Objective:To re-evaluate the effectiveness of exercise interventions in patients with amyotrophic lateral sclerosis (ALS) by conducting a systematic review and provide insights for the implementation and continuous improvement of exercise intervention strategies.Methods:A comprehensive search was conducted across databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, Web of Science, CINAHL, Campbell Collaboration, and the Joanna Briggs Institute Evidence-Based Health Care Center Database. The search covered literature from the inception of the databases until December 19, 2023. Two researchers trained in evidence-based nursing independently screened the literature. The methodological quality of the included studies was assessed using the AMSTAR 2 tool, and the quality of evidence was graded using the GRADE system.Results:Eight systematic reviews were included. The AMSTAR 2 evaluation revealed one review of moderate quality, six of low quality, and one of very low quality. GRADE assessment of 33 outcome indicators showed that one piece of evidence was of moderate quality, 24 were of low quality, and eight were of very low quality.Conclusions:Exercise interventions may improve overall functional outcomes in ALS patients without exacerbating fatigue. However, due to the limitations in the quantity and quality of the included studies, further large-scale, high-quality randomized controlled trials are needed to verify the effects of exercise interventions in ALS patients.

Graph-theory-based pathway analysis is a commonly used method for pathway searching in genome-scale metabolic networks. However, such searching often results in many pathways biologically infeasible due to the presence of currency metabolites (e.g. H⁺, H₂O, CO₂, ATP etc.). Several methods have been proposed to address the problem but up to now there is no well-recognized methods for processing the currency metabolites. In this study, we proposed a new method based on the function of currency metabolites for transferring of functional groups such as phosphate. We processed most currency metabolites as pairs rather than individual metabolites, and ranked the pairs based on their importance in transferring functional groups, in order to make sure at least one main metabolite link exists for any reaction. The whole process can be done automatically by programming. Comparison with existing approaches indicates that more biologically infeasible pathways were removed by our method and the calculated pathways were more reliable, which may facilitate the graph-theory-based pathway design and visualization.
Genome ; Metabolic Networks and Pathways

Objective: To explore the prevalence of ametropia in primary and middle school students in Kaiyuan, Honghe Prefecture, Yunnan Province, to provide a scientific reference for local prevention and control of juvenile myopia. Methods: In September 2021, 38 534 students from 76 primary and secondary schools in Kaiyuan, Honghe Prefecture, Yunnan Province, were selected. The students underwent vision inspection and computer optometry examination. Chi square test was used to compare the prevalence of myopia across gender grade, ethnic group and residence. Results: The prevalence of myopia in primary and secondary schools students was 40.0%, the prevalence of hyperopia was 17.7 %, and that of astigmatism was 21.2%. The prevalence of poor vision was 50.7%, and the total rate of wearing glasses was 17.2 %. The prevalence of myopia among girls (45.7%) was higher than that among boys (34.5%)( χ 2=520.68). The prevalence of myopia among students was higher in urban areas (50.1%) than rural areas (28.4%)( χ 2=1 882.13). The prevalence of myopia in grades 1-9 increased with school grade( χ 2 trend =7 151.41). Significant differences were observed in the prevalence of myopia( χ 2= 1 299.26 ), hyperopia ( χ 2=164.13) and astigmatism ( χ 2=1 091.37) among ethnic groups( P <0.01). Conclusion The prevalence of myopia and astigmatism in primary and middle school students in Kaiyuan, increases with school grade, and the prevalence of myopia varies among ethnic groups. For juvenile myopia prevention and control, attention should be paid to the effects of urban and rural differences, gender differences, and ethnic differences, in a scientific, effective and comprehensive manner.

