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This study aimed to investigate the relationship between venous blood parameters and respiratory functions in patients with amyotrophic lateral sclerosis (ALS) and develop a model to predict respiratory impairment for individual patients with ALS. A total of 416 ALS patients were included in the study, and various hematologic and biochemical laboratory parameters as well as demographic and clinical factors were collected and compared. A multivariable logistic regression model was constructed to assess the association between FVC and venous blood biomarkers and clinical factors. The results showed that along with onset age, bulbar-onset, disease duration, BMI, eosinophil count (EO#), basophil count (BASO#), creatinine (CREA), uric acid (URCI) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL/HDL) ratio were associated with reduced FVC. The area under the ROC curve is 0.735 for the test set and 0.721 for the validation set. The study also developed a relatively acceptable model for predicting respiratory impairment in ALS patients. These findings suggest that EO#, BASO#, CREA, URIC and LDL/HDL ratio can be useful in assessing FVC in ALS and can be easily accessible, accurate, and low-cost parameters.

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Objectives: Patients with essential tremor (ET) syndrome have more prevalent and more serious gait and balance impairments than healthy controls. In this cross-sectional study, we explored whether balance impairments are associated with falls as well as more pronounced non-motor symptoms in patients with ET syndrome. Methods: We assessed the tandem gait (TG) test, as well as falls or near-falls that occurred over the previous year. Non-motor symptoms-including cognitive deficits, psychological and sleep disorders-were evaluated. In univariate analyses, statistical significance was corrected for multiple comparisons using the Benjamini-Hochberg method. Multiple logistic regression was utilized to evaluate the risk factors of poor TG performance in patients with ET syndrome. Results: A total of 358 patients with ET syndrome were divided into the abnormal TG (a-TG) and normal TG (n-TG) groups based on their performances in the TG test. We revealed that 47.2% of patients with ET syndrome had a-TG. The patients with a-TG were older, were more likely female, and were more likely present with cranial tremors and falls or near-falls (all adjusted P < 0.01). The patients with a-TG had significantly lower Mini-Mental Status Examination scores, as well as significantly higher Hamilton Depression/Anxiety Rating Scale and Pittsburgh Sleep Quality Index scores. Multiple logistic regression analysis demonstrated that female sex (OR 1.913, 95% CI: 1.180-3.103), age (OR 1.050, 95% CI: 1.032-1.068), cranial tremor scores (OR 1.299, 95% CI: 1.095-1.542), a history of falls or near-falls (OR 2.952, 95% CI: 1.558-5.594), and the presence of depressive symptoms (OR 1.679, 95% CI: 1.034-2.726) were associated with the occurrence of a-TG in patients with ET syndrome. Conclusion: TG abnormalities may be a predictor of fall risk in patients with ET syndrome and are associated with non-motor symptoms, especially depression.

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Mutations in PINK1 and Parkin are a major cause of Parkinson's disease (PD) pathogenesis. In addition, PINK1 and Parkin are two mitochondrial proteins that jointly contribute to mitochondrial homeostasis via mitophagy. Mitochondrial dysfunction is the most significant mechanism underlying PD pathogenesis. Thus, understanding the regulatory mechanism of PINK1 and Parkin expression is beneficial to the treatment of PD. In this study, we found that miR-421 expression was upregulated in mice treated with MPTP, as well as in SH-SY5Y cells treated with methyl-4-phenylpyridine (MPP+). Inhibition of miR-421 alleviated neurodegeneration in MPTP-treated mice and promoted mitophagy in MPP+-treated SH-SY5Y cells. Bioinformatics software predicted that Pink1 is a downstream target protein of miR-421. In addition, miR-421-induced Pink1 and Parkin inhibition negatively modulates mitophagy in MPP+-treated SH-SY5Y cells. In addition, our study confirmed that Pink1/Parkin is responsible for miR-421-regulated cell mitophagy. Overall, this study revealed that miR-421 regulates nerve cell mitophagy through the Pink1/Parkin pathway.

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Although peripheral venous blood biomarkers are related to respiratory function in Amyotrophic lateral sclerosis (ALS) patients, there are still few prediction models that predict pulmonary function. This study aimed to investigate the venous blood biomarkers associated with respiratory function in patients with ALS from southwest China and to create prediction models based on those clinical biomarkers using logistic regression. A total of 319 patients with ALS from the retrospective cohort and 97 patients with ALS from the prospective cohort were enrolled in this study. A multivariable prediction model for the correlation between peak expiratory flow (PEF) and hematologic, biochemical laboratory parameters, and clinical factors in patients with ALS was created. Along with female patients, bulbar-onset, lower body mass index (BMI), later age of onset, lower level of creatinine, uric acid, triglyceride, and a higher level of high-density lipoprotein cholesterol (HDL_C) were related to reduced PEF. The area under the receiver operating characteristics (ROC) curve is.802 for the test set and.775 for the validation set. The study constructed a multivariable prediction model for PEF in patients with ALS. The results can be helpful for clinical practice to predict respiratory impairment.

