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*

Osteoarthritis is a common degenerative joint disease, and cartilage damage is often considered an early factor in irreversible joint degeneration. Repairing damaged cartilage remains a medical challenge due to its limited ability to self-repair and regenerate. In recent years, the application of tissue engineering strategies to treat cartilage defects has been recognized as an emerging therapeutic avenue. Acellular cartilage matrix (ACM) is an ideal material for cartilage repair and regeneration as it retains the extracellular matrix structure and bioactive components of natural cartilage, mimicking the extracellular environment of natural cartilage to the greatest extent. Type II collagen is the main type of hyaline cartilage and plays an important role in regulating the mechanical properties of cartilage tissue. It has been shown that type II collagen, growth factors and the hypoxic microenvironment play important roles in promoting cartilage regeneration. Type II collagen induces cell aggregation and chondrogenic differentiation in a specific way; Various growth factors contained in the ACM induce Sox9 expression and promote chondrogenic differentiation of stem cells; The hypoxic microenvironment upregulates the expression of type II collagen (COL2A1), Sox9 and maintains chondrocyte phenotype. In addition, ACM has been widely used in cartilage regeneration studies, either as a decellularized scaffold, hydrogel or 3D bioprinting technique for the repair of defective cartilage. Although the ACM-derived biomaterials discussed in this paper have many advantages, there are still some difficulties in their practical applications, such as loss of ACM components and reduced scaffold performance, which are still worth exploring in depth.

OBJECTIVE: To study the changes in hemodynamics during the induction stage of systemic mild hypothermia therapy in neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE). METHODS: A total of 21 neonates with HIE who underwent systemic mild hypothermia therapy in the Department of Neonatology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, from July 2017 to April 2020 were enrolled. The rectal temperature of the neonates was lowered to 34℃ after 1-2 hours of induction and maintained at this level for 72 hours using a hypothermia blanket. The impedance method was used for noninvasive hemodynamic monitoring, and the changes in heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), cardiac output (CO), cardiac index (CI), and total peripheral resistance (TPR) from the start of hypothermia induction to the achievement of target rectal temperature (34℃). Blood lactic acid (LAC) and resistance index (RI) of the middle cerebral artery were recorded simultaneously. RESULTS: The 21 neonates with HIE had a mean gestational age of (39.6±1.1) weeks, a mean birth weight of (3 439±517) g, and a mean 5-minute Apgar score of 6.8±2.0. From the start of hypothermia induction to the achievement of target rectal temperature (34℃), there were significant reductions in HR, CO, and CI ( CONCLUSIONS The systemic mild hypothermia therapy may have a significant impact on hemodynamics in neonates with moderate to severe HIE, and continuous hemodynamic monitoring is required during the treatment.
Cardiac Output ; Child ; Hemodynamics ; Humans ; Hypothermia ; Hypoxia-Ischemia, Brain/therapy* ; Infant ; Infant, Newborn ; Vascular Resistance

Objective: To evaluate the nutritional status by the Controlling Nutritional Status (CONUT) score and its association with the long-term prognosis in patients with acute heart failure (AHF). Methods: This prospective monocentric study consecutively enrolled patients admitted to our hospital for AHF from April 2012 to May 2016. Patients were divided into 3 groups based on the CONUT score at admission: normal (0-1), mild malnutrition (2-4) and moderate-severe malnutrition (5-12) groups. Baseline information was obtained and recorded within 24 hours after admission. All patients were followed up every 3 months by outpatient visit or telephone call until March 2019. The primary endpoint was all-cause mortality. The Kaplan-Meier survival curves and log-rank test were used to compare all-cause mortality between groups. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality after discharge. Results: A total of 396 patients were enrolled in this study, including 114 patients with normal nutritional status, 200 patients with mild malnutrition and 82 patients with moderate-severe malnutrition. One hundred and fifty-eight patients died during a median follow-up of 34 (18, 46) months. The mortality was 32.4% (37/114), 39% (78/200) and 52.4% (43/82) in normal, mild malnutrition and moderate-severe malnutrition groups, respectively. The mortality was significantly higher in the moderate-severe malnutrition group than in normal nutrition group (P<0.05). However, there was no significant difference in mortality between normal and mild malnutrition group as well as between mild and moderate-severe malnutrition group (both P>0.05). Kaplan-Meier curves indicated that patients with high CONUT score group was at higher risk of all-cause mortality compared with those with low CONUT score (P=0.002). Cox proportional hazard analyses showed that the risk of all-cause mortality of moderate-severe malnutrition group was significantly higher than that of normal nutrition group (HR =1.648, 95%CI 1.021-2.660, P=0.041). Conclusions: The CONUT score of patients with AHF at admission is associated with the long-term prognosis. High CONUT score is an independent risk factor for all-cause mortality in AHF patients after discharge.
Heart Failure ; Humans ; Nutrition Assessment ; Nutritional Status ; Prognosis ; Prospective Studies ; Retrospective Studies

