Background and AimTianqi Pingchan Granule (TPG), as a traditional Chinese medicine, is used in the treatment of Parkinson's disease. L-DOPA-induced dyskinesia (LID) is mentioned as a debilitating motor complication in the course of Parkinson's disease. The purpose of this study is to investigate the effects of TPG on LID via the pathway of the glymphatic system.Experimental procedureA rat model of LID was used in this study. The severity of LID was assessed by behavioural tests. Three doses of TPG were administered once a day for 3 weeks to investigate the role of TPG in behavioural characteristics of LID rats. The glymphatic function was evaluated by utilizing intracisternal infusion of a fluorescenttracer. The amyloid-β levels were measured by Enzyme-linked immunosorbent assay. The expression and distribution of, and GFAP were assessed using immunofluorescence.Results and ConclusionDose-dependent effects of TPG in the 1behavioural characteristics were observed. Cortical and striatal influx cerebral spinal fluid tracer were reduced in LID rats with impaired AQP4 polarization. Amyloid-β, AQP4, and reactive astrogliosis was upregulated in LID rats. TPG administration increased cerebral influx of fluorescent tracer, restored polarized localization and expression of AQP4, and attenuated L-DOPA-induced amyloid-β deposits and astrogliosis. This study shows for the first time that glymphatic system function is impaired in LID and TPG attenuates abnormal involuntary movements in rats with LID by protecting the glymphatic system.Section1. Natural Products; 3. Dietary therapy supplements; 4. History, Philosophy and Social-Cultural aspects of Traditional Medicine.Taxonomy (classification by EVISE)identify the disease condition, the experimental approach.

Twenty-four-hour movement behaviors have significant implications for physical and mental health throughout one’s lifespan. Consistent with movement behaviors, several countries have formulated and published 24-h movement guidelines. This review summarized the studies related to 24-h movement guidelines among children and adolescents from six databases (MEDLINE, EMBASE, PubMed, Web of Science, CINAHL, and SPORTDiscus). In a total of 61 studies that discussed compliance with 24-h movement guidelines, the overall adherence rate was very low (7.1%), with boys exceeding girls, children surpassing adolescents, and regional differences. A total of 39 studies examined the associations between 24-h movement guidelines and health indicators. Findings indicated that meeting all three guidelines was favorably associated with adiposity, cardiometabolic health, mental and social health, physical fitness, health-related quality of life, academic achievement, cognitive development, perceived health, dietary patterns, and myopia. Future research should utilize longitudinal and experimental designs to enhance our understanding of the associations between 24-h movement guidelines and health indicators, thereby aiding the formulation and refinement of such guidelines.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, CRD42023481230.

Inflammation significantly impacts Parkinson’s disease (PD), yet the intricate relationship between inflammatory markers and PD remains elusive. To identify the peripheral biomarkers of PD and its correlation with the motor and non-motor symptoms of PD. 79 PD patients and 65 controls were included in this study. Clinical information and the serum levels of IL-8, IL-27, IL-33, β-NGF, AgRP, and TRAILR2 in the participants were collected. Appropriate scales were used to assess the symptoms of PD. For the factors with significant differences in the two groups, multivariable logistic regression was used to determine its relationship with PD. Moreover, spearman correlation was conducted to explore the correlation between the factors and PD related symptoms. The IL-27 level was compared between the cognitively healthy PD group and the mild cognitive impairment in PD (PD-MCI). The serum level of TRAILR2 was positively correlated with age and was not associated with other clinical characteristics related to PD. Compared to controls, the serum levels of IL-27(P = 0.013) were increased whereas the levels of TRAILR2(P = 0.008) were decreased in PD patients. IL-8, IL-33, β-NGF, and AgRP showed no significant differences between the two groups. After controlling for the other variables, IL-27 was considered as an independent risk factor for PD in the multivariable logistic regression model. The receiver operating characteristic (ROC) curve for diagnosing PD with IL-27 yielded an area under the curve (AUC) of 0.621. Additionally, IL-27 level in PD patients was positively correlated with age, the disease duration, LEDD and negatively correlated with the MoCA scores. However, no significant difference was found in IL-27 levels between cognitively healthy PD and PD-MCI groups. Elevated serum IL-27 was a risk factor for PD and positively correlated with the cognitive decline in PD.

