95% CI: 0.06–0.14, p < 0.001); reduced the wound healing time (MD = −11.01, 95% CI: −13.25 to −8.78, p < 0.001) and post‐treatment wound area (MD = −1.73, 95% CI: −2.46 to −1.01, p < 0.001); decreased the C‐reactive protein level (MD = −3.57, 95% CI: −5.13 to −2.00, p < 0.001); and increased vascular endothelial growth factor level (MD = 19.20, 95% CI: 8.36–30.05, p < 0.001). Thus, Chinese herbal medicines combined with NPWT can effectively promote wound healing, reduce inflammation and shorten the disease course in patients with DFU, while demonstrating precise clinical efficacy. [ABSTRACT FROM AUTHOR]

Due to their unique location, airway tumors have a significant impact on patient quality of life and survival. Current research has focused extensively on malignant airway tumors; however, benign airway tumors, especially rare ones, are less understood due to their low incidence. These tumors are often misdiagnosed and mistreated due to diagnostic challenges. Therefore, there is still a lack of consensus on the treatment of some rare benign airway tumors. Our center summarizes the diagnosis and treatment of four rare cases of benign airway stenosis in recent years, highlighting the bronchoscopic manifestations and therapeutic approaches to improve the understanding of these diseases. [ABSTRACT FROM AUTHOR]

Owing to their unique features, including high cargo loading, biodegradability, and tailorability, metal–organic frameworks (MOFs) and their composites have attracted increasing attention in various fields. In this review, application strategies of MOFs and their composites in nanomedicine with emphasis on their functions are presented, from drug delivery, therapeutic agents for different diseases, and imaging contrast agents to sensor nanoreactors. Applications of MOF derivatives in nanomedicine are also introduced. Besides, we summarize different functionalities related to MOFs, which include targeting strategy, biomimetic modification, responsive moieties, and other functional decorations. Finally, challenges and prospects are highlighted about MOFs in future applications.

The tumor microenvironment (TME) is populated by abundant cancer-associated fibroblasts (CAFs) that radically influence the disease progression across many cancers, including the colorectal cancer (CRC). In theory, targeting CAFs holds great potential in optimizing CRC treatment. However, attempts to translate the therapeutic benefit of CAFs into clinic practice face many obstacles, largely due to our limited understanding of the heterogeneity in their origins, functions, and mechanisms. In recent years, accumulating evidence has uncovered some cellular precursors and molecular markers of CAFs and also revealed their versatility in impacting various hallmarks of CRC, together helping us to better define the population of CAFs and also paving the way toward their future therapeutic targeting for CRC treatment. In this review, we outline the emerging concept of CAFs in CRC, with an emphasis on their origins, biomarkers, prognostic significance, as well as their functional roles and underlying mechanisms in CRC biology. At last, we discuss the prospect of harnessing CAFs as promising therapeutic targets for the treatment of patients with CRC.

The protein kinase D (PKD) family is a family of serine-threonine kinases that are members of the calcium/calmodulin-dependent kinase (CaMK) superfamily. PKDs have been increasingly implicated in multiple pivotal cellular processes and pathological conditions. PKD dysregulation is associated with several diseases, including cancer, inflammation, and obesity. Over the past few years, small-molecule inhibitors have emerged as alternative targeted therapy with fewer adverse side effects than currently available chemotherapy, and these specifically targeted inhibitors limit non-specific toxicities. The successful development of PKD inhibitors would significantly suppress the growth and proliferation of various cancers and inhibit the progression of other diseases. Various PKD inhibitors have been studied in the preclinical setting. In this context, we summarize the PKD inhibitors under investigation and their application for different kinds of diseases.

