Probiotics have shown excellent application prospects in preventing and treating many diseases. However, their sensitivity to the harsh environment in vivo always leads to a massive loss of viability and insufficient therapeutic effect. Fortunately, modified probiotics have emerged and provide multiple possibilities for their use in various diseases. Modification not only endows probiotics with extra capacity to resist severe environments but also gives them exogenous characteristics, such as prolonged retention time and improved therapeutic effects. Modified probiotics could combine with other therapies, which has opened up new avenues to enhance the efficacy of probiotic-based therapy. In this review, we have summarized the current physicochemical and biological modification strategies of probiotics. In addition, the progress of research on probiotic-based combination therapy has also been extensively reviewed, which contributes to the enhanced delivery of probiotics or other active constituents and provides new ideas for disease treatment, bioimaging, and diagnosis.

Objective To investigate the differences of language abilities between children with developmental delay(DD)and those with autism spectrum disorder(ASD)aged 3-6 years,and to provide references for clinical differential diagnosis and subsequent rehabilitation therapy.Methods In this study,61 cases of DD children and 61 cases of ASD chil-dren were selected.The language ability of children was assessed using the"Children's Language Ability Assessment Stand-ards and Methods",which evaluated grammar,comprehension,expression and communication abilities.Results Children with DD showed better comprehension and social skills but weaker grammar and expressive abilities.Children with ASD generally had lower levels in all language areas.There was no significant difference in the average language ability or expres-sive ability the two groups(P＞0.05),but the language comprehension ability and communication ability of the ASD group were significantly lower than those of the DD group(P＜0.05).The grammar ability of the ASD group was higher than that of the DD group(P＜0.05).Conclusion The levels of different language areas of children with DD and ASD children are significantly different.Language ability tests can assist in the differential diagnosis of DD and ASD children,and provide reference for language rehabilitation training.

BACKGROUND:Currently,the pathogenesis of Parkinson's disease is not clear.Relevant studies have shown that α-synuclein and mitochondria are closely related to the pathogenesis of Parkinson's disease.It mainly involves oxidative stress,mitochondrial complex damage,calcium homeostasis,mitochondrial dynamics and mitochondrial quality control.OBJECTIVE:To review the association between α-synuclein and mitochondrial damage in Parkinson's disease.METHODS:The first author searched more than 50 documents from CNKI and WanFang databases from 2010 to 2024 using the keywords of"Parkinson's disease,mitochondrial damage and mechanism,α-synuclein"in Chinese as well as more than 750 documents from PubMed between 2010 and 2024 using the keywords of"Parkinson's disease,alpha-synuclein,mitochondria,oxidative stress,calcium homeostasis,mitophagy,mitochondrial dynamics,mitochondrial protein introduction"in English.Finally,70 documents were included for review.RESULTS AND CONCLUSION:Recent studies have confirmed the important role of mitochondrial dysfunction in the pathophysiology of Parkinson's disease,and the interaction between α-synuclein and mitochondria is a particularly significant factor in the pathogenesis of Parkinson's disease.The cascade of events that begin with naturally unfolded α-synuclein and eventually form mature fibril is collectively known as α-synuclein aggregation.The toxicity of aggregation accumulates in dopaminergic neurons and then disrupts mitochondrial function,thereby triggering Parkinson's disease.Therefore,the underlying mechanism of this bidirectional relationship between α-synuclein and mitochondrial dysfunction may provide new insights into the pathophysiology of Parkinson's disease.

