Cognitive dysfunction often occurs in Alzheimer's disease, Parkinson's disease, cerebrovascular disease, or other neurodegenerative diseases, and can significantly impact the life quality of patients and create serious social, psychological, and economic burdens for individuals and their families. Numerous studies have confirmed that exercise can slow the decline in cognitive function through multiple pathways, in which fibronectin type III domain-containing protein 5 (FNDC5) plays an important role. However, the current research on the modulation of FNDC5 by exercise and its ability to improve hippocampal cognitive function lacks a systematic and comprehensive understanding. Therefore, this review focuses on the latest research progress regarding the role of exercise-induced FNDC5 in cognitive function, systematically reviews the positive effects of FNDC5 on cognitive function impairment caused by various factors, and clarifies the specific mechanisms by which exercise-induced FNDC5 improves cognitive function by inhibiting neuroinflammation and improving hippocampal neurogenesis and hippocampal synaptic plasticity. Based on the existing literature, we also identify the areas that require further research in this field. Overall, this review provides a theoretical basis for exercise-based prevention and improvement of cognitive function impairment.
Humans ; Cognition/physiology* ; Fibronectins/physiology* ; Exercise/physiology* ; Hippocampus/physiology* ; Cognitive Dysfunction/prevention & control* ; Neuronal Plasticity ; Animals ; Neurogenesis

Objective:To explore the effect of NOD-like receptor thermal protein 3 ( NLRP3) knockout in γ-aminobutyric acid (GABA)-ergic neurons in the hippocampal CA1 area on improving cognitive dysfunction in mice after traumatic brain injury (TBI). Methods:Forty-eight healthy male NLRP3 flox/flox mice weighing 25-28 g were randomly divided into 4 groups ( n=12): sham-operated+control virus group (SV group), sham-operated+ NLRP3 specific knockout group (SG group), TBI+control virus group (TV group), TBI+ NLRP3 specific knockout group (TG group). TBI in the TV and TG groups was established by free-fall method, while surgical procedures such as scalp incision and cranial window opening without impact were given to the SV and SG groups. Adenovirus was injected into the hippocampal CA1 area of SG and TG groups 21 d before TBI to induce NLRP3 specific knockout in GABA-ergic neurons in the hippocampal CA1 area; empty virus was injected into the CA1 area of SV and TV groups. Cognitive function was evaluated using novel object recognition test 30 and 31 d after TBI, and learning and memory functions were assessed using Morris water maze test 32-36 d after TBI. Field potentials in the hippocampal CA1 area were recorded during novel object recognition 31 d after TBI. After behavioral tests, these mice were sacrificed. Immunofluorescent staining was used to detect the fluorescent intensity of microtubule-associated protein2 (MAP2), glutamic acid decarboxylase 67 (GAD67), and postsynaptic density protein 95 (PSD95) in the hippocampal CA1 area, as well as percentage of pyroptosis-associated inflammatory factor interleukin-18 (IL-18)/GAD67 double-positive neurons in total GAD67 positive neurons. Results:Compared with the SV and SG groups, the TV and TG groups had decreased novel object recognition index, decreased number of platform crossings during the experimental period, increased escape latency on day 3 and day 4 of the training period in Morris water maze test, decreased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, decreased fluorescent intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, increased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Compared with the TV group, the TG group had increased novel object recognition index, increased number of platform crossings in Morris water maze test, decreased escape latency during the training period, increased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, increased fluorescence intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, decreased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Conclusion:Specific inhibition of NLRP3 expression in GABA-ergic neurons in the hippocampal CA1 area can improve cognitive dysfunction in mice after TBI, whose mechanism may be related to inhibited GABA-ergic neuronal pyroptosis in the hippocampal CA1 area.