IntroductionThe primary treatment for non-alcoholic fatty liver disease (NAFLD) is modifying lifestyle through dietary or exercise interventions. In recent decades, it has received increasing attention. However, the lack of bibliometric analysis has posed a challenge for researchers seeking to understand the overall trends in this field.MethodsAs of February 3rd, 2024, 876 articles on treating NAFLD through diet or exercise therapy from 2013 to 2023 had been retrieved. Two software tools, VOSviewer and CiteSpace, were utilized to analyze the growth of publications, countries, institutions, authors, journals, citations, and keywords. Additionally, the keywords with strong citation burstiness were identified to determine the changes and future trends of research hotspots in this field.ResultsChina had the highest number of articles, followed by the United States and South Korea. Yonsei University and Nutrients were the institutions and journals with the most significant contributions. Professor Younossi Zobair M, from the United States, is the most prolific author in this field. Through analyzing the keywords, three research hotspots were identified: research on the pathogenesis of NAFLD, research on the treatment modalities of NAFLD, and research on the risk factors and diagnosis methods of NAFLD. In recent years, the research emphasis in this field has changed, suggesting that future research will focus on two frontier keywords: “oxidative stress” and “aerobic capacity.”ConclusionIn the past eleven years, the attention in this field was still rising, and the authors, journals, countries and so on had formed a considerable cooperative relationship. There were also many highly influential and productive researchers in this field. It is speculated that new research will continue around “aerobic exercise” and “oxidative stress” in the future.

Non-alcoholic fatty liver disease(NAFLD)is a liver condition that is widely prevalent across the world.A considerable number of people with NAFLD have the potential to prog-ress to a more severe form of the condition known as nonalcoholic steatohepatitis(NASH),accompanied by bridging fibrosis.This advancement is more likely if the patient has metabolic risk factors such as obesity or type 2 diabetes that deteriorate over time.Additionally,even slight inflammation or fibrosis in NAFLD can significantly increase the likelihood of progression compared to steatosis alone.This underscores the importance of revising the present methods of monitoring NAFLD patients to ensure early detection and effective management of the disease.

Abstract Background Parkinson’s disease (PD) is a slowly progressive neurodegenerating disease that may eventually lead to disabling condition and pose a threat to the health of aging populations. This study aimed to explore the association of two potential risk factors, selenium and cadmium, with the prognosis of Parkinson’s disease as well as their interaction effect. Methods Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2005–2006 to 2015–2016 and National Death Index (NDI). Participants were classified as Parkinson’s patients by self-reported anti-Parkinson medications usage. Cox regression models and restricted cubic spline models were applied to evaluate the association between PD mortality and selenium intake level as well as blood cadmium level. Subgroup analysis was also conducted to explore the interaction between them. Results A total of 184 individuals were included. In full adjusted cox regression model (adjusted for age, gender, race, hypertension, pesticide exposure, smoking status and caffeine intake), compared with participants with low selenium intake, those with normal selenium intake level were significantly associated with less risk of death (95%CI: 0.18–0.76, P = 0.005) while no significant association was found between low selenium intake group and high selenium group (95%CI: 0.16–1.20, P = 0.112). Restricted cubic spline model indicated a nonlinear relationship between selenium intake and PD mortality (P for nonlinearity = 0.050). The association between PD mortality and blood cadmium level was not significant (95%CI: 0.19–5.57, P = 0.112). However, the interaction term of selenium intake and blood cadmium showed significance in the cox model (P for interaction = 0.048). Subgroup analysis showed that the significant protective effect of selenium intake existed in populations with high blood cadmium but not in populations with low blood cadmium. Conclusion Moderate increase of selenium intake had a protective effect on PD mortality especially in high blood cadmium populations.