Drug problem is a major social and public security problem in the world. Drug abuse poses a great threat to economic development, social stability and public health. In recent years, synthetic drugs represented by methamphetamine have surpassed traditional drugs such as morphine, heroin, ketamine and become one of the most abused drugs in the world. In order to solve the problem of drug abuse, it is of great theoretical value and practical significance to carry out all-round and multi-level scientific research on drug-related issues. Based on the current situation of drug abuse, this article reviews research progresses on the epidemiology of methamphetamine abuse, the monitoring technology, the basic researches on toxicity damage, the withdrawal drug screening, the related clinical comorbidity and the testing technologies, comprehensively presenting the development trend of methamphetamine abuse related issues.
Amphetamine-Related Disorders/epidemiology* ; Heroin ; Humans ; Illicit Drugs ; Methamphetamine/adverse effects* ; Substance Abuse Detection

OBJECTIVETo analyze the clinical and molecular features of a child with carnitine palmitoyltransferase 1A (CPT1A) deficiency.

METHODSClinical data of the child was collected. Blood acylcarnitine was determined with tandem mass spectrometry. DNA was extracted from the child and his parents. All exons and flanking regions of the CPT1A gene were analyzed by PCR and Sanger sequencing.

RESULTSAnalysis showed that the patient carried compound heterozygous mutations c.1787T>C and c.2201T>C of the CPT1A gene, which derived his father and mother, respectively. Both mutations were verified as novel through the retrieval of dbSNP, HGMD and 1000 genome databases. Bioinformatic analysis suggested that the mutations can affect protein function.

CONCLUSIONAcyl carnitine analysis has been the main method for the diagnosis of CPT1A deficiency. The c.1787T>C and c.2201T>C mutations of the CPT1A gene probably underlie the disease in this patient. Gene testing can provide important clues for genetic counseling and prenatal diagnosis.

Base Sequence ; Carnitine O-Palmitoyltransferase ; deficiency ; genetics ; Exons ; Female ; Humans ; Hypoglycemia ; enzymology ; genetics ; Infant ; Lipid Metabolism, Inborn Errors ; enzymology ; genetics ; Male ; Molecular Sequence Data ; Point Mutation ; Pregnancy

Objective To evaluate the combined antibacterial effect of fosfomycin and imipenem against 60 carbapenem-resistant Enterobacteri-aceae ( CRE ) in vitro.Methods Experiment was designed by the checkerboard method , the minimal inhibition concentrations of single antibacterial drug or the combination of fosfomycin and imipenem at dif-ferent concentrations against 60 CRE isolated from inpatients were evalua-ted through agar double dilution method synergy effect of combination was assessed by fractional inhibitory concentration index ( FIC ) .Results Compared with single-use, the minimal inhibitory concentra-tion of thecombination of fosfomycin and imipenem decreased ( P<0.01).The combination of fosfomycin and imipenem demonstrated 23.3%( 14/60 ) synergism , 35.0%( 21/60 ) partial synergism , 1.7%(1/60) additive, 40.0%( 24/60 ) indifference, no antagonism in our study.Conclusion Combination of fosfomycin and imipenem showed synergism or partial synergism against most CRE isolates.

OBJECTIVETo study the effect of Yiqi Bufei Recipe ([see text], YBR) on surgical tolerability, pulmonary compensatory function and post-operation rehabilitation in patients with pulmonary incompetence (PI) after pneumonectomy.

