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With the gradual increase in the production and consumption of shrimp and crabs, a large amount of their shells are directly treated as garbage, resulting in significant environmental pressure. Shrimp and crab shells are rich in chitin. If extracted and prepared, it can not only help reduce environmental pollution but also improve resource utilization. Due to the limitations of existing preparation technologies, production costs, energy conservation and environmental protection, the current utilization of discarded shrimp and crab shells for chitin production remains at a small to medium scale. Therefore, researchers strive to develop new preparation methods and optimizing processes, hoping to expand the production scale of chitin from shrimp and crab shells and improve the efficiency of waste resource utilization. This review mainly elaborates on the research status of preparing chitin from shrimp and crab shell waste using chemical, biological, and physical methods. It also analyzes the advantages, disadvantages, existing problems, and development prospects of various preparation methods, as well as the applications of chitin in bacteriostatic agents, adsorbents, and biofilms. Currently, the traditional acid-base method is mainly used in industry for chitin preparation, with advantages such as mature technology, simple process flow, and convenient operation. However, this method uses strong acids and bases, posing the problem of secondary environmental pollution. In contrast, eutectic solvent method, enzymatic hydrolysis, and microbial fermentation are more environmentally beneficial. Therefore, developing low-cost natural eutectic solvents, constructing recombinant enzymes, and constructing functional microbial communities are the research focuses for preparing chitin from shrimp and crab shell waste in the future.

Abstract With the continuous development of robot-assisted technology, Robot-assisted Laparoscopic Partial Nephrectomy (RALPN) has gradually become an optional method for the treatment of Hemorrhage secondary to angiomyolipoma (HSA). However, there are rare clinical reports of the primary RALPN for HSA. Therefore, this research aims to evaluate the efficacy and safety of primary RALPN for HSA. Fourteen patients(six males and eight females), aged 14–56 years, underwent primary RALPN for HSA and were retrospectively analyzed from 2015 to 2023. The initial blood routine examination revealed decreased hemoglobin in all patients, and Contrast-enhanced computed tomography (CT) indicated retroperitoneal hematoma. After correcting shock and electrolyte imbalance through fluid therapy and medical treatment, all primary RALPN procedures were performed with transabdominal access on the side of the Hemorrhage. After tumor resection and hematoma removal with a monopolar Curved Scissor, the absorbable barbed suture was performed for inner and outer running stitches, respectively. Patient demographic information, perioperative characteristics, and functional outcomes were collected and analyzed. The initial tumor size of fourteen patients ranged from 57 to 145 mm, and the RENAL ranged from 7 to 11. All of the HSA was controlled, and primary RALPN was successful. The operating time it was ranged from 105 to 265 min. Postoperatively, one patient exhibited chylous drainage (Clavien-Dindo II), and another patient developed pleural effusion (Clavien-Dindo III). No postoperative transfusion and Digital Subtraction Angiography (DSA) highly selective embolization of the bleeding vessel was needed. No patients developed urinoma or urinary fistula. Within the follow-up period, the overall complications were manageable. Primary RALPN is a safe and effective procedure for HSA, which may be considered an alternative to selective renal artery embolization.

Exosomes are extracellular vesicles that are released from the cell into the extracellular microenvironment, and are a carrier of biological information transmitted over long distances, which have a dual regulatory effect on the immune system. Studies have shown that viruses can hold the endosomal-exosomal pathway hostage to spread. This review describes the role played by exosomes in viral infections. On the one hand, exosomes can transmit antiviral substances and trigger immune responses against viral infections, and on the other hand, exosomes can serve as potential mediators of viral transmission, which have been shown to be closely related to the transmission and immune escape of a variety of viruses. Understanding the role of exosomes in viral infections is essential for the detection of viruses in the blood, for improving blood safety, and for the search and development of antiviral drugs.

BackgroundThe association between cytokines in peripheral blood and clinical symptoms of multiple system atrophy (MSA) has been explored in only a few studies with small sample size, and the results were obviously controversial. Otherwise, no studies have explored the diagnostic value of serum cytokines in MSA.MethodsSerum cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α), were measured in 125 MSA patients and 98 healthy controls (HCs). Correlations of these serum cytokines with clinical variables were analyzed in MSA patients. Diagnostic value of cytokines for MSA was plotted by receiver operating curves.ResultsNo significant differences were found in sex and age between the MSA group and the HCs. TNF-α in MSA patients were significantly higher than those in HCs (area under the curve (AUC) 0.768), while IL-6 and IL-8 were not. Only Hamilton Anxiety Scale (HAMA) has a positive correlation between with TNF-α in MSA patients with age and age at onset as covariates. Serum IL-6 was associated with HAMA, Hamilton Depression Scale (HAMD), the Unified MSA Rating Scale I (UMSARS I) scores, the UMSARS IV and the Instrumental Activity of Daily Living scores. However, IL-8 was not associated with all clinical variables in MSA patients. Regression analysis showed that HAMA and age at onset were significantly associated with TNF-α, and only HAMA was mild related with IL-6 levels in MSA patients.ConclusionSerum TNF-α and IL-6 levels in MSA patients may be associated with anxiety symptom; however, only TNF-α was shown to be a useful tool in distinguishing between MSA and HCs.

BackgroundThe overlapping clinical manifestations in parkinsonian variant of multiple system atrophy (MSA-P) and Parkinson’s Disease (PD) can complicate clinical diagnostic accuracy, particularly in the early stage. The study aims to uncover the patterns of brain function in the initial phase of the two conditions.MethodsWe recruited 24 MSA-P patients, 34 PD patients and 27 healthy controls (HC). Voxel-wise fractional amplitude of low-frequency fluctuation (fALFF) was compared to characterize regional brain function, followed by seed-based functional connectivity (FC) analysis. Receiver operating characteristic (ROC) analyses were used to examine the diagnostic accuracy of fALFF.ResultsCompared to HC, decreased fALFF was observed in the bilateral basal ganglia (BG) of MSA-P patients, while decreased fALFF was identified in the left BG of PD patients. Additionally, elevated fALFF was found in the superior cerebellum for MSA-P patients and the temporo-occipital cortex for PD patients. Furthermore, PD patients exhibited increased FC in the cortico-striatal loop compared to MSA-P patients. The fALFF of the left caudate distinguished MSA-P from HC with an area under the curve (AUC) of 0.838 (p

Abstract Parkinson’s disease (PD) is a heterogeneous movement disorder with different motor subtypes including tremor dominant (TD), indeterminate and postural instability, and gait disturbance (PIGD) motor subtypes. Plasma glial fibrillary acidic protein (GFAP) was elevated in PD patients and may be regarded as a biomarker for motor and cognitive progression. Here we explore if there was an association between plasma GFAP and different motor subtypes and whether baseline plasma GFAP level can predict motor subtype conversion. Patients with PD classified as TD, PIGD or indeterminate subtypes underwent neurological evaluation at baseline and 2 years follow-up. Plasma GFAP in PD patients and controls were measured using an ultrasensitive single molecule array. The study enrolled 184 PD patients and 95 control subjects. Plasma GFAP levels were significantly higher in the PIGD group compared to the TD group at 2-year follow-up. Finally, 45% of TD patients at baseline had a subtype shift and 85% of PIGD patients at baseline remained as PIGD subtypes at 2 years follow-up. Baseline plasma GFAP levels were significantly higher in TD patients converted to PIGD than non-converters in the baseline TD group. Higher baseline plasma GFAP levels were significantly associated with the TD motor subtype conversion (OR = 1.283, P = 0.033) and lower baseline plasma GFAP levels in PIGD patients were likely to shift to TD and indeterminate subtype (OR = 0.551, P = 0.021) after adjusting for confounders. Plasma GFAP may serve as a clinical utility biomarker in differentiating motor subtypes and predicting baseline motor subtypes conversion in PD patients.

