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*

Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P＜0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

Hyper-IgE syndrome (HIES) comprises a group of rare primary immunodeficiencies, which are characterized by extremely high serum IgE levels, eczema, recurrent skin and pulmonary infections.Signal transduction and activator of transcription 3( STAT3)-HIES is the most common type, which is caused by dominant-negative mutations in STAT3.STAT3-HIES confers broad innate and acquired immune defects, defects in skeletal, connective tissue, and vascular functions, causing a clinical phenotype including eczema, staphylococcal and fungal skin and pulmonary infections, scoliosis and minimal trauma fractures, vascular tortuosity and aneurysm.In this article, the advance in diverse clinical manifestations and management strategies of STAT3-HIES was summarized.

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 investigate the epidemiological and clinical characteristics of human parainfluenza viruses (HPIVs) infection among hospitalized children with community-acquired pneumonia (CAP) in China, and provide basic data for diagnosis, treatment and prevention of HPIVs infection.Methods:From November 2014 to February 2020, 5 448 hospitalized children with CAP were enrolled in 14 hospitals in 11 provinces and municipalities directly under the Central Government in southern China and northern China. Nasopharyngeal aspirates or throat swabs were collected, and the nucleic acids of 18 types respiratory viruses including HPIV1-4 were screened by suspension array technology. Demographic data and clinical information were collected for statistical analysis.Results:The total detection rate of HPIVs in 5 448 children with CAP was 8.83% (481/5 448), and the detection rate in males was higher than that in females (62.79% vs. 37.21%; χ2=0.000, P=0.992). The detection rate of HPIVs in 1~< 3 years age group was higher than that in other age groups, and the difference was statistically significant ( χ2=61.893, P<0.001). The detection rate of HPIVs in the northern region was higher than that in the southern region (9.02% vs 8.65%), but the difference was not statistically significant ( χ2=0.239, P=0.625). The prevalence of HPIV1-4 in northern and southern China was not completely same. HPIV1 was mainly prevalent in autumn in both northern and southern regions. HPIV2 was prevalent in summer in northern China, and the detection rate was low in southern China. HPIV3 reached its peak in both spring and summer in both northern and southern China, but its duration was longer in southern China than in northern China. HPIV4 is mainly popular in autumn in both southern China and northern China. Among 481 children infected with HPIVs, 58.42% (281/481) were infected with HPIV alone, and the main clinical manifestations were cough (90.75%) and fever (68.68%). Out of the HPIV-positive cases, 42.62% (205/481) were co-infected with another type of HPIV or a different virus, while 11.43% (55/481) had co-infections with two or more different viruses. HPIV3 was the most common type of co-infection with other viruses. HPIV3 infection accounted for the largest proportion (76.80%) in 47 HPIVs-positive children with severe pneumonia. Conclusions:HPIVs is one of the most important pathogens causing CAP in children in China, and children under 3 years of age are the main populations of HPIVs infection. The prevalence characteristics of all types of HPIVs in children in the north and south are not completely same. HPIV3 is the dominant type of HPIV infections and causes more severe diseases.

Objective To analyze the expression of m6A methyltransferase like 3(METTL3)gene in pan-tumor and its effect on tumor microenvironment.Methods The Cancer Genome Atlas(TCGA)database was used to analyze the gene sequencing and clinical data of patients with various tumors.The expressions of METTL3 gene in various tumors and its correlations with prognosis and tumor microenvironment were analyzed.Results METTL3 gene expression was upregulated in most malignancies,but only was associated with poor PFS of patients with hepatocellular carcinoma and prostate cancer(P＜0.05).The expression of METTL3 gene was associated with the infiltration levels of many inmmunet cells in hepatocellular carcinoma and prostate cancer,as well as the expression levels of inhibitory immune checkpoint genes(P＜0.05).Conclusions METTL3 gene overexpression could affect the prognosis of hepatocellular carcinoma and prostate cancer,which maybe associated with immune invasion and inhibitory immune checkpoints increased.

Aim To explore the roles of miRNA-132 and its related proteins(Mecp2, CREB)in the mechanism of methamphetamine(MA)-induced neurotoxicity and dependence.Methods The rats were intraperitioneally injected(ip)with MA(10 mg·kg-1·d-1)to establish methamphetamine dependence model with different dependent time courses of 1 week, 2 weeks, and 4 weeks respectively.The miRNA-132 and Mecp2 mRNA were detected by RT-qPCR, and the Mecp2, p-Mecp2, CREB and p-CREB proteins were detected by Western blot in the tissues of frontal cortex and hippocampus.Results In the frontal cortex, the miRNA-132 and Mecp2 mRNA were up-regulated in MA-dependent groups(P<0.05 and P<0.01), while the Mecp2 protein were down-regulated(P<0.01).MA could promote the phosphorylation of Mecp2 protein in the frontal cortex(P<0.01).In hippocampus, the miRNA-132 was down-regulated in the MA-dependent groups, but Mecp2 mRNA was up-regulated(P<0.05).Mecp2 protein increased in MA-dependent 1 week group(P<0.05), and then recovered with the prolonged time of MA dependence, then decreased in MA-dependent 4 weeks groups(P<0.05)in hippocampus.The phosphorylation level of Mecp2 was significantly decreased in the 1 week group(P<0.01), and then increased in the 2 weeks group(P<0.01)in hippocampus.Conclusions MA could induce an abnormal expression of miRNA-132 in the frontal cortex and hippocampus, and miRNA-132 might inhibit the translation of Mecp2 mRNA and induce the decrease expression of Mecp2 protein in the frontal cortex.But in hippocampus, miRNA-132 does not show the correlation with the Mecp2 expression trend of the frontal cortex.And miRNA-132 regulation does not depend on the expression of Mecp2 in hippocampus.

AIM:To evaluate the therapeutic efficacy of intravitreal injections of ranibizumab for macular edema secondary to retinal vein occlusion(RVO)and the prognostic factors for this disorder.METHODS:A retrospective case study. There were 61 patients(61 eyes)with macular edema secondary to RVO who treated in our hospital from April 2020 to February 2021, including 30 cases(30 eyes)of branch retinal vein occlusion(BRVO)patients and 31 cases(31 eyes)of central retinal vein occlusion(CRVO)patients. All patients received 3 times of intravitreal injections of ranibizumab(0.5mg), and some eyes underwent retinal laser therapy. The patients were followed up for 3mo after treatment(the first intravitreal injection)to observe the visual acuity, intraocular pressure, central retinal thickness(CRT)and record the occurrence of ocular and systemic complications.RESULTS: The visual acuity of the included patients after treatment was significantly improved compared with that before treatment, and the CRT was significantly decreased compared with that before treatment(P<0.01), and after 3 times of intravitreal injections, the visual acuity of BRVO and CRVO patients with pre-treatment visual acuity≤1(LogMAR)was better than that of the patients with pre-treatment visual acuity>1(P<0.01), but there was no difference in CRT(all P >0.05). Among BRVO and CRVO patients, 12 and 8 eyes received retinal laser treatment during 3 times of intravitreal injections, respectively. The difference in visual acuity and CRT among the eyes treated with laser and those that were untreated was not significant(P>0.05). No ocular and systemic serious complications emerged during follow-up.CONCLUSIONS: Ranibizumab has high efficacy and safety in the treatment of macular edema secondary to RVO, while visual acuity at baseline may help predict the prognosis.

Humans ; Magnetic Resonance Imaging ; Nocturnal Enuresis/diagnostic imaging*