Retinoic Acid Upregulates METTL14 Expression and the m6A Modification Level to Inhibit the Proliferation of Embryonic Palate Mesenchymal Cells in Cleft Palate Mice.

Cleft palate only (CPO) is one of the most common craniofacial birth defects. Environmental factors can induce cleft palate by affecting epigenetic modifications such as DNA methylation, histone acetylation, and non-coding RNA. However, there are few reports focusing on the RNA modifications. In this study, all-trans retinoic acid (atRA) was used to simulate environmental factors to induce a C57BL/6J fetal mouse cleft palate model. Techniques such as dot blotting and immunofluorescence were used to find the changes in m6A modification when cleft palate occurs. RNA-seq and KEGG analysis were used to screen for significantly differentially expressed pathways downstream. Primary mouse embryonic palate mesenchymal (MEPM) cells were successfully isolated and used for in vitro experimental verification. We found that an increased m6A methylation level was correlated with suppressed cell proliferation in the palatine process mesenchyme of cleft palate mice. This change is due to the abnormally high expression of m6A methyltransferase METTL14. When using siRNAs and the m6A methyltransferase complex inhibitor SAH to interfere with the expression or function of METTL14, the teratogenic effect of atRA on primary cells was partially alleviated. In conclusion, METTL14 regulates palatal mesenchymal cell proliferation and cycle-related protein expression relies on m6A methylation modification, affecting the occurrence of cleft palate.

The effect of indoor air filtration on biomarkers of inflammation and oxidative stress: a review and meta-analysis of randomized controlled trials.

Improvement of indoor air quality is beneficial for human health. However, previous studies have not reached consistent conclusions regarding the effects of indoor air filtration on inflammation and oxidative stress. This study aims to determine the relationship between indoor air filtration and inflammation and oxidative stress biomarkers. We conducted an electronic search that evaluated the association of indoor air filtration with biomarkers of inflammation and oxidative stress in five databases (PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus) from the beginning to April 23, 2023. Outcomes included the following markers: interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), malondialdehyde (MDA), 8-hydroxy-2deoxyguanosine (8-OHdG), and 8-iso-prostaglandinF2α (8-isoPGF2α). We extracted data from the included studies according to the system evaluation and the preferred reporting item for meta-analysis (PRISMA) guidelines and used the Cochrane risk of bias tool to assess bias risk. Our meta-analysis included 15 studies with 678 participants to assess the combined effect size. The meta-analysis demonstrated that indoor air filtration could have a marked reduction in IL-6 (SMD: -0.275, 95% CI: -0.545 to -0.005, p = 0.046) but had no significant effect on other markers of inflammation or oxidative stress. Subgroup analysis results demonstrated a significant reduction in 8-OHdG levels in the subgroup with < 1 day of duration (SMD: -0.916, 95% CI: -1.513 to -0.320; p = 0.003) and using filtrete air filter (SMD: -5.530, 95% CI: -5.962 to -5.099; p < 0.001). Our meta-analysis results depicted that indoor air filtration can significantly reduce levels of inflammation and oxidative stress markers. Considering the adverse effects of air pollution on human health, our study provides powerful evidence for applying indoor air filtration to heavy atmospheric pollution.

[Effectiveness of one-stage posterior eggshell osteotomy and long-segment pedicle screw fixation for ankylosing spondylitis kyphosis combined with acute thoracolumbar vertebral fracture].