Objective:To evaluate the 8 th edition of AJCC/UICC staging system for stage Ⅲ nasopharyngeal carcinoma (NPC) by the survival analysis. All patients were treated with intensity-modulated radiotherapy (IMRT). Methods:Among 1351 treatment-na?ve NPC patients who received radiotherapy/chemoradiotherapy in our hospital from December 2008 to October 2014, 742 and 784 cases were classified as clinical stage Ⅲ based on the criteria of the 7 th and 8 th edition of AJCC/UICC staging systems, respectively. These patients were classified into three subgroups according to the 7 th and 8 th edition of AJCC/UICC staging systems: T 3N 0-1 as G 1( n=226, n=245), T 1-2N 2 as G 2( n=180, n=187) and T 3N 2 as G 3( n=336, n=352). The 5-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and local-regional recurrence-free survival (LRRFS) were analyzed with Kaplan- Meier method. The differences among different groups were evaluated by log-rank test. Results:There were 93.6% patients evaluated by the 8 th AJCC/UICC staging system remained the same cohort with those by the 7 th AJCC/UICC staging system. The 5-year OS, PFS, DMFS and LRRFS of the 8 th and 7 th staging systems were 84.8% and 85.4%, 76.2% and 77.0%, 80.4% and 81.3%, 89.8% and 90.6%, respectively (all P>0.05). The OS, PFS or DMFS significantly differed among three subgroups classified by the 8 th staging system (all P<0.001). In addition, statistical significance was observed between G 1 and G 2, and between G 1 and G 3(both P<0.05), whereas no statistical significance was noted between G 2 and G 3( P=0.183, 0.310, 0.248). Conclusions:The distribution features and clinical endpoints of clinical stage Ⅲ defined by the 8 th AJCC/UICC staging system are similar to those defined by the 7 th AJCC/UICC staging system. The distribution of survival risk significantly differs among different subgroups. N 2 plays a major role in assessing the survival risk of patients with stage Ⅲ NPC. In the era of IMRT plus chemotherapy, the effect of local tumors on clinical prognosis has been diminished. The 8 th AJCC/UICC staging system remains to be further improved.

