It is important to detect and prevent Alzheimer disease (AD) at its early stage. Constituting the early stage sign of AD, amnestic mild cognitive impairment (aMCI) has drawn much attention. Studies have shown that donepezil could reduce the AD assessment scale-cognitive subscale (ADAS-Cog) score in MCI patients and improve the patient's attention and speed of response; however, it also has many side effects. Therefore, the authors aim to explore the effects of Chinese herbal medicine for treating aMCI.

Objective To investigate the substantia nigra (SN) and brainstem raphe (BR) echogenic features of Parkinson's disease (PD) patients with musculoskeletal pain.Methods A total of 115 PD patients recruited in the Second Affiliated Hospital of Soochow University from October 2014 to May 2016 were assessed with the following rating scales:Unified Parkinson's Disease Rating Scale (UPDRS),Hoehn and Yahr Staging Scale (H/Y),Hamilton Rating Scale for Depression (HRSD),Beck Depression Inventory Ⅱ (BDI-Ⅱ) and Visual Analogue Scale (VAS).All the subjects underwent transcranial sonography during the clinical evaluation.And the patients were divided into PD with musculoskeletal pain (n =54) and PD without musculoskeletal pain (n =61) groups,or PD with depression(n =74) and PD without depression(n =41) groups.Results Compared with PD patients without pain,PD patients with musculoskeletal pain had higher scores of UPDRS-Ⅱ,-Ⅲ,HRSD,BDI,NMSQ and H/Y (UPDRS-Ⅱ score:12.56 ±6.01 vs 8.79 ±4.38,t =-3.801,P ＜0.01;UPDRS-Ⅲ score:24.43 ± 12.43 vs 20.07 ± 11.12,t=-1.986,P=0.049;HRSD score:11.65-±6.94 vs 8.38-±5.36,t=-2.844,P=0.005;BDI score:14.09 ±6.20 vs 9.74 ±6.00,t =-3.826,P ＜0.01;NMSQ score:8.57 ± 4.06 vs 5.60 ± 3.38,t=4.193,P＜0.01;H/Y:2.0(1.5,2.6) vs 1.5(1.0,2.0),Z=-3.011,P=0.003).Positive BR was more frequent in depressed than in non-depressed PD patients without pain (63.6％ vs 14.3％;x2 =15.25,P ＜0.01).Positive BR was positively associated with sex(r =0.228,P =0.014),age(r =0.184,P =0.049),disease duration (r =0.196,P =0.035),and depression (r =0.396,P ＜ 0.01).However,positive BR did not correlate with musculoskeletal pain.No correlation was found between positive SN and clinical characteristics of PD patients.Conclusions PD patients with musculoskeletal pain have worse activity of daily living,more severe motor symptoms,more non-motor symptoms,and are more depressed.SN and BR echogenecity do not correlate with musculoskeletal pain,however,hypoechogenic or interrupted BR is associated with depression in PD patients.

To explore the correlation between the cognitive functions and syndromes of traditional Chinese medicine (TCM) in amnestic mild cognitive impairment (aMCI), and to provide evidence for clinical syndrome differentiation treatment.

Objective:To explore the adjunctive diagnostic value of transcranial sonography (TCS) combined with olfactory test in early Parkinson′s disease (PD) and the clinical value of both in the cognitive function of PD patients.Methods:TCS and olfactory test were performed in 157 early PD patients(PD group) and 157 healthy controls(control group) in the Second Affiliated Hospital of Soochow University from January 2018 to January 2022. The differences in clinical characteristics, TCS, and olfactory test results between the two groups were analyzed. The values of TCS, olfactory test, and their combination in diagnosing early PD were evaluated using clinical diagnosis as the gold standard. The correlations of the midbrain area, the midbrain substantia nigra hyperechoic area, and the third ventricle width in TCS examination with the cognitive score were analyzed in the PD group. According to the olfactory test scores, 157 patients with early PD were divided into two groups: 110 cases of PD with olfactory dysfunction (PD-OD) and 47 cases of PD without olfactory dysfunction (PD-NOD). The differences in clinical scores and TCS results between the two groups were compared.Results:The midbrain substantia nigra hyperechoic area, substantia nigra hyperechoic positivity rate, third ventricle width, and olfactory dysfunction rate were higher in the PD group compared to the control group, while the midbrain area and olfactory test scores were lower than those in the control group (all P<0.001). The sensitivity and the coincidence rate of TCS combined with the olfactory test for early PD diagnosis (90.0%, 77.1%) were higher than those of TCS alone (60.0%, 71.3%) and olfactory test alone (70.1%, 72.3%), but the specificity (63.7%) was lower than that of both alone (82.8% for TCS and 75.2% for olfactory test), (all P<0.001). MoCA score, visual space and executive ability, memory, attention, and language were positively correlated with the area of the midbrain ( rs=0.38, 0.32, 0.27, 0.25, 0.23; all P<0.05) and negatively correlated with the width of the third ventricle ( rs=-0.39, -0.22, -0.39, -0.22, -0.32; all P<0.05), and orientation was negatively correlated only with the width of the third ventricle ( rs=-0.24, P<0.05). The MoCA score of PD-OD group[22(18, 25)] was lower than that of PD-NOD group[24(20, 26)]( P=0.040). Conclusions:The combination of TCS and olfactory test can enhance the sensitivity and diagnostic agreement rate for early PD diagnosis, providing some auxiliary value. The cognitive function of PD patients is positively correlated with the midbrain area and negatively correlated with the width of the third ventricle. The cognitive function of PD patients with olfactory dysfunction is lower than that of PD patients without olfactory dysfunction. TCS and olfactory test may help assess cognitive function in PD patients.

