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Methyltransferase-like 3 (METTL3) plays a role in the development of knee osteoarthritis (KOA). However, the mechanism underlying the role of METTL3 in KOA is unclear. This work investigated the effects of MELLT3 on ferroptosis and pain relief in in vitro and in vivo KOA models. Chondrocytes were treated with 10 ng/mL interleukin-1ß (IL-1ß) or 5 µM Erastin (ferroptosis inducer). IL-1ß or Erastin treatment inhibited cell viability and glutathione levels; increased Fe2+, lipid reactive oxygen species and malondialdehyde production; and decreased glutathione peroxidase 4, ferritin light chain and solute carrier family 7 member 11 levels. The overexpression of METTL3 facilitated the N6-methyladenosine methylation of high mobility group box 1 (HMGB1). HMGB1 overexpression reversed the effect of sh-METTL3 on IL-1ß-treated chondrocytes. A KOA rat model was established by the injection of monosodium iodoacetate into the joints and successful model establishment was confirmed by haematoxylin and eosin staining and Safranin O/Fast Green staining. METTL3 depletion alleviated cartilage damage, the inflammatory response, ferroptosis and knee pain in KOA model rats, and these effects were reversed by the addition of HMGB1. In conclusion, METTL3 depletion inhibited ferroptosis and the inflammatory response, and ameliorated cartilage damage and knee pain during KOA progression by regulating HMGB1.
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INTRODUCTION: Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept rapidly throughout the world. So far, no therapeutics have yet proven to be effective. Ribavirin was recommended for the treatment of COVID-19 in China because of its in vitro activity. However, evidence supporting its clinical use with good efficacy is still lacking. METHODS: A total of 208 confirmed severe COVID-19 patients who were hospitalized in Wuhan Union West Campus between 1 February 2020 and 10 March 2020 were enrolled in the retrospective study. Patients were divided into two groups based on the use of ribavirin. The primary endpoint was the time to clinical improvement. The secondary endpoints included mortality, survival time, time to throat swab SARS-CoV-2 nucleic acid negative conversion, and the length of hospital stay. RESULTS: 68 patients were treated with ribavirin while 140 not. There were no significant between-group differences in demographic characteristics, baseline laboratory test results, treatment, and distribution of ordinal scale scores at enrollment, except for coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.01). Treatment with ribavirin was not associated with a difference in the time to clinical improvement (P = 0.48, HR = 0.88, 95% CI = 0.63-1.25). There were also no significant differences between-group in SARS-CoV-2 nucleic acid negative conversion, mortality, survival time, and the length of hospital stay. CONCLUSIONS: In hospitalized adult patients with severe COVID-19, no significant benefit was observed with ribavirin treatment.
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Tratamiento Farmacológico de COVID-19 , Ribavirina , Anciano , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Ribavirina/uso terapéutico , Resultado del TratamientoRESUMEN
Background: Inflammation and immune factors are the core of intervertebral disc degeneration (IDD), but the immune environment and epigenetic regulation process of IDD remain unclear. This study aims to identify immune-related diagnostic candidate genes for IDD, and search for potential pathogenesis and therapeutic targets for IDD. Methods: Gene expression datasets were obtained from the Gene Expression Omnibus (GEO). Differential expression immune genes (Imm-DEGs) were identified through weighted gene correlation network analysis (WGCNA) and linear models for microarray data analysis (Limma). LASSO algorithm was used to identify feature genes related to IDD, which were compared with core node genes in PPI network to obtain hub genes. Based on the coefficients of hub genes, a risk model was constructed, and the diagnostic value of hub genes was further evaluated through receiver operating characteristic (ROC) analysis. Xcell, an immunocyte analysis tool, was used to estimate the infiltration of immune cells. Finally, nucleus pulposus cells were co-cultured with macrophages to create an M1 macrophage immune inflammatory environment, and the changes of hub genes were verified. Results: Combined with the results of WGCNA and Limma gene differential analysis, a total of 30 Imm-DEGs were identified. Imm-DEGs enriched in multiple pathways related to immunity and inflammation. LASSO algorithm identified 10 feature genes from Imm-DEGs that significantly affected IDD, and after comparison with core node genes in the PPI network of Imm-DEGs, 6 hub genes (NR1H3, SORT1, PTGDS, AGT, IRF1, TGFB2) were determined. Results of ROC curves and external dataset validation showed that the risk model constructed with the 6 hub genes had high diagnostic value for IDD. Immunocyte infiltration analysis showed the presence of various dysregulated immune cells in the degenerative nucleus pulposus tissue. In vitro experimental results showed that the gene expression of NR1H3, SORT1, PTGDS, IRF1, and TGFB2 in nucleus pulposus cells in the immune inflammatory environment was up-regulated, but the change of AGT was not significant. Conclusions: The hub genes NR1H3, SORT1, PTGDS, IRF1, and TGFB2 can be used as immunorelated biomarkers for IDD, and may be potential targets for immune regulation therapy for IDD.
