Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To investigate the effect of pioglitazone on white matter injury after cerebral ischemia-reperfusion in mice and its mechanism.Methods:Forty-two young male C57BL/6J mice were randomly divided into sham operation group, model group, and pioglitazone group ( n=14 in each group). The model of cerebral ischemia-reperfusion was induced by transient middle cerebral artery occlusion with suture-occluded method. On the 3 rd and 7 th day after the establishment of the model, the neural function was assessed by the adhesive removal test. The mice were killed on the 7 th day after the establishment of the model. HE staining was used to detect the extent of cerebral infarction. Immunofluorescence staining and Western blot analysis were used to detect the degree of white matter damage and the changes of microglia phenotype. Results:On the 7 th day after cerebral ischemia-reperfusion, the adhesive removal time in the PGZ group was significantly shortened compared with the model group ( P<0.05), the percentage of cerebral infarction volume was significantly reduced ( P<0.05), the ratio of MBP/NF200 fluorescence intensity in the cortical and striatal areas was significantly increased (all P<0.05), and the number of CD16 +/Iba1 + microglia was significantly decreased ( P<0.01), while the number of CD206 +/Iba1 + microglia tended to increase, but there was no statistical difference. Conclusion:Pioglitazone may reduce the degree of white matter injury and nerve function damage in mice with cerebral ischemia-reperfusion, and its mechanism may be associated with regulating the transformation of microglia from M1 type to M2 type.

Objective: To investigate the effect of a metal occlusal surface and stress interruption design on minimally invasive prosthodontics for patients with distal extension absence and insufficient occlusal gingival distance. Methods : We retrospectively studied the case of minimally invasive prosthodontic (Vitallium 2000) combined with a metal occlusal surface for distal extension absence in a patient with insufficient occlusal gingival distance; the stress breaking design and pressure impression technology are examined, and relevant articles are reviewd. Results: The design effectively solves the problems of insufficient occlusal gingival distance, large occlusal force and easy denture fracture. Reviewing the relevant literature, stress interruption design can effectively protect abutment teeth, but the behavior of stress interruption design and stress conduction phenomena in the mouths of patients has not been reported. The T-scan test results of this study showed that before and after wearing the denture, the occlusal force distribution ratio of the patient changed from 77.5% on the left and 22.5% on the right to 61.3% on the left and 38.7% on the right. The occlusal force distribution ratio of the right dentition to the total occlusal force increased by 16.2%, and the occlusal force became better distributed. Further analysis showed that the occlusal forces on the left and right sides were nearly the same in the initial occlusion stage. As the occlusal force was further increased, the proportion of the occlusal force on the right side decreased in the middle of the occlusion stage and further decreased in the final occlusion stage until it reached a dynamic balance. The above T-scan test and literature review results suggest that this dynamic balance phenomenon of bite force is related to the stress interruption design and the stress conduction effect of the split framework. Conclusion The composite of stress interruption design and metal occlusal surface allows for minimally invasive prosthodontics for the treatment of distal extension absence in patients with insufficient occlusal gingival distance.

Ischemic stroke is a type of cerebrovascular disease with high morbidity, high mortality and high disability, which brings a huge medical burden to the society. Long non-coding RNA (lncRNA) H19 is closely associated with the pathophysiological mechanisms such as oxidative stress, inflammation, apoptosis, autophagy, and neurogenesis after ischemic stroke. It has received widespread attention in recent years. This article reviews the pathophysiological mechanism of lncRNA H19 in ischemic stroke, in order to provide new ideas for the diagnosis and treatment of ischemic stroke.