BACKGROUND:Patients with Parkinson's disease (PD) undergoing long-term levodopa therapy are prone to develop levodopa-induced dyskinesia (LID). Amantadine is the main drug recommended for the treatment of LID by current guidelines, but it is far from meeting clinical needs. Tianqi Pingchan Granule (TPG), a compound Chinese herbal medicine, has been developed to relieve symptom of LID. OBJECTIVE:This randomized controlled trial evaluated the efficacy and safety of the combination of TPG and amantadine for LID. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS:This is a randomized double-blind placebo-controlled trial, conducted from January 2020 to August 2021 at 6 sites in Jiangsu, Zhejiang and Shanghai, China. One hundred PD patients with ≥ 0.5 h of LID were randomly assigned to either the TPG plus amantadine group (TPG group) or the placebo plus amantadine group (placebo group), and treated for a period of 12 weeks. To ensure unbiased results, all study participants, investigators and sponsors were unaware of group allocations. Additionally, the data analysts remained blinded until the analysis was finalized. MAIN OUTCOME MEASURES:The primary outcome was assessed using the Unified Dyskinesia Rating Scale (UDysRS) (Range 0-104). The key secondary end point was improvement of motor and non-motor symptoms. Safety analyses included all enrolled patients. RESULTS:One hundred patients were enrolled and randomized into the two treatment groups. The changes in UDysRS at week 12 were -11.02 for the TPG group and -4.19 for the placebo group (treatment difference -6.83 [-10.53 to -3.12]; P = 0.0004). Adverse events were reported for 2 of 50 patients (4.0%) in each of the groups. CONCLUSION:This study indicated that a 12-week treatment of amantadine plus TPG effectively reduced UDysRS scores and was well tolerated, demonstrating the efficacy and safety of TPG for the treatment of LID in PD. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT04173832. PLEASE CITE THIS ARTICLE AS:Zhang Y, Zhu XB, Zhao Y, Cui GY, Li WT, Yuan CX, Huang JP, Wan Y, Wu N, Song L, Zhao JH, Liang Y, Xu CY, Liu MJ, Gao C, Chen XX, Liu ZG. Efficacy and safety of Tianqi Pingchan Granule, a compound Chinese herbal medicine, for levodopa-induced dyskinesia in Parkinson's disease: A randomized double-blind placebo-controlled trial. J Integr Med. 2024; 22(5): 545-551.

Non-alcoholic fatty liver disease (NAFLD) is usually associated with obesity. However, it is crucial to recognize that NAFLD can also occur in lean individuals, which is frequently overlooked. Without an approved pharmacological therapy for lean NAFLD, we aimed to investigate whether the Ganjianglingzhu (GJLZ) decoction, a representative traditional Chinese medicine (TCM), protects against lean NAFLD and explore the potential mechanism underlying these protective effects. The mouse model of lean NAFLD was established with a methionine-choline-deficient (MCD) diet in male C57BL/6 mice to be compared with the control group fed the methionine-choline-sufficient (MCS) diet. After four weeks, physiological saline, a low dose of GJLZ decoction (GL), or a high dose of GJLZ decoction (GH) was administered daily by gavage to the MCD group; the MCS group was given physiological saline by gavage. Untargeted metabolomics techniques were used to explore further the potential mechanism of the effects of GJLZ on lean NAFLD. Different doses of GJLZ decoction were able to ameliorate steatosis, inflammation, fibrosis, and oxidative stress in the liver; GL performed a better effect on lean NAFLD. In addition, 78 candidate differential metabolites were screened and identified. Combined with metabolite pathway enrichment analysis, GL was capable of regulating the glucose and lipid metabolite pathway in lean NAFLD and regulating the glycerophospholipid metabolism by altering the levels of sn-3-O-(geranylgeranyl)glycerol 1-phosphate and lysoPC(P-18:0/0:0). GJLZ may protect against the development of lean NAFLD by regulating glucose and lipid metabolism, inhibiting the levels of sn-3-O-(geranylgeranyl)glycerol 1-phosphate and lysoPC(P-18:0/0:0) in glycerophospholipid metabolism.