Background: There is a pressing need to identify pharmaceuticals that are both safe and efficacious, with lower toxicity, for the treatment of stable angina pectoris in individuals suffering from coronary heart disease. The aim of this paper is to explore the therapeutic value of Shexiang Tongxin Dropping Pills in patients with stable angina pectoris of coronary heart disease complicated with cognitive impairment. Methods: 200 patients with stable angina pectoris combined with cognitive dysfunction and coronary heart disease admitted to our hospital from January 2022 to June 2023 were retrospectively selected as the study objects. According to the treatment method, the subjects were divided into a control group and a study group, with 100 cases in each group. The control group received conventional oral Western medicine, and the study group underwent treatment with Shexiang Tongxin Dropping Pills in addition to traditional Western medicine. The course of treatment was eight weeks. The enhancement in angina pectoris, cognitive function level, self-care ability, and clinical efficacy of both groups were assessed by comparing the conditions before and after the treatment. Results: After treatment, the frequency and duration of angina pectoris attacks in both groups were significantly lower than before, and the study group was lower than the control group (p < 0.05). The Montreal Cognitive Assessment (MoCA) score of both groups was higher than before, and the score of the study group was significantly higher than that of the control group (p < 0.05). Neuropsychiatric Inventory (NPI) scores in both groups were significantly lower than before, and the scores of the study group were significantly lower than those of the control group (p < 0.05). Traditional Chinese Medicine (TCM) syndrome scores in both groups were significantly lower than before, and the scores of the study group were significantly lower than those of the control group (p < 0.05). After treatment, the total effective rate of the control group and the study group was 81.00% and 93.00%, respectively, and the total clinical effective rate of the study group was significantly higher than that of the control group (p < 0.05). Conclusion: Shexiang Tongxin Dropping Pills can effectively reduce the incidence of angina pectoris in patients with stable angina pectoris complicated with coronary heart disease and cognitive dysfunction. It can also regulate the patient's neurological function, improve their cognitive level, and significantly improve clinical efficacy. [ABSTRACT FROM AUTHOR]

Chronic lung diseases include an array of conditions that impact airways and lung structures, leading to considerable societal burdens. Mesenchymal stem cells (MSCs) and their exosomes (MSC-exos) can be used for cell therapy and exhibit a diverse spectrum of anti-inflammatory, antifibrotic, and immunomodulatory properties. Engineered MSC-exos possesses enhanced capabilities for targeted drug delivery, resulting in more potent targeting effects. Through various engineering modifications, these exosomes can exert many biological effects, resulting in specific therapeutic outcomes for many diseases. Moreover, engineered stem cell exosomes may exhibit an increased capacity to traverse physiological barriers and infiltrate protected lesions, thereby exerting their therapeutic effects. These characteristics render them a promising therapeutic agent for chronic pulmonary diseases. This article discusses and reviews the strategies and mechanisms of engineered MSC-exos in the treatment of chronic respiratory diseases based on many studies to provide new solutions for these diseases. [ABSTRACT FROM AUTHOR]

Oral disease, as a class of diseases with very high morbidity, brings great physical and mental damage to people worldwide. The increasing burden and strain on individuals and society make oral diseases an urgent global health problem. Since the treatment of almost all oral diseases relies on materials, the rapid development of advanced materials and technologies has also promoted innovations in the treatment methods and strategies of oral diseases. In this review, we systematically summarized the application strategies in advanced materials and technologies for oral diseases according to the etiology of the diseases and the comparison of new and old materials. Finally, the challenges and directions of future development for advanced materials and technologies in the treatment of oral diseases were refined. This review will guide the fundamental research and clinical translation of oral diseases for practitioners of oral medicine. [ABSTRACT FROM AUTHOR]

Bone nonunion and bone defects frequently occur following high‐energy open injuries or debridement surgeries, presenting complex challenges to treatment and significantly affecting patients' quality of life. At present, there are three primary treatment options available for addressing bone nonunion and bone defects: vascularized bone grafts, the Masquelet technique, and the Ilizarov technique. The Ilizarov technique, also known as distraction osteogenesis, is widely favored by orthopedic surgeons because of several advantages, including minimal soft tissue requirements, low infection risk, and short consolidation time. However, in recent years, the application of the Masquelet technique has resulted in novel treatment methods for managing post‐traumatic bone infections when bone defects are present. Although these new techniques do not constitute a panacea, they continue to be the most commonly employed options for treating complex large bone nonunion and bone defects. This review evaluates the currently available research on the Ilizarov and Masquelet bone transport techniques applied at various anatomical sites. Additionally, it explores treatment durations and associated complications to establish a theoretical foundation that can guide clinical treatment decisions and surgical procedures for the management of bone nonunion and bone defects. [ABSTRACT FROM AUTHOR]