Objective: To explore the safety and effectiveness of one-stage posterior eggshell osteotomy and long-segment pedicle screw fixation in the treatment of ankylosing spondylitis kyphosis combined with acute thoracolumbar vertebral fracture. Methods: A clinical data of 20 patients with ankylosing spondylitis kyphosis combined with acute thoracolumbar spine fracture, who were treated with one-stage posterior eggshell osteotomy and long-segment pedicle screw fixation between April 2016 and January 2022, was retrospectively analyzed. Among them, 16 cases were male and 4 cases were female; their ages ranged from 32 to 68 years, with an average of 45.9 years. The causes of injury included 10 cases of sprain, 8 cases of fall, and 2 cases of falling from height. The time from injury to operation ranged from 1 to 12 days, with an average of 7.1 days. The injured segment was T 11 in 2 cases, T 12 in 2 cases, L 1 in 6 cases, and L 2 in 10 cases. X-ray film and CT showed that the patients had characteristic imaging manifestations of ankylosing spondylitis, and the fracture lines were involved in the anterior, middle, and posterior columns and accompanied by different degrees of kyphosis and vertebral compression; and MRI showed that 12 patients had different degrees of nerve injuries. The operation time, intraoperative bleeding, intra- and post-operative complications were recorded. The visual analogue scale (VAS) score and Oswestry disability index (ODI) were used to evaluate the low back pain and quality of life, and the American spinal cord injury association (ASIA) classification was used to evaluate the neurological function. X-ray films were taken, and local Cobb angle (LCA) and sagittal vertical axis (SVA) were measured to evaluate the correction of the kyphosis. Results: All operations were successfully completed and the operation time ranged from 127 to 254 minutes (mean, 176.3 minutes). The amount of intraoperative bleeding ranged from 400 to 950 mL (mean, 722.5 mL). One case of dural sac tear occurred during operation, and no cerebrospinal fluid leakage occurred after repair, and the rest of the patients did not suffer from neurological and vascular injuries, cerebrospinal fluid leakage, and other related complications during operation. All incisions healed by first intention without infection or fat liquefaction. All patients were followed up 8-16 months (mean, 12.5 months). The VAS score, ODI, LCA, and SVA at 3 days after operation and last follow-up significantly improved when compared with those before operation ( P<0.05), and the difference between 3 days after operation and last follow-up was not significant ( P>0.05). The ASIA grading of neurological function at last follow-up also significantly improved when compared with that before operation ( P<0.05), including 17 cases of grade E and 3 cases of grade D. At last follow-up, all bone grafts achieved bone fusion, and no complications such as loosening, breaking of internal fixation, and pseudoarthrosis occurred. Conclusion: One-stage posterior eggshell osteotomy and long-segment pedicle screw fixation is an effective surgical procedure for ankylosing spondylitis kyphosis combined with acute thoracolumbar vertebral fracture. It can significantly relieve patients' clinical symptoms and to some extent, alleviate the local kyphotic deformity.

Silk Fibroin-Modified Liposome/Gene Editing System Knocks out the PLK1 Gene to Suppress the Growth of Lung Cancer Cells.

Polo-like protein kinase 1 (PLK1) plays a key role in lung cancer cell mitosis. The knockout of PLK1 gene by the CRISPR-Cas9 system can effectively inhibit the proliferation of tumor cells, but there is no suitable vector for in vivo delivery. In this study, CRISPR-Cas9 gene knockout plasmids encoding sgRNA, Cas9 and green fluorescent protein were constructed. Then, the plasmids were packaged with liposome (Lip) and cholesterol-modified Antheraea pernyi silk fibroin (CASF) to obtain the CASF/Lip/pDNA ternary complex. The CASF/Lip/pDNA complex was transfected into lung cancer cells A549 to investigate the transfection efficiency, the PLK1 gene knockout effect and the inhibitory effect on lung cancer cells. The results showed that the transfection efficiency of the CASF/Lip/pDNA complex was significantly higher than that of the Lip/pDNA binary complex, and the expression of PLK1 in cells transfected with CASF/Lip/pDNA complexes was significantly lower than that in cells transfected with Lip/pDNA complexes. The CASF/Lip/pDNA complex significantly increased the apoptosis rate and decreased the proliferation activity of lung cancer cells compared with Lip/pDNA complexes. The cytotoxicity of the complexes was evaluated by coculture with the human bronchial epithelial cells BEAS2B. The results showed that CASF/Lip/pDNA complexes exhibited lower cytotoxicity than Lip/pDNA complexes. The fibroin-modified liposome/PLK1 gene knockout system not only effectively inhibited the growth of lung cancer cells but also showed no obvious toxicity to normal cells, showing potential for clinical application in lung cancer therapy.

Assistive diagnostic indicators for infections related to lumbar posterior interbody fusion internal fixation: platelet count and mean platelet volume.