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OBJECTIVES: Fatigue was considered as a common symptom in amyotrophic lateral sclerosis (ALS). Previous studies about the impact of fatigue on Quality of Life (QoL) in patients with ALS were limited and inconsistent. Besides, a systematic investigation of fatigue in Chinese patients with ALS was lacking. Therefore, this study aimed to comprehensively evaluate the frequency and associated factors of fatigue and impact on QoL in Chinese patients with ALS. PARTICIPANTS AND METHODS: Probable and definitive patients with ALS and age- and gender-matched healthy controls (HCs) were consecutively recruited. The frequency of fatigue between both the groups was determined by the Fatigue Severity Scale (FSS). Disease severity, sleep quality, sleepiness, anxiety, depression, and QoL were evaluated in patients with ALS by the ALS Functional Rating Scale-revised (ALSFRS-R) and the ALS Severity Scale (ALSSS), the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Hamilton Anxiety Rating Scale (HARS), the Hamilton Depression Rating Scale (HDRS), and the McGill Quality of Life Questionnaire (MQOL). Then, clinical characteristics of patients with ALS with fatigue were compared with those without fatigue. Lastly, associated factors of fatigue and impact on QoL in Chinese patients with ALS were assessed. RESULTS: A total of 175 patients with ALS and 175 HCs were included. Fatigue was significantly more frequent in patients with ALS than in controls (32.6 vs. 17.7%, p = 0.001). Patients with ALS with fatigue scored lower on the ALSFRS-R, the ALSSS [lower extremity (LE) + upper extremity (UE)], the total ALSSS, higher in the HARS, HDRS, PSQI, ESS scores, and a poorer QoL. Daytime dysfunction and the ALSSS (LE + UE) score were associated with a higher risk of fatigue. The ALSSS (LE + UE), the FSS, age, the HARS, and the HDRS score were significantly associated with various aspects of QoL. CONCLUSION: This study has described fatigue in Chinese patients with ALS and finding daytime dysfunction and the lower ALSSS (LE + UE) were associated with a higher risk of fatigue. Also, we identified an inverse relationship of fatigue intensity with the psychological domain of QoL.

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Background: Pain was considered a common and neglected symptom in amyotrophic lateral sclerosis (ALS) and had a substantial impact on the quality of life of ALS patients and their caregivers. However, pain in ALS was mainly evaluated from the perspective of nociceptive pain; only three studies referred to neuropathic pain in ALS, and there has been yet no study considering the neuropathic pain characteristics in ALS patients from China. Therefore, the purpose of our study was to determine characteristics of pain (nociceptive pain and neuropathic pain) by three different types of questionnaires. The correlation between pain and clinical parameters in ALS patients was also evaluated. Methods: Patients were eligible if they fulfilled the criteria of probable and definitive ALS according to the revised El Escorial criteria. Healthy normal controls, matched to ALS patients by age and gender, were recruited. Pain was evaluated by numerical pain rating scale (NRS), Brief Pain Inventory (BPI), and Douleur Neuropathique-4 (DN4) in ALS patients and controls. Physical status of ALS patients was evaluated with ALS Functional Rating Scale-revised (ALSFRS-R). Results: 65 patients with sporadic ALS and 100 healthy normal controls in Southwestern China were included. Pain in the preceding week was more frequently reported by patients with ALS (30, 46.2%) than controls (36, 36%) (p = 0.193). DN4 score⩾4 was found in three ALS patients and one control (p = 0.480). Ten ALS patients (33.3%) and twenty-eight controls (77.8%) (p < 0.001) received therapy for pain. ALS patients with a DN4 score ≥ 4 had a longer disease duration and a higher PSI and PII score than ALS cases reporting nociceptive pain (p = 0.041, 0.048, and 0.027, respectively). Pain mainly interfered with ALS patients' mood, enjoyment of life, and the Pain Interference Index (PII) score. Conclusions: Our findings indicated that pain in our ALS cohorts was insufficiently treated and interfered with patients' mood and enjoyment of life. Most notably, we found that ALS patients with a DN4 score⩾4 may have a longer disease duration and a higher PSI and PII score than ALS patients reporting nociceptive pain, which has never been reported, strongly deserving further validation.