Objective:To explore the correlations of sleep quality and architecture with heart rate variability (HRV) in patients with stenoses of vertebrobasilar artery system and internal carotid artery system.Methods:A retrospective study was performed; 72 patients with stenosis or occlusion of the head and neck arteries (not resulting in cerebral infarction) admitted to Department of Neurology, Second Affiliated Hospital of Zhengzhou University from June 2023 to June 2024 were chosen, including 33 patients with moderate-to-severe stenosis or occlusion of the vertebrobasilar system (VB group) and 39 patients with moderate-to-severe stenosis or occlusion of the internal carotid artery system (ICA group). Pittsburgh sleep quality index (PSQI) and polysomnography (PSG) were used to evaluate the sleep quality and architecture, respectively; and 24-hour ambulatory electrocardiogram was used to assess the HRV. Differences in PSQI score, PSG and HRV parameters between the two groups were compared; partial correlation analysis was used to explore the correlations of HRV parameters with PSQI scores and PSG parameters; multivariate linear regression was used to analyze the independent influencing factors for HRV.Results:(1) Compared with the ICA group, the VB group exhibited significantly higher PSQI scores, spontaneous arousal index (SAI), ratio of time of stage 1 non-rapid eye movement sleep/total sleep time (T N1/T t), and apnea-hypopnea index (AHI), while significantly lower ratio of time of rapid eye movement sleep/total sleep time (T R/T t), spindle wave density in stage 2 non-rapid eye movement sleep (N2), lowest blood oxygen saturation, standard deviation of normal to normal intervals (SDNN) of all sinus beats, low-frequency power (LF), and high-frequency power (HF, P<0.05). (2) In both VB group and ICA group, SDNN was negatively correlated with PSQI score ( r=-0.461, P=0.020; r=-0.378, P=0.036). In the VB group, SDNN was negatively correlated with T N1/T t ( r=-0.467, P=0.019) and SAI ( r=-0.551, P=0.004), and positively correlated with ratio of time of stage 3 non-rapid eye movement sleep/total sleep time (T N3/T t, r=0.686, P<0.001) and spindle wave density in N2 ( r=0.518, P=0.008); LF and HF were negatively correlated with SAI ( r=-0.481, P=0.015; r=-0.564, P=0.003). In the ICA group, HF was negatively correlated with spindle wave density in N2 ( r=-0.369; P=0.041). (3) Multivariate linear regression results indicated that T N3/T t (β=0.348, P=0.018), SAI (β=-0.330, P=0.018), and spindle wave density in N2 (β=0.286, P=0.013) were independent influencing factors for Ln_SDNN in patients with moderate-to-severe stenosis or occlusion of the vertebrobasilar system. Conclusion:Patients with stenosis or occlusion of the vertebrobasilar system exhibit poorer subjective sleep quality, increased light sleep, heightened arousal, and reduced sleep stability compared with those with stenosis or occlusion of the internal carotid artery system, which may be caused by the imbalance of autonomic nerve function.

Objective To evaluate the association between self-reported neighborhood walkability environments and mortality in China.Methods The Prospective Urban Rural Epidemiology study in China(PURE-China)recruited 47 931 participants aged 35-70 from 12 provinces in China between 2005 and 2009.Neighborhood environmental indicators were collected using the Neighborhood Environment Walkability Scale(NEWS)questionnaire,with higher scores indicating better walkable environments.The primary outcomes were all-cause mortality and cardiovascular mortality,using Cox fragile model to evaluate the association between community walkability and outcomes,as well as exploring mediating pathways.Results Of 35 490 participants included in this study,60%were female,with a mean(SD)age of 51.5(9.6)years.The median follow-up was 11.7 years.This study found an association between higher community walkability score and reduced risk of all-cause mortality,with the total score(HR=0.85;95%CI,0.80-0.89),land-use mix(HR=0.84;95%CI,0.79-0.88),and crime safety(HR=0.84;95%CI,0.80-0.89)showing the most significant associations.NEWS can affect long-term adverse outcomes through lifestyle.Conclusions In the Chinese population,favorable community walkability is associated with lower all-cause mortality risk,which may support policymakers to take actions to mitigate the adverse effects of poor community en-vironments on health.