Introduction:Gan–jiang–ling–zhu (GJLZ) decoction is a classical traditional Chinese medicine prescription. Through invigorating yang, activating qi and dissipating dampness, GJLZ decoction is widely applied for the treatment of chronic digestive disease, including nonalcoholic fatty liver disease. However, efficacy and mechanism of GJLZ decoction behind nonalcoholic steatohepatitis (NASH) treatment remains unelucidated.Methods: NASH was induced in mice, followed by treatment with GJLZ decoction. Various methods including hematoxylin-eosin, oil red O staining, and triglyceride analysis were employed to evaluate the treatment effects of GJLZ decoction on NASH. Gut microbiota, metabolomics, cell viability assays, immunofluorescence and Western blotting were performed to unveil the mechanism behind GJLZ decoction.Results: GJLZ decoction treatment significantly improved hepatic steatosis in mice with NASH. It led to remodeling of gut flora and metabolite structures, including the 12-tridecenoic acid level. 12-Tridecenoic acid aggravated hepatic steatosis by promoting acetyl-coenzyme A carboxylase alpha (ACC) expression and inhibiting carnitine palmitoyltransferase 1A (CPT1A) expression. GJLZ decoction treatment reduced the 12-tridecenoic acid level, inhibited ACC activity and promoted CPT1A expression.Conclusion: Our results demonstrated that 12-tridecenoic acid aggravated hepatic steatosis by affecting the ACC–CPT1A axis and GJLZ decoction treatment effectively reduced the 12-tridecenoic acid level and improved steatosis.

Objective: This study aimed to investigate the association between single-nucleotide polymorphisms (SNPs) ofPCSK1 (proprotein convertase subtilisin/kexin type 1) related to obesity and nonalcoholic fatty liver disease (NAFLD).Methods: In this case-control observational study, four candidate SNPs (rs6234, rs155971, rs6232, rs3811951) ofPCSK1 were genotyped in 732 NAFLD patients and 823 healthy control participants, all of whom were of ethnic Han Chinese descent. All participants came from Shanghai, China, and joined our study during 2015 to 2016. The frequencies of each allele and genotype, paired linkage disequilibrium, and haplotype were calculated on the SHEsis platform. In addition to SHEsis, five different genetic models (codominant, dominant, recessive, overdominant, and log-additive) were employed to identify the correlation between genotype frequency and NAFLD. This study was approved by the Medical Ethics Committee of Shanghai University of Traditional Chinese Medicine (approved No. 2017LCSY069).Results: In a comparison of NAFLD patients and healthy participants, none of the fourPCSK1 SNPs were significantly correlated with the occurrence of NAFLD (P>0.05), in either genotypic or allelic distribution. The recessive model of rs3811951 appeared to show a correlation (odds ratio=1.077; 95% confidence interval=0.924-1.256;P=0.04), but there was no statistical significance after Bonferroni correction (Pcorr>0.0125).Conclusions: Four obesity-relatedPCSK1 SNPs (rs6234, rs155971, rs6232, rs3811951) showed no significant correlation with the development of NAFLD in a Han Chinese population.

ObjectiveParkinson’s disease (PD) is marked not only by motor symptoms but also by neuropsychiatric manifestations, including demoralization, apathy, and depression. Understanding the clinical distribution and characteristics of these co-occurring symptoms is crucial for improving quality of life of PD patients.MethodsThis study enrolled 195 Chinese PD patients from Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine. The study involved analyzing the clinical characteristics related to the simultaneous presence of demoralization, apathy, and depression in PD patients. Linear regression was employed to elucidate the linear trend between the quantity of negative neuropsychiatric symptoms and cognitive function, as well as motor symptoms and motor complications. SPSS mediation models were utilized to investigate whether the severity of cognitive function mediated the connection between multiple negative neuropsychiatric symptoms and motor symptoms.ResultsAmong PD patients, a notable 57.5% experience the presence of multiple concurrent negative neuropsychiatric symptoms. Our investigation unveiled a correlation where patients with more negative neuropsychiatric symptoms displayed heightened cognitive impairment (P=0.048) and more severe motor symptoms (P=0.024), following a linear trend with increasing symptom numbers. Additionally, cognitive impairment played a partial mediating role in the impact of multiple negative neuropsychiatric symptoms on motor symptoms (β=0.747; 95% bootstrap confidence interval: 0.195 to 1.532).ConclusionsThe co-occurrence of these negative neuropsychiatric symptoms has the potential to worsen cognitive function and motor symptoms in PD patients. Moreover, cognitive impairment was identified as playing a partial mediating role in the relationship between multiple negative neuropsychiatric symptoms and motor symptoms.