METHODSYBR intervention was applied to 60 patients with PI after pneumonectomy (as test group), the pulmonary and cardiac functions changes before and after operation, occurrence of postoperative complications, mortality, and the number of hospitalization days and intensive care unit (ICU) confinement period were observed. Meantime, for the negative and positive controls, the same parameters were observed comparatively in 60 patients with normal lung function, and in 60 patients with PI undergoing a similar operation but untreated with Chinese herbs.

RESULTSLung function in the test group showed insignificant change before and after operation (P >0.05), while significant decrease was seen in the two control groups (P<0.05). Furthermore, the incidences of post-operation complications and mortality as well as the number of hospitalization days and the ICU confinement period in the test group were significantly lower than those in the positive control group respectively (P <0.05).

CONCLUSIONYBR could relieve lung injury after pneumonectomy, improve surgical tolerability, reduce the length of postoperative hospitalization days and ICU confinement period, and lower the incidence of postoperative complications and mortality in patients with PI after pneumonectomy.

Blood Gas Analysis ; China ; epidemiology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Heart Function Tests ; drug effects ; Humans ; Incidence ; Intensive Care Units ; Length of Stay ; Lung ; drug effects ; physiopathology ; surgery ; Male ; Middle Aged ; Pneumonectomy ; adverse effects ; Postoperative Complications ; epidemiology ; etiology ; Respiratory Function Tests ; Treatment Outcome

BACKGROUNDOff-label application of drug-eluting stents (DES) during percutaneous coronary intervention (PCI) was not uncommon in daily practice, however DES in treating Chinese patients with complex lesion subset was under-investigated. The primary objective of the FIREMAN registry was to evaluate the long term efficacy and safety of the Firebird sirolimus-eluting stent (SES) in treating patients with complex coronary lesions. Here we report the mid-term of one-year clinical outcomes and eight-month angiographic follow-up results of FIREMAN registry.

METHODSThe FIREMAN registry was a prospective multi-center registry, which included 1029 consecutive patients undergoing PCI with Firebird SES implantation between September 2006 and July 2007 in 45 centers in China. The clinical follow-up was designed to be performed at 1, 6, 12, 18, 24, 30 and 36 months post index procedure, and non-mandatory angiographic follow-up at 8 months was planned. One hundred percent site monitoring was conducted.

RESULTSLong lesions (59.2%), multi-vessel disease (50.4%), and small vessel disease (31.6%) were mostly found in angiography. Major adverse cardiac events (MACE) occurred in 51 (5.1%) patients at 1 year clinical follow-up, including cardiac mortality in 6 (0.6%), non-fatal myocardial infarction in 11 (1.1%), and target lesion revascularization in 36 (3.5%) of the patients. Definite and probable stent thrombosis (ST) by Academic Research Consortium (ARC) definition occurred in 12 (1.36%) patients at one-year clinical follow-up. The 8-month binary restenosis rate was 5.7% in-segment and 4.3% in-stent, respectively. Late lumen loss was (0.21 ± 0.40) mm in-segment and (0.23 ± 0.36) mm in-stent, respectively. Furthermore, Cox regression analysis revealed that diabetes, small vessel diameter, and chronic total occlusion were independent predictors of ST.

CONCLUSIONSThe results showed that the Firebird SES was effective and safe in treating Chinese patients with complex coronary lesions and occurrence of ST rate at one-year clinical follow-up was acceptable, however further long-term follow-up was still necessary. (NCT00552656)

Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; methods ; Asian Continental Ancestry Group ; Coronary Angiography ; Coronary Disease ; diagnostic imaging ; therapy ; Drug-Eluting Stents ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Sirolimus ; therapeutic use ; Treatment Outcome

Renal angiomyolipoma is a type of benign tumor that occurs sporadically in addition to being associated with tuberous sclerosis. Preoperative embolization of large tumors is important to avoid excessive blood loss during surgery. We reported a patient with a 5505-g giant renal angiomyolipoma in a solitary kidney. The patient was treated with preoperative embolization and radical nephrectomy without complications. This type of treatment for an enormous angiomyolipoma can reduce the risk of uncontrolled hemorrhage caused by rupture of the tumor during the operation and should be considered for the treatment of similar tumors.
Adult ; Angiomyolipoma ; surgery ; Arteries ; surgery ; Embolization, Therapeutic ; methods ; Humans ; Kidney Neoplasms ; surgery ; Male