BACKGROUND: The most severe complication after posterior single-segment lumbar interbody fusion and internal fixation (PIFIF) surgery for degenerative lumbar diseases is deep surgical site infection (DSSI). Preoperatively diagnosing such complications proves to be challenging. Platelets, as acute-phase reactants, undergo changes in response to infections and inflammation. This study aims to assess whether platelet indices can further aid in the diagnosis of DSSI. METHODS: A single-center retrospective study was conducted from January 2016 to February 2021 at Xi'an Jiaotong University-Affiliated Honghui Hospital, involving 83 patients who underwent revision surgery after PIFIF due to lumbar degenerative diseases. Among them, 24 patients were diagnosed with DSSI based on combined bacterial culture and imaging data. Preoperative complete serological indicators including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelet count and mean platelet volume ratio (P/M ratio) were analyzed using receiver operating characteristic (ROC) curve analysis to determine cutoff values, sensitivity, and specificity. This was done to further assess the ability of these serological indicators to identify the occurrence of DSSI after PIFIF. RESULTS: There were no significant differences in baseline demographic characteristics between the two patient groups (P > 0.05). The P/M ratio was 13.54 ± 5.05 in the aseptic revision group, while it was 19.21 ± 6.30 in the DSSI revision patients, showing a significant difference (P < 0.001). ROC curve analysis revealed that the optimal cutoff value for the P/M ratio was 17.50, with a sensitivity of 58.3% and a specificity of 78.6%. The areas under the curve (AUC) for ESR, CRP, and P/M ratio were 0.797, 0.845, and 0.756, respectively. The negative predictive value (NPV) was 87.04%, 89.47%, and 82.45%, respectively; the positive predictive value (PPV) was 58.62%, 69.23%, and 53.84%, respectively, for ESR, CRP, and P/M ratio, respectively. When P/M ratio is used in combination with ESR and CRP, the AUC is 0.887, with a sensitivity of 95.4%, specificity of 67.8%, NPV of 97.56%, PPV of 54.76%. The diagnostic performance of the model for evaluating DSSI is significantly improved compared to using ESR and CRP alone (P < 0.05). CONCLUSION: Platelets and their related serum biomarkers are closely associated with DSSI. The P/M ratio can serve as a reliable test for screening DSSI and is worth considering for inclusion in the assessment of patients at risk of developing DSSI after potential PIFIF surgery.

The top 100 most cited articles in helical tomotherapy: a scoping review.

Objective: The purpose of this scoping review was to explore the top 100 most cited articles in helical tomotherapy (HT) through bibliometric analysis and visualization tools, help researchers comprehensively understand the research hotspots of HT, and provide clear and intuitive network visualization. Methods: The Web of Science Core Collection and the search strategy of "Title (TI)=(tomotherapy)" were used to search for articles related to HT as of 27 May 2023. The top 100 most cited articles were obtained by sorting "citations: highest first". From these top 100 most cited articles, the following information was extracted: journals, years and months, countries, authors, types of tumor treated, and topics. The VOSviewer software was introduced for visualizing all the articles related to HT. Results: The top 100 most cited articles in HT were published between 1999 and 2019. The citation counts of these articles ranges from 326 to 45, with a total of 8,422 citations at the time of searching. The index of citations per year (CPY) ranges from 22.32 to 2.45. These articles originated from 17 countries, with most publications from the United States (n=50), followed by Canada (n=12), Italy (n=10), Germany (n=7) and Belgium (n=5). The International Journal of Radiation Oncology, Biology, Physics published the highest number of articles (n=31), followed by Radiotherapy and Oncology (n=20), Medical Physics (n=13) and Strahlentherapie und Onkologie (n=12). In terms of specific tumor types, head and neck cancer (n=15) is the most common disease, followed by cancers with complex target structures (n=14), breast cancer (n=12), prostate cancer (n=10) and lung cancer (n=8). The most common research topics also include dosimetric comparison (n = 44), quality assurance (n = 12) and Megavoltage CT (n = 8). Conclusion: This scoping review provides a comprehensive list of the 100 most cited articles in HT. This analysis offers valuable insights into the current research directions of HT that can be utilized by researchers, clinicians, and policy-makers.

Astaxanthin alleviates fine particulate matter (PM2.5)-induced lung injury in rats by suppressing ferroptosis and apoptosis.