Objective:Impulse control behaviors (ICBs) frequently coexist with Parkinson's disease (PD). However, the predictors of ICBs in PD remain unclear, and there is limited data on the biological correlates of ICBs in PD. In this study, we examined clinical, imaging, and biological variables to identify factors associated with longitudinal changes in ICBs in early-stage PD. Methods:The data for this study were obtained from the Parkinson's Progression Markers Initiative, an international prospective cohort study that evaluates markers of disease progression in PD. We examined clinical, imaging, and biological variables to determine their associations with ICBs over a period of up to 5 years. Cox regression models were employed to investigate the predictors of ICBs in early-stage, untreated PD. Results:The study enrolled 401 individuals with PD and 185 healthy controls (HC). At baseline, 83 PD subjects (20.7%) and 36 HC (19.5%) exhibited ICBs. Over the course of 5 years, the prevalence of ICBs increased in PD (from 20.7% to 27.3%, p < 0.001), while it decreased in HC (from 19.5% to 15.2%, p < 0.001). Longitudinally, the presence of ICBs in PD was associated with depression, anxiety, autonomic dysfunction, and excessive daytime sleepiness (EDS). However, there was no significant association observed with cognitive dysfunction or motor severity. Treatment with dopamine agonists was linked to ICBs at years 3 and 4. Conversely, there was no association found between ICBs and presynaptic dopaminergic dysfunction. Additionally, biofluid markers in baseline and the first year did not show a significant association with ICBs. A predictive index for ICBs was generated, incorporating three baseline characteristics: anxiety, rapid eye movement sleep behavior disorder (RBD), and p-tau levels in cerebrospinal fluid (CSF). Conclusion:During the early stages of PD, there is a notable increase in ICBs over time. These ICBs are associated with depression, anxiety, autonomic dysfunction, EDS, and the use of dopaminergic medications, particularly dopamine agonists. Anxiety, RBD, and p-tau levels in CSF are identified as predictors for the incident development of ICBs in early PD. Further longitudinal analyses will provide a more comprehensive understanding of the associations between ICBs and imaging findings, as well as biomarkers. These analyses will help to better characterize the relationships and implications of these factors in the context of ICBs in early PD.

We aimed to develop an accurate model to predict live birth for patients receiving in vitro fertilization and embryo transfer (IVF-ET) treatment. This is a prospective nested case–control study. Women aged between 18 and 38 years, whose body mass index (BMI) were between the range of 18.5–24 kg/m2, who had an endometrium of ≥ 8 mm at the thickest were enrolled from 2018/9 to 2020/8. All patients received IVF-ET treatment and were followed up until Jan. 2022 when they had reproductive outcomes. Endometrial samples during the window of implantation (LH + 6 to 9 days) were subjected to analyze specific endometrial receptivity genes’ expression using real-time PCR (RT-PCR). Patients were divided into live birth group and non-live birth group based on IVF-ET outcomes. Clinical signatures relevant to live birth were collected, analyzed, and used to establish a predictive model for live birth by univariate analysis (clinical model). Specific endometrial receptivity genes’ expression was analyzed, selected, and used to construct a predictive model for live birth by The Least Absolute Shrinkage and Selection Operator (LASSO) analysis (gene model). Finally, significant clinical factors and genes were used to construct a combined model for predicting live birth using multivariate logistical regression (combined model). Different models’ Area Under Curve (AUC) were compared to identify the most predictive model. Thirty-nine patients were enrolled in the study, twenty-four patients had live births, fifteen did not. In univariate analysis, the odds of live birth for women with ovulation dysfunction was 4 times higher than that for women with other IVF-ET indications (OR = 4.0, 95