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OBJECTIVE: To analyze the comparation of national early warning score (NEWS), rapid emergency medicine score (REMS) and acute physiology and chronic health evaluation II (APACHE II) score in predicting prognosis of critically ill patients in emergency department (ED). METHODS: A retrospective study was conducted. Critically ill patients, aged > 16 years, hospitalized > 24 hours, and admitted to the ED of Nanhua Hospital Affiliated to South China University from January 2016 to June 2017 were enrolled. NEWS, REMS and APACHE II score were calculated based on the worst value of each index within 24 hours after emergency admission. The primary endpoint was 28-day mortality. The relationship between the three scoring systems and the prognosis of patients was analyzed. The predictive value of three scoring systems for the prognosis of critically ill patients in ED was analyzed by receiver operating characteristic curve (ROC). RESULTS: A total of 119 emergency severe patients were enrolled in the study, and the 28-day mortality was 21.0%. The scores of NEWS, REMS and APACHE II in the death group were significantly higher than those in the survival group (NEWS score: 9.40±3.19 vs. 5.72±2.35, REMS score: 12.64±4.46 vs. 7.97±3.28, APACHE II score: 26.64±6.92 vs. 16.19±5.48, all P < 0.01). With the increase of NEWS, REMS and APACHE II score, the 28-day mortality of patients gradually increased [28-day mortality of NEWS < 5, 5-6, ≥ 7 was 3.03% (1/34), 13.33% (4/34), 64.25% (20/51); 28-day mortality of REMS < 12, 12-16, ≥ 17 was 10.99% (10/91), 50.00% (11/22), 66.67% (4/6); 28-day mortality of APACHE II < 15, 15-24, ≥ 25 was 2.33% (1/43), 15.09% (8/59), 69.57% (16/23), respectively, all P < 0.01]. The ROC curve analysis showed that the areas under the ROC curve (AUC) of NEWS, REMS and APACHE II score for predicting the prognosis of emergency critically ill patients were 0.830 [95% confidence interval (95%CI) = 0.737-0.923], 0.782 (95%CI = 0.671-0.892) and 0.878 (95%CI = 0.800-0.956), respectively (all P = 0.000), and the accuracy of prediction was 57.4%, 48.6%, 65.4%, respectively. CONCLUSIONS: The scores of NEWS, REMS and APACHE II were useful in predicting prognosis of critically ill patients, with the highest accuracy of APACHE II forecast, followed by NEWS, and the lowest of REMS. After comprehensive consideration of cost-effectiveness, NEWS is more reliable in ED.

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BACKGROUND: Metabolic syndrome (MetS) was a risk factor for cardiovascular diseases, yet the prevalence of MetS among nonagenarians and centenarians was rarely reported. Here we investigated the prevalence of MetS and its components among nonagenarians and centenarians in our Zhuang population from Bama, Guangxi Zhuang Autonomous Region, China. METHOD: In Bama area, there registered 881 individuals who lived more than 90 years old in 269,800 local residents and our study involved 307 long-lived participants and 486 local younger (35-68 years) persons, as controls. MetS was defined according to the revised National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATPIII) criteria. RESULTS: The overall prevalence estimates of MetS among longevity group were 28.0% based on NCEP ATPIII criteria. The most common metabolic component was elevated blood pressure (61.1%), followed by raised fasting glucose (39.1%) and low high-density lipoprotein cholesterol (low HDL-C) (28.0%). The prevalence of MetS and abdominal obesity in women (33.6% and 22.1% respectively) was higher than that of men (19.8% and 3.7% respectively) (Prange < .001-0.019). Compared with controls, long-lived individuals were more likely to have two or more metabolic abnormalities (Prange < 0.001), and less likely to have zero or one metabolic abnormality (Prange < 0.001-0.020). CONCLUSION: This study showed substantiality the prevalence and clinical profile of MetS in longevity population in Guangxi Zhuang Autonomous Region, China.

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BACKGROUND: Previous association studies examining the relationship between the APOC1 polymorphism and susceptibility to Alzheimer's disease (AD) have shown conflicting results, and it is not clear if an APOC1 variant acts as a genetic risk factor in AD etiology across multiple populations. METHODS: To confirm the risk association between APOC1 and AD, we designed a case-control study and also performed a meta-analysis of previously published studies. RESULTS: Seventy-nine patients with AD and one hundred fifty-six unrelated controls were included in case-control study. No association was found between the variation of APOC1 and AD in stage 1 of our study. However, our meta-analysis pooled a total of 2092 AD patients and 2685 controls. The APOC1 rs11568822 polymorphism was associated with increased AD risk in Caucasians, Asians and Caribbean Hispanics, but not in African Americans. APOE ε4 carriers harboring the APOC1 insertion allele, were more prevalent in AD patients than controls (χ(2) = 119.46, OR = 2.79, 95% CI = 2.31-3.36, P<0.01). CONCLUSIONS: The APOC1 insertion allele, in combination with APOE ε4, likely serves as a potential risk factor for developing AD.

