Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

ObjectiveTo investigate the distribution of traditional Chinese medicine （TCM） syndrome elements in type 2 diabetes mellitus （T2DM） patients based on maximum body mass index （maxBMI） and explore their association with complication risks. MethodsA retrospective cross-sectional study was used to collect clinical data from hospitalized T2DM patients， extracting age， gender， smoking history， alcohol consumption history， duration of disease， HbA1c level， complications， and TCM syndromes， and extracting the syndrome elements of disease location and disease nature based on their TCM syndromes. MaxBMI was calculated by telephone survey of patients' self-reported maximum body weight； patients with maxBMI ≥24 kg/m² were classified into spleen-heat syndrome group， and those with maxBMI ＜24 kg/m² were classified into consumptive-heat syndrome group. The distribution of TCM syndrome types and syndrome elements of patients in the two groups were analysed. Then the propensity score matching method was used to balance the baseline characteristics between the two groups and compare the differences in the distribution of syndrome types and syndrome elements and the risk of macrovascular and microvascular complications between the two groups. ResultsAmong the 1178 T2DM patients， syndrome elements in spleen-heat patients （1034 cases） were primarily located in the spleen （351 cases， 33.95%）， liver （240 cases， 23.21%）， and stomach （139 cases， 13.44%）， while in consumptive-heat patients （144 cases）， they were concentrated in the spleen （57 cases， 39.58%）， liver （34 cases， 23.61%）， and kidneys （17 cases， 11.81%）； regarding syndrome elements of disease nature， spleen-heat patients were predominantly characterized by qi deficiency （481 cases， 46.52%）， phlegm （353 cases， 22.73%）， and dampness （241 cases， 23.31%）， whereas consumptive-heat patients showed more qi deficiency （84 cases， 58.33%） and yin deficiency （44 cases， 30.56%）. After propensity score matching， 132 cases were included in each group， and no statistically significant differences were observed in the distribution of syndrome elements of disease location between the two groups （P＞0.05）， but the phlegm element was significantly more prevalent in spleen-heat patients than in consumptive-heat patients （P = 0.006）. Regarding the risk of complications， spleen-heat patients had a significantly higher risk of developing macrovascular complications compared to consumptive-heat patients （OR=2.04， P=0.010）， while no significant differences were found between groups in the occurrence of microvascular complications （P＞0.05）. ConclusionThe spleen-heat T2DM patients show a more frequent syndrome element of disease nature of phlegm， and a higher risk of developing macrovascular complications compared to consumptive-heat patients.

Objective To investigate application value of three-dimensional light sheet microscopy imaging for evaluating intraplaque neovascularization in arterial plaques and the efficacy of intervention,and to assess the effect of melatonin(MLT)on neovascularization by these means.Methods Thirty-six ApoE-/-model mice were randomly divided into three groups(n=12):vehicle group,MLT group,and MLT+GW9662 intervention group(MLT+GW).The mice were treated with vehicle,MLT alone,or MLT combined with peroxisome proliferator activated receptor-γ(PPARγ)inhibitor GW9662,respectively.The carotid arteries of the models were three-dimensionally imaged using a light sheet microscopy,and the length,volume and other indicators of neovascularization were quantitatively analyzed using Imaris software.Subsequently,CD31 immunohistochemical staining was performed for verification.Results The light sheet microscopy preliminarily achieved the three-dimensional visualization of intraplaque neovascularization,and its structure was observed to be three-dimensionally reticular and scattered.The results of Imaris quantitative analysis showed that,compared with vehicle group,the total intraplaque neovas cularization length in the MLT group was shortened[(15.79±12.90)mm vs.(33.42±11.16)mm,P<0.05],the total volume was reduced[(1.34±1.47)×10-3 mm3 vs.(13.44±7.35)×10-3 mm3,P<0.05],and the volume ratio was decreased(0.44%±0.47%vs.3.76%±1.74%,P<0.05).The above indicators in MLT+GW group were significantly increased compared with those in MLT group[total length:(35.31±4.69)mm,total volume:(8.87±3.46)×10-3 mm3,volume ratio:2.89%±0.38%;P<0.05].The CD31 immunohistochemical staining also supported the above findings(P<0.05).Conclusions Based on the light sheet microscopy imaging technology,the three-dimensional visualization and quantitative analysis of intraplaque neovascularization were preliminarily realized.It was found that MLT could reduce the overall burden of intraplaque neovascularization,and PPARγ might be involved in its regulatory process.

Objective:To Evaluate the potential causal relationship between the levels of 179 lipids in peripheral blood and the risk of different subtypes of lung cancer by Mendelian randomization analysis.Methods:A two-sample Mendelian randomization analysis was performed using data from the Genome-Wide Association Study(GWAS),and sensitivity analysis was performed to verify the reliability of the results.Single nucleotide polymorphisms(SNPs)were used as instrumental variables,and GWAS data for different subtypes of lung cancer were used as outcome variables.We analyze potential causal associations between the levels of 179 lipids and the risk of different subtypes of lung cancer.Results:The causal relationship between phosphatidylcholine and lung adenocarcinoma was established as a protective factor,and Sphingomyelin and Triacylglycerol have been identified as being linked to lung adenocarcinoma and function as risk factors.Phosphatidylcholine were found to have a causal association with lung squamous cell carcinoma serving as a protective factor,and Phosphatidylethanolamine and Sphingomyelin were identified as risk factors for lung squamous cell carcinoma.However,the effects of different subtypes of Phosphatidylcholine on lung adenocarcinoma and lung squamous cell carcinoma were different.The study did not find evidence that lipids can influence small cell lung carcinoma.Conclusion:This study provides evidence of a causal relationship between lipids level features and different subtypes of lung cancer.