Objective: Non-alcoholic fatty liver disease (NAFLD) affects almost a quarter of the world's population. Although NAFLD often co-exists with obesity, a substantial proportion of NAFLD patients are lean which is relatively unexplored. This study aimed to examine the association between genetic variation in candidate genes, e.g., TBC1D1 and the risk of lean NAFLD in the elderly Chinese Han population. Methods: This is an extension of the research on physical examination in the Zhanjiang community center including 5387 residents, Shanghai, China, in 2017. According to the classification in adult Asian populations, participants were categorized into four groups: lean NAFLD (BMI <23, n = 106), non-lean NAFLD (BMI ≥23, n = 644), lean non-NAFLD (BMI <23, n = 216) and non-lean non-NAFLD (BMI ≥23, n = 253).116 NAFLD-related candidate genes, which cover 179 single nucleotide polymorphisms (SNPs) were included in the KEGG enrichment analysis. Independent samples t-test was adopted for the group comparison. The associations between genetic variations with the specific phenotype in five genetic models were analyzed with the "SNPassoc" R package and rechecked with logistic regression analysis. Mediation models were conducted to explore whether the certain phenotype can mediate the association between SNPs and the risk of lean NAFLD. Results: Compared with lean non-NAFLD individuals, lean NAFLD patients had higher BMI, low-density lipoprotein and triglyceride, and lower HDL. The AMPK signaling pathway, which includes TBC1D1 and ADIPOQ genes, was the most significant (p < .001). The A allele frequency of rs2279028 in TBC1D1 (p = .006) and G allele frequency of rs17366568 in ADIPOQ (p = .038) were significantly lower in lean NAFLD. The association between rs2279028 and the risk of lean NAFLD was mediated by HDL (p = .014). No significant mediation effect was found between rs17366568 and the risk of lean NAFLD. Conclusion: This study, for the first time, indicated that rs2279028 of TBC1D1 may contribute to the progression of lean NAFLD through HDL. This finding provides more evidence for exploring the mechanism of lean NAFLD and suggests practical solutions for the treatment of lean NAFLD.

ObjectiveThis study aimed to assess the evolution of dynamic balance impairment during the course of Parkinson's disease (PD) and to clarify the contribution of striatal dopaminergic innervation to poor dynamic balance.MethodsIn our study, 89 patients with PD (divided into 2 groups according to the H-Y stage) and 39 controls were included. Kinematic data were recorded by a portable inertial measurement unit system. Dopaminergic loss in the striatal subregion was verified through the 11C-CFT PET examination. The severity of white matter hyperintensities (WMHs) was assessed by the Scheltens scale. The correlation between dynamic kinematic parameters and dopamine transporter availability was analyzed by multivariate regression analysis.ResultsPatients with early PD presented with imbalance featured by smaller three-dimensional trunk ROM with reduced trunk coronal angular velocity during walking and with reduced trunk sagittal angular velocity during the stand-to-sit task (all p < 0.05). These abnormalities were not more severe at a later stage. The ROM in the coronal and transverse planes during walking correlated with caudate DAT uptake (β = 0.832, p = 0.006, Q = 0.030, and β = 0.890, p = 0.003, Q = 0.030) after controlling for age, gender, and WMHs. As the disease progressed, the trunk sagittal and transverse angular velocities during walking and trunk sagittal angular velocity when turning and sitting-to-standing were slower, which was accompanied by reduced gait velocity gradually (all p < 0.05). These parameters related to disease progression have no association with striatal DAT uptake (all p > 0.05).ConclusionThe dynamic balance in PD was impaired from the early stages, and the characteristics of the impairment changed differently as the disease progressed. Dopaminergic denervation has a lower contribution to dynamic balance disorders throughout PD.

通过比较R语言和SPSS软件的特点,重点探讨R语言在分子流行病学领域的应用优势.R语言作为一种自由开源的编程语言,具有强大的数据处理和分析能力,适用于处理大规模和复杂的分子数据.其丰富的统计函数和数据包使得医学院校研究生可以进行高级统计建模和生物信息学分析,满足分子流行病学研究的需求.本研究通过R语言在分子流行病学研究中的应用实例,展示了R语言处理相关数据的功能.医学类高等院校教师应根据时代要求和现实需要,培养研究生应用R语言处理分析大数据的能力.