Objectives: Fine particulate matter (PM2.5), a small molecule particulate pollutant, can reach the lungs via respiration and cause lung damage. Currently, effective strategies and measures are lacking to prevent and treat the pulmonary toxicity of PM2.5. Astaxanthin (ASX), a natural xanthophyll carotenoid, has attracted attention due to its unique biological activity. Our research aims to probe into the prevention and treatment of ASX on PM2.5-induced lung injury and clarify its potential mechanism. Methods: Sprague-Dawley (SD) rats were given olive oil and different concentrations of ASX orally daily for 21 days. PM2.5 suspension was instilled into the trachea of rats every two days for one week to successfully develop the PM2.5 exposure model in the PM2.5-exposed and ASX-treated groups of rats. The bronchoalveolar lavage fluid (BALF) was collected, and the content of lung injury-related markers was detected. Histomorphological changes and expression of markers associated with oxidative stress, inflammation, iron death, and apoptosis were detected in lung tissue. Results: PM2.5 exposure can cause changes in lung histochemistry and increase the expression levels of TP, AKP, ALB, and LDH in the BALF. Simultaneously, inflammatory responses and oxidative stress were promoted in rat lung tissue after exposure to particulate matter. Additionally, ASX preconditioning can alleviate histomorphological changes, oxidative stress, and inflammation caused by PM2.5 and reduce PM2.5-related ferroptosis and apoptosis. Conclusion: ASX preconditioning can alleviate lung injury after PM2.5 exposure by inhibiting ferroptosis and apoptosis.

Isolation and identification of bioactive compounds from Antrodia camphorata against ESKAPE pathogens.

Antimicrobial resistance is a major threat to human health globally. Antrodia camphorata was grown in a malt/yeast extract broth liquid medium for 15 days. Then, 4-L fermentation broth was harvested, yielding 7.13 g of the ethyl acetate extract. By tracing the antimicrobial activity, 12.22 mg of the antimicrobial compound was isolated. The structure of 5-methyl-benzo [1,3]-dioxole-4,7-diol (MBBD) was elucidated using NMR and MS data analyses. The antibacterial activity of MBBD was detected through the microbroth dilution method. MBBD exhibited broad-spectrum antibacterial activity. The minimum inhibitory concentration (MIC) range of MBBD for drug-resistant pathogenic bacteria was 64-256 µg/mL, with the lowest MIC observed for Acinetobacter baumannii (64 µg/mL), followed by Pseudomonas aeruginosa (MIC = 128 µg/mL). Klebsiella pneumoniae, Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli were also sensitive, with an MIC of 256 µg/mL. The MIC range of MBBD against 10 foodborne pathogens was 12.5-100 µg/mL. Based on the results of this study, MBBD exhibits broad-spectrum antibacterial activity, particularly demonstrating excellent inhibitory effects against A. baumannii. MBBD will be good candidates for new antimicrobial drugs.

A Novel Technology for 3D-Printing Artificial Vertebral Bodies for Treating Lumbar Spine Adrenal Pheochromocytoma Metastases: A Case Report and Review of the Literature.

BACKGROUND: Pheochromocytoma is an adrenal medullary neuroendocrine tumor that rarely metastasizes to the spine. Currently, its specific treatment methods still present challenges. CASE DESCRIPTION: A 41-year-old male patient who underwent left total adrenalectomy due to pheochromocytoma 3 years ago presented with lower back pain, accompanied by numbness and decreased muscle strength in both legs, as well as decreased sensation. Abnormal transmittance of the L3 vertebral body could be seen on anterior-posterior and lateral lumbar X-rays, irregular bone destruction of the L3 vertebral body was found on CT, and an MRI scan showed that the tumor was located within the L3 vertebral body, protruding into the spinal canal and compressing the epidural sac. No recurrence was found in the abdomen. Preoperatively, perform local embolization of the blood vessels supplying the tumor. First, the L2-3 intervertebral disc, L3-4 intervertebral disc and L3 vertebral body were removed using an anterior approach, the whole tumor was removed, and some of the vertebrae were taken for pathological examination and replaced with a 3D-printed prosthesis. Then, four pedicle screws were placed in the bilateral pedicles of L2 and L4 using the posterior approach, pre-bent connecting rods were installed to replace the bone cortex of the lamina and articular process followed by bone graft fusion of the interlaminar and facet joints. The postoperative results were satisfactory, and there were no perioperative complications. CONCLUSION: Lumbar pheochromocytoma metastasis is rare, difficult to treat, and should be considered in spinal metastases' differential diagnoses so early diagnosis can be made based on medical history and imaging. Preoperative local vascular imaging and embolization of the blood supply vessels were performed. After total en-bloc spondylectomy of the tumor during surgery, a prosthesis was implanted and combined with pedicle screw fixation to reconstruct spinal biomechanical stability, achieving satisfactory results. Therefore, 3D printed artificial vertebral bodies are a good choice for treating adrenal pheochromocytoma lumbar metastasis. The key to successful treatment is close interdisciplinary collaboration in formulating rigorous comprehensive perioperative plans.