Objective:To explore the pathological mechanism of SN hyperechogenicity by investigating the characteristics of substantia nigra (SN) hyperechogenicity on transcranial sonography (TCS) and serum iron metabolism parameters in the postural instability gait difficulty and tremor dominant subtypes of Parkinson′s disease (PD), and the correlation between them.Methods:A total of 155 PD patients recruited in Parkinson′s Disease Specialty in the Second Affiliated Hospital of Soochow University from January 2019 to December 2021 were divided into postural instability gait difficulty group( n=95) and tremor dominant group( n=60). Meanwhile, 49 healthy gender- and age-matched healthy individuals who sought for physical examination during the same period were included as the control group. All subjects underwent TCS and blood test, and the echo of SN between the postural instability gait difficulty group and tremor dominant group, serum iron metabolism parameters among the three groups were compared. The postural instability gait difficulty group and tremor dominant group were subdivided into with SN hyperechogenicity (SN+ )subgroup and without SN hyperechogenicity (SN-) subgroup respectively according to TCS results, and the differences in serum iron metabolism parameters between the subgroups were further compared. The association between SN hyperechogenicity and serum iron metabolism parameters of the postural instability gait difficulty group and tremor dominant group were further analyzed. Results:The total area of bilateral SN+ , the area of SN+ on the larger side, and the ratio of the total area of SN+ to the midbrain area (S/M) in postural instability gait difficulty group were larger than those in tremor dominant group (all P<0.001). The value of serum ceruloplasmin and transferrin in both postural instability gait difficulty group and tremor dominant group were lower than those in control group (all P<0.001), and compared with tremor dominant group and control group, the postural instability gait difficulty group had lower serum ferritin(all P<0.01). In both postural instability gait difficulty group and tremor dominant group, serum ceruloplasmin in SN+ subgroup was lower than that in SN-subgroup ( P=0.001, 0.032). Moreover, there was a negative correlation between serum transferrin and the area of SN hyperechogenicity in two subgroups(postural instability gait difficulty group: rs=-0.454, P<0.001; tremor dominant group: rs=-0.494, P<0.001). Conclusions:Compared with the tremor dominant patients, the postural instability gait difficulty patients have larger area of SN hyperechogenicity and lower serum ferritin level. The area of SN hyperechogenicity is significantly negatively correlated with serum transferrin level, indicating that the production of this imaging characteristics is related to iron metabolism.

