The role of long non-coding RNA in Crohn's disease.

Emerging evidence has illuminated the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating immunological functions and autoimmune responses. In the context of Crohn's disease (CD), an array of novel lncRNAs has been identified in the plasma and intestinal tissues of afflicted individuals, suggesting a dualistic influence on the disease progression, either exacerbating or mitigating its course. Current research has demonstrated the involvement of lncRNAs in competitive endogenous RNA, the inflammation process, epithelial barrier function, gut microbiota imbalance, and epigenetic regulation. This review aims to encapsulate the current knowledge on the lncRNA contribution to CD and underscore potential avenues for future research. LncRNAs are increasingly recognized as significant biomarkers and potential therapeutic targets, holding a key position in the pathogenesis of CD. Furthermore, the unique attributes of circulating lncRNAs, such as minimal side effects, combinational therapy potential, and personalized medicine, render them as promising therapeutic tools for individual health management in CD.

Arthroscopic Modified Subacromial Viewing Portal Repair of Upper Third of Subscapularis Tendon Partial-Thickness Tears.

At present, the repair pattern of upper third of subscapularis tendon partial-thickness tears (upper-third tendon tears) is performed in the glenohumeral joint and conventional subacromial viewing portal, but the visualization of subscapularis tendon and footprint is poor when using a 30° scope. The modified subacromial viewing portal presented in this Technical Note is a modified surgical technique for the repair of upper-third tendon tears. Since the scope forms an angle of 70° with the subscapularis tendon and footprint of lesser tuberosity, satisfactory visualization can be obtained when using 30° scope; the predesigned surgical portal and working space without bony barrier can offer a smooth surgical procedure. Our surgical technique is described in pearls, pitfalls, advantages, and disadvantages.

[Early effectiveness of arthroscopic tri-anchor double-pulley suture-bridge repair of medium-size supraspinatus tendon tears].

Objective: To explore the early effectiveness of arthroscopic tri-anchor double-pulley suture-bridge in treatment of medium-size supraspinatus tendon tears. Methods: Between December 2020 and January 2023, 40 patients with medium-size supraspinatus tendon tears were treated with arthroscopic tri-anchor double-pulley suture-bridge. There were 18 males and 22 females, with an average age of 62.6 years (mean, 45-73 years). Among them, 17 patients had trauma history. The main clinical symptom was shoulder pain with hug resistance test (+). The interval from symptom onset to operation was 10.7 months on average (range, 3-36 months). Visual analogue scale (VAS) score, University of California Los Angeles (UCLA) score, American Shoulder and Elbow Surgeons (ASES) score, and shoulder range of motion (ROM) of forward flexion, abduction, and external rotation were used to evaluate shoulder function. MRI was performed to assess the structural integrity and tension of reattached tendon. Patient satisfactions were calculated at last follow-up. Results: All incisions healed by first intention, no complications such as incision infection or nerve injury occurred. All patients were followed up 12-37 months (mean, 18.2 months). At 12 months after operation, VAS score, UCLA score, and ASES score significantly improved when compared with the preoperative scores ( P<0.05). At 3 and 12 months after operation, the ROM of external rotation significantly improved when compared with preoperative one ( P<0.05), and further improved at 12 months after operation ( P<0.05). However, the ROMs of abduction and forward flexion did not improve at 3 months after operation when compared with those before operation ( P>0.05), but significantly improved at 12 months after operation ( P<0.05). Twenty-six patients underwent MRI at 3-6 months, of which 23 patients possessed intact structural integrity, good tendon tension, and tendon healing; 3 patients underwent tendon re-tear. The self-rated satisfaction rate was 92.5% at last follow-up. Conclusion: Arthroscopic tri-anchor double-pulley suture-bridge in treatment of medium-size supraspinatus tendon tears can maximize the tendon-bone contact area, obtain satisfied early effectiveness with high satisfaction rate and low incidence of tendon re-tear. However, the function of abduction is limited at 3 months after operation, and patients need to adhere to rehabilitation training to further improve the joint activity.

Emergent trends in organ-on-a-chip applications for investigating metastasis within tumor microenvironment: A comprehensive bibliometric analysis.

