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 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.

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.

Ion mobility spectroscopy(IMS)has many advantages such as fast detection speed,high sensitivity,and portability,and thus plays an important role in on-site detection of chemical agents,explosives,drugs,environmental pollutants,and other pollutants.As a key component of IMS,the ion number density and temporal width of the injected ion packets directly determine the IMS detection sensitivity and resolution.In yhis study,the dual-parallel-grid structure of Tyndall-Powell gate(TPG),which could effectively isolate the electric fields within the ionization region,gate region,and drift region,was utilized to develop a dual effect TPG gating method for simultaneously enhancing the mobility discrimination reduction and ion packet temporal width compression,thereby improving the IMS performance.A TPG-IMS platform was thus built up and the effects of parameters such as gate opening pulsed width,gate penetration voltage,and ion injection voltage on the sensitivity and resolving power of IMS were systematically investigated using the dual-effect TPG gating method.The results demonstrated that,when detecting diethyl phosphate(DEP)and diethyl methylphosphate(DEMP)mixture using the dual effect TPG gating method,the peak currents of(DEP)2H+and(DEP·DEMP)H+ions with low K0 values were increased by 18 and 45 times respectively,while maintaining a high resolution of about 90.The limits of detection for DEP and DEMP were decreased from 4 ppb(10-9)to 235 ppt(10-12)and from 5 ppb to 156 ppt,respectively.This gating method only regulated the potential of the TPG grid adjacent to the drift region,without changing the structure of the ion mobility tube,making it convenient to apply on existing commercial instruments.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

This study analyzed and compared the epidemiological characteristics of foodborne listeriosis in the United States and China,to provide evidence for optimizing the listeriosis surveillance program in China.Descriptive statistical analysis was performed on the listeriosis monitoring data from 2009 to 2021 registered in the FDOSS system and the attribution estimates of Listeria monocytogenes(L.monocytogenes)from 2013 to 2021 published by IFSAC.Sporadic and outbreak data on listeriosis in China from the CNKI,Wanfang Medical,and CQVIP databases were collected.From 2009 to 2021,a total of 1 037 listeriosis cases were reported in the United States,including 902 hospitalizations and 165 deaths.The peak of cases caused by Lm con-taminated food was in July.The number of cases,hospitalizations,and deaths accounted for 18.4％(191/1 037),20.5％(185/902),and 22.4％(37/165)of the total,respectively.Most listeriosis outbreaks were attributed to three food groups:dairy products,vegetable crops,and fruits,with attribution percentages ranging from 73.8％to 89.6％.The overall incidence of list-eriosis in China was not high:619 cases were reported from 2009 to 2021,and only 177 cases were recorded in detailed inci-dence years;the maximum number of cases in 2018 was 26.A total of 220 cases were reported with detailed onset months;the highest number of cases in April was 30.Data on listeriosis cases in China are incomplete and sporadic,and only seven cases have been successfully traced to food.Listeriosis surveillance systems in the United States are relatively complete,and there are more foodborne outbreaks.Dairy products,vegetable row crops,and fruits are the most likely causes of disease outbreaks.Although only sporadic cases have been reported in China,China should take actions such as gradually improving multi-department coop-eration mechanisms,achieving data sharing and deepening data mining,and accelerating progress in the detection technology of food-borne pathogenic microorganisms,to ensure food safety and public health.

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.