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 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 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.

The chemical constituents of Litsea coreana were investigated using chromatographic methods, including column chromatography on silica gel, MCI, and semi-preparation HPLC. Two compounds were isolated and identified as hawktealignan A (1) and cinnamophilin (2) by NMR analyses as well as their physical and chemical properties. Compound 1 is a new lignan and compound 2 was isolated from this plant for the first time.

Adult ; Asian People ; China/epidemiology* ; Exons ; Humans ; Male ; Negative Results ; Polymorphism, Genetic/genetics* ; Polymorphism, Single Nucleotide ; Premature Ejaculation/genetics* ; Serotonin Plasma Membrane Transport Proteins/genetics*

To investigate the distribution of ticks and to detect the new bunyavirus in ticks and infection rate in animals in Shanghai,outdoor free ticks were captured by flag method and ticks on animals were collected by animal capture.SFTSV in ticks were detected by real-time RT-PCR.Total antibodies against SFTSV in host animal sera were tested by double antigen sandwich method.Results showed that during 2012-2014,free ticks were captured in Chenshan Park and Jinshan Island,which were all Haemaphysalis longicornis.Ten of seventeen districts found ticks on animals which were dominantly Rhipicephalus sanguineus.No nucleic acid of SFTSV was detected in 143 ticks.Main host animal for ticks was dog,sheep was in the second.Sera in 198 dogs from 6 urban districts,120 swine from Pudong and Fenxian districts and 36 sheep from Chongming District were all SFTSV antibody negative.Ticks were not found with SFTSV in Shanghai during 2012-2014.No SFTSV infection was found in host animals.Therefore,there is no evidence that Shanghai is the natural foci of SFTSV.Further surveillance and investigations should be carried out in the future.

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

β₂-Adrenoceptor agonists are highly effective bronchodilators and are widely used in the treatment of both chronic obstructive pulmonary disease (COPD) and asthma. In the last 15 years, there has been great interest within the pharmaceutical industry in the discovery of a long β₂-adrenoceptor agonist for a mono-therapy or combination therapy. The search for new long-acting β₂-adrenoreceptor agonists (LABA's), for the treatment of asthma and COPD, has become a very active area of drug discovery. This article reviews the mechanisms, potential candidates and research advances of long β₂-adrenoceptor agonists.