Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility ; Administration, Oral ; Polymers/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Emulsions/chemistry* ; Biological Availability ; Animals ; Pharmaceutical Preparations/administration & dosage*

Heart failure with preserved ejection fraction (HFpEF) is a type of heart failure characterized by left ventricular diastolic dysfunction with preserved ejection fraction. With the aging of the population and the increasing prevalence of metabolic diseases, such as hypertension, obesity and diabetes, the prevalence of HFpEF is increasing. Compared with heart failure with reduced ejection fraction (HFrEF), conventional anti-heart failure drugs failed to reduce the mortality in HFpEF due to the complex pathophysiological mechanism and multiple comorbidities of HFpEF. It is known that the main changes of cardiac structure of in HFpEF are cardiac hypertrophy, myocardial fibrosis and left ventricular hypertrophy, and HFpEF is commonly associated with obesity, diabetes, hypertension, renal dysfunction and other diseases, but how these comorbidities cause structural and functional damage to the heart is not completely clear. Recent studies have shown that immune inflammatory response plays a vital role in the progression of HFpEF. This review focuses on the latest research progress in the role of inflammation in the process of HFpEF and the potential application of anti-inflammatory therapy in HFpEF, hoping to provide new research ideas and theoretical basis for the clinical prevention and treatment in HFpEF.
Humans ; Heart Failure ; Stroke Volume/physiology* ; Hypertrophy, Left Ventricular/metabolism* ; Ventricular Dysfunction, Left/metabolism* ; Inflammation/complications* ; Obesity ; Hypertension

Gramineous crops occupy a remarkable proportion of grain crops in the word,and wheat,rice and corn account for more than 80%of the world's food crops. Agricultural residues bring tremendous pressure on the environment,and inefficient development of resources has caused huge waste of resources. At present,the research on agricultural residues mainly focuses on energy,fertilizer,feed and materialization. However, there are still a lot of resources that have not been rationally utilized. The author has found that in recent years,the medicinal research on gramineous crop waste has focused on four varieties-rice,corn,wheat and sugar cane,and their waste rice bran,rice husk,rice straw,corn stigma,corn bract,wheat bran,sugar cane leaf,sugar cane skin. The compounds isolated and identified from agricultural residues include phenylpropanoids,flavonoids,steroids and their glycosides,organic acids and their esters,volatile oil and saccharides. Studies have shown that agricultural residues from gramineous crops have pharmacological activities, such as anti-oxidation,hypolipidemia,hypoglycemia,anti-inflammation,anti-tumor,anti-cardiovascular disease,anti-liver and kidney damage. This paper is a systematic review of the chemical composition and pharmacological effects of agricultural residues from the major gramineous crops,so as to provide useful information for further research and development of agricultural residues.

Objective To prepare isophenylcyclopentylamine hydrochloride capsules and evaluate its quality. Methods The suitable excipients were selected by the drug-excipient compatibility test,and after the formulation and preparation process design and screening,the micromeritic property and hygroscopicity of contents of capsules as well as the basic performance and stability of is-ophenylcyclopentylamine hydrochloride capsules were evaluate. Results The selected formulation was composed of isophenylcyclo-pentylamine hydrochloride 10 mg,anhydrous dibasic calcium phosphate 128.7 mg,mannitol 128.7 mg and aerosil 2.7 mg.The angle of repose of intermediate powders was(30.71±1.09)°,aerated and packed bulk densities were(0.76±0.01)and(0.90±0.02)g/ml re-spectively,Hausner value was 1.19±0.01,Carr′s index was(15.86±1.05)%,indicating good flowability and filling property as well as relatively low humidity.The contents,uniformity of contents and dissolution of capsules fulfilled the requirements.The quality of ca-pusles kept well in the 6-month accelerated and long-term stability test.Conclusion The formulation is simple and reasonable,and the preparation process showed a good reproducibility,which might be suitable for industrialization.

