Objective To observe the clinical efficacy and safety of the combination of rasagiline tablets and pramipexole tablets in the treatment of patients with Parkinson's disease.Methods The Parkinson's disease patients were randomly divided into treatment and control groups.The control group received pramipexole tablets,starting at a dose of 0.375 mg per day,with subsequent increases of 0.75 mg per time every 5-7 days,reaching a final dose of 1.5 mg per day.For patients with persistent poor disease control,the frequency of administration could be adjusted to twice a day,with a maximum daily dose of ≤ 4.5 mg.The treatment group received oral rasagiline in addition to the treatment in the control group,at a dose of 1.0 mg per day,once daily(qd).Both groups of patients were treated for 6 months.The clinical efficacy,inflammatory factors,serological indicators and related scales,as well as the occurrence of adverse drug reactions were compared between the two groups.Results The control group consisted of 67 participants,and the treatment group consisted of 68 participants,with no dropouts in either group.After treatment,the total effective rates of the treatment and control groups were 88.24％(60 cases/68 cases)and 74.63％(50 cases/67 cases)with significant difference(P＜0.05).After treatment,the levels of interferon-γ in treatment and control groups were(4.38±0.74)and(5.20±1.06)mg·L-1;the levels of interleukin-1 β were(0.33±0.05)and(0.59±0.12)ng·L-1;the levels of glutathione peroxidase were(108.24±11.30)and(92.88±9.79)U·μg-1;the modified Webster symptom scores were(7.26±1.05)and(13.15±3.25)points;the levels of γ-aminobutyric acid(GABA)were(278.14±41.32)and(241.86±35.04)mmol·L-1;the levels of insulin growth factor-1(IGF-1)were(170.25±20.34)and(145.18±16.51)ng·L-1,and the differences were statistically significant(all P＜0.05).The main adverse drug reactions of 2 groups were nausea and vomiting,drowsiness and dizziness.The total incidences of adverse drug reactions in treatment and control groups were 11.76％and 8.96％without significant difference(P＞0.05).Conclusion The combination of rasagiline tablets and pramipexole tablets in the treatment of patients with Parkinson's disease has shown definite clinical efficacy.It can alleviate oxidative stress and inflammatory reactions,relieve motor symptoms,regulate the expression levels of serum GABA and IGF-1,and does not significantly increase the incidence of adverse drug reactions.

Objective To establish a dynamic prediction model of fatal massive hemorrhage in trauma based on the vital signs time series data and machine learning algorithms.Methods Retrospectively analyze the vital signs time series data of 7522 patients with trauma in the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database from 2008 to 2019.According to the occurrence of posttraumatic fatal massive hemorrhage,the patients were divided into two groups:fatal massive hemorrhage group(n=283)and non-fatal massive hemorrhage group(n=7239).Six machine learning algorithms,including logistic regression(LR),support vector machine(SVM),random forests(RF),adaptive boosting(AdaBoost),gated recurrent unit(GRU),and GRU-D were used to develop a dynamic prediction models of fatal massive hemorrhage in trauma.The probability of fatal massive hemorrhage in the following 1,2,and 3 h was dynamically predicted.The performance of the models was evaluated by accuracy,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,and area under receiver operating characteristic curve(AUC).The models were externally validated based on the trauma database of the Chinese PLA General Hospital.Results In the MIMIC-Ⅳ database,the set of dynamic prediction models based on the GRU-D algorithm was the best.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.946±0.029,0.940±0.032,and 0.943±0.034,respectively,and there was no significant difference(P=0.905).In the trauma dataset,GRU-D model achieved the best external validation effect.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.779±0.013,0.780±0.008,and 0.778±0.009,respectively,and there was no significant difference(P=0.181).This set of models was deployed in a public web calculator and hospital emergency department information system,which is convenient for the public and medical staff to use and validate the model.Conclusion A set of dynamic prediction models has been successfully developed and validated,which is greatly significant for the early diagnosis and dynamic prediction of fatal massive hemorrhage in trauma.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To analyze the effect of recombinant human thrombopoietin(rhTPO)on platelet(PLT)reconstitution after autologous peripheral blood stem cell transplantation(APBSCT)in patients with multiple myeloma(MM).Methods:The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed.According to whether rhTPO was used during APBSCT,the patients were divided into rhTPO group(80 cases)and control group(67 cases).The time of PLT engraftment,blood product infusion requirements,the proportion of patients with PLT recovery to ≥ 50 × 109/L and ≥ 100 × 109/L at+14 days and+100 days after transplantation,and adverse reactions including the incidence of bleeding were compared between the two groups.Results:There were no significant differences between the two groups in sex,age,M protein type,PLT count at the initial diagnosis,median duration of induction therapy before APBSCT,and number of CD34+cells reinfused(all P＞0.05).The median time of PLT engraftment in the rhTPO group was 10(6-14)days,which was shorter than 11(8-23)days in the control group(P＜0.001).The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U,which was less than 20(0-80)U in the control group(P=0.001).At+14 days after transplantation,the proportions of patients with PLT 2 50 × 109/L in the rhTPO group and the control group were 66.3％and 52.2％,while the proportions of patients with PLT ≥ 100 × 109/L were 23.8％and 11.9％,respectively,with no significant differences(all P＞0.05).At+100 days after transplantation,the proportion of patients with PLT ≥ 50 × 109/L in rhTPO group and control group was 96.3％and 89.6％,respectively(P＞0.05),but the proportion of patients with PLT ≥ 100 × 109/L in rhTPO group was higher than that in control group(75.0％vs 55.2％,P=0.012).There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups.In rhTPO group,the rhTPO administration was well tolerated,and the incidences of abnormal liver and kidney function and infection were similar to those in the control group.Conclusion:When MM patients undergo first-line APBSCT,subcutaneous injection of rhTPO can shorten the time of platelet engraftment,reduce the transfusion volume of blood products,and be well tolerated,moreover,more patients have achieve a high level of PLT recovery after transplantation,which is very important for ensuring the safety of APBSCT and maintenance therapy.

