ObjectiveTo investigate the mechanism of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis extract （ASH） in treating Parkinson's disease （PD） in mice by Data-Independent Acquisition （DIA） proteomics. MethodsThe α-Synuclein （α-Syn） transgenic PD mice were selected as suitable models for PD， and they were randomly assigned into PD， ASH （61.25 mg·kg^-1）， and Madopar （97.5 mg·kg^-1） groups. Male C57BL/6 mice of the same age were selected as the control group， with eight mice in each group. Mice were administrated with corresponding drugs by gavage once a day for 20 days. The pole climbing time and the number of autonomic activities were recorded to evaluate the exercise ability of mice. Hematoxylin-eosin staining was employed to observe neuronal changes in the substantia nigra of PD mice. Immunohistochemistry （IHC） was employed to measure the tyrosine hydroxylase （TH） activity in the substantia nigra and assess the areal density of α-Syn in the striatum. DIA proteomics was used to compare protein expression in the substantia nigra between groups. IHC was utilized to validate key differentially expressed proteins， including Lactotransferrin， Notch2， Ndrg2， and TMEM 166. The cell counting kit-8 （CCK-8） method was used to investigate the effect of ASH on the viability of PD cells with overexpression of α-Syn. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the protein and mRNA levels of Lactotransferrin， Notch2， Ndrg2， and TMEM 166 in PD cells. ResultsCompared with the control group， the model group showed prolonged pole climbing time， diminished coordination ability， reduced autonomic activities （P<0.01）， and reduced swelling neurons. Compared with the model group， ASH and Madopar reduced the climbing time， increased autonomic activities （P<0.01）， and ameliorated neuronal damage. Compared with the control group， the model group showed a decrease in TH activity in the substantia nigra and an increase in α-Syn accumulation in the striatum （P<0.01）. Compared with the model group， the ASH group showed an increase in TH activity and a reduction in α-Syn accumulation （P<0.05）. DIA proteomics revealed a total of 464 differentially expressed proteins in the model group compared with the control group， with 323 proteins being up-regulated and 141 down-regulated. A total of 262 differentially expressed proteins were screened in the ASH group compared with the model group， including 85 proteins being up-regulated and 177 down-regulated. Kyoto encylopedia of genes and genomes （KEGG） pathway analysis indicated that ASH primarily regulated the Notch signaling pathway. The model group showed up-regulation in protein levels of Notch2， Ndrg2， and TMEM 166 and down-regulation in the protein level of Lactotransferrin compared with the control group （P<0.01）. Compared with the model group， ASH down-regulated the protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.05） while up-regulating the protein level of Lactotransferrin （P<0.01）. The IHC results corroborated the proteomics findings. The cell experiment results showed that compared with the control group， the modeling up-regulated the mRNA and protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.01）， while down-regulating the mRNA and protein levels of Lactotransferrin （P<0.01）. Compared with the model group， ASH reduced the mRNA and protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.01）， while increasing the mRNA and protein levels of Lactotransferrin （P<0.05， P<0.01）. ConclusionASH may Synergistically inhibit the Notch signaling pathway and mitigate neuronal damage by down-regulating the expression of Notch2 and Ndrg2. Additionally， by up-regulating the expression of Lactotransferrin and down-regulating the expression of TMEM166， ASH can address brain iron accumulation， intervene in ferroptosis， inhibit mitophagy， and mitigate reactive oxygen species damage， thereby protecting nerve cells and contributing to the treatment of PD.

