BACKGROUND:Currently,spinal cord injury imposes a huge psychological and economic burden on patients and the National Health Service.The prevention,treatment,and rehabilitation of spinal cord injury have become an important topic in the field of medicine.Therefore,it is important to explore new effective therapeutic strategies based on an in-depth understanding of the underlying molecular mechanisms of spinal cord injury.OBJECTIVE:To review the research progress on the mechanism of action of mesenchymal stem cell-derived exosomes loaded with various miRNAs in improving the function of spinal cord injury,and based on the current status of clinical translation,to put forward a few thoughts and outlooks on their clinical use.METHODS:The first author searched CNKI and PubMed databases using"mesenchymal stem cells,exosomes,spinal cord injury,miRNA,pathophysiology,clinical translation,clinical trials,good manufacturing practice"as Chinese and English search terms.The types of literature included treatises and reviews,and the language types were English and Chinese.Finally,72 papers were screened and analyzed.RESULTS AND CONCLUSION:(1)This article outlines the biological properties of exosomes and the advantages that they can serve as good vectors for loading miRNAs.A variety of miRNAs mediated by mesenchymal stem cell-derived exosomes mainly promote the recovery of neuronal function by regulating the expression of nerve regeneration-associated proteins,repressing RAS homologous gene family member A,activating cyclophosphoadenosine effector-binding proteins,and signaling and transcriptional activation proteins 3,and regulating phosphoinositide and tensin homologue/programmed cell death factor 4 pathways.Inflammatory responses were improved by regulating endoplasmic reticulum-to-nucleus signaling 1,expression of interferon regulatory factor 5,Toll-like receptor 4/nuclear factor-kappa B pathway,and down-regulating related pro-inflammatory factors.Angiogenesis was promoted by inhibition of germination-associated domain 1-containing EVH1 and phosphatidylinositol 3-kinase regulatory subunit 2.(2)Further comparative analyses revealed that miR-216-5p,miR-145-5p,and miR-146b improved inflammatory responses by regulating related pathways.Combining these miRNAs may produce more significant effects;hypoxic preconditioning may be a preconditioning method to increase the efficacy of exosomal therapy.(3)There are currently no clinical trials applying mesenchymal stem cell-derived exosomes to spinal cord injury,which is related to the need to meet good manufacturing practices before they can be put into clinical use.Challenges such as the need for large-scale,high-volume cell production,the lack of an efficient and uniform method for isolating exosomes,and the need to pass a strict regulatory approval mechanism prior to clinical use have impeded the clinical entry.(4)miRNAs have great potential as exosomal contents of mesenchymal stem cells in the treatment of spinal cord injury,and their mechanism of action should be explored in depth as well as accelerated to the clinical trial stage in order to provide a new and effective method for the treatment of spinal cord injury.

BACKGROUND:Cellular autophagy maintains metabolism and in vivo homeostasis through the autophagosome-lysosome degradation pathway,which is closely related to the impaired cell death and functional recovery of distal neurons after spinal cord injury,and targeting cellular autophagy to promote the functional recovery of the spinal cord after spinal cord injury is a promising therapeutic direction.OBJECTIVE:To summarize the role of cellular autophagy in spinal cord injury,related regulatory mechanisms of cellular autophagy and therapeutic strategies.METHODS:PubMed and CNKI databases were searched with the search terms of"spinal cord injury,autophagy,regulatory mechanisms,autophagy pathway,therapeutic target"in English and Chinese,respectively.A total of 133 English and 4 Chinese articles were included for review.RESULTS AND CONCLUSION:(1)Autophagy,a form of programmed cell death,has been shown to play a crucial role in the progression and treatment of spinal cord injury.Most studies have shown that moderate activation or promotion of autophagy promotes neurological recovery by decreasing inflammatory responses and apoptosis.A few studies have reported that excessive activation of autophagy,on the contrary,impedes neurological recovery following spinal cord injury.(2)After spinal cord injury,PI3K/AKT/mTOR,MAPK,AMPK and p53 signaling pathways,and factors such as Beclin-1,ATG and LC3 regulate the initiation and development of cell autophagy in a positive or negative manner.(3)Promoting or inhibiting autophagy may be a promising therapeutic strategy to modulate the pathogenesis of traumatic spinal cord injury.And the drugs amlodipine,metformin,and minocycline,the Chinese medicines hawthorn leaf total flavonoids,betulinic acid,oxidized ginseng saponins,acupuncture,and extracellular vesicles of different cellular origins,exosomes and reactive oxygen species-responsive composite fibers as activators of cellular autophagy attenuate secondary injury in response to spinal cord injury by activating cellular autophagy,while the drugs insulin-like growth factor 1 and eladavone,Chinese medicine ginseng saponin,acupuncture,and hydrogel carrying basic fibroblast growth factor as inhibitors of cellular autophagy promote functional recovery after spinal cord injury by inhibiting excessive cellular autophagy.(4)The related regulators of cellular autophagy are interconnected,and the bi-directional effects of cellular autophagy on spinal cord injury make it necessary to further explore the dominant factors that regulate cellular autophagy.(5)Research on the use of autophagy as a therapeutic target for spinal cord injury is mostly carried out in animal models,but there are no autophagy-related drugs used in the clinical practice,and their safety and efficacy need to be further investigated in the clinical field.