Background: With the burgeoning advancements in disease modeling, drug development, and precision medicine, organ-on-a-chip has risen to the forefront of biomedical research. Specifically in tumor research, this technology has exhibited exceptional potential in elucidating the dynamics of metastasis within the tumor microenvironment. Recognizing the significance of this field, our study aims to provide a comprehensive bibliometric analysis of global scientific contributions related to organ-on-a-chip. Methods: Publications pertaining to organ-on-a-chip from 2014 to 2023 were retrieved at the Web of Science Core Collection database. Rigorous analyses of 2305 articles were conducted using tools including VOSviewer, CiteSpace, and R-bibliometrix. Results: Over the 10-year span, global publications exhibited a consistent uptrend, anticipating continued growth. The United States and China were identified as dominant contributors, characterized by strong collaborative networks and substantial research investments. Predominant institutions encompass Harvard University, MIT, and the Chinese Academy of Sciences. Leading figures in the domain, such as Dr. Donald Ingber and Dr. Yu Shrike Zhang, emerge as pivotal collaboration prospects. Lab on a Chip, Micromachines, and Frontiers in Bioengineering and Biotechnology were the principal publishing journals. Pertinent keywords encompassed Microfluidic, Microphysiological System, Tissue Engineering, Organoid, In Vitro, Drug Screening, Hydrogel, Tumor Microenvironment, and Bioprinting. Emerging research avenues were identified as "Tumor Microenvironment and Metastasis," "Application of organ-on-a-chip in drug discovery and testing" and "Advancements in personalized medicine applications". Conclusion: The organ-on-a-chip domain has demonstrated a transformative impact on understanding disease mechanisms and drug interactions, particularly within the tumor microenvironment. This bibliometric analysis underscores the ever-increasing importance of this field, guiding researchers and clinicians towards potential collaborative avenues and research directions.

[Short-term effectiveness of arthroscopic repair via modified subacromial viewing portal in treatment of Lafosse â subscapularis tendon tears].

Objective: To investigate short-term effectiveness of arthroscopic repair via modified subacromial viewing portal (hereinafter referred to as modified viewing portal) in treatment of LafosseⅠsubscapularis tendon tears. Methods: A clinical data of 52 patients with LafosseⅠsubscapularis tendon tears, who underwent the arthroscopic repair via modified viewing portal between October 2020 and November 2022 and met the selective criteria, was retrospectively analyzed. There were 15 males and 37 females with an average age of 63.4 years (range, 41-76 years). Twelve patients had trauma history and the other 40 patients had no obvious inducement. The main clinical symptom was shoulder pain and the hug resistance tests were positive in all patients. The interval between symptom onset and admission ranged from 3 to 26 months (mean, 7.2 months). The shoulder pain and function were evaluated by visual analogue scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score, and University of California Los Angeles (UCLA) score before operation and at 12 months after operation. The shoulder range of motion (ROM) of forward flexion, abduction, and external rotation and the internal rotation strength were measured before operation and at 3 and 12 months after operation. MRI was performed at 3-6 months after operation to assess the tendon healing and the structural integrity and tension of reattached tendon. Patient's satisfactions were calculated at last follow-up. Results: All incisions healed by first intention, no complication such as incision infection or nerve injury occurred. All patients were followed up 12-37 months (mean, 18.5 months). The VAS, UCLA, and ASES scores at 12 months after operation significantly improved when compared with those before operation ( P<0.05). The ROMs of abduction and forward flexion and the internal rotation strength at 3 and 12 months significantly improved when compared with those before operation ( P<0.05); and the ROMs at 12 months significantly improved compared to that at 3 months ( P<0.05). However, there was no significant difference ( P>0.05) in the ROM of external rotation at 3 months compared to that before operation; but the ROM at 12 months significantly improved compared to that before operation and at 3 months after operation ( P<0.05). Thirty-one patients underwent MRI at 3-6 months, of which 28 patients possessed intact structural integrity, good tendon tension and tendon healing; 3 patients underwent tendon re-tear. At last follow-up, 41 patients (78.8%) were very satisfied with the effectiveness, 7 were satisfied (13.5%), and 4 were dissatisfied (7.7%). Conclusion: Arthroscopic repair via modified viewing portal for Lafosse Ⅰsubscapularis tendon tears, which can achieve the satisfactory visualization and working space, can obtain good short-term effectiveness with low overall re-tear risk.

