Wear and corrosion of titanium alloy spinal implants in vivo.

To investigate the wear and corrosion of titanium alloy spinal implants in vivo, we evaluated removed implants and their surrounding scar tissues from 27 patients between May 2019 and April 2021. We performed scanning electron microscopy, energy-dispersive X-ray spectroscopy, and histological analysis. The results revealed metal-like particles in the soft tissues of seven patients, without any considerable increase in inflammatory cell infiltration. Patients with fractures showed lower percentages of wear and corrosion compared with other patients (42% and 17% vs. 59% and 26%). Polyaxial screws exhibited higher wear and corrosion percentages (53% and 23%) compared with uniaxial screws (39% and 3%), although in patients with fracture, the reverse was observed (20% and 0% vs. 39% and 3%). We found that titanium alloy spinal implants experience some degree of wear and corrosion in vivo. The titanium alloy particles formed by wear exhibited good histocompatibility, not causing inflammation, foreign body reactions, or osteolysis. Therefore, spinal implants should be removed cautiously when treating titanium alloy spinal metallosis. The wear and corrosion of the implants increase with the increase in implantation time, although the screw structure does not significantly affect these changes.

Conditioned culture medium of bone marrow mesenchymal stem cells promotes phenotypic transformation of microglia by regulating mitochondrial autophagy.

Objective: To study the mechanism by which conditioned medium of bone marrow mesenchymal stem cells (BMSCs-CM) facilitates the transition of pro-inflammatory polarized microglia to an anti-inflammatory phenotype. Methods: BV2 cells, a mouse microglia cell line, were transformed into a pro-inflammatory phenotype using lipopolysaccharide. The expression of phenotypic genes in BV2 cells was detected using real-time quantitative PCR (RT-qPCR). Enzyme-linked immunosorbent assay was used to measure inflammatory cytokine levels in BV2 cells co-cultured with BMSCs-CM. The expressions of mitophagy-associated proteins were determined using western blot. The mitochondrial membrane potential and ATP levels in BV2 cells were measured using JC-1 staining and an ATP assay kit, respectively. Additionally, we examined the proliferation, apoptosis, and migration of C8-D1A cells, a mouse astrocyte cell line, co-cultured with BV2 cells. Results: After co- culture with BMSCs -CM, the mRNA expression of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase significantly decreased in pro-inflammatory BV2 cells, whereas the expression of CD206 and arginase-1 significantly increased. Moreover, TNF-α and interleukin-6 levels significantly decreased, whereas transforming growth factor-ß and interleukin-10 levels significantly increased. Furthermore, co-culture with BMSCs-CM increased mitophagy-associated protein expression, ATP levels, mitochondrial and lysosomal co-localization in these cells and decreased reactive oxygen species levels. Importantly, BMSCs-CM reversed the decrease in the proliferation and migration of C8-D1A cells co-cultured with pro-inflammatory BV2 cells and inhibited the apoptosis of C8-D1A cells. Conclusion: BMSCs-CM may promote the transition of polarized microglia from a pro-inflammatory to an anti-inflammatory phenotype by regulating mitophagy and influences the functional state of astrocytes.

Jinlida for Diabetes Prevention in Impaired Glucose Tolerance and Multiple Metabolic Abnormalities: The FOCUS Randomized Clinical Trial.

