BACKGROUND:Exercise as a form of active rehabilitation can improve the dysfunction caused by peripheral nerve injury,and different exercise modalities target different lesion sites and recovery mechanisms. OBJECTIVE:To comprehensively analyze the application and mechanisms of different exercise modalities in functional recovery from peripheral nerve injury. METHODS:A computerized search was conducted in PubMed and CNKI databases for relevant literature published before January 2024.The search terms used were"peripheral nerve injury,spinal cord,exercise,cerebral cortex,muscle atrophy,mirror therapy,blood flow restriction training"in both English and Chinese.Finally,77 articles were included for review. RESULTS AND CONCLUSION:Peripheral nerve injury can cause systemic pathological changes such as skeletal muscle atrophy,corresponding spinal cord segmental lesions,and sensorimotor cortex remodeling.Aerobic exercise can improve dysfunction by enhancing the immune response,promoting glial cell polarization,and promoting the release of nerve growth factor.Blood flow restriction exercise can regulate the secretion of muscle growth factor,promote muscle growth and enhance muscle strength.Mirror movement has a good effect in activating the cerebral cortex and reducing cortical remodeling.Different exercise modalities have potential benefits in functional recovery after peripheral nerve injury;however,there are still some problems and challenges,such as the choice of exercise modalities,the control of exercise intensity and frequency,and the detailed analysis of mechanisms.

BACKGROUND:Virtual reality technology is a popular human-computer intelligent interaction technology in recent years,and has been widely used in leisure and entertainment,vocational training,medical rehabilitation and other fields. OBJECTIVE:To explore the potential of virtual reality technology combined with different therapies in functional recovery of patients with peripheral nerveinjury,summarize its mechanism of action,evaluate its application effects and prospects,and discuss its advantages and disadvantages,so as to provide new ideas and methods for rehabilitation practice after peripheral nerve injury.METHODS:The relevant literature of CNKI and PubMed database from inception to May 2024 was retrieved by computer. Chinese and English search terms were "peripheral nerves injury,virtual reality,endoplasmic reticulum stress,muscle atrophy,cerebral cortex,mirror therapy,tendon vibration,treadmill training." Finally,68 articles were included for analysis.RESULTS AND CONCLUSION:(1) Virtual reality technology,as a new auxiliary means,simulates the real environment to provide immersive multi-sensory experiences for patients,greatly enriching the dimensions of rehabilitation training and significantly accelerating the recovery process of patients with peripheral nerve injury. Its mechanism of action is to promote cortical plasticity through multi-sensory stimulation,invading the dormant areas adjacent to the cortex,and these areas responding to other inputs or generating new muscle activation,thereby promoting functional recovery. (2) Virtual reality technology has been widely combined with traditional therapies,showcasing its unique advantages. When combined with mirror therapy,the advantage of virtual reality is breaking the limitation of body position and advancing the time point of rehabilitation intervention. When combined with tendon vibration,virtual reality technology enhances the dual stimulation of visual and tactile perception to enhance the illusion of movement,significantly improving the perception and motor ability of patients,but also raises the issue of increased perception of limb weight. In running machine training,virtual reality technology further leverages its advantages by simulating real-life environments through multi-sensory stimulation to enhance balance and walking function,but problems such as motion sickness still exist. (3) Therefore,in actual applications,due to the fact that virtual reality combined with mirror therapy and tendon vibration will enhance the illusion of movement for patients,it is more suitable for early stages of rehabilitation. Meanwhile,the combination of virtual reality and treadmill training is suitable for the later stage of rehabilitation,helping patients to better return to their daily lives. (4) Although virtual reality technology has shown great potential in peripheral nerve injury rehabilitation,there are still some problems and challenges,such as motion sickness,the design and application of virtual reality rehabilitation games,and ethical considerations. Future research should focus on solving these problems to further promote the development of virtual reality technology in the field of rehabilitation.