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

Objective:To present an evaluation indicator system for access to cancer screening services.Methods:The evaluation indicator pool was constructed through a scoping review. The theoretical framework was constructed based on the multi-source indicators, and the qualitative expert consultation method was employed to form the initial version of the three-level evaluation indicator system. Delphi expert consultation method was conducted in two rounds to evaluate the relevance, importance, and availability of the proposed evaluation indicator system. The expert positive coefficient, authority coefficient, coordination degree of expert opinions, and concentration of expert opinions were subjected to analysis. Subsequently, the three-level evaluation indicator system for access to cancer screening services was adjusted and determined based on the boundary value method and the open opinions of experts. Finally, the combination weight method was employed to determine the weight.Results:The initial version of the indicator system comprised 3 primary (first-level) indicators, 11 secondary (second-level) indicators, and 46 tertiary (third-level) indicators. Delphi expert consultation was conducted for the initial version, and 17 experts ultimately completed it, exhibiting a positive coefficient of 100% and an authority coefficient of 0.87. In comparison to the initial round of consultation, Kendall's W coefficient ranges (0.15-0.43, all P<0.05) of relevance, importance, and availability scores for each tertiary indicator in the second round exhibited an improvement. The analysis of the importance dimension indicates that expert opinions are also more concentrated, as evidenced by an increase of 8.5% and 7.0% in the proportion of the tertiary indicators with an arithmetic mean above 8 and a full mark ratio above 0.5, respectively. The final evaluation indicator system comprises three primary indicators, with the weights of structure evaluation, process evaluation, and outcome evaluation being 0.338, 0.378, and 0.285, respectively. It also comprises 11 secondary indicators and 45 tertiary indicators. Conclusions:The evaluation indicator system developed in this article can be an effective evaluation tool for quantitative comparison of access to cancer screening services across different populations, cancer types, and before and after intervention. Furthermore, it is recommended that the system undergo continuous optimization concerning its application.

Objective:To present an evaluation indicator system for access to cancer screening services.Methods:The evaluation indicator pool was constructed through a scoping review. The theoretical framework was constructed based on the multi-source indicators, and the qualitative expert consultation method was employed to form the initial version of the three-level evaluation indicator system. Delphi expert consultation method was conducted in two rounds to evaluate the relevance, importance, and availability of the proposed evaluation indicator system. The expert positive coefficient, authority coefficient, coordination degree of expert opinions, and concentration of expert opinions were subjected to analysis. Subsequently, the three-level evaluation indicator system for access to cancer screening services was adjusted and determined based on the boundary value method and the open opinions of experts. Finally, the combination weight method was employed to determine the weight.Results:The initial version of the indicator system comprised 3 primary (first-level) indicators, 11 secondary (second-level) indicators, and 46 tertiary (third-level) indicators. Delphi expert consultation was conducted for the initial version, and 17 experts ultimately completed it, exhibiting a positive coefficient of 100% and an authority coefficient of 0.87. In comparison to the initial round of consultation, Kendall's W coefficient ranges (0.15-0.43, all P<0.05) of relevance, importance, and availability scores for each tertiary indicator in the second round exhibited an improvement. The analysis of the importance dimension indicates that expert opinions are also more concentrated, as evidenced by an increase of 8.5% and 7.0% in the proportion of the tertiary indicators with an arithmetic mean above 8 and a full mark ratio above 0.5, respectively. The final evaluation indicator system comprises three primary indicators, with the weights of structure evaluation, process evaluation, and outcome evaluation being 0.338, 0.378, and 0.285, respectively. It also comprises 11 secondary indicators and 45 tertiary indicators. Conclusions:The evaluation indicator system developed in this article can be an effective evaluation tool for quantitative comparison of access to cancer screening services across different populations, cancer types, and before and after intervention. Furthermore, it is recommended that the system undergo continuous optimization concerning its application.