A Comparison of Outcomes between the Wiltse Approach with Pedicle Screw Fixation and the Percutaneous Pedicle Screw Fixation for Multi-Segmental Thoracolumbar Fractures.

OBJECTIVE: Multi-segmental thoracolumbar fracture (MSF) generally refers to fractures occurring in two or more segments of the thoracolumbar spine. With the development of minimally invasive concept, there is little research on its application in the field of MSF. The purpose of this study is to compare two minimally invasive surgical techniques and determine which one is more suitable for treating patients with neurologically intact MSF. METHODS: We retrospectively analyzed the clinical data of 49 MSF patients with intact nerves who were admitted from January 2017 to February 2019. Among them, 25 cases underwent percutaneous pedicle screw fixation (PPSF), and 24 cases underwent Wiltse approach pedicle screw fixation (WAPSF). The operation time, number of fixed segments, blood loss, length of incision, postoperative ambulation time, accuracy of pedicle screw placement, facet joint violation (FJV), number of C-arm exposures, as well as pre- and postoperative visual analogue scale (VAS), Oswestry disability index (ODI), local Cobb's angle (LCA), and percentage of anterior vertebral body height (PAVBH) were recorded for both groups. Paired sample t-test was used for intra-group comparison before and after surgery while independent sample t-test was used for inter-group comparison. RESULTS: The differences in the number of fixed segments, intraoperative bleeding, postoperative bed time, accuracy rate of pedicle screw placement, VAS, and ODI between the two groups were not statistically significant (p > 0.05). However, the operative time and total surgical incision length were significantly shorter in the WAPSF group than in the PPSF group (p < 0.05), and the FJV was significantly higher in the PPSF group than in the WAPSF group (p < 0.05). Also, the PPSF group received more intraoperative fluoroscopy (p < 0.05). The result of LCA and PAVBH in the WAPSF group were significantly better than in the PPSF group (p < 0.05). CONCLUSIONS: Both PPSF and WAPSF were found to be safe and effective in the treatment of MSF without neurological deficits through our study. However, considering radiation exposure, FJV, vertebral height restoration, correction of kyphosis, and learning curve, WAPSF may be a better choice for neurologically intact MSF.

Chinese Experts Consensus and Practice Guideline on Discoid Lateral Meniscus.

Discoid lateral meniscus (DLM) is the most common congenital variant of the lateral meniscus, which is prone to degeneration and lesions, and often leads to knee osteoarthritis. At present, there is no consensus on the clinical practice of DLM, and this expert consensus and practice guidelines on DLM was developed and approved by Chinese Society of Sports Medicine according to the Delphi method. Among 32 statements drafted, 14 statements were excluded for redundant information, and 18 statements achieved consensus. This expert consensus focused on the definition, epidemiology, etiology, classification, clinical manifestations, diagnosis, treatment, prognosis, and rehabilitation of DLM. Restoring the normal shape, retaining appropriate width and thickness, and ensuring the stability of the remnant meniscus is critical to sustaining the physiological function of the meniscus and preserving the knee. The partial meniscectomy with or without repair should be the first-line treatment when possible, given that the clinical and radiological long-term outcomes of total or subtotal meniscectomy are worse.

Application and SARs of Pyrazolo[1,5-a]pyrimidine as Antitumor Agents Scaffold.