Pre-obesity, as a significant risk factor for the progression of metabolic syndrome (MS), has become a prevalent public health threat globally. In this three-year longitudinal study of pre-obese women at baseline, the goal was to clarify the female-specific bidirectional relationship between the risk of MS and blood alanine aminotransferase. In this manuscript, the MS score was determined using the following equation: MS score = 2*waist/height + fasting glucose/5.6 + TG/1.7 + SBP/130-HDL/1.02 for men and 1.28 for women, which is highly related to the risk of MS. With 2,338 participants, a hierarchical nonlinear model with random effects was utilized to analyze the temporal trends of serum characteristics from 2017 to 2019. A bivariate cross-lagged panel model (CLPM) was employed to estimate the structural relations of frequently measured variables at three different time points to determine the directionality of the relationship between the risk of MS and serum characteristics. MassARRAY Analyzer 4 platforms were used to evaluate and genotype candidate SNPs. In this study, the MS score only rose with age in females; it was positively correlated with serum alanine aminotransferase (ALT) in females; the CLPM revealed that the MS score in 2017 predicted ALT in 2018 (β = 0.066, p < 0.001); and ALT in 2018 predicted an MS score in 2019 (β = 0.037, p < 0.050); both relationships were seen in females. Additionally, the MS score in elderly females with NAFLD was related to the rs295 in the lipoprotein lipase (LPL) gene (p = 0.042). Our work showed that there may be female-specific causal correlations between elevated ALT and risk of MS and that the polymorphism rs295 in LPL may serve as a marker for the prognosis of MS. The genetic roles of rs295 in the LPL gene in the onset of MS and the development of ALT in the elderly Chinese Han population are thus provided by this, offering one potential mechanism.

Objective: To analyze the efficacy of different targets low-frequency repetitive transcranial magnetic stimulation (rTMS) for the treatment of tremor Parkinson's disease(PD). Method: A total of 82 patients with primary PD who were admitted to the Department of Neurology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 1, 2020 to March 31, 2021 were prospectively collected. According to the clinical characteristics of major movement disorders, 82 patients with tremor type (TD) were selected to enroll.The patients were randomly divided into 3 groups at a 1∶1∶1 ratio according to the randomized coding sequence of the trial: the primary motor cortex (M1) group with 26 cases, the cerebellum group with 26 cases and the dual-site (M1, cerebellum) group with 30 cases. All patients were treated with 1 Hz low-frequency stimulation of the corresponding target once a day for 5 days a week for 2 weeks, a total of 10 times; The dosage remained unchanged during the treatment for all groups. Before and after 2 weeks' treatment, the patients were assessed with the Unified PD Rating Scale (UPDRS) and PD Quality of Life Questionnaire-39 (PDQ-39) without medication. Cortical excitability, namely transcranial magnetic stimulation motor evoked potential (TMS-MEP), [including resting motor threshold (rMT) and active motor threshold (aMT) examinations], timed up and go (TUG) and electromyographic tremor were conducted. Result: There were 82 patients, 39 males and 43 females, with an average age of (67±8) years. Before the treatment, there was no statistically significant difference in the evaluation indicators among the three groups (all P>0.05). After the treatment, the differences of the UPDRS-Ⅲ score [(38.9±2.5) vs (29.2±3.6) ], UPDRS tremor score [(23.7±2.1) vs (14.6±3.1) ], TUG time [(44.8±3.1) s vs (33.7±4.1) s], tremor amplitude [(480±126) μV vs (276±94) μV], PDQ-39 score [(51±13) vs (45±13) ], rMT [(36±17)% vs (43±13)%], and aMT [(26±16)% vs (31±12)%] were statistically significant (all P<0.01) from those before the treatment. There was no statistical difference in the above factors between the M1 group and cerebellum group (all P>0.05). There was no statistically significant difference in tremor peak frequency among the three groups before and after the treatment (all P>0.05). Conclusions: Dual-site low-frequency rTMS can improve PD tremor, while M1 or cerebellar low-frequency rTMS does not significantly improve PD tremor. Its mechanism may be to improve PD tremor symptoms by regulating cortical excitability.