Importance: Previous studies have shown that Jinlida (JLD) granules, an approved treatment for type 2 diabetes in China, can reduce blood glucose level, reduce glycated hemoglobin (HbA1c), and improve insulin resistance in people with type 2 diabetes. Objective: To evaluate the effect of long-term administration of JLD vs placebo on the incidence of diabetes in participants with impaired glucose tolerance (IGT) and multiple metabolic abnormalities. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial (FOCUS) was conducted across 35 centers in 21 cities in China from June 2019 to February 2023. Individuals aged 18 to 70 years with IGT and multiple metabolic abnormalities were enrolled. Intervention: Participants were randomly allocated 1:1 to receive JLD or placebo (9 g, 3 times per day, orally). They continued this regimen until they developed diabetes, withdrew from the study, were lost to follow-up, or died. Main Outcomes and Measures: The primary outcome was the occurrence of diabetes, which was determined by 2 consecutive oral glucose tolerance tests. Secondary outcomes included waist circumference; fasting and 2-hour postprandial plasma glucose levels; HbA1c; fasting insulin level; homeostatic model assessment for insulin resistance (HOMA-IR); total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels; ankle-brachial index; and carotid intima-media thickness. Results: A total of 889 participants were randomized, of whom 885 were in the full analysis set (442 in the JLD group; 443 in the placebo group; mean [SD] age, 52.57 [10.33] years; 463 [52.32%] female). Following a median observation period of 2.20 years (IQR, 1.27-2.64 years), participants in the JLD group had a lower risk of developing diabetes compared with those in the placebo group (hazard ratio, 0.59; 95% CI, 0.46-0.74; P < .001). During the follow-up period, the JLD group had a between-group difference of 0.95 cm (95% CI, 0.36-1.55 cm) in waist circumference, 9.2 mg/dL (95% CI, 5.4-13.0 mg/dL) in 2-hour postprandial blood glucose level, 3.8 mg/dL (95% CI, 2.2-5.6 mg/dL) in fasting blood glucose level, 0.20% (95% CI, 0.13%-0.27%) in HbA1c, 6.6 mg/dL (95% CI, 1.9-11.2) in total cholesterol level, 4.3 mg/dL (95% CI, 0.8-7.7 mg/dL) in low-density lipoprotein cholesterol level, 25.7 mg/dL (95% CI, 15.9-35.4 mg/dL) in triglyceride levels, and 0.47 (95% CI, 0.12-0.83) in HOMA-IR compared with the placebo group. After 24 months of follow-up, the JLD group had a significant improvement in ankle-brachial index and waist circumference compared with the placebo group. Conclusions and Relevance: The findings suggest that JLD can reduce the risk of diabetes in participants with IGT and multiple metabolic abnormalities. Trial Registration: Chinese Clinical Trial Register: ChiCTR1900023241.

Early effective intervention can significantly reduce all-cause mortality in prediabetic patients: a systematic review and meta-analysis based on high-quality clinical studies.

Background: Reducing the occurrence of diabetes is considered a primary criterion for evaluating the effectiveness of interventions for prediabetes. There is existing evidence that early lifestyle-based interventions can significantly decrease the incidence of diabetes. However, whether effective interventions can reduce long-term outcomes in patients, including all-cause mortality, cardiovascular risks, and the occurrence of microvascular complications, which are the most concerning issues for both patients and clinicians, remains a subject of inconsistent research findings. And there is no direct evidence to answer whether effective intervention has long-term benefits for prediabetic patients. Therefore, we conducted a systematic review and meta-analysis to assess the relationship between early effective intervention and macrovascular and microvascular complications in prediabetic patients. Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for the randomized controlled trials of lifestyle or/and drugs intervention in prediabetes from inception to 2023.9.15. Two investigators independently reviewed the included studies and extracted relevant data. Random or fixed effects model meta-analysis to derive overall relative risk (RR) with 95% CI for all-cause mortality, cardiovascular events, and microvascular complications. Results: As of September 15, 2023, a total of 7 effective intervention studies were included, comprising 26 articles out of 25,671 articles. These studies involved 26,389 patients with a total follow-up duration of 178,038.6 person-years. The results indicate that effective intervention can significantly reduce all-cause mortality in prediabetic patients without a history of cardiovascular disease by 17% (RR 0.83, 95% CI 0.70-0.98). Additionally, effective intervention reduced the incidence of retinopathy by 38% (RR 0.62, 95% CI 0.70-0.98). Furthermore, the study results suggest that women and younger individuals have lower all-cause mortality and cardiovascular mortality. Subsequently, we conducted an in-depth analysis of patients without a history of cardiovascular disease. The results revealed that prediabetic patients with a 10-year cardiovascular risk >10% experienced more significant benefits in terms of all-cause mortality (P=0.01). When comparing the results of all-cause mortality and cardiovascular mortality from the Da Qing Diabetes Prevention Outcome Study longitudinally, it was evident that the duration of follow-up is a key factor influencing long-term benefits. In other words, the beneficial effects become more pronounced as the intervention duration reaches a certain threshold. Conclusion: Early effective intervention, which significantly reduces the incidence of diabetes, can effectively lower all-cause mortality in prediabetic patients without a history of cardiovascular disease (especially those with a 10-year cardiovascular risk >10%), with women and younger individuals benefiting more significantly. Additionally, the duration of follow-up is a key factor influencing outcomes. The conclusions of this study can provide evidence-based guidance for the clinical treatment of prediabetic patients to prevent cardiovascular and microvascular complications. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42020160985.

