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*

Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

OBJECTIVE: To explore the effect of acupuncture therapy on dysphagia in patients with Parkinson's disease. METHODS: This randomized controlled study lasted 42 days and included 112 patients with Parkinson's disease and dysphagia. Participants were randomly assigned to the experimental and control groups (56 cases each group) using the completely randomized design, all under routine treatment. The experimental group was given acupuncture therapy. The primary outcome was Penetration-Aspiration Scale (PAS). The secondary outcomes were (1) Standardized Swallowing Assessment (SSA), and (2) nutritional status including body mass index (BMI), serum albumin, prealbumin, and hemoglobin. Adverse events were recorded as safety indicators. RESULTS: One participant quitted the study midway. There were no significant differences in baseline assessment (P>0.05). After treatment, both groups showed significant improvement in PAS, SSA and nutritional status except for BMI of the control group. There were significant differences between the two groups in the PAS for both paste and liquid, SSA (25.18±8.25 vs. 20.84±6.92), BMI (19.97±3.34 kg/m²vs. 21.26 ±2.38 kg/m²), serum albumin (35.16 ±5.29 g/L vs. 37.24 ±3.98 g/L), prealbumin (248.33 ±27.72 mg/L vs. 261.39 ±22.10 mg/L), hemoglobin (119.09±12.53 g/L vs. 126.67±13.97 g/L) (P<0.05). There were no severe adverse events during the study. CONCLUSION: The combination of routine treatment and acupuncture therapy can better improve dysphagia and nutritional status in patients with Parkinson's disease, than routine treatment solely. (registration No. CLINICALTRIAL gov NCT06199323).
Humans ; Parkinson Disease/therapy* ; Deglutition Disorders/physiopathology* ; Acupuncture Therapy/adverse effects* ; Male ; Female ; Aged ; Middle Aged ; Treatment Outcome ; Nutritional Status ; Body Mass Index

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective To explore the correlation between the actual age and the pulp chamber volume(PCV)and pulp dentinal index(PDI)of the right first molars based on cone beam computed tomog-raphy(CBCT)technology,and to construct an accurate and convenient model for age estimation.Methods CBCT image data of 1 857 Han adults(883 males and 974 females)from the Department of Stomatology,Affiliated Hospital of North Sichuan Medical College were collected.The data were di-vided into training and validation sets at a ratio of 8∶2.A total of 1 485 training samples were used to construct the age estimation model,and 372 samples were used to validate the accuracy of the model.The Mimics 21.0 software was used to measure the PCV and calculate the PDI of the right first molars.Their correlations with age and the differences between different sexes and tooth positions were analyzed.Results Both the PCV and the PDI of the first molars showed strong negative correla-tions with the actual age(r values ranged from 0.82 to 0.89).The differences in PCV and PDI be-tween different sexes and tooth positions were statistically significant(P<0.05).The age estimation model based on PDI was superior to that based on PCV.The model based on the PDI values of the two right first molars(y=73.72-44.15 x3-28.27 x4,where x3 and x4 are the PDI values of the right maxil-lary and mandibular first molars,respectively)was the best,with the R2 of 0.79 and the mean abso-lute error of 4.90 years.Conclusion Both PCV and PDI of the first molars are effective indicators for age estimation.The age estimation model based on the PDI is more convenient and accurate than that based on the PCV,providing a more effective method for age estimation in forensic practice.

Objective To explore whether ferroptosis is involved in α-amanitin-induced hepatocyte in-jury by detecting iron deposition in mice liver tissues,oxidative stress indicators in hepatocytes and L-02 cells,and expressions of ferroptosis-related proteins after α-amanitin exposure.Methods The poi-soning models of α-amanitin C57BL/6J mice and L-02 cell were established.The Lillie ferrous iron staining and Prussian blue staining were used to detect iron deposition;the kits were applied to detect the levels of superoxide dismutase(SOD),catalase(CAT),malondialdehyde(MDA),and glutathione(GSH).Western blotting was performed to analyze expressions of p53,solute carrier family 7 member 11(SLC7A11),and glutathione peroxidase 4(GPX4).Results Compared with the control group,after α-amanitin exposure,positive cell rates of Fe2+and Fe3+in mice liver tissues increased significantly.In the liver tissues of medium(0.35 mg/kg)and high(0.45 mg/kg)dose groups and L-02 cells treated with 1 μmol/L α-amanitin,the level of GSH decreased,the level of MDA increased,and the activities of SOD and CAT decreased significantly.In addition,α-amanitin upregulated the expression of p53 in a concentration-and time-dependent manner and inhibited the expressions of SLC7A11 and GPX4.Con-clusion Ferroptosis plays an important role in α-amanitin-induced hepatocyte injury.Abnormalities of ferroptosis-related indicators can provide references for the forensic identification of α-amanitin poisoning.