BACKGROUND:Currently,spinal cord injury imposes a huge psychological and economic burden on patients and the National Health Service.The prevention,treatment,and rehabilitation of spinal cord injury have become an important topic in the field of medicine.Therefore,it is important to explore new effective therapeutic strategies based on an in-depth understanding of the underlying molecular mechanisms of spinal cord injury.OBJECTIVE:To review the research progress on the mechanism of action of mesenchymal stem cell-derived exosomes loaded with various miRNAs in improving the function of spinal cord injury,and based on the current status of clinical translation,to put forward a few thoughts and outlooks on their clinical use.METHODS:The first author searched CNKI and PubMed databases using"mesenchymal stem cells,exosomes,spinal cord injury,miRNA,pathophysiology,clinical translation,clinical trials,good manufacturing practice"as Chinese and English search terms.The types of literature included treatises and reviews,and the language types were English and Chinese.Finally,72 papers were screened and analyzed.RESULTS AND CONCLUSION:(1)This article outlines the biological properties of exosomes and the advantages that they can serve as good vectors for loading miRNAs.A variety of miRNAs mediated by mesenchymal stem cell-derived exosomes mainly promote the recovery of neuronal function by regulating the expression of nerve regeneration-associated proteins,repressing RAS homologous gene family member A,activating cyclophosphoadenosine effector-binding proteins,and signaling and transcriptional activation proteins 3,and regulating phosphoinositide and tensin homologue/programmed cell death factor 4 pathways.Inflammatory responses were improved by regulating endoplasmic reticulum-to-nucleus signaling 1,expression of interferon regulatory factor 5,Toll-like receptor 4/nuclear factor-kappa B pathway,and down-regulating related pro-inflammatory factors.Angiogenesis was promoted by inhibition of germination-associated domain 1-containing EVH1 and phosphatidylinositol 3-kinase regulatory subunit 2.(2)Further comparative analyses revealed that miR-216-5p,miR-145-5p,and miR-146b improved inflammatory responses by regulating related pathways.Combining these miRNAs may produce more significant effects;hypoxic preconditioning may be a preconditioning method to increase the efficacy of exosomal therapy.(3)There are currently no clinical trials applying mesenchymal stem cell-derived exosomes to spinal cord injury,which is related to the need to meet good manufacturing practices before they can be put into clinical use.Challenges such as the need for large-scale,high-volume cell production,the lack of an efficient and uniform method for isolating exosomes,and the need to pass a strict regulatory approval mechanism prior to clinical use have impeded the clinical entry.(4)miRNAs have great potential as exosomal contents of mesenchymal stem cells in the treatment of spinal cord injury,and their mechanism of action should be explored in depth as well as accelerated to the clinical trial stage in order to provide a new and effective method for the treatment of spinal cord injury.