Objective:To evaluate the value of curative effect in neuromyelitis spectrum disease (NMOSD) based on circulatory function evaluation of intracerebral glymphatic system by using diffusion tensor imaging analysis along the perivascular space.Methods:The clinical and imaging data of 23 patients diagnosed with NMOSD at Tianjin Medical University General Hospital from March 2018 to December 2019 were retrospectively analyzed in this study. The clinical data included expanded disability status scale (EDSS), average relapse rate (ARR) and retinal nerve fiber layer (RNFL) thickness at baseline and 1 year follow-up after treatment. Among the 23 NMOSD patients, there were 22 females and 1 male, aged from 21 to 71 (45±13) years old. All the patients underwent MR scans at both baseline and 1 year after treatment, and the scanning sequences included cerebral 3D-T 1WI, T 2WI, diffusion tensor imaging and cervical spinal sagittal 3D-T 2WI, and the cervical spinal cord volume and bilateral diffusion tensor imaging analysis along the perivascular space index (ALPS index) were calculated. The partial correlation test was used to analyze the correlations between ALPS index and the clinical indicators such as EDSS, ARR, and bilateral RNFL, with the control variables as gender, age, years of education and course of disease. The multiple linear regression model was used to analyze the independent predictors for ALPS index and EDSS after treatment. Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the diagnostic value of NMOSD treatment outcome by using ALPS index. Results:When controlling for gender, age, years of education and course of disease, there were significant negative correlations between right ALPS index and EDSS ( r=-0.50, P=0.048), bilateral average ALPS index and EDSS ( r=-0.53, P=0.034), left ALPS index and ARR ( r=-0.58, P=0.018), while there was significant positive correlations between right ALPS index and RNFL ( r=0.88, P=0.008) at 1 year follow-up after treatment. Multiple linear regression analysis showed that cervical spinal cord volume was an independent impact factor of bilateral average ALPS indexes (β=0.24, 95%CI 0.10-0.38, P=0.002), and bilateral average ALPS indexes (β=-3.22, 95%CI -5.97--0.48, P=0.024) and right RNFL (β=-0.05, 95%CI -0.08--0.02, P=0.002) at baseline were the independent impact factors of EDSS after treatment. ROC curve analysis showed that the bilateral average ALPS index at baseline had the best efficacy in predicting the curative effect of NMOSD patients with AUC=0.92. Conclusions:After treatment, NMOSD patients with severe clinical disability, high frequency of disease attack, poor visual performance, and severe cervical spinal cord atrophy have more serious impairment of intracerebral glymphatic system circulatory function. The ALPS index could help in predicting the clinical curative effect of NMOSD patients.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To understand the prevention and control progress of drinking water-borne endemic fluorosis in Henan Province, to evaluate the effects of prevention and control measures, and provide a basis for adjusting prevention and control strategies.Methods:In 2019, a general survey was conducted in all registered drinking water-borne endemic fluorosis villages in Henan Province to monitor the basic conditions of water improvement, the fluoride content of drinking water and the prevalence of dental fluorosis in children aged 8-12 years. The control compliance (water fluoride content qualified and the detection rate of dental fluorosis of children ≤30%) status of the villages was analyzed, and calculate the compliance rate.Results:A total of 17 504 drinking water-borne endemic fluorosis villages were monitored, among them, 17 352 villages with water improvement and 152 villages without water improvement, with a water improvement rate of 99.1%. Among the 3 685 water improvement projects constructed, 3 448 were in normal operation, and the normal operation rate was 93.6%. There were 13 526 villages with qualified drinking water fluoride content, and the qualified rate of water fluorine was 77.3%; the actual beneficiary population was 11 011 000, and the population benefit rate was 90.1%. The qualified rate of water fluoride in the villages with and without water improvement was 77.9% (13 512/17 352) and 9.2% (14/152), respectively; the qualified rate of water fluoride in the villages with water improvement was significantly higher than that in the villages without water improvement (χ 2=400.58, P < 0.05). A total of 498 527 children of 8 to 12 years old were examined, 68 972 cases of dental fluorosis were detected, the detection rate of dental fluorosis was 13.84%, and the dental fluorosis index was 0.3. The number of villages meeting the control standard was 12 488, and the compliance rate was 71.3%. Conclusions:In Henan Province, the water improvement projects in the drinking water-borne endemic fluorosis areas have been basically implemented, and the disease has been effectively controlled. However, there is still a certain gap with the target of the "13th Five-Year Plan on National Prevention and Control of Endemic Diseases", and timely rectification is needed to ensure the effectiveness of the water improvement projects.

Apoptosis ; Cardiopulmonary Resuscitation ; Humans ; Out-of-Hospital Cardiac Arrest ; Programmed Cell Death 1 Receptor/biosynthesis* ; Return of Spontaneous Circulation ; Th1 Cells ; Th2 Cells