Objective:To investigate and assess the situation of popularization and promotion of domestically innovative medical devices in Liaoning Province,so as to provide a basis for promoting the allocation policy of domestically innovation medical devices.Methods:Self-made questionnaire and on-site filling survey were conducted to implement investigation and analysis for the allocation situation of newly medical equipment of 188 medical institutions in 9 demonstration regions of the Project on Regional Application and Demonstration of Innovative Medical Equipment in Liaoning Province from 2015 to 2020.The allocation data of medical equipment between before(from 2015 to 2017)and after the demonstration projects were implemented(from 2018 to 2020)were compared.The occupancy rate of domestically medical devices(referred as"occupancy ratio of domestic device")was used as an evaluation indicator to assess the status of equipment allocation and application before and after the projects of application and demonstration were implemented in the region of innovative equipment for diagnosis and treatment.Results:In the 9 demonstrational regions of Liaoning province,the number of newly added domestic medical devices during the period from 2018 to 2020 increased from 1,608 units between 2015 and 2017 to 1,703 units.The occupancy ratio of newly added domestic devices increased from 72.7%to 84.9%.The occupancy ratio of domestic devices of newly added key equipment increased from 63.0%to 83.4%,and the growth rate reached 20.4%.In different districts and different grades of medical institution,the increase and application of domestically medical devices appeared difference.Conclusion:The occupancy rate of newly added domestically medical devices in 9 demonstration regions in Liaoning province has generally increased.However,there are still imbalances between different regions and different grades of medical institutions.The manufacturers of domestically medical devices still need strengthen brand building and marketing promotion,so as to further enhance market competitiveness of domestically medical devices.

AIM To investigate the variations in mercury dissolution from HgS-containing traditional medicines in three kinds of simulated gastrointestinal dissolution media.METHODS 39 batches of 15 types of HgS-containing traditional medicines were collected,total mercury content and dissolved mercury concentrations in simulated gastric fluid,simulated intestinal fluid,and L-cysteine-containing simulated intestinal fluid were measured.The maximum daily intake of total mercury and soluble mercury was calculated based on the maximum daily clinical dosage.RESULTS Among the 15 types of medicines,the maximum daily intake of total mercury varied by 156 times,the daily intake of soluble mercury varied by 3 502 times in simulated gastric fluid,313 times in simulated intestinal fluid,and 10 663 times in L-cysteine-containing simulated intestinal fluid,approximately.CONCLUSION For the 15 types of HgS-containing traditional medicines,the daily maximum intake of soluble mercury showed greater variations than that of total mercury.Soluble mercury concentration is more closely correlated with intestinal absorption of mercury and thus represents a more rational quality control indicator for HgS-containing traditional medicines.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To analyze the epidemic trend of influenza-like illness（ILI）cases，etiological detection results，and the evolution of the hemagglutinin（HA）gene of the predominant strains in Hanzhong City，Shaanxi Province during the 2018-2024 influenza seasons.Methods:ILI sentinel surveillance data and network laboratory test results during the 2018-2024 influenza seasons in Hanzhong City，Shaanxi Province were collected for descriptive analysis. The HA gene sequences of 25 predominant strains were obtained through whole-genome deep sequencing method，and then compared with the vaccine strains recommended by the World Health Organization in the same period to analyze the evolution of the virus.Results:A total of 37 770 cases of ILI were reported in Hanzhong City during the 2018-2024 influenza seasons，and the proportion of total ILI cases（ILI%）was 2.87%（37 770/1 316 009）. The epidemic trend of ILI showed an obvious epidemic peak in winter and spring（from December of the current year to March of the following year）. The specimens with the highest positive rate were of type A（H3N2）（39.12%，365/933），and the predominant epidemic strains in each influenza season alternated among A（H1N1）pdm09（in the 2018-2019 and 2022-2023 influenza seasons），A（H3N2）（in the 2019-2020 and 2023-2024 influenza seasons）and B（Victoria）（in the 2021-2022 influenza season）. The phylogenetic relationship gradually became more distant over time across different influenza seasons. Among them，the epidemic strains of A（H1N1）pdm09 belonged to the 6B.1 clade，and the evolution mainly occurred in the Sa and Sb regions of the HA epitope. Meanwhile，the epidemic strains of A（H3N2）belonged to the 3C clade，and the evolution mainly took place in the A，B and C regions of the HA epitope. The strains of the B（Victoria）lineage belonged to the V1a.3a.2 clade，and the evolution mainly occurred in the 120-loop，150-loop，and 190-helix regions of the HA epitope.Conclusions:The influenza epidemic in Hanzhong City has obvious seasonality，and the amino acids of the epidemic strains have shown a certain degree of variation over the years. In future prevention and control work，influenza surveillance should be continuously strengthened，and the change trend of the predominant circulating strains should be closely monitored.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.