Objective:We aimed to analyze the spatio-temporal trend of breast cancer incidence and mortality in Shandong Province from 2012 to 2023 and predict the development trend from 2024 to 2030.Methods:Data on the incidence and mortality of breast cancer in Shandong Province from 2012 to 2023 were obtained from the Shandong Cancer Registry. The incidence, age-specific incidence, mortality, and age-specific mortality in different years, as well as in urban and rural areas, were calculated, and the rates were standardized based on the age composition of the Chinese standard population in 2000. The average annual percent change (AAPC) rate was calculated using Joinpoint 4.8.0.1 software. The global and local spatial autocorrelation analysis were performed using GeoDa 1.12 software. The Bayesian age-period-cohort model was used to predict the trend of breast cancer incidence and mortality from 2024 to 2030.Results:From 2012 to 2023, the breast cancer age-standardized incidence rate (ASIR) showed an increasing trend. The ASIR increased from 30.48/100 000 in 2012 to 39.94/100 000 in 2023 (AAPC=2.59%, P<0.001). The ASIR of urban and rural females also showed an upward trend. Additionally, the ASIR in rural areas (AAPC=3.33%, P<0.001) increased more than that in urban areas (AAPC=1.83%, P=0.002). The incidence peak of breast cancer mainly concentrated in population aged 45-64 years, and with the increase of years, the incidence peak gradually moved forward. The age-standardized mortality rate (ASMR) showed a downward trend. The ASMR decreased from 6.89/100 000 in 2012 to 4.93/100 000 in 2023 (AAPC=-3.12%, P<0.001). The ASMR of urban and rural females also showed a downward trend (urban: AAPC=-3.56%, P=0.007; rural: AAPC=-2.72%, P<0.001). The spatial analysis showed that from 2015 to 2023, the clustering areas of breast cancer incidence and mortality in Shandong had changed significantly. In 2015, the "High-high clusters" of ASIR mainly included Wendeng District in Weihai City, Dongying District, Kenli District, Lijin County, Guangrao County in Dongying City, Tianqiao District, Shizhong District in Jinan City; In 2023, the "High-high clusters" mainly included Jiaxiang County, Liangshan County, Jinxiang County, Wenshang County, Rencheng District in Jining City, Hedong District in Linyi City, Guangrao County in Dongying City. In 2015, the "High-high clusters" of ASMR only included Wenshang County in Jining City. In 2023, the "High-high clusters" mainly included Laizhou County in Yantai City, Junan County and Yishui County in Linyi City, Gaotang County in Liaocheng City, Dongping County and Ningyang County in Taian City. The Bayesian age-period-cohort model predicted that the ASIR trend of breast cancer in Shandong tended to be smooth (AAPC=0.33%, P=0.001). However, the ASMR remained decreasing (AAPC=-4.68%, P<0.001). Conclusions:The breast cancer incidence in Shandong showed an increasing trend, and it is expected to be smooth by 2030. However, the mortality showed a continuous downward trend. The incidence peak was mainly in the population aged 45-64 years, with obvious regional differences. Targeted prevention and control measures should be taken for high-risk groups and areas in Shandong Province.

Objective:To understand spatial aggregation of lung cancer mortality and its changing trends over the past fifty years in different counties and districts of Shandong Province from 1970 to 2021.Methods:The mortality data of lung cancer were obtained from the death registration system of Shandong province and three retrospective surveys of death cause. The mortality rate and age-standardized mortality rate were used to describe the changing trend of lung cancer in different years, and the contribution value of population factors and non-population factors in lung cancer mortality change was calculated by the mortality differential decomposition method. GeoDa 1.20 and ArcGIS 10.8 software were used for spatial autocorrelation analysis and visualization map display.Results:The crude mortality rate of lung cancer in Shandong Province showed a significant upward trend from 1970 to 2021, rising from 7.22 per 100 000 in 1970-1974 to 62.73 per 100 000 in 2020-2021, with an increase of 7.69 times. Meanwhile, the standardized mortality rate of lung cancer exhibited a trend of increasing first and then decreasing. The differential analysis of lung cancer mortality in different years revealed that changes in crude mortality rates were the result of the combined effects of demographic and non-demographic factors. The proportion of population factors (aging population) leading to an increase in lung cancer mortality rate rose from 2.12% in 1990-1992 to 40.20% in 2020-2021. From a spatial distribution perspective, there were significant regional differences in lung cancer mortality rates among counties (cities, districts) in Shandong Province across different eras. Compared to the period of 1970-1974, the lung cancer mortality rates in all counties and districts in 2020-2021 showed a considerable increase, and there were noticeable changes in the areas of high-high and low-low clustering of lung cancer mortality rates across different eras.Conclusion:There have been significant temporal and spatial changes in the mortality rate of lung cancer in Shandong Province from 1970 to 2021. The crude mortality rate has shown an upward trend, while the standardized mortality rate increases first and then decreases. The concentration of lung cancer mortality rates in counties and districts has also undergone significant changes.