Decellularized matrices derived from diseased tissues/organs have evolved in the most recent years, providing novel research perspectives for understanding disease occurrence and progression and providing accurate pseudo models for developing new disease treatments. Although decellularized matrix maintaining the native composition, ultrastructure, and biomechanical characteristics of extracellular matrix (ECM), alongside intact and perfusable vascular compartments, facilitates the construction of bioengineered organ explants in vitro and promotes angiogenesis and tissue/organ regeneration in vivo, the availability of healthy tissues and organs for the preparation of decellularized ECM materials is limited. In this paper, we review the research advancements in decellularized diseased matrices. Considering that current research focuses on the matrices derived from cancers and fibrotic organs (mainly fibrotic kidney, lungs, and liver), the pathological characterizations and the applications of these diseased matrices are mainly discussed. Additionally, a contrastive analysis between the decellularized diseased matrices and decellularized healthy matrices, along with the development in vitro 3D models, is discussed in this paper. And last, we have provided the challenges and future directions in this review. Deep and comprehensive research on decellularized diseased tissues and organs will promote in‐depth exploration of source materials in tissue engineering field, thus providing new ideas for clinical transformation. [ABSTRACT FROM AUTHOR]

Aim: Our previous study revealed that the C‐C motif chemokine receptor 2 (CCR2) is a promising target for periodontitis prevention and treatment. However, CCR2 is a receptor with multiple C‐C motif chemokine ligands (CCLs), including CCL2, CCL7, CCL8, CCL13 and CCL16, and which of these ligands plays a key role in periodontitis remains unclear. The aim of the present study was to explore the key functional ligand of CCR2 in periodontitis and to evaluate the potential of the functional ligand as a therapeutic target for periodontitis. Materials and Methods: The expression levels and clinical relevance of CCR2, CCL2, CCL7, CCL8, CCL13 and CCL16 were studied using human samples. The role of CCL2 in periodontitis was evaluated by using CCL2 knockout mice and overexpressing CCL2 in the periodontium. The effect of local administration of bindarit in periodontitis was evaluated by preventive and therapeutic medication in a mouse periodontitis model. Microcomputed tomography, haematoxylin and eosin staining, tartrate‐resistant acid phosphatase staining, real‐time quantitative polymerase chain reaction, enzyme‐linked immunosorbent assay, bead‐based immunoassays and flow cytometry were used for histomorphology, molecular biology and cytology analysis. Results: Among different ligands of CCR2, only CCL2 was significantly up‐regulated in periodontitis gingival tissues and was positively correlated with the severity of periodontitis. Mice lacking CCL2 showed milder inflammation and less bone resorption than wild‐type mice, which was accompanied by a reduction in monocyte/macrophage recruitment. Adeno‐associated virus‐2 vectors overexpressing CCL2 in Ccl2−/− mice gingiva reversed the attenuation of periodontitis in a CCR2‐dependent manner. In ligation‐induced experimental periodontitis, preventive or therapeutic administration of bindarit, a CCL2 synthesis inhibitor, significantly inhibited the production of CCL2, decreased the osteoclast number and bone loss and reduced the expression levels of proinflammatory cytokines TNF‐α, IL‐6 and IL‐1β. Conclusions: CCL2 is a pivotal chemokine that binds to CCR2 during the progression of periodontitis, and targeting CCL2 may be a feasible option for controlling periodontitis. [ABSTRACT FROM AUTHOR]