Objective:To investigate and analysis of the occurrence and influencing factors of sarcopenia in elderly critically ill patients in the intensive care unit (ICU).Methods:A prospective cohort study was conducted. Elderly patients (aged ≥ 60 years) admitted to the ICU of Tianjin Medical University General Hospital from November 2023 to June 2024 were enrolled. Clinical records were collected, and conduct muscle mass and strength measurements, as well as upper arm circumference and calf circumference were measured. Appendicular skeletal muscle index (ASMI) of less than 7.0 kg/m 2 for males and less than 5.7 kg/m 2 for females was defined as reduced muscle mass, grip strength of less than 28 kg for males and less than 18 kg for females was defined as decreased muscle strength, patients meeting both low muscle mass and low muscle strength criteria were diagnosed with sarcopenia. According to the diagnostic criteria for sarcopenia, patients were divided into sarcopenia group and non-sarcopenia group. Multivariate Logistic regression analysis was applied to identify risk factors for sarcopenia in the elderly and to develop a predictive model for the occurrence of sarcopenia. The predictive value of various risk factors for sarcopenia in elderly critically ill patients were evaluated by receiver operator characteristic curve (ROC curve). The Kaplan-Meier curve for the length of ICU stay of two groups patients were drawn. Results:Finally, 540 elderly critically ill patients were included, including 43 patients with sarcopenia, and the incidence of sarcopenia was 8.0%. Univariate analysis showed that there were significantly differences in body mass index (BMI), number of hospitalizations in the past year, the length of ICU stay, ventilation mode, duration of mechanical ventilation, pre-admission exercise habits, nutritional support methods, upper arm circumference, calf circumference, and albumin infusion between the sarcopenia group and the non-sarcopenia group. Multivariate Logistic regression analysis showed that BMI [odds ratio ( OR) = 0.79, 95% confidence interval (95% CI) was 0.67-0.93, P = 0.004], calf circumference ( OR = 0.64, 95% CI was 0.54-0.76, P < 0.001), and duration of mechanical ventilation ( OR = 1.06, 95% CI was 1.01-1.12, P = 0.034) were associated with an increased risk of sarcopenia in elderly critically ill patients. The ROC curve results showed that the area under the curve (AUC) and 95% CI of BMI, calf circumference, and duration of mechanical ventilation for predicting sarcopenia in elderly critically ill patients were 0.828 (0.767-0.888), 0.889 (0.844-0.933), and 0.397 (0.299-0.496), respectively, with cut-off values of 22.95 kg/m 2, 28.25 cm, and 50.50 days, respectively. The Kaplan-Meier curve showed that the cumulative survival rate of patients with sarcopenia was significantly lower than that of the non-sarcopenia group (Log-Rank test: χ 2 = 5.619, P = 0.018). Conclusion:Lower BMI, smaller calf circumference, and longer duration of mechanical ventilation are associated with an increased risk of sarcopenia in critically ill elderly patients.

Objective:To construct machine learning-based delirium prediction models for ICU patients with multiple trauma and evaluate their prediction efficiency.Methods:A retrospective case-control study was conducted to analyze the clinical data of 417 ICU multiple trauma patients admitted to the First Affiliated Hospital of Zhengzhou University from July 2019 to June 2022, including 305 males and 112 females, aged 18-88 years [(47.8±15.7)years]. The score of acute physiology and chronic health status assessment II (APACHE II) was 0-50 points [(9.80±0.29)points]. The patients were randomly divided into training set ( n=291) and test set ( n=126) with a ratio of 7∶3. The demographic data, past history, treatment and laboratory results of the patients were collected. Lasso regression analysis was applied to screen variables that were significantly correlated to the incidence of delirium in the training set and the variables were then included into the machine learning models. Six machine learning methods including the random forest, gradient boosting tree, extreme gradient boosting, logistic regression, support vector machine and K nearest neighbor were used to construct the delirium prediction models for ICU multiple trauma patients. The accuracy, sensitivity, precision, F1 fraction and area under the curve (AUC) of the receiver′s operating characteristics (ROC) curve were calculated by using the data in the test set to evaluate the prediction efficiency of the models. Results:With regards to the six prediction models, namely random forests, gradient boosting tree, extreme gradient boosting, logistic regression, support vector machine and K nearest neighbor prediction models, the accuracy in the test set was 0.70, 0.68, 0.69, 0.73, 0.70 and 0.60 respectively; the sensitivity was 0.74, 0.80, 0.81, 0.86, 0.85 and 0.69 respectively; the precision was 0.72, 0.69, 0.70, 0.73, 0.71 and 0.65 respectively; the F1 fraction was 0.73, 0.74, 0.75, 0.79, 0.78 and 0.67 respectively; the AUC was 0.72, 0.73, 0.72, 0.80, 0.74 and 0.64 respectively. Among them, the logistic regression model had the best discriminability.Conclusion:Delirium prediction models for ICU patients with multiple trauma have been successfully constructed, among which the logistic regression model has the best prediction efficiency and can serve as an effective tool for early prediction and prevention of delirium in the clinical care of patients with multiple trauma.