Objective:To explore the correlation between transcranial sonography (TCS) combined with serum homocysteine (Hcy), blood glucose, blood lipids, the cognitive status of Parkinson′s disease (PD) patients, and to analyze the clinical application value of these parameters in assessing the cognitive status of PD patients.Methods:A total of 152 PD patients admitted to the Second Affiliated Hospital of Soochow University from January 2020 to June 2023 were retrospectively collected as the PD group, and 101 healthy examinees matched for age and gender during the same period were selected as control group. Clinical data [age, gender, duration of illness, Montreal Cognitive Assessment (MoCA) score, Mini-Mental State Examination (MMSE) score, Unified Parkinson′s Disease Rating Scale Part Ⅲ (UPDRS-Ⅲ) score, Hoehn-Yahr (H-Y) stage, etc.], serum tests (Hcy, blood glucose, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein concentration), and TCS examination results (third ventricular width, midbrain area, peak systolic velocity of bilateral middle cerebral arteries, bilateral middle cerebral artery resistance index, bilateral substantia nigra hyperechoic area) were collected. The two groups were divided into pure PD group and PD group with elevated Hcy, pure control group and control group with elevated Hcy, based on an Hcy concentration threshold of ≥15 μmol/L. The differences in the above parameters among the four groups were compared. The correlation between Hcy and cognitive status (MoCA score, MMSE score) of PD patients and the above parameters were analyzed.Results:The MoCA score and MMSE score of the PD group with elevated Hcy were lower than those of the pure PD group, and the UPDRS-Ⅲ score and H-Y stage were higher than those of the pure PD group (all P<0.001). The order of Hcy concentration from high to low was PD group with elevated Hcy, pure Hcy elevation group, pure PD group, and pure control group. The differences in serum data and TCS data among the four groups were statistically significant (all P<0.001). Spearman correlation analysis showed: ①In the PD group, the concentration of Hcy was positively correlated with glucose concentration, H-Y stage, low-density lipoprotein concentration, right middle cerebral artery resistance index, UPDRS-Ⅲ score, total cholesterol concentration, triglyceride concentration, left middle cerebral artery resistance index, third ventricular width, and age ( rs=0.422, 0.350, 0.348, 0.334, 0.325, 0.300, 0.293, 0.283, 0.221, 0.164, all P<0.05); Hcy concentration was negatively correlated with midbrain area, MMSE score, MoCA score, peak systolic velocity of right middle cerebral artery, peak systolic velocity of left middle cerebral artery, and high-density lipoprotein concentration ( rs=-0.328, -0.282, -0.245, -0.229, -0.224, -0.192, all P<0.05). ②Clinical data, serum data, and TCS data of PD patients were all correlated with MoCA score and MMSE score, with midbrain area showing the largest positive correlation ( rs=0.524, 0.516; both P<0.05) and H-Y stage showing the largest negative correlation( rs=-0.490, -0.468; both P<0.05). Conclusions:PD patients with elevated Hcy have lower cognitive scores than pure PD patients. The correlation between Hcy concentration and blood glucose concentration is the highest in PD patients, followed by H-Y stage. The cognitive scores of PD patients are most correlated with midbrain area and unrelated to substantia nigra hyperechoic area. Lowering serum Hcy concentration in PD patients may be one of the ways to delay cognitive impairment.

Objective:To investigate the association between oxygen saturation (SpO 2) and risk of 3-year all-cause mortality among Chinese older adults aged 65 or over. Methods:The participants were enrolled from Healthy Aging and Biomarkers Cohort Study in year of 2012 to 2014 in 9 longevity areas in China. In this prospective cohort study, 2 287 participants aged 65 or over were enrolled. Data on SpO 2 and body measurements were collected at baseline in 2012, and data on survival outcome and time of mortality were collected at the follow-up in 2014. Participants were divided into two groups according to whether SpO 2 was abnormal (SpO 2<94% was defined as abnormal). Results:The 2 287 participants were (86.5±12.2) years old, 1 006 were males (44.0%), and 315 (13.8%) were abnormal in SpO 2. During follow-up in 2014, 452 were died, 1 434 were survived, and 401 were lost to follow-up. The all-cause mortality rate was 19.8%, and the follow-up rate was 82.5%. The mortality rate of SpO 2 in normal group was 21.1%, and that of abnormal group was 41.6% ( P<0.001). After adjusting for confounding factors, compared to participants with normal SpO 2, participants with abnormal SpO 2 had increased risk of all-cause mortality with HR (95% CI) of 1.62 (1.31-2.02); HR (95 % CI) was 1.49 (0.98-2.26) for males and 1.71 (1.30-2.26) for females in abnormal SpO 2group, respectively; HR (95% CI) was 2.70 (0.98-7.44) for aged 65-79 years old, 1.22 (0.63-2.38) for aged 80-89 years old, and 1.72 (1.35-2.19) for aged over 90 years old in abnormal SpO 2 group, respectively. Conclusion:Abnormal SpO 2 was responsible for increased risk of 3-year all-cause mortality among Chinese elderly adults.

Objective:To investigate the association between oxygen saturation (SpO 2) and risk of 3-year all-cause mortality among Chinese older adults aged 65 or over. Methods:The participants were enrolled from Healthy Aging and Biomarkers Cohort Study in year of 2012 to 2014 in 9 longevity areas in China. In this prospective cohort study, 2 287 participants aged 65 or over were enrolled. Data on SpO 2 and body measurements were collected at baseline in 2012, and data on survival outcome and time of mortality were collected at the follow-up in 2014. Participants were divided into two groups according to whether SpO 2 was abnormal (SpO 2<94% was defined as abnormal). Results:The 2 287 participants were (86.5±12.2) years old, 1 006 were males (44.0%), and 315 (13.8%) were abnormal in SpO 2. During follow-up in 2014, 452 were died, 1 434 were survived, and 401 were lost to follow-up. The all-cause mortality rate was 19.8%, and the follow-up rate was 82.5%. The mortality rate of SpO 2 in normal group was 21.1%, and that of abnormal group was 41.6% ( P<0.001). After adjusting for confounding factors, compared to participants with normal SpO 2, participants with abnormal SpO 2 had increased risk of all-cause mortality with HR (95% CI) of 1.62 (1.31-2.02); HR (95 % CI) was 1.49 (0.98-2.26) for males and 1.71 (1.30-2.26) for females in abnormal SpO 2group, respectively; HR (95% CI) was 2.70 (0.98-7.44) for aged 65-79 years old, 1.22 (0.63-2.38) for aged 80-89 years old, and 1.72 (1.35-2.19) for aged over 90 years old in abnormal SpO 2 group, respectively. Conclusion:Abnormal SpO 2 was responsible for increased risk of 3-year all-cause mortality among Chinese elderly adults.