Network pharmacology: a bright guiding light on the way to explore the personalized precise medication of traditional Chinese medicine.

Network pharmacology can ascertain the therapeutic mechanism of drugs for treating diseases at the level of biological targets and pathways. The effective mechanism study of traditional Chinese medicine (TCM) characterized by multi-component, multi-targeted, and integrative efficacy, perfectly corresponds to the application of network pharmacology. Currently, network pharmacology has been widely utilized to clarify the mechanism of the physiological activity of TCM. In this review, we comprehensively summarize the application of network pharmacology in TCM to reveal its potential of verifying the phenotype and underlying causes of diseases, realizing the personalized and accurate application of TCM. We searched the literature using "TCM network pharmacology" and "network pharmacology" as keywords from Web of Science, PubMed, Google Scholar, as well as Chinese National Knowledge Infrastructure in the last decade. The origins, development, and application of network pharmacology are closely correlated with the study of TCM which has been applied in China for thousands of years. Network pharmacology and TCM have the same core idea and promote each other. A well-defined research strategy for network pharmacology has been utilized in several aspects of TCM research, including the elucidation of the biological basis of diseases and syndromes, the prediction of TCM targets, the screening of TCM active compounds, and the decipherment of mechanisms of TCM in treating diseases. However, several factors limit its application, such as the selection of databases and algorithms, the unstable quality of the research results, and the lack of standardization. This review aims to provide references and ideas for the research of TCM and to encourage the personalized and precise use of Chinese medicine.

The effects of vitamin D on all-cause mortality in different diseases: an evidence-map and umbrella review of 116 randomized controlled trials.

Purpose: To conduct a solid evidence by synthesizing meta-analyses and updated RCTs about the effects of vitamin D on all-cause mortality in different health conditions. Methods: Data sources: Pubmed, Embase, Web of Science, the Cochrane Library, Google Scholar from inception until 25th April, 2022. Study selection: English-language, meta-analyses and updated RCTs assessing the relationships between vitamin D and all-cause mortality. Data synthesis: Information of study characteristics, mortality, supplementation were extracted, estimating with fixed-effects model. A Measurement Tool to Assess Systematic Reviews, Grading of Recommendations Assessment, Development and Evaluation, and funnel plot was used to assess risk of bias. Main outcomes: All-cause mortality, cancer mortality, cardiovascular disease mortality. Results: In total of 27 meta-analyses and 19 updated RCTs were selected, with a total of 116 RCTs and 149, 865 participants. Evidence confirms that vitamin D reduces respiratory cancer mortality (RR, 0.56 [95%CI, 0.33 to 0.96]). All-cause mortality is decreased in patients with COVID-19 (RR, 0.54[95%CI, 0.33 to 0.88]) and liver diseases (RR, 0.64 [95%CI, 0.50 to 0.81]), especially in liver cirrhosis (RR, 0.63 [95%CI, 0.50 to 0.81]). As for other health conditions, such as the general health, chronic kidney disease, critical illness, cardiovascular diseases, musculoskeletal diseases, sepsis, type 2 diabetes, no significant association was found between vitamin D and all-cause mortality. Conclusions: Vitamin D may reduce respiratory cancer mortality in respiratory cancer patients and all-cause mortality in COVID-19 and liver disorders' patients. No benefits showed in all-cause mortality after vitamin D intervention among other health conditions. The hypothesis of reduced mortality with vitamin D still requires exploration. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=252921, identifier: CRD42021252921.

Research Progress on the Mechanisms of Polysaccharides against Gastric Cancer.