Pyrazolo[1,5-a]pyrimidines are fused heterocycles that have spawned many biologically active antitumor drugs and are important privileged structures for drug development. Pyrazolo[1,5- a]pyrimidine derivatives have played an important role in the development of antitumor agents due to their structural diversity and good kinase inhibitory activity. In addition to their applications in traditional drug targets such as B-Raf, KDR, Lck, and Src kinase, some small molecule drugs with excellent activity against other kinases (Aurora, Trk, PI3K-γ, FLT-3, C-Met kinases, STING, TRPC) have emerged in recent years. Therefore, based on these antitumor drug targets, small molecule inhibitors containing pyrazolo[1,5-a]pyrimidine scaffold and their structure-activity relationships are summarized and discussed to provide more reference value for the application of this particular structure in antitumor drugs.

Research Progress on Small Molecules Inhibitors Targeting TRK Kinases.

BACKGROUND: Trk gene fusions are an important driver in the development of cancers, including secretory breast cancer and infantile congenital sarcoma. Since the first-generation of small molecule Trk inhibitors (Larotrectinib and Entrectinib) came to market, research on small molecule TRK inhibitors, especially second-generation inhibitors that break through the resistance problem, has developed rapidly. Therefore, this article focuses on the research progress of first-generation drugs and second-generation drugs that break through drug resistance. METHODS: We used the database to search for relevant and cutting-edge documents, and then filtered and selected them based on the content. The appropriate articles were analyzed and classified, and finally, the article was written according to the topics. RESULTS: The phenomenon of Trk protein fusion and its relation to tumors are described, followed by an explanation of the composition and signaling pathways of Trk kinases. The representative Trk inhibitors and the development of novel Trk inhibitors are classified according to whether they overcome drug resistance problems. CONCLUSION: This paper provides a theoretical reference for the development of novel inhibitors by introducing and summarizing the representative and novel Trk inhibitors that break through the drug resistance problem.

Identification of Potential Molecular Targets and Active Ingredients of Mingmu Dihuang Pill for the Treatment of Diabetic Retinopathy Based on Network Pharmacology.

Objective: Mingmu Dihuang Pill (MMDHP) is a traditional Chinese formula that has shown remarkable improvements of dry eyes, tearing, and blurry vision; however, the mechanisms underlying MMDHP treatment for diabetic retinopathy have not been fully understood. This study is aimed at identifying the molecular targets and active ingredients of MMDHP for the treatment of diabetic retinopathy based on network pharmacology. Methods: All active ingredients of MMDHP were retrieved from TCMSP and BATMAN-TCM databases, and the targets of active ingredients of MMDHP were predicted on the SwissTargetPrediction website. Diabetic retinopathy-related target sets were retrieved from GeneCards and OMIM databases, and the intersecting targets between targets of active ingredients of MMDHP and potential therapeutic targets of diabetic retinopathy were collected to generate the traditional Chinese medicine-ingredient-target-diabetic retinopathy network and to create the protein-protein interaction network. In addition, GO terms and KEGG pathway enrichment analyses were performed to identify the potential pathways, and molecular docking was employed to verify the binding of active ingredients of MMDHP to key targets of diabetic retinopathy. Results: Network pharmacology predicted 183 active ingredients and 904 targets from MMDHP, and 203 targets were intersected with the therapeutic targets of diabetic retinopathy. The top 10 hub targets included PIK3RA, TP53, SRC, JUN, HRAS, AKT1, VEGFA, EGFR, ESR1, and PI3KCA. GO terms and KEGG pathway enrichment analyses identified AGE-RAGE, PI3K-AKT, and Rap1 signaling pathways as major pathways involved in MMDHP treatment for diabetic retinopathy. Molecular docking confirmed a good binding affinity of active ingredients of MMDHP, including luteolin, acacetin, naringenin, and alisol B, with AKT1, SRC, and VEGFA as the three key targets of diabetic retinopathy. Conclusion: MMDHP may be effective for the treatment of diabetic retinopathy through active ingredients luteolin, acacetin, naringenin, and alisol B via AKT1, SRC, and VEGFA in AGE-RAGE, PI3K-AKT, and Rap1 signaling pathways.

Guidelines on the Diagnosis and Treatment of Lateral Meniscal Lesions: A Consensus Statement by the Chinese Society of Sports Medicine.