Objective:To evaluate the effect of coronary microvascular dysfunction (CMD) on left atrial and ventricular function in patients with ischemia and non-obstructive coronary artery disease (INOCA) under the drug stress of regadenoson by speckle tracking imaging and left ventricular pressure-strain ring ultrasound technology.Methods:A total of 43 patients with INOCA who were admitted to the Department of Cardiology of the First Bethune Hospital of Jilin University from May 2022 to October 2023 were prospectively enrolled, and drug stress tests were performed. The coronary flow velocity reserve (CFVR) values were obtained by transthoracic Doppler echocardiography, and the INOCA patients with CFVR<2.0 were assigned to the CMD group ( n=24), and those with CFVR≥2.0 were assigned to the contrast group (CON group, n=19), and 20 healthy people without chest pain matched by clinical data were selected as the negative group (NEG group). The differences in general clinical data, routine echocardiography before and after stress, left atrial strain, and myocardial work parameters were compared between the groups. The correlation analysis of intra-group parameters was performed, and then the ROC curve was used to evaluate the diagnostic value of ultrasound parameters for INOCA. Results:Compared with the CON group and the NEG group, the ratio of early diastoic velocity E peak of mitral value orifice to the late diastoic velocity A peak(E/A) decreased and the ratio of early diastoic velocity E peak of mitral valve orifice to the early diastoic velocity e′ of the mitral valve annulus(E/e′) increased in the CMD group, and the differences were statistically signnificant (all P<0.05).There were statistically significant differences in left atrial strain parameters including left atrial strain reservoir (LASr), left atrial conduit strain (LAScd), left atrial contraction strain (LASct) between CON group and CMD group before and after stress (all P<0.05).However, there were no statistically significant differences between CON group and CMD group in myocardial work parameters including global longitudinal strain (GLS), peak strain dispersion (PSD), global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE) at rest (all P>0.05), and there were significant differences only after stress (all P<0.05). E/e′ was negatively correlated with LASr and LAScd in the CMD group and CON group ( rs=-0.36, r=-0.31; all P<0.05), GLS was positively correlated with GWI, GCW, GWE( r=0.81, 0.61, 0.37; all P<0.05). GLS was positively correlated with GWI, GCW and GWE at stress state( r=0.66, 0.51, 0.52; all P<0.05), and negatively correlated with GWW ( rs=-0.39, P<0.05). PSD was positively correlated with GWW ( rs=0.30, P<0.05), and negatively correlated with GWI, GCW and GWE ( r=-0.46, -0.40, -0.38; all P<0.05). Univariate regression analysis showed that left atrial strain and myocardial work had good predictive values for CMD, and the predictive values of rest LASr and stress GLS were higher, with AUC values of 0.927 and 0.882, respectively. Conclusions:In patients with INOCA and CMD, the left atrial strain capacity decreases at both rest and stress state, and the myocardial work capacity decreases only under the stress. The changes in parameters of left atrial strain and myocardial work provide new ultrasound parameters and predictors for clinical evaluation of CMD.