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Background: Distal radius fractures are a common type of fracture. For patients treated with closed reduction with splinting, a period of rehabilitation is still required after the removal of the splint. However, there is a general lack of attention and low compliance to rehabilitation training during this period, so it is necessary to build a rehabilitation training monitoring system to improve the efficiency of patients' rehabilitation. Methods: A wearable rehabilitation training wristband was proposed, which could be used in the patient's daily rehabilitation training scenario and could recognize four common wrist rehabilitation actions in real-time by using three thin film pressure sensors to detect the pressure change curve at three points on the wrist. An algorithmic framework for classifying rehabilitation training actions was proposed. In our framework, an action pre-detection strategy was designed to exclude false detections caused by switching initial gestures during rehabilitation training and wait for the arrival of the complete signal. To classify the action signals into four categories, firstly an autoencoder was used to downscale the original signal. Six SVMs were then used for evaluation and voting, and the final action with the highest number of votes would be used as the prediction result. Results: Experimental results showed that the proposed algorithmic framework achieved an average recognition accuracy of 89.62%, an average recognition recall of 88.93%, and an f1 score of 89.27% on the four rehabilitation training actions. Conclusion: The developed device has the advantages of being small size and easy to wear, which can quickly and accurately identify and classify four common rehabilitation training actions. It can easily be combined with peripheral devices and technologies (e.g., cell phones, computers, Internet) to build different rehabilitation training scenarios, making it worthwhile to use and promote in clinical settings.
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Background: Chemonucleolysis is a minimally invasive treatment of lumbar disc herniation (LDH). However, the low specificity of the enzyme and the existence of serious adverse events limit the application of chemonucleolysis. Clinical studies in recent years have shown that Chondroitin sulfate ABC endolyase (condoliase) is a potential therapeutic enzyme for LDH. Aim. A meta-analysis was conducted to determine the efficacy and safety of condoliase in LDH treatment. Methods: We searched Web of Science, Embase, PubMed, and Cochrane Library databases. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. The outcomes were the total effective rate, Oswestry Disability Index (ODI) score change, the proportion of lumbar surgery after condoliase treatment, herniated mass volume change, Pfirrmann grade change, and adverse events. Review Manager 5.3 and Stata 12.0 were used for meta-, sensitivity, and bias analysis. Results: Ten studies were included. A single-arm meta-analysis showed that the total effective rate was 78% [95% confidence interval (CI) 75%-81%], the proportion of surgery was 9% (95% CI 7%-12%), the proportion of Pfirrmann grade change was 43% (95%CI 38%-47%), and the adverse events were 4% (95% CI 2%-6%) after condoliase treatment. The two-arm meta-analysis showed that the ODI score change [standardized mean difference (SMD) -2.46, 95% CI -3.30 to -1.63] and the herniated mass volume change (SMD -16.97, 95% CI -23.92 to -10.03) of the condoliase treatment group were greater than those of the placebo control group, and there was no difference in adverse events between the two groups (OR 1.52, 95% CI 0.60-3.85). The results of sensitivity and publication bias analyses showed that the results were robust. Conclusion: Condoliase intradiscal injection has excellent eutherapeutic and safety for LDH, thus, has considerable potential as a treatment option besides conservative treatment and surgical intervention for LDH. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375492, PROSPERO (CRD42022375492).
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Introduction: This study explored the state of rational drug use among older adults in central China, aiming to unveil factors influencing their medication literacy and proposing targeted improvement measures. Methods: A cross-sectional study involving 454 participants aged 60 and above was conducted in Hubei province between February 1 and May 30, 2023, with data collected through face-to-face interviews by pharmacists. Multiple logistic regression analysis was conducted to determine factors that affected medication literacy. Results: Of the 412 valid questionnaires, findings revealed inadequate knowledge of rational drug use among older adults in central China. Those who fully understood (105, 25.49%, OR = 9.349, p < 0.001, 95%CI = 3.884-22.502) or partially understood (228, 55.34%, OR = 3.295, p = 0.002, 95%CI = 1.548-7.013) drug instructions exhibited significantly higher medication literacy than those who did not understand (79, 19.17%). Subsequent research revealed a lack of awareness in reading drug instructions or difficulty in understanding them. Most older adults seldom heard of but exhibited high acceptance of medication guidance services. Discussion: In conclusion, the ability to comprehend drug instructions significantly influenced the medication literacy of older adults. Initiatives such as revising age-appropriate drug instructions could effectively enhance rational drug use among this demographic.