Parallelism and non-parallelism in diabetic nephropathy and diabetic retinopathy.

Diabetic nephropathy (DN) and diabetic retinopathy (DR), as microvascular complications of diabetes mellitus, are currently the leading causes of end-stage renal disease (ESRD) and blindness, respectively, in the adult working population, and they are major public health problems with social and economic burdens. The parallelism between the two in the process of occurrence and development manifests in the high overlap of disease-causing risk factors and pathogenesis, high rates of comorbidity, mutually predictive effects, and partial concordance in the clinical use of medications. However, since the two organs, the eye and the kidney, have their unique internal environment and physiological processes, each with specific influencing molecules, and the target organs have non-parallelism due to different pathological changes and responses to various influencing factors, this article provides an overview of the parallelism and non-parallelism between DN and DR to further recognize the commonalities and differences between the two diseases and provide references for early diagnosis, clinical guidance on the use of medication, and the development of new drugs.

Lessons learned from annotation of VAERS reports on adverse events following influenza vaccination and related to Guillain-Barré syndrome.

BACKGROUND: Vaccine Adverse Events ReportingSystem (VAERS) is a promising resource of tracking adverse events following immunization. Medical Dictionary for Regulatory Activities (MedDRA) terminology used for coding adverse events in VAERS reports has several limitations. We focus on developing an automated system for semantic extraction of adverse events following vaccination and their temporal relationships for a better understanding of VAERS data and its integration into other applications. The aim of the present studyis to summarize the lessons learned during the initial phase of this project in annotating adverse events following influenza vaccination and related to Guillain-Barré syndrome (GBS). We emphasize on identifying the limitations of VAERS and MedDRA. RESULTS: We collected 282 VAERS reports documented between 1990 and 2016 and shortlisted those with at least 1,100 characters in the report. We used a subset of 50 reports for the preliminary investigation and annotated all adverse events following influenza vaccination by mapping to representative MedDRA terms. Associated time expressions were annotated when available. We used 16 System Organ Class (SOC) level MedDRA terms to map GBS related adverse events and expanded some SOC terms to Lowest Level Terms (LLT) for granular representation. We annotated three broad categories of events such as problems, clinical investigations, and treatments/procedures. The inter-annotator agreement of events achieved was 86%. Incomplete reports, typographical errors, lack of clarity and coherence, repeated texts, unavailability of associated temporal information, difficulty to interpret due to incorrect grammar, use of generalized terms to describe adverse events / symptoms, uncommon abbreviations, difficulty annotating multiple events with a conjunction / common phrase, irrelevant historical events and coexisting events were some of the challenges encountered. Some of the limitations we noted are in agreement with previous reports. CONCLUSIONS: We reported the challenges encountered and lessons learned during annotation of adverse events in VAERS reports following influenza vaccination and related to GBS. Though the challenges may be due to the inevitable limitations of public reporting systems and widely reported limitations of MedDRA, we emphasize the need to understand these limitations and extraction of other supportive information for a better understanding of adverse events following vaccination.

Interpretable Machine Learning Model to Predict Bone Cement Leakage in Percutaneous Vertebral Augmentation for Osteoporotic Vertebral Compression Fracture Based on SHapley Additive exPlanations.

STUDY DESIGN: Retrospective study. OBJECTIVES: Our objective is to create comprehensible machine learning (ML) models that can forecast bone cement leakage in percutaneous vertebral augmentation (PVA) for individuals with osteoporotic vertebral compression fracture (OVCF) while also identifying the associated risk factors. METHODS: We incorporated data from patients (n = 425) which underwent PVA. To predict cement leakage, we devised six models based on a variety of parameters. Evaluate and juxtapose the predictive performances relied on measures of discrimination, calibration, and clinical utility. SHapley Additive exPlanations (SHAP) methodology was used to interpret model and evaluate the risk factors associated with cement leakage. RESULTS: The occurrence rate of cement leakage was established at 50.4%. A binary logistic regression analysis identified cortical disruption (OR 6.880, 95% CI 4.209-11.246), the basivertebral foramen sign (OR 2.142, 95% CI 1.303-3.521), the fracture type (OR 1.683, 95% CI 1.083-2.617), and the volume of bone cement (OR 1.198, 95% CI 1.070-1.341) as independent predictors of cement leakage. The XGBoost model outperformed all others in predicting cement leakage in the testing set, with AUC of .8819, accuracy of .8025, recall score of .7872, F1 score of .8315, and a precision score of .881. Several important factors related to cement leakage were drawn based on the analysis of SHAP values and their clinical significance. CONCLUSION: The ML based predictive model demonstrated significant accuracy in forecasting bone cement leakage for patients with OVCF undergoing PVA. When combined with SHAP, ML facilitated a personalized prediction and offered a visual interpretation of feature importance.