Gastric cancer is a common type of cancer that poses a serious threat to human health. Polysaccharides are important functional phytochemicals, and research shows that polysaccharides have good anti-gastric cancer effects. We collated all relevant literature published from 2000 to 2020 and found that more than 60 natural polysaccharides demonstrate anti-gastric cancer activity. At the present, the sources of these polysaccharides include fungi, algae, tea, Astragalus membranaceus, Caulis Dendrobii, and other foods and Chinese herbal medicines. By regulating various signaling pathways, including the PI3K/AKT, MAPK, Fas/FasL, Wnt/ß-catenin, IGF-IR, and TGF-ß signaling pathways, polysaccharides induce gastric cancer cell apoptosis, cause cell cycle arrest, and inhibit migration and invasion. In addition, polysaccharides can enhance the immune system and killing activity of immune cells in gastric cancer patients and rats. This comprehensive review covers the extraction, purification, structural characterization, and mechanism of plant and fungal polysaccharides against gastric cancer. We hope this review is helpful for researchers to design, research, and develop plant and fungal polysaccharides.

Modeling early changes associated with cartilage trauma using human-cell-laden hydrogel cartilage models.

BACKGROUND: Traumatic impacts to the articular joint surface are known to lead to cartilage degeneration, as in post-traumatic osteoarthritis (PTOA). Limited progress in the development of disease-modifying OA drugs (DMOADs) may be due to insufficient mechanistic understanding of human disease onset/progression and insufficient in vitro models for disease and therapeutic modeling. In this study, biomimetic hydrogels laden with adult human mesenchymal stromal cells (MSC) are used to examine the effects of traumatic impacts as a model of PTOA. We hypothesize that MSC-based, engineered cartilage models will respond to traumatic impacts in a manner congruent with early PTOA pathogenesis observed in animal models. METHODS: Engineered cartilage constructs were fabricated by encapsulating adult human bone marrow-derived mesenchymal stem cells in a photocross-linkable, biomimetic hydrogel of 15% methacrylated gelatin and promoting chondrogenic differentiation for 28 days in a defined medium and TGF-ß3. Constructs were subjected to traumatic impacts with different strains or 10 ng/ml IL-1ß, as a common comparative method of modeling OA. Cell viability and metabolism, elastic modulus, gene expression, matrix protein production and activation of catabolic enzymes were assessed. RESULTS: Cell viability staining showed that traumatic impacts of 30% strain caused an appropriate level of cell death in engineered cartilage constructs. Gene expression and histo/immunohistochemical analyses revealed an acute decrease in anabolic activities, such as COL2 and ACAN expression, and a rapid increase in catabolic enzyme expression, e.g., MMP13, and inflammatory modulators, e.g., COX2. Safranin O staining and GAG assays together revealed a transient decrease in matrix production 24 h after trauma that recovered within 7 days. The decrease in elastic modulus of engineered cartilage constructs was coincident with GAG loss and mediated by the encapsulated cells. The acute and transient changes observed after traumatic impacts contrasted with progressive changes observed using continual IL-1ß treatment. CONCLUSIONS: Traumatic impacts delivered to engineered cartilage constructs induced PTOA-like changes in the encapsulated cells. While IL-1b may be appropriate in modeling OA pathogenesis, the results of this study indicate it may not be appropriate in understanding the etiology of PTOA. The development of a more physiological in vitro PTOA model may contribute to the more rapid development of DMOADs.

Anterior cruciate ligament reconstruction with lateral extra-articular tenodesis reduces knee rotation laxity and graft failure rate: A systematic review and meta-analysis.

PURPOSE: To determine whether the addition of lateral extra-articular tenodesis (LET) to anterior cruciate ligament reconstruction (ACLR) reduces rotational laxity of the knee, and to compare the clinical results of this treatment with those of ACLR alone. METHODS: PubMed, Embase, and Cochrane Library were searched by two researchers for clinical studies comparing ACLR with and without LET. Studies with only evidence levels I and II and studies in which anterior lateral ligament reconstruction was performed with grafts were excluded. The risk of bias of the studies was assessed using the Cochrane risk-of-bias and modified Downs & Black tools. The outcomes included (1) functional outcomes; (2) knee laxity measures; (3) knee injury osteoarthritis and outcome score; and (4) complications. The outcomes of the two groups were extracted, summarized and compared. RESULTS: A total of 234 studies were retrieved and 223 were excluded. Eleven clinical studies with 1745 patients were included in our meta-analysis. Compared to the patients who underwent ACLR alone, the patients who underwent ACLR with LET had reduced pivot-shift (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.31 to 0.74, p = 0.0009), and lower graft failure rate (OR 0.34, 95% CI 0.20 to 0.55, p < 0.0001). CONCLUSION: Compared with ACLR only, ACLR combined with LET can effectively reduce rotation laxity of the knee joint, and reduce the graft failure rate in high-risk patients. However, the effects on the function and activity level of patients cannot be confirmed.