Abstract The Ebinur Lake Basin is an ecologically sensitive area in an arid region. Investigating its land use and land cover (LULC) change and assessing and predicting its ecosystem service value (ESV) are of great importance for the stability of the basin's socioeconomic development and sustainable development of its ecological environment. Based on LULC data from 1990, 2000, 2010, and 2020, we assessed the ESV of the Ebinur Lake Basin and coupled the grey multi-objective optimization model with the patch generation land use simulation model to predict ESV changes in 2035 under four scenarios: business-as-usual (BAU) development, rapid economic development (RED), ecological protection (ELP), and ecological–economic balance (EEB). The results show that from 1990 to 2020, the basin was dominated by grassland (51.23%) and unused land (27.6%), with a continuous decrease in unused land and an increase in cultivated land. In thirty years, the total ESV of the study area increased from 18.62 billion to 67.28 billion yuan, with regulation and support services being the dominant functions. By 2035, cultivated land increased while unused land decreased in all four scenarios compared with that in 2020. The total ESV in 2035 under the BAU, RED, ELP, and EEB scenarios was 68.83 billion, 64.47 billion, 67.99 billion, and 66.79 billion yuan, respectively. In the RED and EEB scenarios, ESV decreased by 2.81 billion and 0.49 billion yuan, respectively. In the BAU scenario, provisioning and regulation services increased by 6.05% and 2.93%, respectively. The ELP scenario, focusing on ecological and environmental protection, saw an increase in ESV for all services. This paper can assist policymakers in optimizing land use allocation and provide scientific support for the formulation of land use strategies and sustainable ecological and environmental development in the inland river basins of arid regions.

BackgroundRecent research has indicated the significance of immune activation in amyotrophic lateral sclerosis (ALS). However, the impact of peripheral immunity on cognitive impairment in sporadic ALS remains poorly characterized. Therefore, we aim to assess the relationship between peripheral immune parameters and cognitive impairment in patients with sporadic ALS.MethodsA case–control study involving 289 patients with sporadic ALS was conducted. All participants underwent cognitive assessment and measurements of blood immune parameters. The main outcomes included adjusted odds ratios (ORs) in multivariate logistic regression analysis and adjusted coefficients in a multivariate linear regression model. Sensitivity analysis was performed with stratification by the King’s clinical stage.ResultsCognitive impairment was observed in 98 (33.9%) patients. Higher counts of leukocyte (OR, 0.53; 95% CI, 0.29 to 0.95; p = 0.03), neutrophil (OR, 0.48; 95% CI, 0.26 to 0.88; p = 0.02), and monocyte (OR, 0.33; 95% CI, 0.18 to 0.60; p

BackgroundThe relationship between routine cerebrospinal fluid (CSF) testing and the disease phenotype of amyotrophic lateral sclerosis (ALS) is unclear, and there are some contradictions in current studies.MethodsThis study aimed to analyze the relationship between CSF profiles and disease phenotype in ALS patients. We collected 870 ALS patients and 96 control subjects admitted to West China Hospital of Sichuan University. CSF microprotein, albumin, IgG, index of IgG (IgGindex), albumin quotient (QALB), and serum IgG were examined.ResultsIn ALS patients, CSF IgG, and QALB were significantly increased, while CSF IgGindex was decreased, compared with control subjects. Approximately one-third of ALS patients had higher CSF IgG levels. The multiple linear regression analysis identified that CSF IgGindex was weakly negatively associated with ALS functional rating scale revised (ALSFRS-R) scores (β = −0.062, p = 0.041). This significance was found in male ALS but not in female ALS. The Cox survival analyses found that upregulated CSF IgG was significantly associated with the increased mortality risk in ALS [HR = 1.219 (1.010–1.470), p = 0.039].ConclusionIn the current study, the higher CFS IgG was associated with increased mortality risk of ALS. CSF IgGindex may be associated with the severity of ALS. These findings may be sex-specific.

Abstract Background Reactive astrogliosis has been demonstrated to have a role in Parkinson’s disease (PD); however, astrocyte-specific plasma glial fibrillary acidic protein (GFAP)’s correlation with PD progression remains unknown. We aimed to determine whether plasma GFAP can monitor and predict PD progression. Methods A total of 184 patients with PD and 95 healthy controls (HCs) were included in this prospective cohort study and followed-up for 5 years. Plasma GFAP, amyloid-beta (Aβ), p-tau181, and neurofilament light chain (NfL) were measured at baseline and at 1- and 2-year follow-ups. Motor and non-motor symptoms, activities of daily living, global cognitive function, executive function, and disease stage were evaluated using the Unified Parkinson’s Disease Rating Scale (UPDRS) part III, UPDRS-I, UPDRS-II, Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), and Hoehn and Yahr (H&Y) scales at each visit, respectively. Results Plasma GFAP levels were higher in patients with PD (mean [SD]: 69.80 [36.18], pg/mL) compared to HCs (mean [SD]: 57.89 [23.54], pg/mL). Higher levels of GFAP were observed in female and older PD patients. The adjusted linear mixed-effects models showed that plasma GFAP levels were significantly associated with UPDRS-I scores (β: 0.006, 95% CI [0.001–0.011], p = 0.027). Higher baseline plasma GFAP correlated with faster increase in UPDRS-I (β: 0.237, 95% CI [0.055–0.419], p = 0.011) and UPDRS-III (β: 0.676, 95% CI [0.023–1.330], p = 0.043) scores and H&Y stage (β: 0.098, 95% CI [0.047–0.149], p < 0.001) and faster decrease in MoCA (β: − 0.501, 95% CI [− 0.768 to − 0.234], p < 0.001) and FAB scores (β: − 0.358, 95% CI [− 0.587 to − 0.129], p = 0.002). Higher baseline plasma GFAP predicted a more rapid progression to postural instability (hazard ratio: 1.009, 95% CI [1.001–1.017], p = 0.033). Conclusions Plasma GFAP might be a potential biomarker for monitoring and predicting disease progression in PD.

Abstract Background The progression of sleep disturbances remains unclear in patients with early multiple system atrophy (MSA). We aimed to explore the frequency, severity, and coexistence of 2-year longitudinal changes of sleep disturbances including REM sleep behavior disorder (RBD), excessive daytime sleepiness (EDS), and Parkinson’s disease-related sleep problems (PD-SP) in early MSA. Methods MSA patients with a disease duration

Myotonic dystrophy (DM) encompasses a spectrum of neuromuscular diseases characterized by myotonia, muscle weakness, and wasting. Recent research has led to the recognition of DM as a neurological disorder. Cognitive impairment is a central nervous system condition that has been observed in various forms of DM. Neuroimaging studies have increasingly linked DM to alterations in white matter (WM) integrity and highlighted the relationship between cognitive impairment and abnormalities in WM structure. This review aims to summarize investigations into cognitive impairment and brain abnormalities in individuals with DM and to elucidate the correlation between these factors and the potential underlying mechanisms contributing to these abnormalities.