The ideal treatment timing for diabetic retinopathy: the molecular pathological mechanisms underlying early-stage diabetic retinopathy are a matter of concern.

Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients' quality of life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs to treat diabetic macular edema such as the anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted the crucial role of early intervention in DR for halting or delaying disease progression. This holds immense significance in enhancing patients' quality of life and alleviating the societal burden associated with medical care costs. The non-proliferative stage represents the early phase of DR. In comparison to the proliferative stage, pathological changes primarily manifest as microangiomas and hemorrhages, while at the cellular level, there is a loss of pericytes, neuronal cell death, and disruption of components and functionality within the retinal neuronal vascular unit encompassing pericytes and neurons. Both neurodegenerative and microvascular abnormalities manifest in the early stages of DR. Therefore, our focus lies on the non-proliferative stage of DR and we have initially summarized the mechanisms involved in its development, including pathways such as polyols, that revolve around the pathological changes occurring during this early stage. We also integrate cutting-edge mechanisms, including leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, cell death (ferroptosis and pyroptosis), and other related mechanisms. The current status of drug therapy for early-stage DR is also discussed to provide insights for the development of pharmaceutical interventions targeting the early treatment of DR.

N6-methyladenosine (m6A) methylation in kidney diseases: Mechanisms and therapeutic potential.

The N6-methyladenosine (m6A) modification is regulated by methylases, commonly referred to as "writers," and demethylases, known as "erasers," leading to a dynamic and reversible process. Changes in m6A levels have been implicated in a wide range of cellular processes, including nuclear RNA export, mRNA metabolism, protein translation, and RNA splicing, establishing a strong correlation with various diseases. Both physiologically and pathologically, m6A methylation plays a critical role in the initiation and progression of kidney disease. The methylation of m6A may also facilitate the early diagnosis and treatment of kidney diseases, according to accumulating research. This review aims to provide a comprehensive overview of the potential role and mechanism of m6A methylation in kidney diseases, as well as its potential application in the treatment of such diseases. There will be a thorough examination of m6A methylation mechanisms, paying particular attention to the interplay between m6A writers, m6A erasers, and m6A readers. Furthermore, this paper will elucidate the interplay between various kidney diseases and m6A methylation, summarize the expression patterns of m6A in pathological kidney tissues, and discuss the potential therapeutic benefits of targeting m6A in the context of kidney diseases.

Research trends of omics in ulcerative colitis: A bibliometric analysis.

Background: Omics has emerged as a promising biological science to shed light on the etiology, pathogenesis, and treatment of ulcerative colitis (UC). At present, although research on the omics of UC has drawn global attention, there is still a lack of bibliometric analysis in this field. This study aimed to access the trends and hotspots of omics in UC research. Method: Publications related to omics in UC from 1 January 2000 to 15 October 2022 were retrieved from the Web of Science Core Collection database. VOSviewer, CiteSpace, and the online bibliometric analysis platform "Bibliometrix" were adopted to extract and visualize information. Results: A total of 385 publications were finally included and the annual number of publications fluctuated. The trend in publications increased rapidly after 2019. The United States showed its dominant position in several publications, total citations, and international collaborations. The top five research organizations for publications on the research of omics in UC were Harvard Medical School, the Icahn School of Medicine at Mount Sinai, Karolinska Institutet, the Brigham and Women's Hospital, and the Massachusetts General Hospital. Ashwin Ananthakrishnan from the Massachusetts General Hospital was the most productive author, and Séverine Vermeire from the Catholic University of Leuven was co-cited most often. Inflammatory bowel disease was the most popular and co-cited journal in this field. The reference with citation bursts and trend topics showed that "ulcerative colitis," "inflammatory bowel disease," "microbiome," "transcriptomics," "genomics," "metabolomics," "proteomics," "dysbiosis," "biomarkers," "loci," and "therapy" are currently research hotspots. Conclusion: Our study presents several important insights into the research trends and developments in the field of omics in UC, which will provide key information for further research.