Objective:To understand the status of drinking water-borne endemic fluorosis in Henan Province, so as to provide scientific basis for improving prevention and control strategies.Methods:Ten counties (districts, referred to as counties) were selected from drinking water-borne endemic fluorosis areas of Henan Province in 2018. Three villages in each project county were selected according to the disease status of mild, moderate and severe conditions, and the operation status of water improvement projects, water fluoride content and dental fluorosis among children aged 8 to 12 years in each diseased village were monitored.Results:Totally 30 villages were surveyed, all of which were in the water improvement projects; a total of 25 water improvement projects were monitored, all of them were in normal operation, and the water fluoride exceeding standard rate was 28.00% (7/25), the qualified rate of water fluoride in the water improvement projects was 72.00% (18/25). Among them, 21 villages were in normal operation and the water fluoride in the water improvement projects met national standard. In which the detection rate of dental fluorosis among children aged 8 to 12 years was 36.71% (606/1 651), the index of dental fluorosis was 0.74, and the epidemic intensity was extremely mild. Water fluoride of water improvement projects in 9 villages exceeded the national standard, where the detection rate of dental fluorosis among children aged 8 to 12 years was 43.57% (261/599), the index of dental fluorosis was 0.78, and the epidemic intensity was extremely mild. The detection rate of dental fluorosis among children in the villages where the water fluoride of water improvement projects exceeded the national standard was higher than that in the villages where the water fluoride of water improvement projects met the national standard (χ 2=8.752, P < 0.01). Conclusions:The excessive fluorine content in the water of water improvement projects is still serious, and the epidemic is still severe. It is necessary to strengthen the scientific demonstration of the water improvement project construction and the project acceptance upon completion, so as to prevent unqualified projects from being put into use. We will carry out regular water quality monitoring and promptly rectify projects with water quality exceeding the standards.

Objective: To observe the clinical efficacy of different dialysis frequency and methods in the treatment of chronic renal failure uremia patients, and to provide a reliable reference for clinical practice. Methods: From February 2016 to February 2017, 140 chronic renal failure uremic patients who admitted to the Department of Nephrology at Taizhou Central Hospital were selected and divided into the observation group and the control group by complete random distribution method, with 70 cases in each group.The patients in the control group received 3 times of regular hemodialysis treatment per week, while the observation group received 3 times of regular hemodialysis combined with 1 time of hemodiafiltration treatment per week.The clinical treatment effects and complications of the two groups were compared. Results: Compared with blood uric acid(BUA)[(532.09±71.05)mmol/L], serum creatinine(Scr)[(734.34±63.08)μmol/L], blood urea(BUN)[(23.84±2.58)mmol/L], serum phosphorus[(1.98±0.37)mmol/L], parathyroid hormone(PTH)[(464.37±113.92)ng/L], β₂ microglobulin(β₂-MG)[(13.48±6.38)mg/L]in the control group, BUA[(495.89±58.23)mmol/L], Scr[(684.34±77.32)μmol/L], BUN[(20.62±1.77)mmol/L], serum phosphorus[(1.74±0.44)mmol/L], PTH[(352.14±123.25)ng/L], β₂-MG[(9.58±5.45)mg/L] were significantly lower in the observation group, the differences were statistically significant (t=3.29, 4.19, 8.61, 3.49, 5.59, 3.88, all P<0.01). Compared with the incidence rate of pruritus in the control group(61.43%), the incidence rate of pruritus in the observation group(34.29%) was significantly lower (χ²=9.72, P<0.01), the incidence of other complications had no statistically significant differences(χ²=1.14, 1.58, 3.08, all P>0.05). Conclusion Hemodialysis 3 times combined with 1 time of hemodiafiltration per week has significant advantage in the treatment of chronic renal failure uremia patients, which can effectively remove urine toxin molecules and reduce the incidence of complications, and it is worthy of clinical application.

To assess the background field removal method usually used in quantitative susceptibility mapping (QSM), and to analyze the cause of serious artifacts generated in the truncated -space division (TKD) method, this paper discusses a variety of background field removal methods and proposes an improved method to suppress the artifacts of susceptibility inversion. Firstly, we scanned phase images with the gradient echo sequence and then compared the quality and the speed of reconstructed images of sophisticated harmonic artifact reduction for phase data (SHARP), regularization enable of SHARP (RESHARP) and laplacian boundary value (LBV) methods. Secondly, we analyzed the reasons for reconstruction artifacts caused by the multiple truncations and discontinuity of the TKD method, and an improved TKD method was proposed by increasing threshold truncation range and improving data continuity. Finally, the result of susceptibility inversion from the improved and original TKD method was compared. The results show that the reconstruction of SHARP and RESHARP are very fast, but SHARP reconstruction artifacts are serious and the reconstruction precision is not high and implementation of RESHARP is complicated. The reconstruction speed of LBV method is slow, but the detail of the reconstructed image is prominent and the precision is high. In the QSM inversion methods, the reconstruction artifact of the original TKD method is serious, while the improved method obtains good artifact suppression image and good inversion result of artifact regions.
Algorithms ; Artifacts ; Brain ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Phantoms, Imaging