Objective To learn the awareness and influencing factors of mental health knowledge in Yinzhou District. Methods The multi-stage cluster sampling was used to investigate 1239 residents by using the questionnaire of the residents' mental health awareness. Results The total awareness rate was 61.3％, and the awareness rate that was relatively low was mainly concentrated on "World Suicide Prevention Day" (29.9％),"mental illness was a problem in mind" (32.1％),"mental illness was due to the stimulation" (44.0％) . Multiple linear regression analysis found that the residents who were older (β=0.039, P<0.05), lived in city (β=2.073, P<0.05), worked as administrators, technicians, and waiters compared with self-employed, retired and unemployed (β: -2.350 - -1.591, P <0.05) scored higher. Conclusion The residents' awareness of mental health knowledge is low. The urban residents, self-employed, workers, farmers, are the key populations to be educated with mental health system.

Objective To establish the three-dimensional finite element model of human lower cervical spine C3-7 motion segments after anterior cervical corpectomy and fusion (ACCF) surgery with titanium mesh and bone graft, and to analyze the stability of cervical spine and stress distribution of internal fixation devices after ACCF surgery. Methods The finite element model of cervical spine C3-7 segments after ACCF of C5 segment with titanium mesh, bone graft, plate and screw fixation was established，and C3-7 segment intact model of cervical vertebra was also constructed. The torque moment of 0.5, 1.0, 1.5, 2.0 N﹒m was applied to the ACCF surgery model. The ROM, maximum stress in facet joint and stress distributions on internal fixation devices under flexion, extension, lateral bending and torsion movement were analyzed. Results ROM of reconstructed C5 segment increased with the torque moment increasing after ACCF surgery. In the case of 1.0 N﹒m torque moment and 50 N preload, the ROM of reconstructed C5, C3-4, C6-7 and C3-7 segment was reduced by 81%, 62%, 58% and 80% compared with the intact model. The maximum stress in facet joint of reconstructed C5 segment reduced and the stress in adjacent segments significantly increased. The stress of titanium mesh was mainly distributed on the compression side of movement, and high stress was located in the roots of screws. Conclusions ACCF surgery can promote the stability of cervical spine, decrease the stress in facet joint of operation segment, and has better treatment effect on easing compression from spinal cord caused by cervical spondylotic myelopathy. The research results will provide some theoretical basis for clinical application of ACCF.

Objective To establish the three-dimensional finite element model of human lower cervical spine C3-7 motion segments after anterior cervical corpectomy and fusion (ACCF) surgery with titanium mesh and bone graft,and to analyze the stability of cervical spine and stress distribution of internal fixation devices after ACCF surgery.Methods The finite element model of cervical spine C3-7 segments after ACCF of C5 segment with titanium mesh,bone graft,plate and screw fixation was established,and C3-7 segment intact model of cervical vertebra was also constructed.The torque moment of 0.5,1.0,1.5,2.0 N · m was applied to the ACCF surgery model.The ROM,maximum stress in facet joint and stress distributions on internal fixation devices under flexion,extension,lateral bending and axial rotation movement were analyzed.Results ROM of reconstructed C5 segment increased with the torque moment increasing after ACCF surgery.In the case of 1.0 N · m tomue moment and 50 N preload,the ROM of reconstructed C5,C3-4,C6-7 and C3-7 segment was reduced by 81％,62％,58％ and 80％ compared with the intact model.The maximum stress in facet joint of reconstructed C5 segment reduced and the stress in adjacent segments significantly increased.The stress of titanium mesh was mainly distributed on the compression side of movement,and high stress was located in the roots of screws.Conclusions ACCF surgery can promote the stability of cewical spine,decrease the stress in facet joint of operation segment,and has better treatment effect on easing compression from spinal cord caused by cervical spondylotic myelopathy.The research results will provide some theoretical basis for clinical application of ACCF surgery.

BACKGROUNDUrine output (UO) is an essential criterion of the Kidney Disease Improving Global Outcomes (KDIGO) definition and classification system for acute kidney injury (AKI), of which the diagnostic value has not been extensively studied. We aimed to determine whether AKI based on KDIGO UO criteria (KDIGOUO) could improve the diagnostic and prognostic accuracy, compared with KDIGO serum creatinine criteria (KDIGOSCr).

METHODSWe conducted a secondary analysis of the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a 2-month prospective cohort study (July 1, 2009 to August 31, 2009) involving 3063 patients in 22 tertiary Intensive Care Units in Mainland of China. AKI was diagnosed and classified separately based on KDIGOUOand KDIGOSCr. Hospital mortality of patients with more severe AKI classification based on KDIGOUOwas compared with other patients by univariate and multivariate regression analyses.