Objective:To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection.Methods:A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study.Results:The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months.Conclusions:MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

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.

Aim To explore the protective effect of an-thocyanin B2(PCB2)on hydrogen peroxide(H2O2)induced oxidative damage and apoptosis in human oli-godendrocytes(MO3.13)and the underlying mecha-nism.Methods The optimal concentration of H2O2 and PCB2 for action was screened,and divided into normal group,PCB2 group(100 mg·L-1 PCB2 treat-ment for 24 hours),H2 O2 model group(500 μmol·L-1 H2O2 treatment for 24 hours),and H2O2+PCB2 group(500 μmol·L-1 H2O2 and 100 mg·L-1 PCB2 co-treated for 24 hours).FRAP method was used to detect the antioxidant capacity of PCB2;CCK-8 meth-od was used to detect the survival rate of cells in each group,while LDH method was used to assess cytotoxic-ity.Microenzyme-linked immunosorbent assay and ELISA were used to examine the levels of LDH,NO,H2O2,as well as the activities of CAT and SOD in each group of cells.Immunofluorescence and Western blot were used to detect the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4 in each group of cells.FerroOrange fluorescent probe was used to de-tect the intracellular content of ferrous ions(Fe2+).Results H2O2 could induce MO3.13 oxidative dam-age and lead to cell ferroptosis,while PCB2 could alle-viate MO3.13 oxidative damage and ferroptosis.Com-pared with the H2O2 model group,PCB2 intervention could significantly increase LDH content in MO3.13,reduce NO and H2O2 content,and improve SOD and CAT activity,and up-regulate the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4.Conclusion PCB2 can enhance cellular antioxidant capacity and alleviate H2O2 induced MO3.13 oxidative damage through the NRF2/HO-1/xCT/GPX4 axis.

Objective To compare the short-term clinical effects of unilateral dual-channel endoscopic discectomy(UBED)and percutaneous endoscopic intervertebral discectomy(PEID)in the treatment of L5S,Lumbar disc herniation,LDH.Methods From January 2019 to January 2021,a total of 57 cases of L5S,LDH treated by UBED or PEID were analyzed retrospectively,including 30 cases in UBED group and 27 cases in PEID group.The operation time,intraoperative fluoroscopy times,postoperative hospitalization days and surgical complications were compared between the two groups.The visual analogue scale(VAS)and oswestry disability index(ODI)were used to compare the postoperative quality of life of the two groups,and the modified MacNab criteria was used to evaluate the clinical efficacy in the last follow-up.Results The operation time of UBED group and PEID group was(75.30±8.44)minutes and(68.37±4.63)minutes,respectively,and the difference between the two groups was statistically significant(P＜0.05).VAS and ODI of 1 week,3 months,1 year and 1.5 years after surgery in 2 groups were significantly decreased compared with those before surgery,with statistical significance(P＜0.05).The VAS score of low back pain in UBED group was higher than that in PEID group[(3.87±1.14)points vs(2.70±0.67)points]at 1 week after surgery(P＜0.05),and there was no significant difference in VAS and ODI at the other time points(P＞0.05).There was no statistical difference in the results of modified MacNab criteria in the last follow-up(P＞0.05).There were 2 cases of dural tear in PEID group,1 case of dural tear in UBED group and 1 case of temporary nerve root injury in PEID group after operation,all of which were cured after symptomatic treatment.Conclusion Compared with PEID,UBED has a longer operation time,more trauma and more obvious low back pain in the short term after operation.The short-term curative effect of the two operations on L5S1 LDH is similar,the incidence of complications is low,and the times of fluoroscopy are few.Both operations are safe and effective.