Objective To investigate the differences of language abilities between children with developmental delay(DD)and those with autism spectrum disorder(ASD)aged 3-6 years,and to provide references for clinical differential diagnosis and subsequent rehabilitation therapy.Methods In this study,61 cases of DD children and 61 cases of ASD chil-dren were selected.The language ability of children was assessed using the"Children's Language Ability Assessment Stand-ards and Methods",which evaluated grammar,comprehension,expression and communication abilities.Results Children with DD showed better comprehension and social skills but weaker grammar and expressive abilities.Children with ASD generally had lower levels in all language areas.There was no significant difference in the average language ability or expres-sive ability the two groups(P＞0.05),but the language comprehension ability and communication ability of the ASD group were significantly lower than those of the DD group(P＜0.05).The grammar ability of the ASD group was higher than that of the DD group(P＜0.05).Conclusion The levels of different language areas of children with DD and ASD children are significantly different.Language ability tests can assist in the differential diagnosis of DD and ASD children,and provide reference for language rehabilitation training.

BACKGROUND:Currently,the pathogenesis of Parkinson's disease is not clear.Relevant studies have shown that α-synuclein and mitochondria are closely related to the pathogenesis of Parkinson's disease.It mainly involves oxidative stress,mitochondrial complex damage,calcium homeostasis,mitochondrial dynamics and mitochondrial quality control.OBJECTIVE:To review the association between α-synuclein and mitochondrial damage in Parkinson's disease.METHODS:The first author searched more than 50 documents from CNKI and WanFang databases from 2010 to 2024 using the keywords of"Parkinson's disease,mitochondrial damage and mechanism,α-synuclein"in Chinese as well as more than 750 documents from PubMed between 2010 and 2024 using the keywords of"Parkinson's disease,alpha-synuclein,mitochondria,oxidative stress,calcium homeostasis,mitophagy,mitochondrial dynamics,mitochondrial protein introduction"in English.Finally,70 documents were included for review.RESULTS AND CONCLUSION:Recent studies have confirmed the important role of mitochondrial dysfunction in the pathophysiology of Parkinson's disease,and the interaction between α-synuclein and mitochondria is a particularly significant factor in the pathogenesis of Parkinson's disease.The cascade of events that begin with naturally unfolded α-synuclein and eventually form mature fibril is collectively known as α-synuclein aggregation.The toxicity of aggregation accumulates in dopaminergic neurons and then disrupts mitochondrial function,thereby triggering Parkinson's disease.Therefore,the underlying mechanism of this bidirectional relationship between α-synuclein and mitochondrial dysfunction may provide new insights into the pathophysiology of Parkinson's disease.