Abstract Background Patients with amyotrophic lateral sclerosis (ALS) demonstrate great heterogeneity in the age at onset (AAO), which is closely related to the course of disease. However, most genetic studies focused on the risk of ALS, while the genetic background underlying AAO of ALS is still unknown. Methods To identify genetic determinants influencing AAO of ALS, we performed genome-wide association analysis using a Cox proportional hazards model in 2,841 patients with ALS (Ndiscovery = 2,272, Nreplication = 569) in the Chinese population. We further conducted colocalization analysis using public cis-eQTL dataset, and Mendelian randomization analysis to identify risk factors for AAO of ALS. Finally, functional experiments including dual-luciferase reporter assay and RT-qPCR were performed to explore the regulatory effect of the target variant. Results The total heritability of AAO of ALS was ~ 0.24. One novel locus rs10128627 (FRMD8) was significantly associated with earlier AAO by ~ 3.15 years (P = 1.54E-08, beta = 0.31, SE = 0.05). This locus was cis-eQTL of NEAT1 in multiple brain tissues and blood. Colocalization analysis detected association signals at this locus between AAO of ALS and expression of NEAT1. Furthermore, functional exploration supported the variant rs10128627 was associated with upregulated expression of NEAT1 in cell models and patients with ALS. Causal inference suggested higher total cholesterol, low-density lipoprotein, and eosinophil were nominally associated with earlier AAO of ALS, while monocyte might delay the AAO. Conclusions Collective evidence from genetic, bioinformatic, and functional results suggested NEAT1 as a key player in the disease progression of ALS. These findings improve the current understanding of the genetic role in AAO of ALS, and provide a novel target for further research on the pathogenesis and therapeutic options to delay the disease onset.

The ecological security of oasis cities in arid and semi-arid regions is highly susceptible to changes in regional landscape patterns and the degree of coordination between human activities and the environment. At the same time, the ecological security of urban landscapes also profoundly affects the success of regional economic and environmental coordination and development. This study is based on land use data from 1990, 2000, 2010, and 2020, as well as land use data from the natural development scenario (NLD), economic development scenario (ECD), ecological development scenario (ELD) and ecological-economic development scenario (EED) simulated by the patch-generating land use simulation (PLUS) model in 2030. From the perspective of production-living-ecological land (PLEL), it analyzes the changes in the past and future landscape ecological security and coupling coordination characteristics of Bole. The results show that from 1990 to 2020, Bole was mainly dominated by grassland ecological land (GEL) and other ecological land (OEL), accounting for a total proportion of 69.51%, with a large increase in production and living land area; the average value of landscape ecological risk is decreasing, and the landscape ecological security of Bole is developing towards benignity; the area of highly coupled coordination zone is decreasing continuously, while that of basic coordination zone and moderate coordination zone is increasing continuously. Under the 2030 EED scenario, the overall changes in various types of land use are not significant, and the average value of landscape ecological risk is the smallest, but it is higher than that in 2020 as a whole; under EED scenario, the area of highly coordinated zone and moderate coordinated zone is the largest among four scenarios, and the best coupling coordination level among the four scenarios. Landscape ecological security and its coupling coordination will be affected by land use patterns. Optimizing regional land use patterns is of great significance for improving urban landscape ecological security and sustainable high-quality development.

BackgroundCystatin C (CysC) levels in amyotrophic lateral sclerosis (ALS) have been found changes, however, the associations between serum CysC levels and the progression and survival of ALS remain largely unknown.MethodsA total of 1,086 ALS patients and 1,026 sex-age matched healthy controls (HCs) were enrolled in this study. Serum CysC, other renal function, and metabolic parameters were measured. Correlation analysis and binary logistic regression were used to explore the factors related to serum CysC. Kaplan–Meier curve and Cox regression model were used for survival analysis.ResultsCysC levels were significantly higher in ALS patients compared to HCs (0.94 vs. 0.85 mg/L, p

Abstract Objectives High visit‐to‐visit blood pressure variability (BPV) was found to be associated with cognitive decline in the elderly. This study aimed to investigate the impact of visit‐to‐visit BPV on cognition in patients with early‐stage Parkinson's disease (PD). Design This is a retrospective analysis of a prospective cohort. Setting and participants A total of 297 patients with early‐stage PD (103 mild cognitive impairments [PD‐MCI] and 194 normal cognitions [PD‐NC] at baseline) were included from the Parkinson's Progression Markers Initiative study. Methods Variation independent of mean (VIM) of the first year was used as the indicator of BPV. The Montreal Cognitive Assessment (MoCA) was used to assess global cognition. Patients were divided into PD‐MCI and PD‐NC according to the MoCA score at baseline. Longitudinal cerebrospinal fluid (Aβ‐42, Aβ, α‐synuclein, neurofilament light protein, tau phosphorylated at the threonine 181 position, total tau, glial fibrillary acidic protein) and serum (neurofilament light protein) biomarkers were assessed. The Bayesian linear growth model was used to evaluate the relationship between baseline BPV and the rate of change in cognition and biomarkers. Results Higher systolic VIM of the first year was related to a greater rate of decline in MoCA score in the following years in PD‐MCI (β = −.15 [95% CI −.29, −.01]). No association was found between BPV and biomarkers. Conclusion and implications Higher systolic VIM predicted a steeper decline in cognitive tests in PD‐MCI independently from the mean value of blood pressure, orthostatic hypotension, and supine hypertension.

ObjectivesMutations in glucocerebrosidase (GBA1) can change the clinical phenotype of Parkinson’s disease (PD). This study aimed to explore the clinical characteristics of freezing of gait (FOG) in PD patients with GBA1 mutations.MethodsA whole-exome sequencing analysis was used to identify the GBA1 mutations (pathogenic or likely pathogenic) and exclude other PD-related gene mutations. A forward binary logistic regression model was conducted to identify the associated factors of FOG. The stepwise multiple linear regression analysis models were used to explore the effect of FOG on quality of life.ResultsThe prevalence of FOG in patients with GBA1 mutations (30/95, 31.6%) was significantly higher than those in patients without GBA1 mutations (152/760, 20%) (p = 0.009). A higher (i.e., worse) Unified PD Rating Scale part III score (OR = 1.126, 95%CI = 1.061–1.194, p

BackgroundMalnutrition is associated with poor survival in some diseases. However, the nutritional status in multiple system atrophy (MSA) is unknown, and the significance of malnutrition for the prediction of mortality in MSA has not been well established.ObjectiveWe aimed to determine the prevalence of malnutrition and the prognostic value of malnutrition in patients with early-stage MSA.MethodsPatients diagnosed with early phase MSA (disease duration

Abstract We modified the original Unified Multiple System Atrophy Rating Scale (UMSARS) for remote video-based visits by excluding ocular motor dysfunction, increased tone, and body sway, resulting in a 23-item UMSARS (mUMSARS-23). The mUMSARS-23 demonstrated excellent reliability and strong validity when compared to the original scale, making it a promising tool for conducting video-based virtual assessments in patients with multiple system atrophy.