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Alfabetización en Salud , Humanos , Anciano , Estudios Transversales , Encuestas y Cuestionarios , China , Cumplimiento de la MedicaciónRESUMEN
Purpose: The aim of this study was to investigate the effect of Zhiqiao Gancao decoction (ZQGCD) on hyperalgesia in lumbar disc herniation (LDH) and its mechanism. Methods: The potential mechanism of ZQGCD's therapeutic effect on LDH was investigated through network pharmacology, which involved screening the targets of eight components that were absorbed into the bloodstream. The effects of CCR2 inhibitors and ZQGCD-containing serum on the excitability of the CCL2/CCR2 signaling pathway and dorsal root ganglion neurons (DRGn) were investigated in vitro. The effects of CCR2 inhibitors and ZQGCD on the expression of the CCL2/CCR2 signaling pathway and ASIC3 in the rat intervertebral disc and dorsal root ganglion (DRG), the degree of disc degeneration, the threshold of foot retreat, and the latency of foot retreat in LDH rats were examined in vivo. The binding affinities and interaction modes between CCR2 and the components absorbed into the blood were analyzed using the AutodockVina 1.2.2 software. Results: Network pharmacology revealed that ZQGCD could treat LDH through a mechanism involving the chemokine signaling pathway. It was observed that the CCR2 inhibitor and ZQGCD-containing serum downregulated CCR2 and ASIC3 expression and decreased cell excitability in DRGn. The CCL2/CCR2 signaling pathway was activated in the degenerated intervertebral disc and DRG of LDH rats, increased the expression of ASIC3, and decreased the mechanical allodynia domain and thermal hyperalgesia domain. However, a CCR2 inhibitor or ZQGCD could ameliorate the above changes in LDH rats. The target proteins, CCL2 and CCR2, exhibited a robust affinity for the eight components that were absorbed into the bloodstream. Conclusion: The CCL2/CCR2 pathway was activated in the intervertebral disc and DRG of LDH rats. This was accompanied by upregulation of ASIC3 expression, increased excitability of DRGn, and the occurrence of hyperalgesia. ZQGCD improves hyperalgesia in LDH rats by inhibiting the CCL2/CCR2 pathway and downregulating ASIC3 expression.
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Hiperalgesia , Desplazamiento del Disco Intervertebral , Ratas , Animales , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Desplazamiento del Disco Intervertebral/tratamiento farmacológico , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
Background: Closed reduction is the preferred treatment for distal radius fractures. However, it requires a multiple experienced medical staff and manually maintaining stable traction is difficult. Additionally, doctors cannot assess the reduction status of a fracture in real-time through radiographic images, which may lead to improper reduction. Furthermore, post-fracture complications such as joint adhesion, stiffness, and impaired mobility pose a challenge for the doctors. So it is necessary to optimize the treatment process of the distal radius fracture through technological means. Methods: A robot-assisted closed reduction and rehabilitation system, which could assist doctors throughout the entire process of reduction, fixation, and rehabilitation of distal radius fractures, was developed. A mechanical system, composed of two grippers and a cooperative robotic arm, was used to grasp and tract the affected limb. A doctor controlled the robot through a joystick console and Windows application program. A biplane radiographic device was integrated into the system, which is not only convenient for doctors to view radiographic images of the fracture at any time but also for them to select the rotation axis of the wrist on the images before reduction and rehabilitation. Important information including the anteroposterior and lateral radiographic data and force and position parameters during the reduction and rehabilitation process were displayed on a graphic user interface. Results: Experimental results showed that the proposed robotic system can meet the technical requirements for the reduction and rehabilitation of distal radius fractures, all the rotation angles could be achieved, a maximum force of more than 50 N could be achieved in all traction directions, and the error in selecting the wrist joint rotation axis line using radiographic images was less than 5 mm. Conclusion: The developed robot-assisted system was shown to be suitable for closed reduction and rehabilitation of distal radius fractures, contributing a potential improvement in the quality of the procedures.