Objective: To investigate the effects of extreme high and low temperatures on admission risk of acute ischemic stroke (AIS) and its etiology subtypes. Methods: From January 1, 2016 to December 31, 2017, the data of inpatients with AIS from Zhongnan Hospital of Wuhan University and the meteorological data and air pollution data from China Meteorological Data Network in the same period were collected continuously. According to TOAST etiology criteria, the patients were divided into large artery atherosclerosis (LAA), small vessel occlusion (SVO), cardioembolism (CE), and stroke of other etiology (SOE). A time series analysis of the distributed lag model was used to investigate the effects of extreme high and low temperatures on the admission of patients with AIS and its etiology subtype, and air pollution, air pressure, humidity, and wind speed were used as confounding factors to exclude interference. Results: A total of 1 413 patients with AIS were enrolled, including 906 men (64.4%), age 67.7±12.8 years. The thresholds of extreme low temperature (1%, 5% and 10% of the average temperature) were 0.7 ℃, 3.3 ℃, and 4.9 ℃. The thresholds of extreme high temperature (90%, 95% and 99% of the average temperature) were 29.2 ℃, 31.6 ℃, and 32.9 ℃. Extreme high temperature increased the risk of hospitalization in patients with AIS (lag 0 day; relative risk [RR] 1.54, 95% confidence interval [CI] 1.01-2.34). It was mainly related to the increased risk of hospitalization in patients with CE subtype (lag 0 day; RR 7.64, 95% CI 1.19-49.09). There was no significant correlation between the extreme low temperature and the risk of hospitalization of AIS (lag 2 days; RR 0.99, 95% CI 0.71-1.37), but it significantly increased the risk of hospitalization in patients with LAA subtypes (lag 2 days; RR 3.04, 95% CI 1.33-6.95), and it was still statistically significant at lag 3 days (RR 2.87, 95% CI 1.57-5.25) and lag 4 days (RR 2.19, 95% CI 1.15-4.15). Conclusion Extreme high temperature may increase the risk of hospitalization in patients with AIS and CE subtypes, while extreme low temperature may increase the risk of hospitalization in patients with LAA subtypes.

Traditional Chinese medicine (TCM) syndromes have a certain genetic background. It is of great significance to study the essence of syndromes, and through genetic polymorphism research, the objectification of TCM syndromes can be realized. There are multiple relationships between genetic polymorphisms and TCM syndromes:including the relationship between internal factors and external manifestations, the relationship between macrocosmic view and microcosmic view, and the relationship between objectivity and subjectivity. This article reviews the current research progress on the correlation between genetic polymorphism and TCM syndromes in order to provide some ideas for the objectification of syndromes.

Ischemic stroke is a common neurological disease. MicroRNAs not only play an important role in acute phase of ischemic stroke, but also regulate neurogenesis and angiogenesis after stroke. This article reviews the research progress and prospects of microRNAs as a therapeutic target for ischemic stroke.

Objective To investigate the effect of short-term environmental ozone (O3) exposure on hospitalization risk of acute ischemic stroke (AIS) and its subtypes.Methods From January 1,2016 to December 31,2017,the hospitalization data of patients with AIS from Zhongnan Hospital of Wuhan University,air pollutant data published by China Air Quality Online Monitoring and Analysis Plafform,and the meteorological data published by China Meteorological Data Network were collectcd.According to TOAST etiological classification criteria,the patients with AIS were divided into large-artery atherosclerosis (LAA),small-artery occlusion (SVO),cardioembolism (CE),and stroke of other etiology (SOE).The effect of short-term O3 exposure on the hospitalization risk of AIS and its subtypes was analyzed retrospectively using a distributed lag non-linear model of time series analysis.Results A total of 1 413 patients with AIS were enrolled,including 910 males (64.4％),aged 67.7± 12.8 years (range,18-99 years).Short-term O3 exposure increased the overall hospitalization risk of AIS [relative risk (RR) 1.06,95％ confidence interval (CI) 0.99-1.13],mainly caused by increased hospitalization risks of LAA (RR 1.17,95％ CI 1.02-1.34;lag 5 d) and SVO (RR 1.24,95％ CI 1.06-1.45;lag 3 d).After introducing double pollutant (O3 + other pollutants) model its RR did not have significant changes.A stratified analysis based on demographic characteristics and vascular risk factors showed that the different populations had different sensitivities to the acute hazard effects of O3.Conclusion Short-term exposure to O3 could significantly increase the hospitalization risks of LAA and SVO.