Abstract Background It has been more than 2 years since the 2019 novel coronavirus disease (COVID-19) pandemic destabilized the world, adversely affecting not only physical health, but also mental health. During this time, frontline medical workers were at a greater health risk, especially female medical workers. Changes or abnormalities in the menstrual cycle—an important indicator of women’s health—may jeopardize female reproductive functioning. Considering that emotional health and sleep status may be related to the menstrual cycle, this study aimed to investigate the association between menstrual cycle changes, anxiety, sleep dysfunction, and other factors among female medical workers during the COVID-19 pandemic. Methods A cross-sectional survey was conducted by distributing online questionnaires to female medical workers in China from February to May 2022. The study included 160 women aged 18–45 years old. The questionnaires covered data related to the participants’ sociodemographic characteristics, medical and reproductive history, and lifestyle. The Rating Scale for Clinical Manifestations of Menopathy (SCMM), Self-Rating Anxiety Scale (SAS), and Sleep Dysfunction Rating Scale (SDRS) were utilized. Data were analyzed using chi-square tests, t-tests, and linear regression analysis. Results A total of 160 female medical staff were randomly selected in this research, of whom seven scored less than 3 points, 85 scored 3–11 points, and 68 scored more than 11 points on the total score of the SCMM. Compared to pre-pandemic scores, scores of dizziness and tinnitus were significantly higher during the COVID-19 pandemic. Scores corresponding to the following clinical symptoms were also higher during the pandemic: Menopathy, including hypaphrodisia, dim complexion, abnormal urination, languidness, dim menstruation, thin menstruation, dysmenorrhea, and empty or saggy lower abdomen (p

Abstract Background Recently, several rare variants of SPTLC1 were identified as disease cause for juvenile amyotrophic lateral sclerosis (ALS) by disrupting the normal homeostatic regulation of serine palmitoyltransferase (SPT). However, further exploration of the rare variants in large cohorts was still necessary. Meanwhile, SPTLC2 plays a similar role as SPTLC1 in the SPT function. Methods To explore the genetic role of SPTLC1 and SPTLC2 in ALS, we analyzed the rare protein-coding variants in 2011 patients with ALS and 3298 controls from the Chinese population with whole exome sequencing. Fisher’s exact test was performed between each variant and disease risk, while at gene level over-representation of rare variants in patients was examined with optimized sequence kernel association test (SKAT-O). Results Totally 33 rare variants with minor allele frequency

Shrinking cities suffer from a decreased level of resident activities. As a result, areas with low levels of resident activities may become breeding grounds for social issues. To ease and prevent social issues, it is important to deploy physical space optimisation strategies to effectively guide the distribution of resident activities in shrinking cities. To support the development of such spatial strategies, this paper introduces machine learning-based methods for analysing the nuanced non-linear relationship between resident activities and physical space in shrinking cities. Utilising dual-scale grids, this study calculates multi-source spatial elements, which are subsequently integrated with resident activity data to construct a gradient boosting decision tree model. It then analyses the weight of different spatial elements’ impacts on resident activities and their nonlinear relationships. The model proposed in this study demonstrates good precision in construing the relationship between resident activities and physical space. Based on the research findings, strategies for different types of spatial development in shrinking cities are drawn out. This paper advocates for the application of this analytical approach before conducting spatial planning in shrinking cities to maximise the effectiveness of spatial development in guiding resident activities.

The management of wound healing represents a significant clinical challenge due to the complicated processes involved. Chitosan has remarkable properties that effectively prevent certain microorganisms from entering the body and positively influence both red blood cell aggregation and platelet adhesion and aggregation in the bloodstream, resulting in a favorable hemostatic outcome. In recent years, chitosan-based hydrogels have been widely used as wound dressings due to their biodegradability, biocompatibility, safety, non-toxicity, bioadhesiveness, and soft texture resembling the extracellular matrix. This article first summarizes an overview of the main chemical modifications of chitosan for wound dressings and then reviews the desired properties of chitosan-based hydrogel dressings. The applications of chitosan-based hydrogels in wound healing, including burn wounds, surgical wounds, infected wounds, and diabetic wounds are then discussed. Finally, future prospects for chitosan-based hydrogels as wound dressings are discussed. It is anticipated that this review will form a basis for the development of a range of chitosan-based hydrogel dressings for clinical treatment.

BackgroundParkinson’s disease (PD) is recognized as the second most prevalent progressive neurodegenerative disease among the elderly. However, the relationship between PD and plasma homocysteine (Hcy), vitamin B12, and folate has yielded inconsistent results in previous studies. Hence, in order to address this ambiguity, we conducted a meta-analysis to summarize the existing evidence.MethodsSuitable studies published prior to May 2023 were identified by searching PubMed, EMBASE, Medline, Ovid, and Web of Science. The methodological quality of eligible studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Meta-analysis and publication bias were then performed using R version 4.3.1.ResultsThe results of our meta-analysis, consisting of case–control and cross-sectional studies, showed that PD patients had lower folate and vitamin B12 levels (SMD [95%CI]: −0.30[−0.39, −0.22], p

Abstract Background Recently, several rare variants of TP73 were identified as potential disease cause for amyotrophic lateral sclerosis (ALS) in the European population. However, further replication was still necessary, especially in cohorts with different ethnic backgrounds. Methods To explore the genetic role of TP73 in ALS in the Asian population, we analyzed the rare protein-coding variants in 2011 patients with ALS and 3298 controls with whole-exome sequencing. Fisher’s exact test was performed between each variant and disease risk, while at gene level over-representation of rare variants in patients was examined with optimized sequence kernel association test. Results Totally 24 rare variants with minor allele frequency

Abstract Background The progression of motor and non-motor symptoms (NMS) and the sensitivity of each item of the Unified Multiple System Atrophy Rating Scale (UMSARS) to change remain unclear in Chinese patients with early-stage multiple system atrophy (MSA). We investigated the evolution of motor symptoms and NMS in early-stage MSA and the sensitivity of each item included in the UMSARS to change over a 2-year follow-up. Methods Motor symptoms and NMS were recorded at baseline and at 1- and 2-year follow-ups based on the UMSARS and the NMS scale. Generalized estimating equation models were used. The sensitivity of an item included in the UMSARS to change was assessed by calculating a standardized effect using the mean annual change divided by the standard deviation of the change. Results We enrolled 246 consecutive patients with MSA and 97 MSA completed the 2-year follow-up. The mean total UMSARS score increased by 11.90 and 22.54 points at the 1- and 2-year follow-ups, respectively. UMSARS-I items associated with motor functions were more sensitive to change and those associated with autonomic dysfunction showed less sensitivity to change. Items 4 (tremor at rest), 5 (action tremor), and 3 (ocular motor dysfunction) of the UMSARS-II were less sensitive to change. The prevalence and severity of NMS significantly increased over the 2-year follow-up. Conclusions We observed significant progression in motor symptoms and NMS in patients with early-stage MSA. Our results provide useful information to support the revision of the UMSARS.