Objective:To explore the correlations of sleep quality and architecture with heart rate variability (HRV) in patients with stenoses of vertebrobasilar artery system and internal carotid artery system.Methods:A retrospective study was performed; 72 patients with stenosis or occlusion of the head and neck arteries (not resulting in cerebral infarction) admitted to Department of Neurology, Second Affiliated Hospital of Zhengzhou University from June 2023 to June 2024 were chosen, including 33 patients with moderate-to-severe stenosis or occlusion of the vertebrobasilar system (VB group) and 39 patients with moderate-to-severe stenosis or occlusion of the internal carotid artery system (ICA group). Pittsburgh sleep quality index (PSQI) and polysomnography (PSG) were used to evaluate the sleep quality and architecture, respectively; and 24-hour ambulatory electrocardiogram was used to assess the HRV. Differences in PSQI score, PSG and HRV parameters between the two groups were compared; partial correlation analysis was used to explore the correlations of HRV parameters with PSQI scores and PSG parameters; multivariate linear regression was used to analyze the independent influencing factors for HRV.Results:(1) Compared with the ICA group, the VB group exhibited significantly higher PSQI scores, spontaneous arousal index (SAI), ratio of time of stage 1 non-rapid eye movement sleep/total sleep time (T N1/T t), and apnea-hypopnea index (AHI), while significantly lower ratio of time of rapid eye movement sleep/total sleep time (T R/T t), spindle wave density in stage 2 non-rapid eye movement sleep (N2), lowest blood oxygen saturation, standard deviation of normal to normal intervals (SDNN) of all sinus beats, low-frequency power (LF), and high-frequency power (HF, P<0.05). (2) In both VB group and ICA group, SDNN was negatively correlated with PSQI score ( r=-0.461, P=0.020; r=-0.378, P=0.036). In the VB group, SDNN was negatively correlated with T N1/T t ( r=-0.467, P=0.019) and SAI ( r=-0.551, P=0.004), and positively correlated with ratio of time of stage 3 non-rapid eye movement sleep/total sleep time (T N3/T t, r=0.686, P<0.001) and spindle wave density in N2 ( r=0.518, P=0.008); LF and HF were negatively correlated with SAI ( r=-0.481, P=0.015; r=-0.564, P=0.003). In the ICA group, HF was negatively correlated with spindle wave density in N2 ( r=-0.369; P=0.041). (3) Multivariate linear regression results indicated that T N3/T t (β=0.348, P=0.018), SAI (β=-0.330, P=0.018), and spindle wave density in N2 (β=0.286, P=0.013) were independent influencing factors for Ln_SDNN in patients with moderate-to-severe stenosis or occlusion of the vertebrobasilar system. Conclusion:Patients with stenosis or occlusion of the vertebrobasilar system exhibit poorer subjective sleep quality, increased light sleep, heightened arousal, and reduced sleep stability compared with those with stenosis or occlusion of the internal carotid artery system, which may be caused by the imbalance of autonomic nerve function.

Parkinson's disease (PD) is one of the hotspots in the research field of neurodegenerative diseases, and its pathogenesis is still controversial. Trace metal elements play an important role in normal growth and development of the human body. Metal ions can cross the blood-brain barrier and enter the brain, leading to α-synapnuclein aggregation, mitochondrial dysfunction, and degeneration of dopaminergic neurons, and then inducing the occurrence of PD. This article mainly reviewed the potential mechanisms of metal elements in PD, discussed the role of metabolic imbalance of common trace metals (copper, iron, manganese, and zinc) in PD, and put forward new insights into the treatment of PD.

Background: Dysregulation of intestinal flora is a key risk factor for colorectal cancer (CRC). In recent years, traditional Chinese medicine preparations and probiotics have been increasingly applied in the prevention of CRC. Aims: To investigate the preventive effect of Panax notoginseng saponins (PNS) combined with Bacillus subtilis on CRC. Methods: Thirty female BALB/c mice were randomly divided into normal control group (NC group), model group, PNS group, Bacillus subtilis group and PNS combined with Bacillus subtilis group (PaB group). CRC mice model was constructed by azoxymethane (AOM)/dextran sulfate sodium (DSS) method. During the experiment, the mice were weighed, and disease activity index (DAI) score was evaluated. The length of colorectum and tumor number were measured. Serum interleukin (IL) - 6 and IL - 10 contents were determined by ELISA. 16S rRNA sequencing was used to analyze the composition of intestinal flora. Results: Compared with model group, DAI score was significantly decreased (P<0.001), colorectal length was significantly increased (P<0.001), number of tumor was significantly decreased (P<0.001), tumor volume was significantly decreased (P<0.01), serum IL-6 content was significantly decreased (P<0.000 1), and serum IL-10 content was significantly increased in PaB group (P<0.000 1). The results of intestinal flora sequencing showed that Simpson index was significantly decreased in PaB group than in model group (P<0.05), Shannon index and Chao index were significantly increased (P<0.05), abundance of Bacteroidota was significantly increased (P<0.01), abundances of Firmicutes, Helicobacter and Oscillibacter were significantly decreased (P all <0.05), abundance of Lactococcus was significantly increased (P<0.05). Conclusions: The combination of PNS and Bacillus subtilis can effectively alleviate the occurrence of CRC caused by AOM/DSS, and its mechanism may be related to the improvement of composition of intestinal microbial community.