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OBJECTIVE: To explore the practice of comprehensive pharmacy management mode under the strategy of healthy China. METHODS: Combining with hospital practice, the advantages and disadvantages of comprehensive pharmacy management mode were discussed and considered. RESULTS: The comprehensive pharmacy has advantages in improving work efficiency, optimizing resource allocation, refining pharmacy management, checking the compatibility of Chinese and Western medicines, and improving service quality, and it also increases the labor intensity of staff and is prone to prescription dispensing errors. CONCLUSION: Hospitals with mature conditions and permission can use the management mode of comprehensive pharmacy.
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Farmacia , China , Hospitales , HumanosRESUMEN
PURPOSE: Researches revealed that probiotics maybe a potential strategy for COVID-19, whereas there is a lack of related evidence. This study aims to analyze the role of probiotics on severe COVID-19 patients. METHODS: In the current retrospective single-center study, we collected data of 311 consecutive severe patients with confirmed COVID-19 in Wuhan Union Hospital from Feb 3rd to Feb 20th, 2020. Epidemiological, clinical and medication characteristics were compared and analyzed between patients with or without probiotics. RESULTS: In total, 93 of the 123 patients (75.61%) who were treated with probiotics survived to hospital discharge with the median inpatient day of 32 days and mean virus clearance time of 23 days, which were significantly longer than those of patients without probiotics. There were no bias in laboratory parameters, except for IL-6 and ESR, which were significantly higher in patients treated probiotics. We tracked the dynamic changes of 8 selected laboratory parameters (IL-6, CRP, total T lymphocytes, NK cells, B lymphocyte, CD4 + T cells, CD8 + T cells and CD4/CD8 ratio) and found that probiotics could not reduce the increased IL-6 levels but possessed the ability to moderate the immunity and decreased the incidence of secondary infection in COVID-19 patients. CONCLUSIONS: Probiotics could be an effective strategy for the treatment of COVID-19 patients to reduce the secondary infection and moderated the immunity.
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COVID-19/terapia , Probióticos/uso terapéutico , Anciano , Linfocitos B/inmunología , Relación CD4-CD8 , COVID-19/sangre , COVID-19/inmunología , Femenino , Humanos , Inflamación/terapia , Interleucina-6/sangre , Células Asesinas Naturales/inmunología , Masculino , Persona de Mediana Edad , Receptores Inmunológicos/sangre , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Linfocitos T/inmunología , Resultado del TratamientoRESUMEN
The objective was to introduce a new endoscopic technique-interspinous plasty for low back pain from Baastrup's disease; based on clinical manifestations, imaging findings and diagnostic test, to discuss a detailed diagnostic procedure for Baastrup's disease; and to explore the mechanism of interspinous plasty in pain relief. To our knowledge, there is no report about the results of endoscopic lumbar technique for Baastrup's disease. This study described the successful full-endoscopic surgical treatment for Baastrup's disease, providing a brand-new therapeutic method for patients. Clinical manifestations, imaging findings, including X-ray, computed tomography (CT) and magnetic resonance imaging, and a "positive" diagnostic test with local anesthetic were used to confirm Baastrup's disease in the three included patients. The interspinous plasty procedure, which aimed to recover a physiological gap between the adjacent spinous processes, was performed by full-endoscopic resection of marginal osteophytes. The removal of local inflamed tissue and reducing inflammation via intraoperative saline irrigation also lead to pain relief. Clinical outcomes included visual analog scale (VAS) for low back pain and the Oswestry Disability Index (ODI). The distance between the adjacent spinous processes was measured from the preoperative and postoperative CT scan. We calculated and recorded the difference between preoperative and postoperative measurements. Technical procedures and advantages of interspinous plasty are introduced. The three patients showed improvement in terms of the postoperative VAS of low back pain (from 8 to 2, from 7 to 1 and from 8 to 2) and ODI (from 68.9% to 33.3%, from 77.8% to 28.9% and from 71.1% to 28.9%, respectively) at the 12-month follow-up. Compared postoperative ODI index, the ODI index increased from 26.7% to 33.3% and from 24.4% to 28.9% in two of the cases at the 12-month follow-up. At 1 week, CT confirmed an obvious reduction in the marginal osteophytes between the adjacent spinous processes. Compared with those on preoperative CT images, the distance between adjacent spinous processes on postoperative CT was enlarged from 1 to 4 mm, and a repeated CT scan 3 months later reconfirmed little recrudescent osteoproliferation. In selected cases, full-endoscopic surgical treatment for chronic mechanical back pain as part of the phenomena of Baastrup's disease may be beneficial. The operations in this study were performed under local anesthesia, with satisfactory early clinical outcomes and a low incidence of complications or adverse events. This may be a feasible therapeutic method or an alternative option for patients who cannot tolerate general anesthesia surgery.
