ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective To evaluate the changes in postoperative plasma β-endorphin(β-EP)levels in patients who had received perioperative electroacupuncture(EA)treatment in 10 randomized controlled trials(RCTs)and examine the impact of EA on postoperative pain.Methods This meta-analysis evaluated the changes in plasma β-EP levels and visual analog scale(VAS)12,24 and 48 hours after surgery in patients receiving perioperative EA.It also assessed the changes in plasma serotonin(5-hydroxytryptamine,5-HT)and prostaglandin E2(PGE2)levels at 24 hours postsurgery.A comprehensive search was conducted in the China National Knowledge Infrastructure(CNKI),Wanfang,Chongqing VIP database,Chinese Biomedical Database(CBM),Web of Science,and PubMed databases.RCTs on perioperative EA and β-EP published from the inception of the websites up to July 25,2023,were retrieved.Effect size aggregation,literature quality assessment,and bias analysis were performed using RevMan 5.3 software,and sensitivity analysis was conducted via R 4.3.1.Results A total of 10 RCTs involving 706 patients were included.EA in conjunction with conventional anesthesia significantly increased plasma β-EP levels at 12 hours postsurgery[standard mean difference(SMD)=2.79,95%CI(1.85,3.72),Z=5.81,P＜0.00001],24hours postsurgery[SMD=1.87,95%CI(0.9,2.83),Z=3.79,P=0.0001],and 48 hours postsurgery[SMD=2.02,95%CI(1.49,2.54),Z=7.50,P＜0.00001].EA reduced plasma PGE2 levels at 24 hours postsurgery and plasma 5-HT levels at 24 hours postsurgery,and the VAS at 12,24 and 48 hours after surgery also decreased.Conclusion These findings suggest that perioperative EA markedly elevates plasma β-EP levels,reduces pain-inducing factors in plasma,and effectively alleviates acute postoperative pain.

The main characteristics of neurodegenerative diseases represented by Alzheimer’s disease (AD) and Parkinson’s disease (PD) is the progressive irreversible loss of neurons, leading to varying degrees of pathological changes and loss of cognitive function. There is still no effective treatment. With the acceleration of global aging society, the incidence of neurodegenerative diseases is rapidly increasing, becoming a serious global public health concern that urgently requires the development of effective therapeutic strategies. The Hippo signaling pathway, a highly evolutionarily conserved pathway, consists of the core components MST1/2, LATS1/2, and downstream effectors, transcriptional co-activators YAP and TAZ. It plays a crucial role in the regulation of various biological processes such as cell proliferation, differentiation, development, and apoptosis. Dysregulation of the Hippo pathway contributes to the development of many diseases, including cancer, cardiovascular diseases, immune disorders, etc. Therefore, targeting the dysregulated components of the Hippo pathway may be an effective strategy for treating various diseases. Increasing evidence indicates that the Hippo pathway is excessively activated in the development of neurodegenerative diseases, manifested by increased expression of MST1 and downregulation of YAP. Stabilizing the Hippo pathway levels has shown improvements in AD and PD. However, most studies on the Hippo pathway in AD and PD focus on changes in the expression levels of Hippo pathway components, and research in other neurodegenerative diseases is still lacking. Therefore, further investigation is needed to fully understand the mechanistic role of the Hippo pathway in neurodegenerative diseases. Meanwhile, miRNA, similarly dysregulated in neurodegenerative diseases and serving as biomarkers, is a primary target for miRNA therapy in neurodegenerative diseases, including AD and PD. Activating or inhibiting dysregulated miRNAs is the main strategy of miRNA therapy during the neurodegenerative disease development. Evidence suggests that the interaction between the Hippo pathway and miRNA can result in widespread biological effects and crosstalk in the occurrence of different types of diseases. However, studies on the interplay between the Hippo pathway and miRNA in neurodegenerative diseases are relatively scarce. In this paper, we predicted the miRNAs related to Hippo pathway through bioinformatics database, and further screened the miRNAs with crosstalk relationship with Hippo signaling pathway through experiments in combination with PubMed. Then, the mechanism of action of Hippo signaling pathway related miRNAs in AD and PD is further elucidated. It is reported that the Hippo pathway and its related miRNA may exert neuroprotective effects by reducing oxidative stress, improving neuroinflammation, stabilizing autophagy levels, maintaining neuronal mitochondrial function, and ameliorating blood-brain barrier dysfunction, thereby delaying the progression of AD and PD. However, research on miRNA directly regulating the Hippo pathway to improve AD and PD is limited, and observations of the Hippo pathway and its related miRNA in other neurodegenerative diseases are scarce. However, considering the regulatory relationship between the Hippo pathway and miRNA in multiple diseases and their respective roles in key mechanisms of neurodegenerative diseases, such as oxidative stress and neuroinflammation, the crosstalk between miRNA and the Hippo pathway holds a crucial regulatory role in the development of neurodegenerative diseases. Thus, the interaction pathways of the Hippo pathway and its related miRNA may be a pivotal avenue for exploring effective therapeutic strategies for neurodegenerative diseases in the future.