Objective:To describe the distribution characteristics and trends of mortality and spatial aggregation of esophageal cancer in Shandong Province from 1970 to 2021.Methods:The mortality data of esophageal cancer were obtained from the death registration system of Shandong Province and three national all-cause mortality retrospective surveys. The crude mortality rate (CMR) and age-standardized mortality rate (ASMR, the Segi′s world standard population) were used to describe the mortality of esophageal cancer. Mortality differential decomposition was applied to quantify the contributions of demographic and non-demographic factors. The death levels of esophageal cancer in different counties (cities and districts) in Shandong Province from 1970 to 1974 and 2020 to 2021 were visualized by the ArcGIS 10.8 software, and global and local autocorrelation analyses were conducted by using the GeoDa 1.12 software.Results:The CMR of esophageal cancer in Shandong Province increased first and then decreased from 1970 to 2021. The CMR of esophageal cancer decreased from 17.59/100 000 in the period of 1970—1974 to 14.32/100 000 in the period of 2020—2021. The ASMR of esophageal cancer decreased from 20.04/100 000 in the period of 1970—1974 to 6.53/100 000 in the period of 2020—2021. Compared with the period of 1970—1974, both demographic and non-demographic factors contributed to the increase in esophageal cancer mortality rate from 1990 to 1992. However, demographic factors continued to contribute to the increase in esophageal cancer mortality rate from 2004 to 2005, 2011 to 2013, and 2020 to 2021, while non-demographic factors contributed to the continuous decrease in esophageal cancer mortality rate. The global autocorrelation analysis results showed that the Moran′s I index of ASMR of esophageal cancer in each county (city, district) of Shandong Province from 1970 to 1974 and from 2020 to 2021 were 0.67 and 0.57, respectively. Local autocorrelation analysis showed that there were 19 and 13 areas of high-high clustering of esophageal cancer in the periods of 1970—1974 and 2020—2021, respectively, with 12 overlapping counties (cities, districts). Conclusion:From 1970 to 2021, the CMR of esophageal cancer increases first and then decreases, while the ASMR of esophageal cancer gradually decreases in Shandong Province. The distribution of esophageal cancer mortality has significant spatial aggregation and changes over time.

Objective:To explore the spatial clustering of the mortality rate of cervical cancer in different counties (cities, districts) in Shandong Province from 1970 to 2021 and its 50-year changing trend, so as to provide basis for the implementation and evaluation of prevention and control strategies and programs such as cervical cancer screening, early diagnosis and treatment, human papilloma virus (HPV) vaccination, etc.Methods:The mortality data of cervical cancer were obtained from the death registration system of Shandong Province and the data of three retrospective surveys of death causes. The mortality rate and age-standardized mortality rate (using the population composition of China in 1964) are used to describe the changing trend of cervical cancer in different years. The contribution values of population factors and non-population factors in cervical cancer mortality change are calculated by mortality differential decomposition method. ArcGIS 10.8 software is used for spatial distribution and spatial autocorrelation analysis.Results:From 1970 to 2021, the crude mortality rate and age standardized mortality rate of cervical cancer in Shandong Province showed a trend of first rapid decline and then slow increase. The crude mortality rate and standardized mortality rate of female cervical cancer in Shandong Province in 1970-1974 were the highest, reaching 17.22/10 5 and 13.17/10 5, respectively. In 2004-2005, it dropped to the lowest levels of 1.50/10 5 and 0.83/10 5. Subsequently, it slowly rose to 4.12/10 5 and 1.56/10 5 in 2020-2021. The differential analysis of cervical cancer mortality in different years found that the change of cervical cancer mortality was caused by the combined action of population factors and non-population factors. Among them, demographic factors (aging population) led to the increase of cervical cancer mortality, but non-demographic factors (early diagnosis and treatment, HPV infection level, medical technology level, etc) lead to the decrease of cervical cancer mortality. Compared with 1970-1974, with the passage of time, the absolute values of the contribution values of population factors and non-population factors showed an increasing trend, while the contribution of non-population factors was greater than that of population factors, which led to the decline of cervical cancer mortality. From the perspective of spatial distribution, there were great regional differences in the mortality rate of cervical cancer in different counties of Shandong Province. In 2020-2021, the mortality rate of cervical cancer in all counties decreased to a great extent compared with that in 1970-1974, and the high-high and low-low concentration areas of cervical cancer mortality in different years changed obviously. The high-aggregation areas of the cervical cancer mortality rate in Shandong Province from 2020 to 2021 were mainly distributed in some counties and districts of Linyi City, Zaozhuang City, and Heze City in the southwest. Conclusions:There are significant temporal and spatial changes in the mortality rate of cervical cancer in Shandong Province from 1970 to 2021. According to these trends and their geographical and spatial clustering, prevention and control strategies of cervical cancer in different regions should be further formulated and evaluated.