Background: The lateral meniscus is a unique structure of the knee joint, and its anatomy, function, pathological process, and treatment are distinct from those of the medial meniscus. To date, no consensus on the management of lateral meniscal lesions has been published, and clinical decision-making is challenging. To facilitate this, consensus and practice guidelines for lateral meniscal lesions were developed and endorsed by the Chinese Society of Sports Medicine. Study Design: Consensus statement. Methods: This project followed the Delphi approach to the consensus process, involving steering, rating, and peer review groups. A total of 61 experts in the fields of sports medicine and arthroscopic surgery were invited to participate in the compilation of a consensus statement on lateral meniscal lesions. (The discoid lateral meniscus was addressed by separate consensus.) To begin, the steering group drafted a set of questions and replies regarding lateral meniscal lesions. An online panel discussion was then held to provide initial agreement and comments on the statements, followed by a round of anonymous voting. Results and feedback were sent to the steering group for a second draft. A second round of voting was then held, and each statement was discussed during a combined meeting of the steering and rating groups. Finally, a consensus draft was evaluated by a review group. Results: Fifty-three questions and answers addressing lateral meniscal lesions were drafted, and 20 statements were excluded because of redundant information during the first round of voting. Ultimately, 33 statements were completed, 9 of which were unanimous. Conclusion: This expert consensus process focused on the anatomy, function, pathological processes, and treatment of lateral meniscal lesions. Accepted recommendations in these areas can assist doctors and therapists in standardizing the management of related pathology. The consensus statement indicates that certain types of lateral meniscal tears that were previously considered irreparable can be repaired. Preservation of the lateral meniscus should be the first-line treatment whenever possible, because the long-term clinical and radiological outcomes are worse after partial meniscectomy.

Influence of Voice Interactive Educational Robot Combined with Artificial Intelligence for the Development of Adolescents.

In the context of multicultural information, to explore and analyze the use effect of voice interactive educational robot in the classroom of adolescent students, and the physical and mental impact of movie characters on adolescent students, and to lay the foundation for studying the positive development of adolescents, under the guidance of positive psychology theory, the relationship between positive psychology and adolescent mental health is analyzed, the application of adolescent educational robot is discussed, and the relationship between adolescent educational robot combined with movies characters and positive development of adolescent is analyzed. The questionnaire is used to collect data, including the questionnaire on the influence of movie characters on the positive development of adolescents, the questionnaire of pre- and postpopularization of artificial intelligence in primary and secondary schools, and the satisfaction questionnaire of voice interactive educational robot. The reliability and validity of the questionnaire are analyzed. The results show that students who watch more than 20 movies are 20% in grade one and that is only 10% in grade three. 79% of the students think that the movie characters have an impact on themselves. The distribution of the number of the grade two students exposed to the movie is relatively uniform, 40% of them watch 10-20 movies, and 82% of them think that the movie characters have an impact on themselves; the Cronbach coefficient of classroom satisfaction questionnaire is 0.929 > 0.9, the average value of the correlation of total correction items of the corresponding item is 0.612 > 0.5, the Kaiser-Meyer-Olkin measurement value is 0.812 > 0.6, and the Sig value is 0.000 < 0.05, indicating that the reliability and validity of the questionnaire are very high and 92.3% of the students are very satisfied with the classroom. This shows that voice interactive educational robot combined with movie characters can promote the positive development of adolescents.

CancerSCEM: a database of single-cell expression map across various human cancers.

With the proliferating studies of human cancers by single-cell RNA sequencing technique (scRNA-seq), cellular heterogeneity, immune landscape and pathogenesis within diverse cancers have been uncovered successively. The exponential explosion of massive cancer scRNA-seq datasets in the past decade are calling for a burning demand to be integrated and processed for essential investigations in tumor microenvironment of various cancer types. To fill this gap, we developed a database of Cancer Single-cell Expression Map (CancerSCEM, https://ngdc.cncb.ac.cn/cancerscem), particularly focusing on a variety of human cancers. To date, CancerSCE version 1.0 consists of 208 cancer samples across 28 studies and 20 human cancer types. A series of uniformly and multiscale analyses for each sample were performed, including accurate cell type annotation, functional gene expressions, cell interaction network, survival analysis and etc. Plus, we visualized CancerSCEM as a user-friendly web interface for users to browse, search, online analyze and download all the metadata as well as analytical results. More importantly and unprecedentedly, the newly-constructed comprehensive online analyzing platform in CancerSCEM integrates seven analyze functions, where investigators can interactively perform cancer scRNA-seq analyses. In all, CancerSCEM paves an informative and practical way to facilitate human cancer studies, and also provides insights into clinical therapy assessments.