The crucial role and mechanism of insulin resistance in metabolic disease.

Insulin resistance (IR) plays a crucial role in the development and progression of metabolism-related diseases such as diabetes, hypertension, tumors, and nonalcoholic fatty liver disease, and provides the basis for a common understanding of these chronic diseases. In this study, we provide a systematic review of the causes, mechanisms, and treatments of IR. The pathogenesis of IR depends on genetics, obesity, age, disease, and drug effects. Mechanistically, any factor leading to abnormalities in the insulin signaling pathway leads to the development of IR in the host, including insulin receptor abnormalities, disturbances in the internal environment (regarding inflammation, hypoxia, lipotoxicity, and immunity), metabolic function of the liver and organelles, and other abnormalities. The available therapeutic strategies for IR are mainly exercise and dietary habit improvement, and chemotherapy based on biguanides and glucagon-like peptide-1, and traditional Chinese medicine treatments (e.g., herbs and acupuncture) can also be helpful. Based on the current understanding of IR mechanisms, there are still some vacancies to follow up and consider, and there is also a need to define more precise biomarkers for different chronic diseases and lifestyle interventions, and to explore natural or synthetic drugs targeting IR treatment. This could enable the treatment of patients with multiple combined metabolic diseases, with the aim of treating the disease holistically to reduce healthcare expenditures and to improve the quality of life of patients to some extent.

Thiolated chitosan nanoparticles for stable delivery and smart release of As2O3 for liver cancer through dual actions.

In this work, multifunctional thiolated chitosan derivatives (DCA-CS-PEG-FA-NAC) were synthesized, and arsenic trioxide (ATO) was loaded onto the derivatives through glutathione (GSH)-sensitive AsIII-S bonds, and stable CS-ATO nanodrugs were prepared by simple self-assembly method. By adjusting the thiol substitution degree of CS, the drug loading capacity of the nanodrugs was significantly improved, which could reach 20 ATO per CS molecule (DCA10.7-CS-PEG3.1-FA-NAC20.2-ATO). In vitro release studies obviously showed the low leakage of ATO under physiological conditions while over 95 % ATO was released after 24 h under GSH. In vitro and in vivo investigations demonstrated that the DCA10.7-CS-PEG3.1-FA-NAC20.2-ATO nanodrug could significantly enhance the tumor intracellular accumulation of ATO, reduce the toxic and side effects of ATO on healthy organs, and improve the therapeutic effect of ATO on the HepG2 mice tumor model (tumor inhibition rate was as high as 86.4 %), indicating the potential application of ATO in clinical treatment of liver cancer.

A20 ameliorates disc degeneration by suppressing mTOR/BNIP3 axis-mediated mitophagy.

BACKGROUND: The pathological mechanism of intervertebral disc degeneration (IDD) is an unanswered question that we are committed to exploring. A20 is an anti-inflammatory protein of nucleus pulposus (NP) cells and plays a protective role in intervertebral disc degeneration. OBJECTIVE: This study aims to investigate the molecular mechanism by which A20 attenuates disc degeneration. METHODS: The proteins of interest were measured by immunoblotting, immunofluorescence, ELISA assay, and immunohistochemical technique to conduct related experiments. Immunofluorescence assays and mitochondrial membrane potential (JC-1) were used to assess mitophagy and mitochondrial fitness, respectively. RESULTS: Here, we demonstrated that A20 promoted mitophagy, attenuated pyroptosis, and inhibited the degradation of the extracellular matrix, consequently significantly ameliorating disc degeneration. Mechanistically, A20 reduces pyroptosis and further suppresses cellular mTOR activity. On the one hand, A20-induced mTOR inhibition triggers BNIP3-mediated mitophagy to ensure mitochondrial fitness under LPS stimulation, as a result of mitigating mitochondrial dysfunction induced by LPS. On the other hand, A20-induced mTOR inhibition reduces the loss of mitochondrial membrane potential and the generation of Mitochondrial ROS. CONCLUSION: The study revealed that A20 promotes BNIP3-mediated mitophagy by suppressing mTOR pathway activation against LPS-induced pyroptosis.