Objective: To observe the neuro-protective effect of Levocarnitine on severe hand, foot and mouth disease (HFMD) after enterovirus 71(EV71) infection, to preliminarily explore the possible mechanism preliminarily. Methods: One hundred and thirty-two children with EV71 infection and HFMD combined with serum S100 protein and neuronspecific enolase (NSE) abnormalities who were admitted to Children′s Hospital Affiliated to Zhengzhou University from March 2015 to July 2016 were enrolled in the study.They were divided into the routine group and the Levocarnitine group by the random number grouping method.The routine group (66 cases, including 32 males and 34 females, median age of 2 years and 3 months) was given symptomatic treatment such as antiviral therapy while the Levo-carnitine group (66 cases, including 36 males and 30 females, median age of 2 years and 5 months) was treated with Levocarnitine for neuroprotection on the basis of routine group.Forty healthy children (23 males and 17 females, median age of 2 years and 6 months) who were examined at the Children′s Hospital Affiliated to Zhengzhou University during the same period were selected as the healthy control group.The levels of S100, NSE, soluble apoptosis-related factors (sFas), soluble apoptosis-related factor ligands (sFasL), malondialdehyde (MDA), superoxide dismutase (SOD) in serum were compared between the healthy control group and children with HFMD.The levels of above-mentioned indexes in cerebrospinal fluid and serum, efficacy-related indicators such as duration of fever, white blood cell count on the 3^rd day of treatment, time to remission of nervous system symptoms, time of disease progression and critical conversion rate were compared between 2 groups of children with HFMD.The correlation between sFas, sFasL, MDA, SOD and S100, NSE was performed Results: (1) The levels of S100 [(0.38±0.16) μg/L vs. (0.06±0.23) μg/L], NSE [(43.70±8.80) μg/L vs. 10.10±3.60) μg/L], sFas [(6.61±1.86) μg/L vs. (3.88±1.22) μg/L], sFasL[(101.40±20.7) μg/L vs. (54.4±13.3) μg/L] and MDA[(11.98±2.54) nmol/L vs. (4.08±1.45) nmol/L] in serum of HFMD group were significantly higher than those of the healthy control group (t=-12.245, -22.895, -8.273, -12.803, -17.960, all P<0.05), while the SOD level [(57.10±10.40) kU/L vs. (70.3±14.4) kU/L] was significantly lower (t=5.457, P<0.05). (2) With the extension of treatment time for HFMD children in the two groups, S100 and NSE in cerebrospinal fluid, S100, NSE, sFas, sFasL and MDA in serum decreased, while SOD level increased.On the 3^rd and 7^th day after treatment, S100 (t₃=3.491, t₇=14.434), NSE (t₃=2.920, t₇=23.490) in cerebrospinal fluid, S100 (t₃=5.277, t₇=3.614), NSE (t₃=4.652, t₇=10.525), sFas (t₃=6.399, t₇=7.514), sFasL (t₃=11.155, t₇=8.804) and MDA (t₃=6.348, t₇=7.499) in serum of Levocarnitine group were significantly lower than those of routine group (all P<0.05), while SOD (t₃=3.162, t₇=-3.529) was significantly higher than that of routine group (P<0.05). (3) The relief time of neurological symptom in levocarnitine group was significantly shorter than that in the routine group [(1.23±0.65) d vs. (1.84±0.47) d], and WBC on the 3^rd day after treatment [(9.14±2.93)×10⁹/L vs. (7.12±2.58)×10⁹/L] and the progression time of the disease [(29.74±7.85) h vs. (17.36±8.73) h] were significantly better than the those in the routine group (t=-6.178, 4.204, 8.567, all P<0.05). The critical conversion rates of Levocarnitine group and the routine group were 7.58% and 18.18%, respectively, and the difference in critical conversion rate was not statistically significant (χ²=2.316, P>0.05). (4)There was a positive correlation between S100 and sFas, sFasL, MDA in children with HFMD (r=0.373, 0.735, 0.334, P<0.05). NSE was positively correlated with sFas and sFasL (r=0.479, 0.601, all P<0.05), while SOD and S100 were negatively correlated with NSE (r=-0.425, -0.460, all P<0.05). Conclusions Levocarnitine has good curative effect on severe HFMD in children infected by enterovirus EV71, which can effectively protect the cranial nerves.The mechanism may be related to scavenging oxygen free radicals and blocking nerve cell apoptosis.

Objective: To investigate the value of abnormal expression of HLA-DR on peripheral blood monocytes in evaluating the immune function status, clinical prognosis and severity of patients with hand, foot and mouth disease (HFMD). Methods: From June 2017 to October 2018, 100 cases of mild HFMD, 80 cases of severe HFMD, 32 cases of critical HFMD and 40 healthy children (control group) were recruited in this study. The patients were divided into two groups, lower DR group (DR-L, HLA-DR expression<30%) and normal DR group (DR-N, HLA-DR expression>30%) according to the HLA-DR expression on monocytes. Flow cytometry was used to detect the CD14⁺ monocytes expressing HLA-DR and the absolute count of lymphocyte subsets. Immunoturbidimetry was used to detect the levels of IgG, IgM and IgA in plasma samples. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of IFN-γ and IL-10 in plasma samples. Pediatric critical illness score (PCIS) and the pediatric risk of mortality Ⅲ (PRISM Ⅲ) were used to estimate the severity of HFMD. Results: ① There were significant differences in HLA-DR expression on monocytes among children with mild, severe and critical HFMD (F=47.102, P<0.05). Patients with critical HFMD had the lowest HLA-DR expression (P<0.05). ② The numbers of CD14⁺ monocytes, CD3⁺ T cells, CD4⁺ T cells, CD8⁺ T cells, B cells and NK cells in peripheral blood of the DR-L group were significantly lower than those of the DR-N group and the normal group, especially in patients with severe or critical HFMD (P<0.05). ③ There was no significant difference in the level of IgG, IgA or IgM among the DR-L, DR-N and control groups (P>0.05). ④ Compared with the DR-N group, the DR-L group showed decreased IFN-γ level and increased IL-10 level in plasma (P<0.05). The ratio of IFN-γ/IL-10 of the DR-L group was lower than that of the DR-N group and control group (P<0.05). HLA-DR expression was negatively correlated with the concentration of IL-10 in plasma (r=-0.704, P<0.05), and positively correlated with the IFN-γ/IL-10 ratio (r=0.773, P<0.05). ⑤ Compared with the DR-N group, the DR-L group showed lower PCIS and higher PRISM Ⅲ. HLA-DR expression was positively correlated with PCIS (r=0.715, P=0.00) and negatively correlated with PRISM Ⅲ (r=-0.610, P=0.00). ⑥ The incidence of pulmonary edema, pulmonary hemorrhage and cardiopulmonary failure and the mortality of HFMD patients in the DR-L group were significantly higher than those in the DR-N group (P<0.05). Conclusions Patients with severe or critical HFMD had cellular immune dysfunction and abnormal HLA-DR expression on CD14⁺ monocytes. Assessing the expression of HLA-DR on monocytes could be used to evaluate the cellular immunity of patients with severe or critical HFMD. Lower expression of HLA-DR on CD14⁺ monocytes might be associated with severe HFMD and poor prognosis.