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Endoscopía/métodos , Dolor de la Región Lumbar/cirugía , Enfermedades de la Columna Vertebral/cirugía , Cuerpo Vertebral/cirugía , Anciano , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Dimensión del DolorRESUMEN
BACKGROUND: A considerable proportion of patients hospitalized with coronavirus disease 2019 (COVID-19) acquired secondary bacterial infections (SBIs). The etiology and antimicrobial resistance of bacteria were reported and used to provide a theoretical basis for appropriate infection therapy. METHODS: This retrospective study reviewed electronic medical records of all the patients hospitalized with COVID-19 in the Wuhan Union Hospital between January 27 and March 17, 2020. According to the inclusion and exclusion criteria, patients who acquired SBIs were enrolled. Demographic, clinical course, etiology, and antimicrobial resistance data of the SBIs were collected. Outcomes were also compared between patients who were classified as severe and critical on admission. RESULTS: Among 1495 patients hospitalized with COVID-19, 102 (6.8%) patients had acquired SBIs, and almost half of them (49.0%, 50/102) died during hospitalization. Compared with severe patients, critical patients had a higher chance of SBIs. Among the 159 strains of bacteria isolated from the SBIs, 136 strains (85.5%) were Gram-negative bacteria. The top three bacteria of SBIs were A. baumannii (35.8%, 57/159), K. pneumoniae (30.8%, 49/159), and S. maltophilia (6.3%, 10/159). The isolation rates of carbapenem-resistant A. baumannii and K. pneumoniae were 91.2 and 75.5%, respectively. Meticillin resistance was present in 100% of Staphylococcus aureus and Coagulase negative staphylococci, and vancomycin resistance was not found. CONCLUSIONS: SBIs may occur in patients hospitalized with COVID-19 and lead to high mortality. The incidence of SBIs was associated with the severity of illness on admission. Gram-negative bacteria, especially A. baumannii and K. pneumoniae, were the main bacteria, and the resistance rates of the major isolated bacteria were generally high. This was a single-center study; thus, our results should be externally examined when applied in other institutions.
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Coinfección/tratamiento farmacológico , Coinfección/epidemiología , Farmacorresistencia Bacteriana/fisiología , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones Estafilocócicas/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Betacoronavirus , COVID-19 , China/epidemiología , Coinfección/mortalidad , Infecciones por Coronavirus/patología , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Pandemias , Neumonía Viral/patología , Estudios Retrospectivos , SARS-CoV-2 , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
The treatment of bone defects caused by various reasons is still a major problem in orthopedic clinical work. Many studies on osteogenic implant materials have used various biologically active factors such as osteogenic inducers, but these biologically active factors have various side effects. Therefore, in this study, silk fibroin (SF) was used as a scaffold material, mesoporous bioactive glass nanoparticles (MBGNs) as a sustained release carrier, and the traditional Chinese drug icariin (ICA) was loaded to promote bone formation. The experiments in this study have proven that SF/MBGNs-ICA scaffolds can successfully load and release ICA for a long time, and the sustained-release ICA can promote the proliferation and differentiation of BMSCs for a long time. This controlled-release ICA organic/inorganic two-component scaffold material is expected to become a new bone grafting solution.
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OBJECTIVE: To observe the effect of acupoint injection with astragalus parenteral solution in rat chronic pelvic inflammatory disease (CPID). METHODS: Fifty female Wistar rats were randomly divided into 6 groups: CPID model was induced in 4 groups, in addition to control group and false surgery group. The rats were given acupoint (Guanyuan and Zusanli) injection with astragalus parenteral solution and saline. The drug group was fed with Qianjinpian solutions. The histopathologic changes of uterus were observed and serum IL-2 and TNF-alpha levels detected. RESULT: The rats in the model group showed chronic inflammatory changes, the animals in astragalus parenteral injection group and Qianjinpian group showed little histopathological changes. The serum TNF-alpha levels in the model group were significantly higher than those in the normal group and the astragalus parenteral injection group; while the IL-2 levels in model group were significantly lower than those of other 5 groups. The TNF-alpha and IL-2 levels in astragalus parenteral injection group were similar to those of normal group. CONCLUSION: The treatment of chronic pelvic inflammatory disease with acupoint injection of astragalus parenteral solution might be effective.