BACKGROUND:Peripheral nerve injuries can cause severe functional disabilities in patients,and long-segment nerve defects often fail to regenerate spontaneously.In recent years,tissue engineering techniques have gradually been applied to the repair of long-segment nerve injuries,yet research hotspots and development trends are unclear.OBJECTIVE:To analyze the research hotspots and trends in the field of peripheral nerve tissue engineering over the past 20 years using bibliometric software.METHODS:CiteSpace 6.2R6 software was employed to conduct highly cited analysis and keyword analysis on peripheral nerve tissue engineering literature published from 2004 to 2024 in the Web of Science and China National Knowledge Infrastructure(CNKI)databases.The keyword analysis encompasses keyword co-occurrence analysis,keyword clustering analysis,keyword timeline analysis,and keyword emergence analysis.RESULTS AND CONCLUSION:A total of 2 961 articles from the Web of Science database and 1171 articles from the CNKI database were included.The number of publications in the Web of Science database showed fluctuations but exhibited an overall increasing trend year by year,while the publication volume in the CNKI database remained relatively stable annually.Most of the top ten most cited articles in the Web of Science database were review articles.The results of the keyword analysis from Web of Science and CNKI databases indicated that the most studied nerve tissue engineering materials over the past 20 years include silk fibroin,collagen,chitosan,polycaprolactone,polylactic acid,and graphene.The biochemical cues investigated in these materials include olfactory ensheathing cells,Schwann cells,stem cells,and nerve growth factors.The most commonly employed external physical factor is electrical stimulation applied to the materials.Among various tissue engineering techniques,electrospinning technology and 3D printing technology have been the most extensively researched.

BACKGROUND:Cervical disc degeneration is a common degenerative disease,and inflammatory proteins play an important role in cervical disc degeneration,but the specific mechanisms involved remain to be thoroughly investigated.OBJECTIVE:Using the Mendelian randomization method to assess the potential causal relationship between 91 inflammatory proteins and cervical disc degeneration.METHODS:Genome-wide association analysis statistics for 91 inflammatory proteins(from GCST90274758 to GCST90274848)were obtained from the Genome-Wide Association Analysis Catalog of publicly available genome-wide association analysis data and genome-wide association analysis data for cervical disc degeneration from the Finngen database(finngen_R10_M13_CERVICDISCV).Inverse variance weighting,MR-Egger regression,weighted median,weighted modeling,and simple modeling were used to investigate the causal relationship between inflammatory proteins and cervical disc degeneration.Sensitivity analyses were performed to test whether the results of the Mendelian randomization analysis were reliable,and then the inverse Mendelian randomization analysis was performed in the same way.RESULTS AND CONCLUSION:The results of the forward analysis showed that a total of six inflammatory proteins were significantly and causally associated with cervical disc degeneration,of which glial cell lineage-derived neurotrophic factor(odds ratio(OR)=1.095,95%confidence interval(CI):1.012-1.184,P=0.023),interleukin 4(OR=1.094,95%CI:1.002-1.194,P=0.045)and monocyte chemotactic protein-1 levels(OR=1.062,95%CI:1.001-1.127,P=0.048)showed a direct positive causal association with the risk of cervical disc degeneration;interleukin 17C(OR=0.906,95%CI:0.839-0.979,P=0.013),interleukin 18(OR=0.924,95%CI:0.866-0.986,P=0.017)and interleukin 2 levels(OR=0.894,95%CI:0.821-0.973,P=0.010)showed a direct negative causal association with the risk of cervical disc degeneration.The results of the inverse analysis showed that when cervical disc degeneration was used as exposure data,there was no significant causal relationship with any of the 91 inflammatory proteins.The results of the sensitivity analysis showed that the Cochran's Q test for the two-way Mendelian randomization,the MR-Egger regression method,and the MR-PRESSO results had P values greater than 0.05,indicating that there was no significant heterogeneity or multiplicity in the analysis of the causal effect between inflammatory proteins and cervical disc degeneration.To conclude,there may be a relatively significant potential causal relationship between glial cell line-derived neurotrophic factor,interleukin 4,monocyte chemotactic protein-1,interleukin 17C levels,interleukin 18,and interleukin 2 levels and cervical disc degeneration,which provides valuable clues for research on the potential mechanisms of cervical disc degeneration as well as early prevention and drug treatment of cervical disc degeneration.