A20 attenuates pyroptosis and apoptosis in nucleus pulposus cells via promoting mitophagy and stabilizing mitochondrial dynamics.

BACKGROUND: A20 is an anti-inflammatory molecule in nucleus pulposus (NP) cells. The anti-inflammatory properties of A20 are mainly attributed to its ability to suppress the NF-κB pathway. However, A20 can protect cells from death independently of NF-κB regulation. This study aimed to investigate the effects of A20 on pyroptosis and apoptosis of NP cells induced by lipopolysaccharide (LPS). METHODS: NP cells induced by LPS were used as an in vitro model of the inflammatory environment of the intervertebral disc. Pyroptosis, apoptosis, and mitophagy marker proteins were detected. Then, NP cells were transfected with A20 overexpressed lentivirus or A20-siRNA. Annexin V FITC/PI, Western blotting, and immunofluorescence assays were used to detect the apoptosis, pyroptosis, and mitophagy of NP cells. Furthermore, the expressions of A20, related proteins, and related inflammatory cytokines were detected by western blotting, and ELISA. RESULTS: Apoptosis and pyroptosis of NP cells increased gradually treated with LPS for 12 h, 24 h, and 48 h. Differently, the level of mitophagy increased first and then decreased, and was the highest at LPS treatment for 12 h. Overexpression or knockdown of A20 in NP cells revealed that A20 attenuated the pyroptosis, apoptosis, and production of inflammatory cytokines of NP cells induced by LPS, while A20 sponsored mitophagy, reduced ROS production and collapse of mitochondrial membrane potential (ΔΨm). Moreover, A20 also promoted mitochondrial dynamic homeostasis and attenuated LPS-induced excessive mitochondrial fission. Excitingly, inhibition of mitophagy attenuated the effect of A20 on the negative regulation of pyroptosis of NP cells induced by LPS. Pyroptosis was accompanied by a large release of inflammatory cytokines. Inhibition of pyroptosis also significantly reduced apoptosis of NP cells. Finally, The mitochondria-targeted active peptide SS-31 inhibited LPS-induced pyroptosis and ROS production in NP cells. CONCLUSIONS: To sum up, A20 attenuates pyroptosis and apoptosis of NP cells via promoting mitophagy and stabilizing mitochondrial dynamics. Besides, A20 reduces LPS-induced NP cell apoptosis by inhibiting NLRP3 inflammasome-mediated pyroptosis. It provides theoretical support for the reduction of functional NP cell loss in the intervertebral disc through the gene-targeted intervention of A20.

A nerve growth factor persistent delivery scaffold seeded with neurally differentiated bone marrow mesenchymal stem cells promoted the functional recovery of spinal cord injury in rats.

The objective was to design a scaffold that could continuously deliver nerve growth factor (NGF) combined with neurally differentiated bone marrow mesenchymal stem cells (BMSCs) to promote better recovery of spinal cord injury (SCI) in rats. BMSCs were induced to differentiate into neurons for 6 days in vitro, and then seeded on a NGF persistent delivery scaffold, both were transplanted to SCI rats in combination. Relevant extensive tests were conducted 1, 4 and 8 weeks after transplantation. The results showed that the scaffold had a stable ability to continuously release NGF and that the BMSCs on the scaffold could successfully differentiate into nerve cells. The results of Bacco, Beattie and Bresnahan (BBB) scores, inclined plane tests and electrophysiological investigations revealed that the rats in the combined regimen had better locomotor functional recovery. The results of H&E/Nissl staining, Golgi staining and immunofluorescence showed that the rats in the combined regimen retained the most neurons and had the least cavities and more formations of dendritic spines. Similarly, the positive rate was high for MAP2, NeuN and MBP, and low for GFAP. The graft of the NGF persistent delivery scaffold seeded with neurally differentiated BMSCs significantly reduced the formation of cavities and glial scars at the SCI sites and promoted neuronal survival, axonal regeneration and locomotor function recovery. Compared with the single graft of NGF persistent delivery scaffold or the single graft of neurally differentiated BMSCs, this combined scheme had a better effect in promoting the recovery of SCI.