N- Demethylsinomenine (NDSM), the in vivo demethylated metabolite of sinomenine, has exhibited antinociceptive efficacy against various pain models and may become a novel drug candidate for pain management. However, no reported analytical method for quantification of N- Demethylsinomenine in a biological matrix is currently available, and the pharmacokinetic properties of N- Demethylsinomenine are unknown. In the present study, an ultra-high performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method for quantification of N- Demethylsinomenine in rat plasma was developed and utilized to examine the preclinical pharmacokinetic profiles of N- Demethylsinomenine. The liquid-liquid extraction using ethyl acetate as the extractant was selected to treat rat plasma samples. The mixture of 25% aqueous phase (0.35% acetic acid-10 mM ammonium acetate buffer) and 75% organic phase (acetonitrile) was chosen as the mobile phases flowing on a ZORBAX C18 column to perform the chromatographic separation. After a 6-min rapid elution, NDSM and its internal standard (IS), metronidazole, were separated successfully. The ion pairs of 316/239 and 172/128 were captured for detecting N- Demethylsinomenine and IS, respectively, using multiple reaction monitoring (MRM) under a positive electrospray ionization (ESI) mode in this mass spectrometry analysis. The standard curve met linear requirements within the concentration range from 3 to 1000 ng/mL, and the lower limit of quantification (LLOQ) was 3 ng/mL. The method was evaluated regarding precision, accuracy, recovery, matrix effect, and stability, and all the results met the criteria presented in the guidelines for validation of biological analysis method. Then the pharmacokinetic profiles of N- Demethylsinomenine in rat plasma were characterized using this validated UPLC-MS/MS method. N- Demethylsinomenine exhibited the feature of linear pharmacokinetics after intravenous (i.v.) or intragastric (i.g.) administration in rats. After i. v. bolus at three dosage levels (0.5, 1, and 2 mg/kg), N- Demethylsinomenine showed the profiles of rapid elimination with mean half-life (T1/2Z) of 1.55–1.73 h, and extensive tissue distribution with volume of distribution (VZ) of 5.62–8.07 L/kg. After i. g. administration at three dosage levels (10, 20, and 40 mg/kg), N- Demethylsinomenine showed the consistent peak time (Tmax) of 3 h and the mean absolute bioavailability of N- Demethylsinomenine was 30.46%. These pharmacokinetics findings will aid in future drug development decisions of N- Demethylsinomenine as a potential candidate for pain analgesia.

BackgroundThe 2008 criteria for the diagnosis of multiple system atrophy (MSA) has been widely used for more than 10 years, but the sensitivity is low, particularly for patients in the early stage. Recently, a new MSA diagnostic criteria was developed.ObjectiveThe objective of the study was to assess and compare the diagnostic utility of the new movement disorder society (MDS) MSA criteria with the 2008 MSA criteria.MethodsThis study included patients diagnosed with MSA between January 2016 and October 2021. All patients underwent regular face-to-face or telephonic follow-ups every year until October 2022. A total of 587 patients (309 males and 278 females) were retrospectively reviewed to compare the diagnostic accuracy of the MDS MSA criteria to that of the 2008 MSA criteria (determined by the proportion of patients categorized as established or probable MSA). Autopsy is the gold standard diagnosis of MSA, which is not available in clinical practice. Thus, we applied the 2008 MSA criteria at the last review as the reference standard.ResultsThe sensitivity of the MDS MSA criteria (93.2%, 95% CI = 90.5–95.2%) was significantly higher than that of the 2008 MSA criteria (83.5%, 95% CI = 79.8–86.6%) (P < 0.001). Additionally, the sensitivity of the MDS MSA criteria was maintained robustly across different subgroups, defined by diagnostic subtype, disease duration, and the type of symptom[s] at onset. Importantly, the specificities were not significantly different between the MDS MSA criteria and the 2008 MSA criteria (P > 0.05).ConclusionThe present study demonstrated that the MDS MSA criteria exhibited good diagnostic utility for MSA. The new MDS MSA criteria should be considered as a useful diagnostic tool for clinical practice and future therapeutic trials.

This study analyzed the sources of total metal elements using the positive matrix factorization (PMF) model and conducted human health risk assessment for adults and children using the health risk assessment model recommended by the United States Environmental Protection Agency (USEPA). According to the health risk assessment, As is the main contributor to the non-carcinogenic risk of groundwater in Tengzhou, with drinking water as the main exposure route. Regarding carcinogenic risks (CR), the values of As and Cr for adults and children were higher than 1 × 10−4, with drinking water as the main exposure route. Therefore, As is the largest contributor to the CR of groundwater for adults and children and drinking water is the main exposure route in the study area. The primary exposure pathways are oral intake and dermal contact, with oral intake presenting a significant risk. The carcinogenic risks according to principal component analysis (PCA) and PMF analysis showed that the main sources of heavy metals in shallow groundwater in Tengzhou City are agricultural, industrial, natural, and industrial deposition sources, with contribution rates of 21.7%, 27.2%, 31.0%, and 20.1%, respectively. In particular, natural sources are the largest contributor to the accumulation of heavy metals.

Abstract Objective Impaired cognitive function is a central symptom of schizophrenia and is often correlated with inferior global functional outcomes. However, the role of some neurobiological factors such as cortical structure alterations in the underlying cognitive damages in schizophrenia remains unclear. The present study attempted to explore the neurobiomarkers of cognitive function in drug-naive, first-episode schizophrenia by using structural magnetic resonance imaging (MRI). Methods The present study was conducted in patients with drug-naive, first-episode schizophrenia (SZ) and healthy controls (HCs). MRI T1 images were pre-processed using CAT12. Surface-based morphometry (SBM) was utilised to evaluate structural parameters such as cortical thickness and sulcus depth. The positive and negative syndrome scale (PANSS) and Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus cognitive battery (MCCB) were employed to estimate the psychotic symptoms and cognition, respectively. Results A total of 117 patients with drug-naive first-episode schizophrenia (SZ) and 98 healthy controls (HCs) were included. Both the cortical thickness and sulcus depth in the frontal lobe were lower in patients with SZ than in the HCs under family-wise error correction (p

Abstract The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, can predict the prognosis of neurodegenerative diseases. However, the significance of NLR for the prognosis of multiple system atrophy (MSA) has not been reported. We aimed to examine the prognostic significance of NLR in MSA. A total of 169 MSA patients and 163 matched healthy controls (HCs) were enrolled. MSA patients were divided into three groups according to the tertiles of their NLR. Kaplan–Meier survival analysis and Cox regression model were used to assessing the effect of NLR on survival. An independent validation cohort of 56 consecutive patients with probable MSA who met the inclusion criteria was included. The NLR was significantly higher in patients with MSA than that in HCs. The survival duration in patients with MSA in group 3 was shorter than that in patients in the other two groups (P = 0.013). In the multivariable Cox regression model, a higher NLR increased the risk of mortality in patients with MSA after adjusting for confounding factors (HR = 1.922, P = 0.035). Additionally, a higher NLR increased the risk of mortality in MSA with predominant cerebellar ataxia (MSA-C) (HR = 2.398, P = 0.033) and in men (HR = 3.483, P = 0.027). The concordance index for the multivariate Cox regression model was more than 0.7 both in the primary cohort and external validation cohort. Patients with MSA had a higher NLR than did HCs. A high NLR increased the risk of mortality with MSA, especially in MSA-C and in men.

Objective: The predictive factors for wheelchair dependence in patients with multiple system atrophy (MSA) are unclear. We aimed to explore the predictive factors for early-wheelchair dependence in patients with MSA focusing on clinical features and blood biomarkers. Methods: This is a prospective cohort study. This study included patients diagnosed with MSA between January 2014 and December 2019. At the deadline of October 2021, patients met the diagnosis of probable MSA were included in the analysis. Random forest (RF) was used to establish a predictive model for early-wheelchair dependence. Accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of the model. Results: Altogether, 100 patients with MSA including 49 with wheelchair dependence and 51 without wheelchair dependence were enrolled in the RF model. Baseline plasma neurofilament light chain (NFL) levels were higher in patients with wheelchair dependence than in those without (P = 0.037). According to the Gini index, the five major predictive factors were disease duration, age of onset, Unified MSA Rating Scale (UMSARS)-II score, NFL, and UMSARS-I score, followed by C-reactive protein (CRP) levels, neutrophil-to-lymphocyte ratio (NLR), UMSARS-IV score, symptom onset, orthostatic hypotension, sex, urinary incontinence, and diagnosis subtype. The sensitivity, specificity, accuracy, and AUC of the RF model were 70.82 %, 74.55 %, 72.29 %, and 0.72, respectively. Conclusion: Besides clinical features, baseline features including NFL, CRP, and NLR were potential predictive biomarkers of early-wheelchair dependence in MSA. These findings provide new insights into the trials regarding early intervention in MSA.