Objective:To investigate the correlation of CD8 positive tumor-infiltrating lymphocytes (CD8 + TIL) density and programmed-death receptor ligand 1 (PD-L1) expression in rectal cancer with clinicopathological characteristics and prognosis of patients after neoadjuvant chemoradiotherapy. Methods:The clinicopathological data of 166 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgery in the Beijing Chao-Yang Hospital, Capital Medical University from January 2015 to December 2018 were retrospectively analyzed. CD8 + TIL density and PD-L1 expression were detected by using immunohistochemistry. The correlation of CD8 + TIL density and PD-L1 expression with clinicopathological characteristics of patients after neoadjuvant chemoradiotherapy was analyzed. Kaplan-Meier method was used to analyze the disease-free survival (DFS) and Cox regression risk model was used to make univariate and multivariate analysis of the influencing factors for DFS. Results:Among 166 LARC patients, 81 cases (48.8%) had high density of CD8 + TIL, 85 cases (51.2%) had low density of CD8 + TIL; 63 cases (38.0%) had PD-L1 expression, and 103 cases (62.0%) had non-expression of CD8 + TIL. The expression rate of PD-L1 in CD8 + TIL high density group was higher than that in CD8 + TIL low density group [50.6% (41/81) vs. 25.9%(22/85), χ2 = 10.78, P < 0.001]. According to the density of CD8 + TIL and PD-L1 expression, immunophenotype was divided among 4 groups; the 3-year DFS rate of the CD8 + TIL high density /PD-L1 expression group was 87.1%, which was higher than that of the other groups (CD8 + TIL low density /PD-L1 expression group was 72.8%, CD8 + TIL high density /PD-L1 non-expression group was 67.0%, CD8 + TIL low density /PD-L1 non-expression group was 64.3%), and the difference was statistically significant ( P < 0.05). Univariate analysis showed that tumor differentiation degree, TNM stage, CD8 + TIL density, PD-L1 expression and CD8 + TIL density /PD-L1 expression were correlated with the DFS of patients (all P < 0.05). Multivariate analysis results showed that CD8 + TIL high density /PD-L1 expression was an independent protective factor for DFS ( HR = 0.049, 95% CI 0.005-0.497, P = 0.011), while TNM stage 3 was an independent risk factor for DFS ( HR = 2.752,95% CI 1.300-5.825, P = 0.008). Conclusions:In LARC after neoadjuvant therapy, CD8 + TIL density is positively correlated with the expression of PD-L1, and the high density of CD8 + TIL/PD-L1 expression is an independent influencing factor for good prognosis, suggesting that these patients may benefit from the immunotherapy.

Objective: To investigate loneliness and associated factors among adolescents with mixed anxiety and depressive disorder(MADD), and to provide reference for drawing up effective and targeted interventions. Methods: Using convenience sampling method, 265 adolescents with MADD in Daqing Third Hospital were selected from September 2020 to June 2021. General information questionnaire, Pittsburgh sleep quality index(PSQI), Resilience Scale for Chinese Adolescents(RSCA), Child and Adolescent Peer Relationship Scale and UCLA Loneliness Scale were used to investigate the status and influencing factors of loneliness among adolescents with MADD. Results: The average score of UCLA among 265 adolescents with MADD was (56.49±10.83). The results of univariate analysis showed that age, gender, burden of medical expenses, drinking behavior and parents migrant work had statistically significant differences in the UCLA scores. The results of Pearson correlation analysis showed that loneliness in MADD adolescents was negatively correlated with psychological resilience( F/t=57.65, -60.62, 21.92, 8.52, 16.22, P <0.01), and positively correlated with sleep quality and interpersonal distress( F/t=-0.69, 0.76, 0.50, P <0.01). The results of multiple stepwise regression analysis showed that phase of study, sex, burden of medical expenses, interpersonal distress, sleep quality and resilience were the influencing factors of loneliness among adolescents with MADD( B=0.11, 0.13, 0.09, 0.46, 0.10,-0.24, P <0.01). Conclusion Adolescents with MADD have moderate loneliness, which needs to be improved. Nursing staff should pay attention to the negative emotional experience such as loneliness among adolescents with MADD, and reduce their loneliness by improving sleep quality and resilience, reducing interpersonal distress.

Objective:To construct the access standard of nursing service project according to the feasibility, operational risk and difficulty of "Internet+ nursing service" home-based nursing project operation, so as to provides references for establishing the management method of "Internet+ nursing service".Methods:From March to August 2021, nursing service projects in the existing "Internet+ nursing service" platform were collected, and relevant literature and policies were referred to build an "Internet+ nursing service" project pool, including 64 nursing service items. The convenient sampling method was adopted to select 19 hospital nursing managers, community nursing managers, clinical nursing and nursing education experts in the field of "Internet+ nursing service" in Beijing from November 2021 to January 2022. Delphi method was adopted to conduct expert letter inquiry, and to evaluate the feasibility of home operation, difficulty score, risk score and access suggestions of nursing service projects.Results:The results showed that 61 nursing service items had the feasibility of home nursing operation. The nursing operations of intravenous injection, intravenous infusion and indwelling needle infusion were not suitable for home operation. Among them, the operators of the five items such as transfusion port maintenance, wound dressing change, peritoneal dialysis, ostomy nursing and disease rehabilitation guidance should be competent only after they passed the training and assessment of specialized nurses and had the operation experience of the project due to the difficulty of operation or the medium and high level of risk. Hair care and warm water bath were of low difficulty and low risk to be operated at home and they could be completed by trained caregivers or nursing workers. Operators of 54 items such as oral care, perineal scrubbing, rapid blood glucose monitoring, etc., should have nurse practicing certificate, nurse or above title, and have more than 5 years of related work experience.Conclusions:The access standard of "Internet+ nursing service" project established in this study is highly scientific and reliable, which can provide useful reference for establishing the access management method of "Internet+ nursing service".