Objective To evaluate the diagnostic value of dermoscopy and reflectance confocal microscopy (RCM) alone or in combination for melanocytic nevus.Methods A total of 37 patients with clinically diagnosed melanocytic nevus were collected.Skin lesions were firstly examined by dermoscopy and RCM,then were resected to be subjected to histopathological examination for final diagnosis.The imaging features of melanocytic nevus were summarized.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of different skin imaging techniques were calculated,and the consistency was analyzed between skin imaging techniques and histopathological examination.Results Based on the dermoscopic and RCM findings,2 kinds of nevus cells with different morphological features were observed in the dermis of intradermal nevus.One kind of nevus cells was characterized by a nonfusional,highly-refractive round structure in the papillary dermis under RCM,and by a brown or light brown homogenous pattern under dermoscopy,which was observed in 5 skin lesions.The other kind of nevus cells appeared as irregular,highly-refractive cell clumps in the papillary dermis under RCM,and by a cobblestone or globular pattern under dermoscopy,which was observed in 31 skin lesions.For the diagnosis of melanocytic nevus,the sensitivity,specificity,accuracy,positive predictive value and negative predictive value of RCM combined with dermoscopy were 91.7％,87.5％,90.9％,97.1％ and 70％ respectively,those of RCM were 86.1％,75％,84％,93.9％ and 54.5％ respectively,and those of dermoscopy were 77.8％,87.5％,75％,96.3％ and 41.2％ respectively.All the diagnostic indices of RCM combined with dermoscopy were higher than those of RCM or dermoscopy alone,except that the specificity was equal to that of dermoscopy alone.RCM showed higher sensitivity,accuracy and negative predictive value,but lower specificity and positive predictive value compared with dermoscopy.There were no significant differences in the diagnostic yield in melanocytic nevus between RCM combined with dermoscopy or RCM alone and histopathological examination (x2 =0.25,0.57,P =0.63,0.45,Kappa value =0.72,0.53,respectively).However,a significant difference in the diagnostic yield in melanocytic nevus was observed between dermoscopy and histopathological examination (x2 =5.81,P =0.012).Conclusion RCM combined with dermoscopy shows higher diagnostic accuracy for melanocytic nevus compared with RCM or dermoscopy alone.