Background: Variants in the annexin A11 gene (ANXA11) have been reported to be associated with amyotrophic lateral sclerosis (ALS). These variants may be involved in the pathogenesis of ALS by causing defects in intracellular protein trafficking. However, the genetic spectrum and clinical characteristics of ALS patients with ANXA11 variants are largely unknown. Methods: Genetic analysis was performed on 1587 Chinese patients with ALS. Eight software packages were used to predict the deleteriousness of missense variants. In addition, we searched PubMed, Embase, and Web of Science for relevant literature and meta-analysed variant frequencies. Results: In our ALS cohort, we identified 20 non-synonymous variants in 29 ALS patients, including one stop-gain, one frameshift, and 18 rare missense variants with seven predicted pathogenic variants. In a literature review of 11 reported studies that included 69 patients, 37 ANXA11 variants were reported, with a frequency of 1.7%, which was similar to that in our cohort (1.8%). Both our cohort and previous reports showed that ANXA11 carriers were more commonly males than females (12/17 vs. 19/31). Patients carrying ANXA11 variants affecting the C-terminal of the protein had earlier disease onset and shorter survival times than those carrying variants affecting the N-terminal. We found a relatively longer median survival time than that previously reported (53.6 months vs. 46.0 months). Additionally, Caucasian ANXA11 carriers were more likely to have cognitive impairment, typically frontotemporal dementia (FTD) than their Asian counterparts (20.0% vs. 14.3%). While more than half of the patients in our cohort had cognitive impairment, none had FTD. Conclusion: In our and previously published cases, ALS-associated ANXA11 variants predominantly affected the N- and C-terminal conserved domains. ANXA11 variant carriers are typically male and cognitively impaired. Our study extends the genotypic and phenotypic spectra of ALS patients with ANXA11 variants. Further expansion of the sample size is needed to analyse the clinical and non-motor symptom characteristics of patients and to deepen the understanding of the pathogenesis of ANXA11-associated ALS.

The improvement of habitat quality is of great significance to biodiversity conservation. Irrational development activities lead to the degradation of habitat quality and loss of biodiversity, especially in arid inland areas where the ecological environment is fragile. In this study, the InVEST model is used to evaluate the habitat quality and degradation degree of the Ebinur Lake Basin from 1990 to 2020, while the PLUS model is used to predict the land use change in the Ebinur Lake Basin under various scenarios. Combined with the results of ecological zoning planning, the spatial distribution of land use and habitat quality under the inertia development (ID) and ecological protection (EP) scenarios in 2030 were compared and analyzed, and the optimal scenario was selected. The following four conclusions are drawn: (1) From 1990 to 2020, cultivated land, grassland, and construction land significantly increased, while forest land, water bodies, and unused land significantly decreased. (2) The habitat quality of the watershed showed an increasing trend followed by a decreasing trend. The area proportion of high habitat quality has always exceeded 50 % of the total area of the watershed with a high level of habitat quality. (3) Furthermore, combined with habitat quality and the human footprint index (HFI), ecological zoning planning for the basin was conducted. The three ecological zones were divided into key protected areas, key restoration areas, and moderate development zones, with area proportions of 53.69 %, 29.37 %, and 16.93 %, respectively. (4) By comparing habitat quality under the ID scenario and the EP scenario in 2030, we found that the area of high habitat quality increased by 2730.06 km2 under the EP scenario, which improved the overall level of habitat quality, and was more conducive to the ecological security protection of the basin. The results of this study may benefit the analysis of the temporal and spatial variation characteristics of habitat quality in the Ebinur Lake Basin and provide a reference for the improvement of habitat quality in the inland arid region.

BackgroundAccumulating evidence has suggested that cystatin C is associated with cognitive impairment in patients with neurodegenerative diseases. However, the association between cystatin C and cognitive decline in patients with multiple system atrophy (MSA) remains largely unknown.ObjectivesThe objective was to determine whether cystatin C was independently associated with cognitive decline in patients with early-stage MSA.MethodsPatients with MSA underwent evaluation at baseline and the 1-year follow-up. Cognitive function was evaluated with Montreal cognitive assessment (MoCA). Changes in the MoCA score and the absolute MoCA score at the 1-year assessment were considered the main cognitive outcome. The cystatin C concentrations in patients with MSA and age, sex, and body mass index matched-healthy controls (HCs) were measured. A multiple linear regression model was used to test the association between cystatin C and cognitive decline.ResultsA total of 117 patients with MSA and 416 HCs were enrolled in the study. The cystatin C levels were significantly higher in patients with MSA than in HCs (p

The prevalent use of foliar calcium fertilizers in peanut production is inorganic, but calcium absorbed from the foliar has poor availability. Sorbitol-chelated calcium is a novel organic foliar calcium fertilizer that has rarely been studied for application in peanut production. To explore whether calcium absorption and peanut yields can be affected by foliar application of sorbitol-chelated calcium, this study conducted two field experiments using Virginia peanut (Huayu-22) in 2020 and 2021. The five spray treatments included: deionized water (CK), sorbitol (Sor), calcium nitrate (CaN), a mixture of sorbitol and calcium nitrate (SN), and sorbitol-chelated calcium (SC). The yield of peanuts treated with sorbitol-chelated calcium was increased by 12.31-16.63%, 10.22-11.83%, 6.31-9.69%, and 4.18-6.99% compared to the CK, Sor, CaN, and SN treatments, respectively. Sorbitol-chelated calcium had the lowest contact angle due to the wetting effect of sorbitol, which promoted calcium absorption by leaves. Sorbitol-chelated calcium improved the leaf calcium concentration by 13.12-19.32% and kernel calcium concentration by 6.49-8.15% compared to the CK treatment. Foliar fertilization increased the calcium concentration of each subcellular fraction of leaves and changed the distribution of calcium in mesophyll cells. This change was directly observed by transmission electron microscopy. Additionally, spraying sorbitol alone obtained similar effects to spraying calcium nitrate alone, indicating that the benefits of sorbitol itself were not negligible. The results of the principal component and correlation analysis showed that the increase in calcium concentrations and the change in calcium distribution improved the pod traits of the peanut, thus affecting the peanut yield. The above results showed that from the perspective of calcium absorption and distribution, sorbitol-chelated calcium is a more effective foliar calcium fortifier for peanuts and effectively improves peanut yields.