Mycoplasma pneumoniae is a common causative pathogen of communityacquired pneumonia. An accurate and sensitive detection method is important for evaluating disease severity and treatment efficacy. Digital droplet PCR (ddPCR) is a competent method enabling the absolute quantification of DNA copy number with high precision and sensitivity. We established ddPCR for M. pneumoniae detection, using clinical specimens for validation, and this showed excellent specificity for M. pneumoniae. The limit of detection of ddPCR was 2.9 copies/reaction, while that for real-time PCR was 10.8 copies/reaction. In total, 178 clinical samples were used to evaluate the ddPCR assay, which correctly identified and differentiated 80 positive samples, whereas the real-time PCR tested 79 samples as positive. One sample that tested negative in real-time PCR was positive in ddPCR, with a bacterial load of three copies/test. For samples that tested positive in both methods, the cycle threshold of real-time PCR was highly correlated with the copy number of ddPCR. Bacterial loads in patients with severe M. pneumoniae pneumonia were significantly higher than those in patients with general M. pneumoniae pneumonia. The ddPCR showed that bacterial loads were significantly decreased after macrolide treatment, which could have reflected the treatment efficacy. The proposed ddPCR assay was sensitive and specific for the detection of M. pneumoniae. Quantitative monitoring of bacterial load in clinical samples could help clinicians to evaluate treatment efficacy. [ABSTRACT FROM AUTHOR]

Background: Rapidly progressive glomerulonephritis (RPGN) is clinically manifestations as a rapidly progressive renal failure and pathologically as crescentic and necrotizing lesions with infiltration of inflammatory cells in the glomeruli. Uremic encephalopathy (UE) usually develops in patients who are suffering from acute or chronic renal failure. Objective: The purpose of this article is to provide reference for clinical diagnosis and treatment of renal disease complicated with seizures. Patients Two cases of anti‐glomerular basement membrane type rapidly progressive glomerulonephritis complicated with seizures were reported. Materials & Methods: In case 1, a 40‐year‐old woman was hospitalized for the treatment of nausea, anorexia, and fever. On admission, she presented with elevated serum inflammatory indicators, moderate anemia, and advanced acute kidney injury requiring hemodialysis. Her anti‐glomerular basement membrane (GBM) antibody in serum and renal tissues was found to be extremely high. She was finally diagnosed with anti‐GBM disease. She was treated with a combination of corticosteroid pulse therapy, oral cyclophosphamide and prednisolone, and plasma exchange, while continued to require maintenance hemodialysis for end‐stage kidney disease. During treatment, she suddenly suffered blindness, seizure, and consciousness disturbance. She was diagnosed as posterior reversible leukoencephalopathy syndrome by magnetic resonance imaging (MRI). The posterior reversible leukoencephalopathy syndrome subsided quickly after control of her hypertension and reinforcement of immunosuppressive treatment. In case 2, the patient also developed epileptic symptoms on the basis of GBM disease, and was given treatment similar to that of Case 1, so that the epileptic symptoms were controlled. Result: Reversible posterior leukoencephalopathy syndrome, especially when accompanied by cerebral hemorrhage, may lead to irreversible and lethal neurological abnormalities, and nephrologists should, therefore, be aware of the potential risk of reversible posterior leukoencephalopathy syndrome in patients with anti‐GBM disease. We can discuss the current two cases in the light of the previous literature. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder in older adults. There is increasing evidence that BP has connections with renal diseases, such as glomerulopathy and neoplasm; it is also linked to the receipt of renal replacement therapy. In this review, we summarize the current evidence that BP is a comorbidity of common renal diseases. Furthermore, our exploration of the characteristics and possible mechanisms underlying these connections provides insights that may facilitate the prevention, diagnosis, and management of BP. There is mounting proof that BP is not just a skin immunological disorder but rather a systemic immune-mediated illness. Quantities of case reports focused on BP as a renal disease comorbidity and the coexistence of them is not accidental. However, the underlying mechanisms are still needed to be investigated. Clinicians should be alert to the comorbidities in order to facilitate effective treatment and improve patient prognosis. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA), the commonest arthritis, is characterized by the progressive destruction of cartilage, leading to disability. The Current early clinical treatment strategy for OA often centers on anti‐inflammatory or analgesia medication, weight loss, improved muscular function and articular cartilage repair. Although these treatments can relieve symptoms, OA tends to be progressive, and most patients require arthroplasty at the terminal stages of OA. Recent studies have shown a close correlation between joint pain, inflammation, cartilage destruction and synovial cells. Consequently, understanding the potential mechanisms associated with the action of synovial cells in OA could be beneficial for the clinical management of OA. Therefore, this review comprehensively describes the biological functions of synovial cells, the synovium, together with the pathological changes of synovial cells in OA, and the interaction between the cartilage and synovium, which is lacking in the present literature. Additionally, therapeutic approaches based on synovial cells for OA treatment are further discussed from a clinical perspective, highlighting a new direction in the treatment of OA. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel disease (IBD) always suffer from severe abdominal pain and appear to be at high risk for colorectal cancer. Recently, the co-delivery of targeted drugs and gut microbiota has developed into an attractive strategy. A new strategy using gut microbiota fermentation to overcome the interspace diffuse resistance from the mucus layer to control drug release in inflammatory bowel sites (IBS sites) has not yet been available. Here, we designed an alginate hydrogel microsphere encapsulating bifidobacterium (Bac) and drug-modified nanoscale dietary fibers (NDFs). The hydrogel microsphere is responsible for protecting drugs from acidic and multi-enzymatic environments and delivering drugs to the colorectum. Subsequently, the fermentation of Bac by digesting NDFs and proteins as carbon and nitrogen sources can promote drug release and play a probiotic role in the gut microbiota. In vitro evidence indicated that small-sized NDF (NDF-1) could significantly promote short-chain fatty acid (SCFA) expression. Notably, NDF-1 hydrogel microspheres showed a boost release of 5-ASA in the IBS sites, resulting in the amelioration of gut inflammation and remodeling of gut microbiota in chronic colitis mice. This study developed a controlled release system based on microbial fermentation for the treatment of IBD. [ABSTRACT FROM AUTHOR]