Objective To investigate the effects of alveolar epithelial cells (AEC) on bronchopulmonary dysplasis(BPD) induced by hyperoxia in newborn rats.Methods The model of BPD induced by hyperoxia in neonatal rats was established.HE staining was used to observe the alveolar septum and alveoli development.The expression of the specific surfactant protein C (SPC) on type Ⅱ alveolar epithelial cells (AEC Ⅱ) and the expression of specific aquaporin 5 (aquaporin5 AQP5) on type Ⅰ alveolar epithelial cells (type Ⅰ alveolar epithelialcells,AECⅠ) were measured by immunohistochemistry.Results There was no significant difference of AQP5 between experimental groups and control group at 1 d,but significantly lower expression of AQP5 could be seen in experimental group1 on day3 (P ＜ 0.05).And then,the AQP5 level of lung tissue of newborn rats at 5,7,14d after experiment in groupl was significantly lower than that of in air control group (P ＜ 0.05).The expression of SPC protein had no significant difference between experimental groups and control group at 1 d,but the SPC level of lung tissue of newborn rats at 3,7,14d after experiment in group1 was significant lower than that of in air control group (P ＜ 0.05).Conclusion Hyperoxia exposure leads to the expression of SP-C and AQP5 decreased,which may be key points for the development of BPD.AECⅡ may play an important role in the repairation of alveolar epithelial cells in neonatal rats with BPD induced by hyperoxia.

Objective To describe a rhesus monkey model of temporal lobe epilepsy (TLE) established via repetitive unilateral intra-amygdala kainic acid (KA) injection and provide experimental basis for epileptogenic network and related research. Methods Eight male adult rhesus monkeys were randomly divided into KA injection group (n=6) and saline injection group (n=2). Brain stereotaxic technique, micro catheter implantation into the right amygdaloid nucleus, subcutaneous bladder connection, and continuous video-EEG monitoring were performed, and KA or saline injection into their right amygdala was achieved. Interictal epileptic discharges (IEDs), ictal discharges and behavioural performance between the two groups were compared right after injection and within 6 months of first discharge. Results Typical IEDs were recorded in the 6 monkeys from KA injection group after 2-4 times of KA injection, with focal spike waves discharges at the right temple area as manifestation; ictal discharges were recorded in 4 monkeys, with discharge patterns of discharges from the right temple area to the whole brain as manifestation, and during epileptic attack, these 4 monkeys suddenly stopped and dumbfounded without obvious limb seizures. Monkeys from the saline injection group showed no obvious abnormal behaviors. Conclusion Through a modified protocol of unilateral repetitive intra-amygdala KA injection, a rhesus monkey model with high similarity of behavioral and brain electrical features to TLE is developed.

Objective To evaluate the diagnostic yield and safety of transbronchial lung biopsy (TBLB) under virtual bronchoscopic navigation (Direct Path), endobronchial ultrasonography with a guide sheath (GS) and rapid on-site evaluation using an ultrathin bronchoscopy (UNRE) for bacterial infection located in the peripheral third of the lung field. Methods Ninety-seven patients with bacterial infection, which located in the peripheral third of the lung field on CT images, were ran-domly assigned to UNRE (n=49) or non-UNRE (NUNRE, n=48) groups, who were treated in General Hospital of Tianjin Medical University between April 1, 2014 and March 31, 2015. The TBLB guided by UNRE was performed in two groups. The diagnostic yield, safety and complication rate were compared between two groups. Moreover, the differences of autofluo-rescence intensity of alveolar macrophage in alveolar lavage fluid were compared between two groups of patients. Results The diagnostic yield was significantly higher in UNRE group than that of NUNRE group (81.6% vs 56.2%, χ2=7.313, P <0.01). The diagnostic yield was higher in UNRE group with bronchus sign compared to that of NUNRE. All patients had a mild bleeding at the time of biopsy. There were no hemoptysis, pneumothorax or other serious complications. The autofluores-cence intensity of alveolar macrophage was different in different levels of infection in patients. Conclusion The procedure of UNRE has higher diagnostic rate and fewer complications. The careful selection of suitable cases can further improve the diagnostic accuracy. The autofluorescence intensity of alveolar macrophage in alveolar lavage fluid indicates the severity of infection in patients.