BackgroundThe different clinical characteristics and prognostic values of the motor-nonmotor subtypes of Parkinson’s disease (PD) have been established by previous studies. However, the consistency of motor-nonmotor subtypes in patients with early-stage Parkinson’s disease required further investigation. The present study aimed to evaluate the consistency of motor-nonmotor subtypes across five years of follow-up in a longitudinal cohort.Materials and methodsPatients were classified into different subtypes (mild-motor–predominant, intermediate, diffuse malignant; or tremor-dominant, indeterminate, postural instability and gait difficulty) according to previously verified motor-nonmotor and motor subtyping methods at baseline and at every year of follow-up. The agreement between subtypes was examined using Cohen’s kappa and total agreement. The determinants of having the diffuse malignant subtype as of the fifth-year visit were explored using logistic regression.ResultsA total of 421 patients were included. There was a fair degree of agreement between the baseline motor-nonmotor subtype and the subtype recorded at the one-year follow-up visit (κ = 0.30 ± 0.09; total agreement, 60.6%) and at following years’ visits. The motor-nonmotor subtype had a lower agreement between baseline and follow-up than did the motor subtype. The baseline motor-nonmotor subtype was the determinant of diffuse malignant subtype at the fifth-year visit.ConclusionMany patients experienced a change in their motor-nonmotor subtype during follow-up. Further studies of consistency in PD subtyping methods should be conducted in the future.

Abstract Objective There is increasing evidence that amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease impacting large-scale brain networks. However, it is still unclear which structural networks are associated with the disease and whether the network connectomics are associated with disease progression. This study was aimed to characterize the network abnormalities in ALS and to identify the network-based biomarkers that predict the ALS baseline progression rate. Methods Magnetic resonance imaging was performed on 73 patients with sporadic ALS and 100 healthy participants to acquire diffusion-weighted magnetic resonance images and construct white matter (WM) networks using tractography methods. The global and regional network properties were compared between ALS and healthy subjects. The single-subject WM network matrices of patients were used to predict the ALS baseline progression rate using machine learning algorithms. Results Compared with the healthy participants, the patients with ALS showed significantly decreased clustering coefficient C p (P = 0.0034, t = 2.98), normalized clustering coefficient γ (P = 0.039, t = 2.08), and small‐worldness σ (P = 0.038, t = 2.10) at the global network level. The patients also showed decreased regional centralities in motor and non-motor systems including the frontal, temporal and subcortical regions. Using the single-subject structural connection matrix, our classification model could distinguish patients with fast versus slow progression rate with an average accuracy of 85%. Conclusion Disruption of the WM structural networks in ALS is indicated by weaker small-worldness and disturbances in regions outside of the motor systems, extending the classical pathophysiological understanding of ALS as a motor disorder. The individual WM structural network matrices of ALS patients are potential neuroimaging biomarkers for the baseline disease progression in clinical practice.

Abstract Idiopathic blepharospasm shows a female predominance in prevalence, whether there are sex-related differences in distributions of nonmotor symptoms (NMSs) and predictors of quality of life are unknown. Four hundred and twenty-five patients with idiopathic blepharospasm were consecutively recruited, and underwent assessments including dystonia severity, mood disturbances, sleep disturbances, cognition, ocular symptoms, and quality of life. Frequencies and distributions of NMSs, and predictors of quality of life in female and male patients were investigated. NMSs existed in majority of male (94.0%) and female (95.8%) patients. The frequencies of depression, cognition dysfunction, and poor sleep quality were higher in female patients, while the frequency of excessive daytime sleepiness was higher in male patients. More female (79.5%) patients had multiple NMS domains affected than male (70.1%) patients (p = 0.040). Quality of life was associated with depression, anxiety and motor severity for female patients (adjusted R2 = 0.367, p

Abstract Background Cognitive impairment is a common non-motor symptom in patients with Parkinson’s disease (PD). Mild cognitive impairment (MCI) is also prevalent in nondemented PD patients, even in newly diagnosed PD patients. The possible impacts of MCI on brain function activities for PD patients need more investigation, and the potential of emerging technologies for detecting underlying pathophysiology of cognitive signs in PD can be further improved. Method Forty-seven newly diagnosed drug-naïve PD patients (28 PD-MCI patients and 19 PD patients with cognitively unimpaired (PD-CU)) and 28 healthy controls (HCs) underwent resting-state functional MRI. The connectivity patterns of specific networks were investigated through the independent component analysis among PD-MCI, PD-CU and HCs groups. Results The independent component analysis revealed significantly decreased functional connectivity (FC) of the default mode network, visual network and sensorimotor network in the PD-MCI subgroup compared with the HC group. Furthermore, FC of the default mode network was positively correlated with memory scores from the brief visuospatial memory test-revised, and FC of the visual network was positively correlated with visuospatial scores from the clock copying test in the PD-MCI group. In all patients with PD, FC of the sensorimotor network negatively correlated with motor severity scores from the Unified PD Rating Scale (UPDRS) part III. On the other hand, the potential damage was more likely to occur in FC between the sensorimotor network and limbic network, and between the ventral attention network and visual network in all PD patients. Conclusions Newly diagnosed drug-naïve PD-MCI patients showed characteristic damage of FC within the default mode network, visual network and sensorimotor network, and all PD patients presented impaired FC between the sensorimotor network and limbic network, and FC between the ventral attention network and visual network. These network-wide functional aberrations may underline the pathophysiology of PD.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by loss of the upper and lower motor neurons from the motor cortex, brainstem, and spinal cord. Most ALS cases are sporadic, with 5–10% having a positive family history. Autosomal dominant polycystic kidney disease (ADPKD) is a heritable renal disease that eventually results in end-stage kidney disease. PKD1 is the most prevalent causative gene for ADPKD, accounting for ~85% of cases. Both diseases are currently considered untreatable. In this study, we report a large family that includes 10 patients with ALS phenotype, 3 asymptomatic SOD1-H47R carriers, and 6 with the ADPKD phenotype. Using whole exome sequencing, we found a novel likely pathogenic variant (p.R2787P) in PKD1 among patients with ADPKD, and a pathogenic variant (p.H47R) in SOD1 among patients with ALS. This study highlights the possibility that two different autosomal dominantly inherited diseases can co-exist independently within the same family. Phenotype—genotype correlations among these patients are also described. This research contributes novel phenotype and genotype characteristics of ALS with SOD1 mutations and ADPKD with PKD1 mutations.

Abstract Background Multiple system atrophy (MSA) is an incurable neurodegenerative disease. We aimed to investigate the health‐related quality of life (HRQoL) and the determinants of HRQoL in patients with MSA. Methods The five‐level EuroQol five‐dimensional questionnaire (EQ‐5D‐5L) was used to evaluate patients’ HRQoL. The results of HRQoL were indicated by the EQ‐5D‐5L index values and visual analog scale (EQ VAS) scores. Specific scales were used to measure disease severity, cognition, frontal lobe function, anxiety, depression, fatigue, and sleep disorders. The beta mixture model and the linear regression model were used to explore the determinants of HRQoL in patients with MSA. Results A total of 205 patients with cerebellar variants (MSA‐C; 53.9%) and 175 patients with parkinsonian variants (MSA‐P; 46.1%) were included in this cross‐sectional study. The mean values of the EQ‐5D‐5L index values and EQ VAS scores were .558 and 59.5, respectively. Problem with mobility was the problem reported by the highest proportion of patients (92.1%), followed by problems with usual activities (88.7%), self‐care (81.3%), anxiety/depression (72.1%), and pain/discomfort (53.9%). The determinants of the lower EQ‐5D‐5L index values in patients with MSA were greater disease severity, fatigue, Parkinson's disease‐related sleep problems (PD‐SP), depressive mood, and anxious mood. Greater disease severity, fatigue, and depressive mood were associated with lower EQ VAS scores. Conclusion The problem reported most frequently by Chinese individuals with MSA was mobility. In addition to the greater disease severity of MSA, fatigue, PD‐SP, depression, and anxiety were determinants of poor HRQoL.