BACKGROUND:Cellular autophagy maintains metabolism and in vivo homeostasis through the autophagosome-lysosome degradation pathway,which is closely related to the impaired cell death and functional recovery of distal neurons after spinal cord injury,and targeting cellular autophagy to promote the functional recovery of the spinal cord after spinal cord injury is a promising therapeutic direction.OBJECTIVE:To summarize the role of cellular autophagy in spinal cord injury,related regulatory mechanisms of cellular autophagy and therapeutic strategies.METHODS:PubMed and CNKI databases were searched with the search terms of"spinal cord injury,autophagy,regulatory mechanisms,autophagy pathway,therapeutic target"in English and Chinese,respectively.A total of 133 English and 4 Chinese articles were included for review.RESULTS AND CONCLUSION:(1)Autophagy,a form of programmed cell death,has been shown to play a crucial role in the progression and treatment of spinal cord injury.Most studies have shown that moderate activation or promotion of autophagy promotes neurological recovery by decreasing inflammatory responses and apoptosis.A few studies have reported that excessive activation of autophagy,on the contrary,impedes neurological recovery following spinal cord injury.(2)After spinal cord injury,PI3K/AKT/mTOR,MAPK,AMPK and p53 signaling pathways,and factors such as Beclin-1,ATG and LC3 regulate the initiation and development of cell autophagy in a positive or negative manner.(3)Promoting or inhibiting autophagy may be a promising therapeutic strategy to modulate the pathogenesis of traumatic spinal cord injury.And the drugs amlodipine,metformin,and minocycline,the Chinese medicines hawthorn leaf total flavonoids,betulinic acid,oxidized ginseng saponins,acupuncture,and extracellular vesicles of different cellular origins,exosomes and reactive oxygen species-responsive composite fibers as activators of cellular autophagy attenuate secondary injury in response to spinal cord injury by activating cellular autophagy,while the drugs insulin-like growth factor 1 and eladavone,Chinese medicine ginseng saponin,acupuncture,and hydrogel carrying basic fibroblast growth factor as inhibitors of cellular autophagy promote functional recovery after spinal cord injury by inhibiting excessive cellular autophagy.(4)The related regulators of cellular autophagy are interconnected,and the bi-directional effects of cellular autophagy on spinal cord injury make it necessary to further explore the dominant factors that regulate cellular autophagy.(5)Research on the use of autophagy as a therapeutic target for spinal cord injury is mostly carried out in animal models,but there are no autophagy-related drugs used in the clinical practice,and their safety and efficacy need to be further investigated in the clinical field.

BACKGROUND: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). METHODS: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. RESULTS: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. CONCLUSION Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child ; Humans ; Neurodevelopmental Disorders/epidemiology* ; Genetic Testing ; Phenotype ; Brain/pathology* ; Genetic Background ; SOX Transcription Factors/genetics*

Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.
Humans ; Neoplasms/pathology* ; Biomarkers ; Prognosis ; Oceans and Seas ; China/epidemiology*

Objective:To study the prevalence and distribution of adult thyroid diseases in urban and rural areas of Hebei Province.Methods:A multi-stage stratified cluster sampling method was used to select Renqiu City and Licun Town, Luquan City of Hebei Province as the urban and rural survey sites, respectively. Questionnaire survey, physical examination and thyroid B ultrasound examination were conducted on local permanent residents (≥ 5 years of residencies) over 18 years old. The fasting venous blood sample was collected to determine the serum thyroid function indicaters.Results:A total of 2 650 adults were surveyed, including 1 393 urban residents and 1 257 rural residents (1 357 males and 1 293 females). A total of 435 patients with thyroid diseases were diagnosed, the detection rate was 16.42%. There were seven thyroid diseases, including subclinical hypothyroidism (60.92%, 265/435), Hashimoto's thyroiditis (34.02%, 148/435), hypothyroidism (4.83%, 21/435), simple goiter (3.22%, 14/435), hyperthyroidism (2.53%, 11/435), subclinical hyperthyroidism (2.53%, 11/435), and thyroid cancer (1.84%, 8/435). The detection rates of thyroid diseases in urban and rural areas were 21.18% (295/1 393) and 11.14% (140/1 257), respectively. The detection rates of thyroid diseases in males and females were 11.42% (155/1 357) and 21.66% (280/1 293), respectively. The detection rates of thyroid diseases in 18-< 30, 30-< 40, 40-< 50, 50-< 60 and ≥60 years old were 13.46% (91/676), 14.81% (81/547), 15.42% (89/577), 20.94% (85/406) and 20.05% (89/444), respectively. There were statistically significant differences between different areas, gender and age groups (χ 2 = 48.54, 50.53, 14.68, P < 0.05). Conclusions:The detection rate of subclinical hypothyroidism in adults in urban and rural areas of Hebei Province is relatively high, followed by Hashimoto's thyroiditis. Attention should be paid to the screening, evaluation, and intervention of thyroid function among urban female populations.