Objective:In the context of the aging trend of China's population,it aims to analyze the trend of elderly disabled population growth in various regions and calculate the potential payment pressure of long-term care insurance for the disabled population,thereby providing policy implications for China's long-term care insurance system.Methods:A model for estimating the amount of expenditure on long-term care insurance fund was constructed,using the population age structure of each province in China from 2025 to 2060 obtained from the random forest model,and combining multi-source data such as the disability rate of the elderly population and the care cost of disabled elderly people to predict the number of elderly disabled people and the payment amount of long-term care insurance in each province in the future.Results:The aging trend in China will continue to intensify and exhibit a significant structural feature.The peak of the aging ratio in northeastern regions such as Inner Mongolia,Heilongjiang,Jilin,and Liaoning will come earliest,while the number of elderly people with disabilities in provinces with large populations such as Shandong,Sichuan,and Henan are relatively larger.Guangdong will have the largest number of disabled elderly people by 2055.Conclusion:It is suggested that the long-term care insurance system should be steadily advanced,with national-level support for the construction of the system in Northeast China and populous provinces.

Objective:In the context of the aging trend of China's population,it aims to analyze the trend of elderly disabled population growth in various regions and calculate the potential payment pressure of long-term care insurance for the disabled population,thereby providing policy implications for China's long-term care insurance system.Methods:A model for estimating the amount of expenditure on long-term care insurance fund was constructed,using the population age structure of each province in China from 2025 to 2060 obtained from the random forest model,and combining multi-source data such as the disability rate of the elderly population and the care cost of disabled elderly people to predict the number of elderly disabled people and the payment amount of long-term care insurance in each province in the future.Results:The aging trend in China will continue to intensify and exhibit a significant structural feature.The peak of the aging ratio in northeastern regions such as Inner Mongolia,Heilongjiang,Jilin,and Liaoning will come earliest,while the number of elderly people with disabilities in provinces with large populations such as Shandong,Sichuan,and Henan are relatively larger.Guangdong will have the largest number of disabled elderly people by 2055.Conclusion:It is suggested that the long-term care insurance system should be steadily advanced,with national-level support for the construction of the system in Northeast China and populous provinces.

Objective:In the context of the aging trend of China's population,it aims to analyze the trend of elderly disabled population growth in various regions and calculate the potential payment pressure of long-term care insurance for the disabled population,thereby providing policy implications for China's long-term care insurance system.Methods:A model for estimating the amount of expenditure on long-term care insurance fund was constructed,using the population age structure of each province in China from 2025 to 2060 obtained from the random forest model,and combining multi-source data such as the disability rate of the elderly population and the care cost of disabled elderly people to predict the number of elderly disabled people and the payment amount of long-term care insurance in each province in the future.Results:The aging trend in China will continue to intensify and exhibit a significant structural feature.The peak of the aging ratio in northeastern regions such as Inner Mongolia,Heilongjiang,Jilin,and Liaoning will come earliest,while the number of elderly people with disabilities in provinces with large populations such as Shandong,Sichuan,and Henan are relatively larger.Guangdong will have the largest number of disabled elderly people by 2055.Conclusion:It is suggested that the long-term care insurance system should be steadily advanced,with national-level support for the construction of the system in Northeast China and populous provinces.

Objective:In the context of the aging trend of China's population,it aims to analyze the trend of elderly disabled population growth in various regions and calculate the potential payment pressure of long-term care insurance for the disabled population,thereby providing policy implications for China's long-term care insurance system.Methods:A model for estimating the amount of expenditure on long-term care insurance fund was constructed,using the population age structure of each province in China from 2025 to 2060 obtained from the random forest model,and combining multi-source data such as the disability rate of the elderly population and the care cost of disabled elderly people to predict the number of elderly disabled people and the payment amount of long-term care insurance in each province in the future.Results:The aging trend in China will continue to intensify and exhibit a significant structural feature.The peak of the aging ratio in northeastern regions such as Inner Mongolia,Heilongjiang,Jilin,and Liaoning will come earliest,while the number of elderly people with disabilities in provinces with large populations such as Shandong,Sichuan,and Henan are relatively larger.Guangdong will have the largest number of disabled elderly people by 2055.Conclusion:It is suggested that the long-term care insurance system should be steadily advanced,with national-level support for the construction of the system in Northeast China and populous provinces.

Objective:In the context of the aging trend of China's population,it aims to analyze the trend of elderly disabled population growth in various regions and calculate the potential payment pressure of long-term care insurance for the disabled population,thereby providing policy implications for China's long-term care insurance system.Methods:A model for estimating the amount of expenditure on long-term care insurance fund was constructed,using the population age structure of each province in China from 2025 to 2060 obtained from the random forest model,and combining multi-source data such as the disability rate of the elderly population and the care cost of disabled elderly people to predict the number of elderly disabled people and the payment amount of long-term care insurance in each province in the future.Results:The aging trend in China will continue to intensify and exhibit a significant structural feature.The peak of the aging ratio in northeastern regions such as Inner Mongolia,Heilongjiang,Jilin,and Liaoning will come earliest,while the number of elderly people with disabilities in provinces with large populations such as Shandong,Sichuan,and Henan are relatively larger.Guangdong will have the largest number of disabled elderly people by 2055.Conclusion:It is suggested that the long-term care insurance system should be steadily advanced,with national-level support for the construction of the system in Northeast China and populous provinces.