Emerging insights into molecular mechanisms underlying pyroptosis and functions of inflammasomes in diseases.

Pyroptosis is a form of necrotic and inflammatory programmed cell death, which could be characterized by cell swelling, pore formation on plasma membranes, and release of proinflammatory cytokines (IL-1ß and IL-18). The process of pyroptosis presents as dual effects: protecting multicellular organisms from microbial infection and endogenous dangers; leading to pathological inflammation if overactivated. Two pathways have been found to trigger pyroptosis: caspase-1 mediated inflammasome pathway with the involvement of NLRP1-, NLRP3-, NLRC4-, AIM2-, pyrin-inflammasome (canonical inflammasome pathway) and caspase-4/5/11-mediated inflammasome pathway (noncanonical inflammasome pathway). Gasdermin D (GSDMD) has been proved to be a substrate of inflammatory caspases (caspase-1/4/5/11), and the cleaved N-terminal domain of GSDMD oligomerizes to form cytotoxic pores on the plasma membrane. Here, we mainly reviewed the up to date mechanisms of pyroptosis, and began with the inflammasomes as the activator of caspase-1/caspase-11, 4, and 5. We further discussed these inflammasomes functions in diseases, including infectious diseases, sepsis, inflammatory autoimmune diseases, and neuroinflammatory diseases.

Role of long non-coding RNA in tumor drug resistance.

Chemotherapy has been extensively used in tumor treatment, including either systemic or local treatment. Miserably, in many kinds of cancers, chemotherapy is gradually insensitive. The mechanisms of tumor drug resistance have been widely explored, yet have not been fully characterized. With several studies in the development of drug resistance, recent works have highlighted the involvement of non-coding RNAs in tumor development. A growing number of long non-coding RNAs (lncRNAs) have been identified as transcripts of larger than 200 nucleotides in length, which have low coding potential, but potentially coding small peptides with 50-70 amino acids. Despite so often being branded as transcriptional noise, it is becoming increasingly clear that a large number of lncRNAs are crucial molecular regulators of the processes of tumor involving the initiation and progression of human tumor. More recently, accumulating evidence is revealing an important role of lncRNA in tumor drug resistance and lncRNA expression profiling can be correlated with the evolution of tumor drug resistance. The long non-coding-RNA-mediated form of drug resistance brings yet another mechanism of drug resistance. So, exploiting the newly emerging knowledge of lncRNAs for the development of new therapeutic applications to overcome human tumor drug resistance will be significant.

[Molecular Epidemiology of Echovirus 30 in Longyan City, Fujian, China, 2011～2014].

We studied the molecular epidemiology of echovirus 30 in sporadic cases of viral encephalitis in Longyan City, Fujian, China, from 2011 to 2014.Specimens of cerebrospinal fluid from patients diagnosed with viral encephalitis or infection of the central nervous system were collected. Viruses were isolated by cell culture. Identification of the echovirus 30 serotype and genetic analyses were undertaken. Amplification of virus protein(VP)-1gene sequences was done by reverse transcription-polymerase chain reaction. A total of 168 strains of enterovirus were isolated in 608 cases from 2011 to 2014,of which 60 strains were echovirus 30.The epidemic "peak" of echovirus 30 was from June to August. The age range of patients was wide, with 65% of cases under 10 years of age. Clinical manifestations were pyrexia, headache and vomiting.Cerebrospinal fluid was clear, and the number of cells and protein was increased. The epidemic strains in Longyan City from 2011 to 2014belonged to the "h" genotype, and there were two transmission chains. Compared with the viral encephalitis strains from the outbreak in Fujian Province in 2011,they were highly homologous, but a new amino-acid variation of VP1 protein I 120 V was found in Longyan City strains from 2014.The viral encephalitis strains from the outbreak in Fujian Province in 2011 were present in Longyan City strains, and two transmission chains are still circulating,but there were new mutations in the virus strains from 2014.Continuous monitoring will aid:(i)early detection of viral variants that may accumulate;(ii)assessment of the risk of epidemics.