Objective To investigate the role of Kelch-like-epichlorohydrin-associated protein 1/nuclear factor erythroid-derived factor-2-related factor 2(Keap1-Nrf2)and nuclear factor-κB(NF-κB)signaling pathways in sepsis-associated encephalopathy(SAE).Methods Male C57BL/6J mice of SPF were randomly divided into four groups(n=10):the control group and LPS 6 h,24 h and 48 h groups.The behavioral changes of the mice were assessed based on their general conditions and open field test(OFT).ELISA was used to measure the levels of pro-inflammatory cytokines in mouse serum,and the antioxidant capacity assay kit to examine antioxidant activity in brain tissues of mice.Real-time quantitative PCR(qPCR)was adopted to detect the mRNA levels of toll-like receptor4(Tlr4),NF-κB,Keap1 and Nrf2 in the hippocampus,and to determine protein expressions of NF-κB a Nrf2、Keap1 and Tlr4 with Western blotting.Results Compared to the control group,the serum concentrations of interleukin 6(IL-6)in lipopolysaccharide(LPS)groups increased at 6 h,and reached the peak at 24 h and 48 h(P＜0.01).The levels of serum interleukin 18(IL-18)in the LPS groups increased significantly at 6 h and 24 h(P＜0.01)but there was no statistically significant difference compared with the 48h group.The results indicated the activity of superoxide dismutase(SOD)and glutathione(GSH)in brain tissues in LPS groups increased(P＜0.01).OFT results showed the time spent in the center of the open field,the distance covered around the center,and total distance covered by mice in LPS groups were significantly reduced(P＜0.01),except for the time spent in the center of the open field in the LPS 24 h group.The mRNA expressions of Tlr4 and(LPS 6 h,48 h)NF-κB in the hippocampus tissue of mice in LPS groups were elevated(P＜0.05),so were the mRNA expressions of Keap1 and Nrf2 in LPS 6 h group.Additionally,the protein expressions of NF-κB,Keap1 and Tlr4 increased in LPS groups,so did the protein expression of Nrf2 in LPS 24 h and 48 h groups(P＜0.05).Conclusion Keap1-Nrf2 and NF-κB signaling pathways may play a certain role in SAE.

Objective: To understand the relationship between visual impairment and risk of all-cause mortality in the elderly aged 65 years and older in 8 longevity areas in China. Methods: The data of the elderly aged 65 years and older in the project in 2012 were obtained from Healthy Aging and Biomarkers Cohort Study, a sub-cohort of the Chinese Longitudinal Healthy Longevity Survey, including physical measurement and survival status, and a follow-up for survival outcomes were conducted in 2014 and 2017 respectively. Cox proportional hazard regression model was used to analyze the influence of visual impairment on mortality. Gender and age specific analysis was conducted. Results: A total of 1 736 elderly adults were included. A total of 943 deaths occurred during the 5-year follow-up period with a 5-year mortality rate of 54.3%. The 5-year mortality rate was 76.7% in the group with visual impairment, and 47.6% in the group without visual impairment (P<0.001). After adjusting for demographic information, life style and some disease factors, the risk of 5-year mortality in the group with visual impairment group was 1.30 times higher than that in the group without visual impairment (HR=1.30, 95%CI: 1.09-1.55). In the females, the risk for mortality in the group with visual impairment was 1.48 times higher than that in the group without visual impairment (HR=1.48, 95%CI:1.20-1.84). However, vision status was not associated with the risk for mortality in males (HR=1.02, 95%CI: 0.72-1.43). The risk for mortality in the group with visual impairment was 1.39 times higher than that in the group without visual impairment in the elderly aged over 90 years (HR=1.39, 95%CI: 1.13-1.70). Vision status was not associated with mortality risk in the elderly aged 65-79 years and 80-89 years (HR=1.37, 95%CI: 0.61-3.07; HR=0.95, 95%CI: 0.61-1.48). Conclusion In the elderly people in China, visual impairment is a risk factor for mortality.