Objective:To analyze the clinical characteristics of pertussis cases diagnosed by two pathological detection methods: bacterial culture and real-time polymerase chain reaction (RT-PCR), and to explore the applicable value of two pathological detection methods in the diagnosis of pertussis.Methods:Bilateral nasopharyngeal swabs and clinical information of 165 children suspected of pertussis were collected by Hebei Children′s Hospital from April 2019 to January 2020. The bacterial culture and RT-PCR for nasopharyngeal swab specimens were performed in all cases. Chi-square test was used to analyze the cases of pertussis diagnosed by the above two methods.Results:Based on clinical diagnosis, the sensitivity of bacterial culture and RT-PCR for the diagnosis of pertussis was 61.70% (58/94) and 86.17% (81/94), and the specificity was 92.96% (66/71) and 71.83% (51/71), respectively. The positive rate of RT-PCR in children of all ages, seasons and cough courses is higher than that of bacterial culture. Children with pertussis diagnosed by bacterial culture and RT-PCR were basically similar in age, season, and cough course distribution, with the most common cases ≤3 months old, a high incidence trend in summer and autumn, and the course of coughing in children was mostly within 15-21days. The positive rate of bacterial culture in the diagnosis of pertussis in children is affected by the age of the children, and there are statistical differences between children in different age groups (χ2= 11.929, P=0.036). The positive rate of bacterial culture was the highest in children with >3 years old (51.85% [14/27]), followed by children with ≤3 months old (48.72% [19/39]), and the lowest in children with >6-12 months old (15.00% [3/20]). Moreover, the positive rate of bacterial culture in the diagnosis of pertussis in children is also affected by the cough course of the children, and there are statistical differences between children in different cough course groups (χ2=9.841, P=0.020). The positive rate of bacterial culture was the highest in children with cough course 15-21 days (49.23% [32/65]), followed by 43.59% (17/39) in children with cough course 8-14 days, and the lowest in children with cough course of less than 7 days (22.86% [8/35]). Conclusions:Compared with RT-PCR, bacterial culture has lower sensitivity and higher specificity in the detection of pertussis. These two detection methods have their own advantages and limitations. Medical institutions at all levels should comprehensively analyze different laboratory detection methods. Only by combining the two methods can the diagnostic value and level be effectively improved.

OBJECTIVES: At present, the research on clear aligner of molar distalization mainly focuses on the upper jaw, while the research on mandibular molars is few.This study aims to evaluate the therapeutic effect of mandibular molars distalization with clear aligner via cone beam CT (CBCT) and Dolphin software. METHODS: Twenty cases of mandibular molars with clear aligner were included according to the inclusion and exclusion criteria. CBCT was taken before treatment (T0) and when the first molar was moved in place (T1). Dolphin software was used to measure the effectiveness of molar distalization. Three-dimensional changes in direction and the impact on the incisors and facial soft and hard tissues were evaluated. RESULTS: The effective rates of crown and root distalization of the second and first mandibular molars were 74%, 49%, and 71%, 47%, respectively. The second and first molars were both the distal buccal cusp with the largest distalization [(2.15 ± 0.91) mm and (1.85±1.09) mm], respectively, with significant difference between the T0 and T1 ( CONCLUSIONS Clear aligner can effectively move mandibular molars farther, the crown is more effective than the root, and it is tilted. The second mandibular molar is more effective than the first mandibular molar in its distant displacement and three-dimensional changes. Molar distalization causes minor changes in mandibular incisors and facial soft and hard tissues.
Cephalometry ; Maxilla ; Molar ; Orthodontic Appliances, Removable ; Tooth Movement Techniques