Inflammation is a crucial pathological feature in cancers and kidney diseases, playing a significant role in disease progression. Cyclin-dependent kinases CDK4 and CDK6 not only contribute to cell cycle progression but also participate in cell metabolism, immunogenicity and anti-tumor immune responses. Recently, CDK4/6 inhibitors have gained approval for investigational treatment of breast cancer and various other tumors. Kidney diseases and cancers commonly exhibit characteristic pathological features, such as the involvement of inflammatory cells and persistent chronic inflammation. Remarkably, CDK4/6 inhibitors have demonstrated impressive efficacy in treating non-cancerous conditions, including certain kidney diseases. Current studies have identified the renoprotective effect of CDK4/6 inhibitors, presenting a novel idea and potential direction for treating kidney diseases in the future. In this review, we briefly reviewed the cell cycle in mammals and the role of CDK4/6 in regulating it. We then provided an introduction to CDK4/6 inhibitors and their use in cancer treatment. Additionally, we emphasized the importance of these inhibitors in the treatment of kidney diseases. Collectively, growing evidence demonstrates that targeting CDK4 and CDK6 through CDK4/6 inhibitors might have therapeutic benefits in various cancers and kidney diseases and should be further explored in the future. [ABSTRACT FROM AUTHOR]

Chronic inflammation, in general, refers to systemic immune abnormalities most often caused by the environment or lifestyle, which is the basis for various skin diseases, autoimmune diseases, cardiovascular diseases, liver diseases, digestive diseases, cancer, and so on. Therapeutic strategies have focused on immunosuppression and anti-inflammation, but conventional approaches have been poor in enhancing the substantive therapeutic effect of drugs. Nanomaterials continue to attract attention for their high flexibility, durability and simplicity of preparation, as well as high profitability. Nanotechnology is used in various areas of clinical medicine, such as medical diagnosis, monitoring and treatment. However, some related problems cannot be ignored, including various cytotoxic and worsening inflammation caused by the nanomaterials themselves. This paper provides an overview of functional nanomaterial formulations for the prevention, diagnosis and treatment of chronic inflammation-related diseases, with the intention of providing some reference for the enhancement and optimization of existing therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Neutrophil granulocytes are essential components of innate immune response. An absolute number of neutrophils are a fundamental indicator of host defense. With increasing severity of neutropenia, either due to the disease or as a result of chemotherapy for hematologic malignancies, there is an exponential increase in the risk of severe infection. In such conditions, granulocyte transfusion is considered a potential therapeutic option due to its phagocytic properties. The study was undertaken to analyze data of granulocyte collections and transfusions in resource-constrained Settings. Methods: In this observational prospective study, granulocytes were harvested by combined administration of granulocyte colony-stimulating factors and dexamethasone mobilization and transfused to severely neutropenic patients. Data on granulocyte collections and transfusion, various determinants of donor, and procedural characteristics and patient outcomes, with respect to 30-day mortality, were analyzed. Results: After granulocyte transfusion, patients' posttransfusion white blood cell and neutrophils increased significantly. Higher platelet counts in the harvested products resulted into significant increment of patients' platelet