A Descriptive Analysis of Capsule Endoscopy Events in the FDA Manufacturer and User Facility Device Experience (MAUDE) Database.

Introduction: The malfunction of capsule endoscopy (CE) devices is a significant reason for the failure of CE procedures, which could hinder and prevent diagnosis. Unfortunately, malfunction-related adverse events (AEs) caused by CE devices are rarely reported in publications. Although most malfunction-related AEs could not lead to physical harm, they could reduce the efficiency of medical care and increase medical costs. The manufacturer and user facility device experience (MAUDE) database, a publicly accessible resource for patient safety, contains not only the common complications of CE but also valuable malfunction-related AEs, which have been underutilized. Therefore, the study aims to discover and analyze the possible AEs associated with CE and demonstrate the utility of the MAUDE reports to promote patient safety. Materials and Methods: We acquired MAUDE reports of CE systems from January 01, 2008, to July 31, 2020, through a systematic search strategy. We utilized the manufacturers, brand names, and product codes as search terms from which medical device reports including structured data and narrative texts were extracted, followed by a manual review of the narrative texts, reporter occupation, device involved, event type and the phase of the event; finally, patient outcomes were recorded and analyzed as per CE categories and characteristics. Results: A total of 377 CEs medical device reports were retrieved, and 342 reports were included after reviewing. There were 327 mandatory reports (96%) and 15 voluntary reports (4%). These reports referred to capsule endoscope (n = 213), sensing system (n = 66), patency capsule (n = 38), and capsule delivery device (n = 26). A total of 349 CE-related AEs were identified, including complications (n = 228), malfunction-related AEs (n = 109), and other events (n = 12). The composition of AEs was not the same for the CE devices. Complications were major AEs of capsule endoscope and patency capsule, but malfunction-related AEs were the most common in AEs of sensing systems and capsule delivery devices. Conclusion: MAUDE serves as an invaluable data source for investigating malfunction-related AEs. In addition to common complications, malfunction of CE devices could threaten patient safety in CE procedures. Improving awareness of the malfunction of CE devices and raising adequate training for staff working in gastrointestinal (GI) endoscopic units could be critical and beneficial in preventing malfunction-related AEs.

Comparative analysis of three types of titanium mesh cages for anterior cervical single-level corpectomy and fusion in term of postoperative subsidence.

A titanium mesh cage (TMC) is a common device used for interbody fusion in anterior cervical corpectomy and fusion (ACCF) surgery, with postoperative subsidence being a common complication. Among the many influencing factors, there is a paucity of research on the end-covers of the TMC. A total of 62 patients with cervical spondylotic myelopathy were treated with single-level ACCF. TMC without end-covers (group A), traditional TMC with end-covers (group B) and new TMC with end-covers (group C) were used as the fusion device. We evaluated the surgery time, intraoperative blood loss, postoperative drainage volume, postoperative fusion, falling height of the fused segment, cervical curvature and severe subsidence rate (the number of falling height of the fused segment > 3 mm/total surgical cases in the group). In addition, the Japanese Orthopaedic Association score was used for neurological status assessment and a 10-point Visual Analog Scale for postoperative neck pain. The results showed that the falling height of the fused segment in group A (1.9 ± 0.6 mm) was significantly greater than in group B (0.9 ± 0.2 mm) and group C (0.8 ± 0.3 mm). The area of the end-covers increased gradually in group A, group B and group C, while the severe subsidence rate of group A (8/20, 40%), group B (5/22, 23%) and group C (2/20, 10%) gradually decreased. The surgery time and blood loss in group B (116.4 ± 12.2 min, 183.5 ± 36.4 mL) were higher than those in group A (90.22 ± 5.60 min, 110.4 ± 20.8 mL) and group C (92.8 ± 8.47 min, 114 ± 24.0 mL). These results showed that there was a correlation between the postoperative subsidence and the end-covers of TMC. The larger the end-cover area was, the lower the severe postoperative subsidence rate was. In addition, the design of the end-covers extending inward was more conducive to the operation.

Asthma Exacerbation Prediction and Risk Factor Analysis Based on a Time-Sensitive, Attentive Neural Network: Retrospective Cohort Study.