BACKGROUND:Electrical stimulation is an effective treatment plan for peripheral nerve injuries,but different frequencies of electrical stimulation have different mechanisms and applications for promoting peripheral nerve recovery.OBJECTIVE:To systematically sort out and summarize the roles and applications of different frequencies of electrical stimulation in the treatment of peripheral nerve injuries,and to deeply analyze the advantages and disadvantages of various methods in order to find the most beneficial treatment strategy for patients'nerve recovery.METHODS:Computer-based searches were conducted in the China National Knowledge Infrastructure(CNKI)and PubMed databases from the inception of the databases to May 2024.The search terms included"peripheral nerve injury,electrical stimulation,low frequency electrical stimulation,medium frequency electrical stimulation,high frequency electrical stimulation,TENS,interfering electricity,short wave,ultrashort wave,frequency"in both English and Chinese.Ultimately,74 relevant documents were included for analysis.RESULTS AND CONCLUSION:Peripheral nerve injury,a common clinical disease,can cause sensory and motor dysfunction in patients.Low-frequency electrical stimulation can promote cell proliferation and accelerate the expression of nerve growth factor within the cell after electrical stimulation,promote macrophage recruitment and infiltration,accelerate the clearance of myelin debris,and promote myelin regeneration of damaged axons.Medium-frequency electrical stimulation can act on deeper tissues and is better for relieving neuropathic pain.High-frequency electrical stimulation can promote the proliferation of Schwann cells and macrophages,inhibit inflammatory factors,and rapidly recruit cells to the site of nerve injury,accelerating the speed of nerve repair.Different frequencies of electrical stimulation have their own advantages in promoting the recovery of peripheral nerve injuries,but there are still some issues,such as differences in the site of electrical stimulation and the treatment plans for various disease types.

BACKGROUND:Electromyographic biofeedback therapy has demonstrated unique advantages of non-invasive,real-time feedback,personalized treatment and promotion of neuroplasticity,and can promote the recovery of motor function in patients with spinal cord injury.OBJECTIVE:To review the current application status and therapeutic effects of electromyographic biofeedback combined with exercise therapy,robotic exoskeletons,and virtual reality technology in the recovery of motor function after spinal cord injury.METHODS:Relevant literature was retrieved from CNKI and PubMed databases up to May 2024.The search terms included"spinal cord injury,EMG biofeedback,physical therapy,robotic exoskeleton,VR,motor function,exercise"in both English and Chinese.Finally,71 articles were included for review.RESULTS AND CONCLUSION:Mechanisms by which electromyographic biofeedback therapy promotes spinal cord injury rehabilitation include promoting neural plasticity changes,strengthening neuromuscular connections and improving movement patterns.Electromyographic biofeedback,as an emerging tool for treating spinal cord injury,is often used in conjunction with other therapeutic methods,including exercise therapy,robotic exoskeletons,and VR,to promote the recovery of motor function after spinal cord injury.The effectiveness of combination therapy has been significantly improved.However,there are still some problems and challenges,such as the lack of detailed analysis of the mechanism,the lack of large-scale trials that provide strong evidence for combined efficacy,and the limited adaptability of the technology.Future research can focus on these aspects:to improve the personalization and accuracy of electromyographic biofeedback;to develop new rehabilitation equipment and expand the application areas of electromyographic biofeedback combined with more advanced technologies or engineering equipment;to apply electromyographic biofeedback to gait training systems,respiratory training systems,and limb-linkage rehabilitation systems,so as to improve the accuracy of the feedback and the effect of personalized treatment plans.At the same time,the ease of use and comfort of the equipment will be improved.