count and markedly reduced demands of platelet transfusions, reducing chances of alloimmunization. Eighty-five percent of patients could be saved, showed improvements in their clinical conditions, and were discharged from hospital in stable condition. Conclusion: Granulocyte transfusions are an important therapeutic modality in neutropenic patients with resistant infections, until spontaneous recovery of neutrophil count occurs in patients. Cost Reduction of some of the resources should be considered for LMIC as lower price will encourage more facilities willing to offer similar procedures to aid patients. Training workforce for new and novel processes is need of hour and will add value by equipping LMIC facilities in serving the patients. Granulocyte transfusions are life-saving tool and found to be safe and well tolerated by recipients. They can play a vital role in improving outcomes and saving patients in resource-constraint countries, where there is increasing emergence of multidrug-resistant bacterial infections. [ABSTRACT FROM AUTHOR]

Universal chemotherapy in glioblastoma patients causes chemoresistance and further limits immune cells by creating an immunosuppressive tumor microenvironment that are difficult to solve by single‐drug therapeutic approaches. Here, this work designs hybrid drug‐loaded nanoliposomes by co‐loading the chemotherapeutic drug temozolomide (TMZ) and nitric oxide (NO) prodrug JS‐K with sphingosine‐1‐phosphate molecules (S1P) on the surface. The S1P‐S1P receptors axis endows nanoliposomes with rapid targeting and lysosomal escaping capability. Then, fine‐tuned TMZ release and NO gas production following JS‐K release in glioma microenvironment decrease chemoresistance and increase tumor immunogenicity through inhibiting the cellular autophagy as well as inducing mitochondrial dysfunction. RNA sequencing analysis demonstrates that the NO gas generation reprograms glioma microenvironment immune and inflammation‐related pathways. The positive immune response in turn effectively activates the enhanced efficacy of chemotherapy. NO gas generated nanoliposomes thus have attractive paradigm‐shifting applications in the treatment of "cold" tumors across a range of immunosuppressive indications. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia resulting from insulin secretion defects or insulin resistance. The global incidence of DM has been gradually increasing due to improvements in living standards and changes in dietary habits, making it a major non-communicable disease that poses a significant threat to human health and life. The pathogenesis of DM remains incompletely understood till now, and current pharmacotherapeutic interventions are largely inadequate, resulting in relapses and severe adverse reactions. Although DM is not explicitly mentioned in traditional Chinese medicine (TCM) theory and clinical practice, it is often classified as "Xiaoke" due to similarities in etiology, pathogenesis, and symptoms. With its overall regulation, multiple targets, and personalized medication approach, TCM treatment can effectively alleviate the clinical manifestations of DM and prevent or treat its complications. Furthermore, TCM exhibits desirable therapeutic effects with minimal side effects and a favorable safety profile. This paper provides a comprehensive comparison and contrast of Xiaoke and DM by examining the involvement of TCM in their etiology, pathogenesis, treatment guidelines, and other relevant aspects based on classical literature and research reports. The current TCM experimental research on the treatment of DM by lowering blood glucose levels also be generalized. This innovative focus not only illuminates the role of TCM in DM treatment, but also underscores the potential of TCM in DM management. [ABSTRACT FROM AUTHOR]