Abstract The progression of global non-motor symptoms (NMS) in Chinese patients with Parkinson’s disease (PD) has not been explored. We aimed to examine the longitudinal evolution of overall NMS in a 3-year prospective Chinese cohort with early-stage PD. We included 224 patients with early PD who underwent annual evaluation of motor and non-motor symptoms. NMS was assessed using the non-motor symptoms scale (NMSS). We observed an increased number of NMS in the majority of the NMSS domains except mood/apathy and sexual dysfunctions. Significant deterioration was observed in the sleep/fatigue, perceptual problems/hallucinations, attention/memory, gastrointestinal, urinary, and miscellaneous domains during the follow-up (P

PurposeThe study aimed to evaluate the health-related quality of life (HRQoL) measured by the five-level EuroQol-5 dimensions (EQ-5D-5L) in patients with cervical dystonia, and to explore the determinants of HRQoL in patients with cervical dystonia.MethodsEQ-5D-5L health state profiles were converted into a single aggregated “health utility” score. A calibrated visual analog scale (EQ VAS) was used for self-rating of current health status. Multiple linear regression analysis was used to explore the factors associated with HRQoL in cervical dystonia.ResultsA total of 333 patients with cervical dystonia were enrolled in the analysis, with an average age of 44.3 years old. The most common impaired dimension of health was anxiety/depression (73.6%), followed by pain/discomfort (68.2%) and usual activities (48%). The median health utility score was 0.80, and the median EQ VAS score was 70.2. Multivariate linear regression analysis indicated that disease duration and the scores of the Hamilton Depression Rating Scale (HDRS), Pittsburgh sleep quality index (PSQI), Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Part I, and TWSTRS Part III were associated with the health utility scores. After adjusting other parameters, the TWSTRS Part III score and the HDRS score were significantly associated with the EQ VAS scores (p < 0.05).ConclusionThis study evaluated HRQoL in patients with cervical dystonia using the Chinese version of the EQ-5D-5L scale. We found that, besides motor symptoms, non-motor symptoms, including depression, pain, and sleep quality, could be greater determinants of HRQoL in patients with cervical dystonia. Management of non-motor symptoms, therefore, may help improve HRQoL in patients with cervical dystonia.

The ecological environment of inland river basins in arid zones is extremely fragile, and even small changes in the ecosystem may greatly influence the ecological protection of the basin. Most of the previous studies on the construction and optimization of ecological safety patterns, directly used large areas of water, grassland, and woodland as ecological source sites without considering the connectivity between landscapes. In this study, the large landscape connectivity index and the probability of connectivity values were used to determine the ecological source areas, taking landscape connectivity into account. Ebinur lake basin is an important barrier in northwest China. Taking Ebinur lake basin as a research object, the results show that: (1) there are 20 important ecological sources in the Ebinur Lake basin, mainly in the water and forest-grassland areas, including two waters ecological source areas in Ebinur Lake and Sayram Lake; (2) 190 ecological corridors were estimated by the minimum cumulative resistance model, and 59 level 1 ecological corridors were mainly located in the western part of Ebinur Lake, and 70 level 2 ecological corridors were also mainly located in the western part of Ebinur Lake by the gravity model after removing the redundant ecological corridors. (3) Based on hotspot and spatial directional analyses of ecological resistance and habitat quality, the ecological security pattern of 'four zones and two belts' was constructed. This can provide a reference for the protection and restoration of the ecological environment in the inland basin of the arid zone.

BackgroundSex is an important factor in studying the relationship between the APOE gene, lipid profiles, and AD. However, few studies have focused on the effect of sex on lipids in AD and normal controls with different APOE genes.Materials and MethodsA total of 549 participants, including 298 AD patients and 251 body mass index (BMI)-matched healthy controls (HCs), were enrolled. Lipid profiles and APOE genes in both AD patients and HCs were determined.Results(1) TC and LDL were higher in AD patients than in HCs, only in APOEε4 carrying populations, but not in non-carrying populations. (2) TC and LDL were higher in APOEε4 allele carriers than in non-carriers, only in AD populations, but not in HCs. (3) The TC of APOEε2 carriers was lower than that of non-carriers in the male AD population, but not in the female AD population, female HCs, and male HCs. (4) The increased LDL level may increase the risk of AD in female people carrying APOEε4.ConclusionThe TC and LDL levels of APOEε4 carriers were higher than those of non-carriers, and the effect was more significant in the female AD population. The TC levels in APOEε2 carriers were lower than those in non-carriers, which was more significant in the male AD population.

Abstract Objective To evaluate whether the control status of type 2 diabetes mellitus (DM) influences the progression of Parkinson’s disease (PD). Methods We conducted a prospective cohort study from March 2009 to August 2020. Patients at baseline were categorized into DM and non‐DM groups, and those with DM were further classified into the well and poorly controlled DM groups based on the 7.0% of glycated hemoglobin (HbA1C) levels. Multivariate Cox proportional hazards regression models were used to explore the predictors for PD‐related outcomes by hazard ratios (HRs) and 95% confidence intervals (CIs). Results Of the 379 patients enrolled, 49 (12.9%) had DM, and 22 of DM (44.9%) were poorly controlled. The adjusted HRs were 2.060 (95% CI 1.165‐3.641) for United Rating Scale (UPDRS) III score increased ≥14 in the poorly controlled‐DM group, and 1.066 (95% CI 0.572‐1.986) in the well‐controlled DM group, relative to the non‐DM group (p trend = 0.025), after adjusting for sex, age, age of onset, body mass index, and UPDRS III and Montreal Cognitive Assessment (MoCA) scores at baseline. The adjusted HRs were 2.079 (95% CI 1.212‐3.566) for reaching Hoehn & Yahr stage ≥3 in the poorly controlled DM group, and 0.879 (95% CI 0.413‐1.871) in the well‐controlled DM group, compared with the non‐DM group (p trend = 0.021). Time to death or time to MoCA 3‐point decrease were not significantly different among the three groups. Interpretation Poorly controlled DM is an independent risk factor contributing to motor progression in PD. Our study highlights the importance of adequate control of diabetes in PD.

Abstract Chronic pain is a significant public health problem that afflicts nearly 30% of the global population, but current pharmacotherapies are insufficient. Previous report indicated that N-demethylsinomenine, an active metabolite of sinomenine, is efficacious against postoperative pain. The present study investigated whether N-demethylsinomenine is effective for chronic painful conditions or whether repeated treatment alters its effect. Both chronic constriction injury (CCI) surgery and complete Freund’s adjuvant (CFA) intraplantar injection induced significant and reliable mechanical allodynia at least for 7 days. Acute treatment with N-demethylsinomenine (10–40 mg/kg, i.p.) dose-dependently attenuated the mechanical allodynia both in CCI-induced neuropathic pain and CFA-induced inflammatory pain in mice. The potency of N-demethylsinomenine for reducing CFA-induced mechanical allodynia was slightly higher than sinomenine. During the period of repeated treatment, N-demethylsinomenine maintained its anti-allodynic effect against both neuropathic and inflammatory pain without producing carry-over effect. Pretreatment with bicuculline, a selective γ-aminobutyric acid type A (GABAA) receptor antagonist, almost completely blocked the anti-allodynia of N-demethylsinomenine (40 mg/kg) both in CCI and CFA-treated mice. Our findings indicated that N-demethylsinomenine exhibits GABAA receptor-mediated anti-allodynic effects in mouse models of neuropathic and inflammatory pain, suggesting it may be a useful novel pharmacotherapy for the control of chronic pain.