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Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) share several clinical and neuropathologic features, and studies suggest that several gene mutations and polymorphisms are involved in both conditions. Matrix metalloproteinase-9 (MMP-9) is implicated in the pathogenesis of PD and ALS, and the C(-1562)T polymorphism in the MMP-9 gene leads to higher promoter activity. We therefore investigated whether this polymorphism predisposes to both PD and sporadic ALS (sALS). Samples from 351 subjects with PD and 351 healthy controls from two major cities in China were compared, while samples from 226 subjects with sALS were compared to the same number of controls from three centers in China. A possible association between the C(-1562)T polymorphism in the MMP-9 gene and PD or sALS was assessed by restriction fragment length polymorphism (RFLP) analysis. Our results show a significant association between the C(-1562)T polymorphism in the MMP-9 gene and risk of PD (odds ratio = 2.268, 95% CI 1.506-3.416, p<0.001) as well as risk of sALS (odds ratio = 2.163, 95% CI 1.233-3.796, p = 0.006), supporting a role for MMP-9 polymorphism in the risk for PD and sALS.

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The gene encoding RhoA guanine nucleotide exchange factor 10(ARHGEF10) has been reported to be a risk factor for atherothrombotic stroke (AS) in Japanese. The single-nucleotide polymorphism (SNP) rs4376531 in intron 16 on ARHGEF10 is associated with AS and may play a role in the disease pathology. In order to explore the nature of this association in greater detail and in a new ethnic group, we carried out a case-control study to determine whether the rs4376531 polymorphism in ARHGEF10 is a risk factor of AS in Han Chinese people. This study was carried out to assay the frequency of genotypes and alleles of SNP rs4376531 in ARHGEF10 in patients with ischemic stroke and healthy controls using the polymerase chain reaction and the restriction fragment length polymorphism (PCR-RFLP) technique. A total of 383 individuals with AS in West China Hospital and 214 unrelated healthy controls were recruited. The frequencies of the G allele and GG genotype of the rs4376531 polymorphism were higher in the patients with AS than in control individuals: frequency of G, 91.0% vs 83.4%, P<0.001; GG, 82.2% vs 67.8%, P<0.001. After adjusting for sex, age, and multiple cardiovascular risk factors, the homozygous GG genotype for this variant was associated with a higher risk of AS, with an adjusted odds ratio of 4.99 (95% CI, 2.55-7.81, P< 0.001). Our findings suggest that the rs4376531 polymorphism in the ARHGEF10 gene is a risk factor for AS in the Han Chinese population.

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Mutations in the alpha-synuclein (SNCA) gene have been shown to be responsible for a rare familial form of Parkinson's disease (PD). Furthermore, polymorphic variants in multiple regions of the gene have been associated with susceptibility to idiopathic PD in different populations. Previous studies in Japanese have found a strong association between idiopathic PD and the single-nucleotide polymorphism (SNP) rs7684318, which is located within an intron of the SNCA gene. Our aim was to verify these findings and to further explore the nature of the association in a subset of Han Chinese PD patients. A case-control study of the SNP rs7684318, comprising 332 PD patients and 300 healthy controls, was carried out in Han Chinese populations from two centers in mainland China. The rs7684318 polymorphism was determined by PCR-restriction fragment length polymorphism (PCR-RFLP) analysis. The SNP rs7684318 of the SNCA gene showed a strong association with PD (P<0.01). Among our PD patients, mean age at disease onset and gender did not differ significantly between rs7684318 carriers and non-carriers. Our findings suggested that the SNP rs7684318 (T>C) transition of the SNCA gene contributes to PD susceptibility in Chinese Han population, which is consistent with the earlier study form Japan.

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Common genetic variants that increase the risk for Parkinson's disease (PD) may differentiate patient subgroups and influence future individual therapeutic strategies. Previous studies have found associations between PD and polymorphisms located within the leucine-rich repeat kinase 2 (LRRK2) gene in ethnic Han Chinese from Taiwan and Singapore. Herein, we performed a case-control study and provide evidence supporting the LRRK2 R1628P variant as a risk factor for PD in 2 separate Chinese Han populations from mainland China. A total of 328 PD patients and 300 control individuals were genotyped using PCR-restriction fragment length polymorphism analysis. Differences in genotype frequencies between groups were assessed by the chi-square test. In the PD group, 17 patients (5.2%) were heterozygous for the R1628P variant. This was significantly higher than for the control group [2.0%, P<0.05].No one carrier of the LRRK2 G2385R variant was detected in all the carriers of the R1628P variant. Our results confirm that the LRRK2 R1628P variant contributes to the pathogenesis of PD in Chinese Han populations.

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