Sarcopenia is the age‐related loss of skeletal muscle mass and muscle strength or physical function. It is most common in elderly individuals. Due to its high incidence, insidious onset, and extensive impact on the body, it has a huge impact on the family medical burden and the social public health expenditure in China. The understanding of sarcopenia in China is still lacking, and the recommendations for prevention, control, and intervention are not clear and unified. The purpose of this consensus report is to standardize the prevention, control, and intervention methods for sarcopenia in elderly patients in China; improve the efficacy of intervention; reduce complications during the intervention process; and reduce the risk of falls, fractures, disability, hospitalization, and even death in elderly individuals. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) increases the susceptibility to a variety of infections that are often difficult to diagnose and can be asymptomatic or symptoms are atypical. Usually, this is a great challenge for rheumatologists, because it is difficult to distinguish infection and aseptic inflammation at an early stage. Prompt diagnosis and treatment of bacterial infections in immunosuppressed individuals is critical for clinicians, and early exclusion of infection allows for specific treatment of inflammatory diseases and avoids the unnecessary use of antibiotics. However, for patients with clinically suspected infection, traditional laboratory markers are not specific for bacterial infection and cannot be used to distinguish outbreaks from infections. Therefore, new infection markers that can distinguish infection from underlying disease are urgently needed for clinical practice. Here, we review the novel biomarkers in RA patients with infection. These biomarkers include presepsin, serology and haematology, as well as neutrophils, T cells, and natural killer cells. Meanwhile, we discuss meaningful biomarkers that distinguish infection from inflammation and develop novel biomarkers for clinical applications, allowing clinicians to make better decisions when diagnosing and treating RA. [ABSTRACT FROM AUTHOR]

BackgroundThere has been increasing awareness that post-motion triggered rocking self-vertigo can last for months or years, a disorder known as Mal de Debarquement Syndrome (MdDS). A similar feeling of oscillating self-motion can occur without a motion trigger in some individuals, leading to controversy about whether motion triggered (MT) and non-motion triggered (non-MT) symptoms ultimately represent the same disorder. Recognizing the similarities and differences between MT and non-MT MdDS can prevent unnecessary diagnostic testing and lead to earlier and more effective treatments.MethodsStandardized questionnaire assessment and follow-up interviews of individuals with persistent MT or non-MT MdDS (>1 month) examined at a University Dizziness Clinic.FindingsQuestionnaires were available on 80 individuals with persistent MT MdDS and 42 with non-MT MdDS. Sex distribution (81% female) and age of onset (mean 43.4 ± 12.2 years MT; 42.1 ± 15.2 years non-MT) were comparable between MT and non-MT MdDS (p > 0.05). Mean duration of illness was significantly longer in the non-MT group (82.8 ± 64.2 months) than the MT group (35.4 ± 46.4 months) (p 50% individuals with a positive response). Physical therapy was modestly helpful in the MT (56%) subtype but not in non-MT (15%). Vestibular therapy made as many individuals worse as better in MT and none improved in the non-MT group.ConclusionGeneral demographic characteristics and exacerbating factors are similar in MT and non-MT MdDS, but there are differences in the duration of illness, effect of motion on symptoms, and response to therapy. Recognizing clinical features of MdDS subtypes may allow for better tailoring of therapy and potentially serve as classification criteria for new clinical designations.

Tumor-associated macrophages (TAMs) play an important role in tumor growth and metastasis. However, the involvement of TAMs infiltration in pulmonary osteosarcoma (OS) metastasis remains poorly understood. Therefore, the effect of OS cells on macrophages migration was investigated by in vivo and in vitro experiments to evaluate the infiltration and mechanism of TAMs in pulmonary OS metastases. The results showed that the zinc finger protein ZIM3 was upregulated in OS cells than in osteoblasts and activated the expression of CCL25, which subsequently promoted the migration of M2 macrophages. CCL25 or ZIM3 silencing in OS cells inhibited the infiltration of M2 macrophages and the formation of pulmonary metastatic nodules in a mouse model of pulmonary OS metastasis and prolonged the survival of the mice. Furthermore, bioinformatics analyses revealed that CCL25 and ZIM3 expressions are negatively correlated with the prognosis of OS patients. In conclusion, this study found that a large number of M2 TAMs were recruited into pulmonary metastatic nodules of OS through the activation of the ZIM3-CCL25 axis in OS cells, thereby facilitating OS metastasis. Therefore, the suppression of ZIM3-CCL25-induced recruitment of M2 TAMs to the metastatic sites might be considered as a therapeutic approach to inhibit the growth of pulmonary OS metastases. [ABSTRACT FROM AUTHOR]