BACKGROUND: Asthma exacerbation is an acute or subacute episode of progressive worsening of asthma symptoms and can have a significant impact on patients' quality of life. However, efficient methods that can help identify personalized risk factors and make early predictions are lacking. OBJECTIVE: This study aims to use advanced deep learning models to better predict the risk of asthma exacerbations and to explore potential risk factors involved in progressive asthma. METHODS: We proposed a novel time-sensitive, attentive neural network to predict asthma exacerbation using clinical variables from large electronic health records. The clinical variables were collected from the Cerner Health Facts database between 1992 and 2015, including 31,433 adult patients with asthma. Interpretations on both patient and cohort levels were investigated based on the model parameters. RESULTS: The proposed model obtained an area under the curve value of 0.7003 through a five-fold cross-validation, which outperformed the baseline methods. The results also demonstrated that the addition of elapsed time embeddings considerably improved the prediction performance. Further analysis observed diverse distributions of contributing factors across patients as well as some possible cohort-level risk factors, which could be found supporting evidence from peer-reviewed literature such as respiratory diseases and esophageal reflux. CONCLUSIONS: The proposed neural network model performed better than previous methods for the prediction of asthma exacerbation. We believe that personalized risk scores and analyses of contributing factors can help clinicians better assess the individual's level of disease progression and afford the opportunity to adjust treatment, prevent exacerbation, and improve outcomes.

Clinical Strategy for Optimal Traditional Chinese Medicine (TCM) Herbal Dose Selection in Disease Therapeutics: Expert Consensus on Classic TCM Herbal Formula Dose Conversion.

The clinical therapeutics of traditional Chinese medicine (TCM) constitutes a complicated process which involves theory, diagnosis, and formula prescription with specific herbal dosage. Zhang Zhong-Jing's classic work, Treatise on Febrile and Miscellaneous Diseases, has been influencing TCM practice for almost 2000 years. However, during this extended period of time in Chinese history, the Chinese weight measurement system experienced noticeable changes. This change in the weight measurement system inevitably, and perhaps even negatively, affected TCM herbal dosage determination and treatment outcome. Thus, in modern society, a full understanding of the accuracy of herbal dose selection has a critical importance in the TCM daily practice of delivering the best treatment to the patients suffering from different illnesses. In the 973 Project of the Chinese National Basic Research Program, expert consensus on classic TCM formula dose conversion has been reached based on extensive literature review and discussion on the dose-effect relationship of classic TCM formulas. One "liang" in classic TCM formulas is equivalent to 13.8 g. However, based on many TCM basic and clinical studies of variable herbal formula prescriptions and herbal drug preparations, the rule of one liang equals 13.8 g should be adjusted according to different disease conditions. Recommended by the committee on TCM formula dose-effect relationship of the China Association of Chinese Medicine and the World Federation of Chinese Medicine Societies, the following expert consensus has been reached: (i) One liang converts to 6-9 g for the severely and critically ill patients. (ii) One liang converts to 3-6 g for the patients suffering from chronic diseases. (iii) One liang converts to 1-3 g in preventive medicine. The above conversions should be used as a future TCM practice guideline. Using this recommended guideline should enhance the effectiveness of daily TCM practice.

[Analysis on dosage of traditional Chinese medicine decoction pieces stipulated in Chinese pharmacopoeia].

Chinese Pharmacopoeia I (2010 edition) covers dosage and usage of traditional Chinese medicinal herbs and decoction pieces, and provides dosage ranges of most of decoction pieces. By using the descriptive statistical method, the article discusses the distribution of maximum dosage, minimum dosage and dosage range of decoction pieces set forth in Chinese Pharmacopoeia, and compares toxic drugs and non-toxic drugs. Altogether 617 drugs are included into the study. Except for 16 decoction pieces whose dosages are not clear, all of the remaining decoction pieces are covered by Chinese Pharmacopoeia, with the maximum common dosage, minimum common dosage and dosage range of 3, 10 and 6 g. Upon comparison, we discovered that Chinese Pharmacopoeia sets stricter standards for toxic drugs than non-toxic drugs. Compared with dosages in classical prescriptions and actual clinical usages, dosage ranges described in Chinese Pharmacopoeia are much narrower. There is no significant difference between drugs that can be used as foods or healthcare foods and other drugs according to Chinese Pharmacopoeia.