We investigated the prevalence and clinical metabolic characteristics of lean nonalcoholic fatty liver disease (NAFLD) in an elderly Chinese population and assessed the relevance of lipid markers and genetic variation. All 5,338 community subjects underwent detailed clinical and laboratory examinations and were divided into three groups: lean (Body mass index (BMI) < 23 kg/m 2 , n = 2,012), overweight (BMI = 23–24.9 kg/m 2 , n = 1,354), and obese (BMI ≥ 25 kg/m 2 , n = 1,972). Single nucleotide polymorphisms were selected based on those reported in previous NAFLD or obesity genome-wide association studies. The frequencies of alleles and genotypes were calculated and statistically analyzed with Pearson’s χ 2 tests. One-way ANCOVA was used to test the association between positive SNPs and metabolic parameters in lean NAFLD individuals. Our results showed that the C allele frequency of rs2279026, the G allele of rs2279028, the C allele of rs780093, and the C allele frequency of rs1260326 were higher in obese NAFLD than in lean NAFLD (P < 0.05). In addition, we observed an association between the CC of rs1421085, TT of rs3751812, AA of rs8050136, and AA of rs9939609 genotypes in the FTO gene and low-density lipoprotein levels ( P < 0.05). In conclusion, our findings provide a unique perspective on the prevalence, genetic characteristics, and metabolic profile of NAFLD in older lean individuals in China. This is the first study to examine the association between genetic variants in the FTO , TFAP2B and GCKR genes and NAFLD in a cohort of lean individuals.

Objectives: To evaluate the clinical efficacy of the stratification medical treatment based on the motor complications risk estimation in improving the quality of life, motor symptoms and delaying the motor complications in Parkinson's patients. Methods: Outpatients and inpatients from Xinhua Hospital, Shanghai Jiao Tong University, were recruited between November 2019 and June 2020. The participants were all clinically diagnosed with PD and treated with anti-PD medications, but had no history of motor complications, with the 8-item Parkinson's disease questionnaire summary index (PDQ-8 SI)>18.59. At baseline, the demographic characteristics, PD medical history, levodopa dosage (LD) and levodopa equivalent dosage (LED) were collected, and the evaluation of PDQ-8, Unified Parkinson's disease rating scale (UPDRS)-Ⅱ and Ⅲ, Hoehn and Yahr (H&Y) grade, Hamilton anxiety scale-14 (HAMA-14), Hamilton depression scale-24 (HAMD-24), mini-mental state examination (MMSE), Pittsburgh sleep quality index (PSQI), and Epworth sleepiness scale (ESS) tools was accomplished in all participants. Meanwhile, a Parkinson's disease risk estimation scale for motor complications was used to assess patients' risk of motor complications, and thus the medication was stratified in PD patients accordingly. During the 6-month and 12-month follow-ups, the evaluation of the above-mentioned parameters was repeated in all participants. At the 3-month and 9-month follow-ups, the information of anti-PD medications, the occurrence of motor complications (motor fluctuations and dyskinesia) and adverse drug reactions were recorded, and PDQ-8 was also evaluated. Results: Two hundred and fifty-one patients completed the 1-year follow-up, with 135 males and 116 females. At baseline, the median age of the patients was 66 (60, 71) years and the median PDQ-8 SI was 31.2 (21.9, 40.6). Additionally, 15.9% (40/251) of the patients were at high risk of motor fluctuation, and 7.2% (18/251) were at high risk of dyskinesia. There were significant differences in the age of onset, disease duration, PD treatment duration, the scores of UPDRS-Ⅱ and Ⅲ, H&Y Grade, and PDQ-8 SI among PD patients of different risk groups (all P<0.05). In the 12th month, the median of PDQ-8 SI, Δ PDQ-8 SI and Δ UPDRS-Ⅲ was 12.5 (9.4, 18.8), -15.6 (-21.9, -9.4) and -9(-16, -4), respectively, which was statistically different from that of baseline (all P<0.05). The change of UPDRS-Ⅱ scores in the group with high risk of motor fluctuation was statistically different from that in the groups with low and moderate risk (P<0.05). The changes of PSQI score, LD and LED in the group with high risk of dyskinesia was statistically different from those in the groups with low and moderate risk (all P<0.05). During the follow-up, the incidence of motor fluctuation and dyskinesia was 9.56% (24/251) and 5.97% (15/251), respectively. Conclusion: The stratification medical treatment might have a positive intervention effect on promoting a better quality of life, improving motor symptoms and delaying motor complications in PD patients.