RESULTSThe prevalence of AKI increased from 52.4% based on KDIGOSCrto 55.4% based on KDIGOSCrcombined with KDIGOUO. KDIGOUOalso resulted in an upgrade of AKI classification in 7.3% of patients, representing those with more severe AKI classification based on KDIGOUO. Compared with non-AKI patients or those with maximum AKI classification by KDIGOSCr, those with maximum AKI classification by KDIGOUOhad a significantly higher hospital mortality of 58.4% (odds ratio [OR]: 7.580, 95% confidence interval [CI]: 4.141-13.873, P< 0.001). In a multivariate logistic regression analysis, AKI based on KDIGOUO (OR: 2.891, 95% CI: 1.964-4.254, P< 0.001), but not based on KDIGOSCr (OR: 1.322, 95% CI: 0.902-1.939, P = 0.152), was an independent risk factor for hospital mortality.

CONCLUSIONUO was a criterion with additional value beyond creatinine criterion for AKI diagnosis and classification, which can help identify a group of patients with high risk of death.

Acute Disease ; mortality ; Aged ; Creatinine ; blood ; Critical Illness ; mortality ; Female ; Hospital Mortality ; Humans ; Kaplan-Meier Estimate ; Kidney Diseases ; blood ; mortality ; pathology ; urine ; Logistic Models ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Risk Factors

Objective To study biomechanical properties such as range of motion (ROM), intervertebral disc stress, ligament tension of inferior cervical spinal segment after the treatment of Discover, Prodisc-C artificial intervertebral disc replacement, and anterior cervical discectomy and fusion (ACDF), as well as mechanical property changes of the prosthesis after implantation. Methods Three kinds of operation plan on C5-6 cervical disc degeneration were established: Discover model, Prodisc-C model and ACDF model, as well as C4-7 segment original model of cervical vertebra. Biomechanical property changes after operation in cervical spine C4-7 segment in sagittal, coronal and transverse section were analyzed. Results ROM changes of cervical segment C5-C6 were as following: in Discover model it increased by 12.7%-73.1%, Prodisc-C model increased by 74%-98%, ACDF decreased by 55.8%-71.8%. The stress of C4-5 intervertebral disc after Discover artificial disc replacement showed no obvious increase, while the stress of C6-7 intervertebral disc decreased by 33.2%-54.2% under flexion, extension and axial rotation conditions. The amplification of ligament tension in Discover model decreased by 30%-40% as compared to that in Prodisc-C model. The maximum stress of Discover model (36.72 MPa) appeared under flexion condition, which was smaller than that in Prodisc-C model. Conclusions Artificial disc replacement can help to keep movement performance for segment after surgery. As a newly developed artificial intervertebral disc prosthesis, Discover makes some progress in the aspect of decreasing ligament stress and maintaining spinal stability. The research findings will provide theoretical basis for the clinical study on ACDF and artificial cervical intervertebral disc replacement surgeries.

Objective:To investigate the correlationship between early morning blood pressure ,brachial‐ankle artery pulse wave velocity (baPWV ) and risk factors of cardiovascular diseases (early morning blood ,blood lipid ,blood glucose , homocysteine [HCY] ,glomerular filtration rate [eGFR] ,carotid artery plaque) .Methods:Early morning blood pressure was monitored in 297 patients with primary hypertension ,and baPWV ,blood lipid ,blood glucose ,HCY ,eGFR and carotid artery color Doppler were examined .SAS 9 .2 was used to analyze the relationship between baPWV and early morning blood pressure , blood lipid ,blood glucose ,HCY ,carotid plaque and age .The independent risk factors of baPWV were analyzed by regression analysis (Stepwise) .Results:BaPWV was significantly correlated with age ,early morning blood pressure ,low density lipoprotein cholesterol (LDL‐C) ,eGFR and carotid artery plaque (P< 0 .05) .BaPWV was not significantly correlated with fasting glucose or HCY .The regression analysis showed that the early morning blood pressure ,LDL‐C and carotid artery plaque were the independent risk factors of baPWV ( P < 0 .05 ) . Conclusions: The early morning hypertension and hypercholesteremia are correlated with arteriosclerosis in patients with essential hypertension .