Precise Diabetic Wound Therapy: PLS Nanospheres Eliminate Senescent Cells via DPP4 Targeting and PARP1 Activation.

Diabetic ulcers, a difficult problem faced by clinicians, are strongly associated with an increase in cellular senescence. Few empirical studies have focused on exploring a targeted strategy to cure diabetic wounds by eliminating senescent fibroblasts (SFs) and reducing side effects. In this study, poly-l-lysine/sodium alginate (PLS) is modified with talabostat (PT100) and encapsulates a PARP1 plasmid (PARP1@PLS-PT100) for delivery to target the dipeptidyl peptidase 4 (DPP4) receptor and eliminate SFs. PARP1@PLS-PT100 releases encapsulated plasmids, displaying high selectivity for SFs over normal fibroblasts by targeting the DPP4 receptor, decreasing senescence-associated secretory phenotypes (SASPs), and stimulating the secretion of anti-inflammatory factors. Furthermore, the increased apoptosis of SFs and the disappearance of cellular senescence alleviates SASPs, accelerates re-epithelialization and collagen deposition, and significantly induces macrophage M2 polarization, which mediates tissue repair and the inflammatory response. This innovative strategy has revealed the previously undefined role of PARP1@PLS-PT100 in promoting diabetic wound healing, suggesting its therapeutic potential in refractory wound repair.

N6-Methyladenosine Methyltransferase METTL14-Mediated Autophagy in Malignant Development of Oral Squamous Cell Carcinoma.

N6-methyladenosine (m6A) is the most abundant internal mRNA modification in eukaryotes and is related to stability, localization, or translation efficiency in tumorigenesis. Autophagy plays an important role in the occurrence and development of tumours. However, the relationship between m6A and autophagy remains unclear. In this study, we used a rapamycin-induced autophagy model of oral squamous cell carcinoma (OSCC) cells, and observed increased m6A RNA methylation. When autophagy was activated, the methyltransferase-like 14 (METTL14) expression was upregulated and influenced the proliferation, migration, and invasiveness of OSCC cells. Through meRIP-seq and RNA-seq analysis, we found that METTL14 directly combined with eukaryotic translation initiation factor gamma 1 (eIF4G1) mRNA and decreased its RNA stability. According to the dual-luciferase reporter and mutagenesis assay, the mutated site 1 of exon 11 of eIF4G1 is the key target of METTL14. Knockdown of the main m6A binding protein YTHDF2 may rescue the shortened half-life of eIF4G1 mRNA induced by METTL14 overexpression. Furthermore, an in vivo tumour xenograft model confirmed that a high METTL14 expression can effectively reduce OSCC growth. Additionally, using clinical samples, we found that patients with advanced or moderately/poorly differentiated tumours exhibited lower METTL14 levels. Taken together, our results revealed that METTL14 mediated eIF4G1 expression via m6A modification and regulated autophagy levels and biological functions in OSCC. Our findings not only expand our understanding of the correlation between autophagy and RNA methylation in tumorigenesis but also present an opportunity to develop new therapeutic options.

An autofluorescence-based isolation of Leydig cells for testosterone deficiency treatment.

Effective procedures for the purification of Leydig cells (LCs) can facilitate functional studies and transplantation therapies. However, current methods to purify LCs from testes are still far from satisfactory. Here, we found that testicular autofluorescence existed in the interstitium along with the gradual maturation of LCs from birth to adulthood. These autofluorescent cells were further isolated by fluorescence-activated cell sorting (FACS) and determined to be composed of LCs and macrophages. To further purify LCs, we combined two fluorescence channels of FACS and successfully separated LCs and macrophages. Of note, we confirmed that the obtained LCs not only possessed high purity, viability and quantity but also had intact steroidogenic activity and excellent responsiveness to luteinizing hormone. Moreover, subcutaneous transplantation of isolated LCs could alleviate the symptoms of testosterone deficiency in castrated mice. In summary, we established an effective autofluorescence-based method for isolating LCs. This method will aid in the future success of using LCs for basic and translational applications.