Aim To design the pyrimidoindole deriva-tive N-butyl-9H-pyrimido[4,5-b]indole-2-carboxamide(BFPI)and synthesize it to investigate whether it in-hibits macrophage pyroptosis and foaming effects through the NLRP3/Caspase-1 pathway.Methods BFPI was synthesized using 2,4,6-triethoxycarbonyl-l,3,5-triazine and 2-aminoindole as starting materials and structurally characterized by 1H NMR,13C NMR,and ESI-MS.The in vitro cultured mouse monocyte macro-phage cell line RAW264.7 was divided into blank,model(PA)and therapeutic(BFPI)groups,and the cells in each group were treated with the corresponding culture medium for 24 h.The proliferative viability was detected by MTT assay,and the formation of intracel-lular lipid droplets was detected by oil red O staining,and NLRP3 was detected by Western-blot and RT-qPCR,caspase-1 and MCP-1 mRNA and protein ex-pression levels by Western blot and RT-qPCR.Results Compared with the blank group,the proliferation vi-ability of cells in the model group significantly de-creased and the formation of lipid droplets significantly increased;compared with the model group,the prolif-eration viability of cells in the treatment group signifi-cantly increased and the formation of lipid droplets sig-nificantly decreased,and the differences were statisti-cally significant(P＜0.01);compared with the blank group,the cellular NLRP3,caspase-1 and MCP-1 mR-NA and protein expression levels of cells in the model group significantly increased;compared with the model group,the expression levels of the above indexes of the cells in the treatment group significantly decreased,and the difference was statistically significant(P＜0.01).Conclusions BFPI contributes to delaying macrophage-derived foam cell formation during athero-genesis by inhibiting macrophage NLRP3,caspase-1,and MCP-1 expression and thereby promoting their pro-liferation and inhibiting lipid phagocytosis.

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

Humans ; Leg/pathology* ; Skin Neoplasms/pathology* ; Lymphoma, Large B-Cell, Diffuse/pathology*

Humans ; Renal Artery ; Constriction, Pathologic ; Hypertension, Renovascular/therapy* ; Vascular Diseases ; Renal Artery Obstruction/therapy* ; Embolization, Therapeutic

Objective: To understand the current situation and the main influencing factors of residents' satisfaction with the built environment of China's Hygienic City Initiative. Methods: From the list of China's hygienic cities (excluding county-level cities), 61 cities were randomly selected in equal proportion and the eligible respondents were randomly selected by using the "Questionnaire Star" network platform to carry out the online questionnaire survey. A self-made satisfaction evaluation scale was used to investigate the satisfaction of the included respondents with the urban built environment and search for relevant data on the city level. The two-level multi-factor mixed effect model was constructed to analyze the influencing factors of residents' satisfaction with the built environment of China's Hygienic City Initiative. Results: The age range of 2 465 respondents was mainly between 18 and 40 years old (79.9%), with males being the main group (45.8%). The total score of residents' satisfaction with the built environment of China's hygienic cities was (69.14±13.24) points. Based on four standardized dimensions of sense of gain, the result showed that the satisfaction of urban governance had the highest score (65.08 points), followed by urban environmental sanitation (63.68 points), urban lifestyle (59.97 points) and urban basic function (59.02 points). The analysis results of the two-level multi-factor mixed effect model showed that compared with residents with an annual average concentration of inhalable fine particles in the environment>48 micrograms/cubic meter, residents with an average concentration between 38 and 48 micrograms/cubic meter [β (95%CI): 1.65 (0.08, 3.21)] and≤37 micrograms/cubic meter or less [β (95%CI): 1.98 (0.53, 3.43)] had higher satisfaction. Compared with residents whose proportion of the secondary industry to GDP was≤40.9%, residents in cities with a larger proportion had a lower satisfaction level [residents with a proportion of 40.9%-48.03%, β (95%CI):-2.21 (-3.93, -0.49); residents with a proportion greater than 48.03%, β (95%CI):-2.58 (-4.58, -0.59)]. Compared with residents with a junior high school or lower education level, residents with a higher education level had a lower satisfaction level [β (95%CI):-2.37 (-4.57, -0.17)]. Residents of universities and above [β (95%CI):-3.82 (-6.05, -1.60)], regularly participate in physical exercise [β (95%CI): 5.78 (4.71, 6.84)] and self-rated good health status [β (95%CI): 6.39 (5.33, 7.45)] had a higher satisfaction level. Conclusion: The satisfaction of residents with the built environment of China's hygienic cities is still acceptable. Satisfaction is related to individual characteristics such as residents' cultural level, type of residence, frequent participation in physical exercise, and self-rated good health status, as well as urban-level factors such as green coverage rate in built-up areas, annual average concentration of inhalable fine particles, and the proportion of GDP in the secondary industry.
Male ; Humans ; Cities ; Personal Satisfaction ; Health Status ; Built Environment ; China

Background: and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.