Achalasia is a primary esophageal motility disorder manifested by dysphagia and chest pain that impair patients’ quality of life, and it also leads to chronic esophageal inflammation by food retention and increases the risk of esophageal cancer. Although achalasia has long been reported, the epidemiology, diagnosis and treatment of achalasia are not fully understood. The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. In this paper, epidemiology, diagnosis treatment, as well as possible pathogenesis of achalasia will be reviewed and summarized. The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI), a complex neurological disorder, triggers a series of devastating neuropathological events such as ischemia, oxidative stress, inflammatory events, neuronal apoptosis, and motor dysfunction. However, the classical necrosome, which consists of receptor-interacting protein (RIP)1, RIP3, and mixed-lineage kinase domain-like protein, is believed to control a novel type of programmed cell death called necroptosis, through tumour necrosis factor-alpha/tumour necrosis factor receptor-1 signalling or other stimuli. Several studies reported that necroptosis plays an important role in neural cell damage, release of intracellular pro-inflammatory factors, lysosomal dysfunction and endoplasmic reticulum stress. Recent research indicates that necroptosis is crucial to the pathophysiology of a number of neurological disorders and SCIs. In our review, we summarize the potential role of programmed cell death regulated by necroptosis in SCI based on its molecular and pathophysiological mechanisms. We also summarize the targets of several necroptosis pathways, which provide a more reliable reference for the treatment of SCI. [ABSTRACT FROM AUTHOR]

Objective: The Coronavirus Disease 2019 (COVID-19) has brought severe damage to global health and socioeconomics. In China, traditional Chinese medicine (TCM) is the most important complementary and alternative medicine (CAM) and it has shown a beneficial role in the prevention and treatment of COVID-19. However, it is unknown whether patients are willing to accept TCM treatment. The objective of our study is to investigate the acceptance, attitude, and independent predictors of TCM among asymptomatic COVID-19 patients admitted to Shanghai fangcang hospital during the outbreak of the COVID-19 pandemic in Shanghai in 2022. Methods: A cross-sectional study was conducted on asymptomatic COVID-19 patients in the largest fangcang hospital in Shanghai, China, from April 22, 2022, to May 25, 2022. Based on the literature review of previous similar studies, a self-report questionnaire was developed to assess the patients' attitude and acceptance of TCM, and a multivariate logistic regression analysis was conducted to determine the independent predictors of TCM acceptance. Results: A total of 1,121 patients completed the survey, of whom 91.35% were willing to accept CAM treatment whereas 8.65% of participants showed no willingness. Multivariate logistic regression analysis revealed that the patients who have received two doses of COVID-19 vaccine (OR = 2.069, 95%CI: 1.029–4.162, P = 0.041 vs. not received), understood the culture of TCM (OR = 2.293, 95%CI: 1.029–4.162, P = 0.014 vs. not understood), thought the TCM treatment is safe (OR = 2.856, 95%CI: 1.334–6.112, P = 0.007 vs. not thought), thought the TCM treatment is effective (OR = 2.724, 95%CI: 1.249–5.940, P = 0.012 vs. not thought), and those who informed their attending physician if using TCM for treatment (OR = 3.455, 95%CI:1.867–6.392, P < 0.001 vs. not informed) were more likely to accept TCM treatment. However, patients who thought TCM might delay your treatment (OR = 0.256, 95%CI: 0.142–0.462, P < 0.001 not thought) was an independent predictor for unwillingness to accept TCM treatment. Conclusion: This study preliminarily investigated the acceptance, attitude, and predictors of intention to receive TCM among asymptomatic COVID-19 patients. It is recommended to increase the publicity of TCM, clarify the impact of TCM and communicate with attending doctors that meet the healthcare needs of asymptomatic COVID-19 patients. [ABSTRACT FROM AUTHOR]