[Screening of active fractions with antithrombotic effect from Caragana jubata].

The antithrombotic effect of Caragana jubata (Pall.)Poir.ethanolic extract (TE)was evaluated by inferior vena cava thrombosis in rats and acute pulmonary thrombosis in mice. To search for the bioactive fractions of TE, comparison on acute pulmonary thrombosis was made between the two main fractions of TE (TE-1 and TE-2). Besides, pharmacological effects of TE, TE-1 and TE-2 on bleeding time and clotting time were also studied. Reference substances combined with UPLC/DAD-q-TOF-MS were applied to identify the main six compounds and other chemical constituents of the TE. The results showed that TE could significantly reduce the rat thrombosis weight in all doses (P<0.01) and improve the protective rate to mice in medium and high doses (P<0.05). TE-2 showed a stronger effect on protecting the mice from paralysis or death and prolonging the bleeding time and clotting time than TE-1. Chemical constituents in TE mainly include isoflavones, pterocarpans and stilbenoids. Constituents in TE-2 were mainly isoflavones and pterocarpans, while those in TE-1 were mainly stilbenoids, which could be inferred that all of these three kinds of constituents may be responsible for the antithrombotic effects of Caragana jubata.

[Genetic analysis of Echovirus 11 isolated from patients with viral encephalitis in Longyan, China].

This study aimed to analyse the genetically characterize isolates of Echovirus 11 from Longyan City,Fujian Province,and to reveal their genetic relationships with other isolates from China and abroad. Cerebrospinal fluid specimens from patients diagnosed with viral encephalitis or central nervous system (CNS) infections were collected from Longyan First Hospital between January and December 2011. Seven Echo11 strains were isolated and identified using the RIMV serum panel. The entire VP1 coding regions of four strains were sequenced and typed as Echo11 by an online blast program and,subsequently, phylogenet- ic analyses of the VP1 sequences of these stains and others published on GenBank were conducted. There were 600 nucleotides (nt) in each complete VP1 coding region that encoded 200 amino acids (aa). Among those four Echo11 strains, the sequence identities of nt and aa were 100% and 99%-100% respectively. And phylogenetic analyses indicate belong to subtype DS, the homology compared with DS strain (GU393713) were 93% (nt) and 99% (aa). The sequence identities for the nt and aa were 75%-76% and 90%, respectively, between the current isolates from Longyan and the Gregory prototype strain found in 1953. The sequence identity of nt and aa between the Longyan virus strains and the domestic Shandong strains isolated in 2010 were lower, at 74% and 88%-89%, respectively. However,the highest level of ho- mology was found when the Longyan strains were compared with the Netherlands strain (GU393773) found in 2007 (nt and aa identity: 94%-95% and 98%-99%, respectively). The relatively low levels of similarity between domestic isolates suggest that different transmission routes exist for Echo11 in mainland China.

[Analysis of genetic characteristics of ECHO6 virus isolated from an epidemic outbreak of encephalitis in Longyan, China].

This study aimed to analyze the etiology of the encephalitis outbreak in Longyan, Fujian Province, China in 2010, in order to provide valuable information for this prevention and control of this disease. Pathogens were confirmed from cerebrospinal fluid samples with fluorescent RT-PCR, virus isolation (RD cells), and neutralization tests. Then, the VP1 fragments or whole genome nucleotide sequences were determined for four virus strains using PCR. Homology was assessed using the MegAlign software, and a phylogenetic evolutionary tree was drawn using Mega 4.0 software. The results confirmed that the etiology of the outbreak was the ECHO6 intestinal virus, and the nucleotide sequence of the VP1 segment indicated that the C2 subtype was responsible. The genome sequence consisted of 7407 nucleotides, and resembled the genome of other ECHO and CoxB viruses with homology levels of 78.5%-87.3%. The encephalitis outbreak in Longyan in 2010 was caused by the ECHO6 C2 subtype intestinal virus, and its complete genome sequence length is similar to the standard strain (U16283) with a sequence homology of 80.4%.