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*

Combined allergic rhinitis and asthma syndrome (CARAS) is one of the common chronic airway inflammatory diseases in children. With the development of epigenetics, research on CARAS has gradually extended from protein levels to molecular levels, such as transcription and post-transcriptional regulation. N6-methyladenosine (m6A) methylation and ferroptosis have emerged as promising research hotspots in recent years, playing crucial roles in tumors, growth and development, and allergic diseases. This paper aims to summarize the characteristics of m6A and ferroptosis, along with their roles in the onset and progression of CARAS in children, thereby providing new insights and strategies for the diagnosis and treatment of childhood CARAS.
Humans ; Adenosine/physiology* ; Asthma/etiology* ; Ferroptosis ; Rhinitis, Allergic/etiology* ; Child

Objective:To evaluate the efficacy and safety of combining third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) with brain radiotherapy in patients with newly diagnosed EGFR mutation-positive non-small cell lung cancer (NSCLC) with brain metastases. Methods:A retrospective analysis was performed on the clinical data of patients with newly diagnosed EGFR-mutant NSCLC with brain metastases who received first-line treatment with third-generation EGFR-TKI with or without brain radiotherapy at the Fourth Affiliated Hospital of Guangxi Medical University between January 2018 and December 2022. Patients treated with EGFR-TKI plus brain radiotherapy were assigned to the combination group, while those treated with EGFR-TKI alone were assigned to the monotherapy group. Intracranial progression-free survival (iPFS), progression-free survival (PFS), overall survival (OS), intracranial disease control rate (iDCR), intracranial objective response rate (iORR), and adverse events were compared between groups. Subgroup analyses were performed according to EGFR exon 19 deletion (19del) and exon 21L858R mutation status. Survival was estimated using the Kaplan-Meier method, with the log-rank test applied for group comparisons and univariate analysis, while multivariate analysis was conducted using Cox proportional hazards regression model. Results:A total of 107 patients were included: 57 (53%) in the monotherapy group and 50 (47%) in the combination group. The combination therapy significantly improved iORR (80% vs. 60%, P=0.023), prolonged median OS (37.7 vs. 31.6 months, P=0.004), and extended median iPFS (21.8 vs. 16.7 months, P=0.018). The iDCR was 100% in both groups, and the difference in median PFS was not statistically significant (18.6 vs. 15.2 months, P=0.086). In the 19del subgroup ( n=53), patients in the combination group had longer OS ( P=0.028) and iPFS ( P=0.028). In the 21L858R subgroup ( n=54), the median OS was also longer in the combination group ( P=0.050). Multivariate analysis identified TKI monotherapy and an Eastern Cooperative Oncology Group (ECOG) performance status score=2 as independent adverse prognostic factors for iPFS, while TKI monotherapy, age ≥65 years, ECOG score=2, and >3 brain metastases were the independent adverse prognostic factors for OS. The incidence of adverse events did not differ significantly between groups (all P>0.05). Conclusions:First-line combination therapy with third-generation EGFR-TKI and cranial radiotherapy provides superior efficacy and acceptable safety compared with EGFR-TKI monotherapy in patients with EGFR-mutant lung adenocarcinoma and brain metastases. Both EGFR 19del and 21L858R mutation subgroups benefit from the combined treatment approach.

Diabetes-related cognitive impairment(DCI)is a major complication of type 2 diabetes melli-tus(T2DM).Although exercise is essential in alleviating DCI,the underlying mechanisms remain un-clear.The aim of this study is to investigate the role and mechanism of exosomal miR-126a-5p induced by exercise in ameliorating DCI.Twenty-four 16-week-old male db/db mice were randomly divided into dia-betes group(n=12;DM)and exercise intervention group(n=12;DE).The control group consisted of male m/m mice of the same age group(n=12;CON).The DE group underwent 8 weeks of moderate in-tensity treadmill training(10 m/min,5 days a week).In the MWM experiment,compared to the CON group,the DM group exhibited prolonged escape latency(P<0.01),reduced swimming speed and target quadrant time(P<0.001),and decreased expression of miR-126a-5p and EX-miR-126a-5p in hipp-ocampal tissue(P<0.001).After exercise intervention,the DE group showed improved performance with decreased escape latency(P<0.05),increased swimming speed and target quadrant time(P<0.05),and elevated levels of exosomal miR-126a-5p(P<0.001).Morphological staining revealed a de-crease in the expression and proportion of NeuN in hippocampal neurons and an increase in the expression and proportion of glial cells in the CA1 and CA3 regions of DM group mice compared to CON group mice(P<0.05),while DE group mice showed increased fluorescence intensity and proportion of neurons(P<0.05).Western blotting analysis revealed that the DM group also showed significant upregulation of amy-loid β(Aβ),high mobility group box 1(Hmgb1),and NF-κB in the hippocampus(P<0.05),which were reduced after exercise(P<0.05).Moreover,exosomal miR-126a-5p overexpression greatly de-creased the levels of Hmgb1,NF-κB,and amyloid precursor protein(APP)in HT22 cells and TNF-α,IL-1β in supernatant exposed to HG(P<0.05),while inhibition of miR-126a-5p led to increased levels of these proteins(P<0.05).In conclusion,eight weeks of treadmill exercise improved cognitive function in db/db mice,likely through the EXs-miR-126/HMGB1/NF-κB pathway to reduce inflammation in hip-pocampal tissue.

Objective:To observe the intervention effect of personalized nutrition program combined with rehabilitation training in stroke rehabilitation patients.Methods:86 stroke rehabilitation patients who were admitted to our hospital from January 2023 to June 2024 were prospectively selected,they were divided into control group and study group according to the random number table method,with 43 cases in each group,the control group received rehabilitation training,while the study group received personalized nutrition program combine with rehabilitation training.Simple Fugl Meyer motor function(FMA)score,immune function indicators[immunoglobulin(Ig)A,IgG,complement C3,IgM,complement C4],National Institutes of Health Stroke Scale(NIHSS),nutritional status indicators[albumin(ALB),prealbumin(PA),total protein(TP),hemoglobin(HB)],Stroke Specific Quality of Life Scale(SS-QOL),Barthel Index(BI)score were compared between the two groups.Results:NIHSS score in the study group at 8 weeks after intervention was lower than that in the control group,and SS-QOL score,BI score,FMA score,IgM,IgA,IgG,complement C3,complement C4,ALB,HB,TP and PA were higher than those in the control group(P＜0.05).Conclusion:Personalized nutrition program combined with rehabilitation training in stroke rehabilitation patients,can reduce neurological damage,improve limb motor function,enhance nutritional status,immunity,and quality of life.

Diabetes-related cognitive impairment(DCI)is a major complication of type 2 diabetes melli-tus(T2DM).Although exercise is essential in alleviating DCI,the underlying mechanisms remain un-clear.The aim of this study is to investigate the role and mechanism of exosomal miR-126a-5p induced by exercise in ameliorating DCI.Twenty-four 16-week-old male db/db mice were randomly divided into dia-betes group(n=12;DM)and exercise intervention group(n=12;DE).The control group consisted of male m/m mice of the same age group(n=12;CON).The DE group underwent 8 weeks of moderate in-tensity treadmill training(10 m/min,5 days a week).In the MWM experiment,compared to the CON group,the DM group exhibited prolonged escape latency(P<0.01),reduced swimming speed and target quadrant time(P<0.001),and decreased expression of miR-126a-5p and EX-miR-126a-5p in hipp-ocampal tissue(P<0.001).After exercise intervention,the DE group showed improved performance with decreased escape latency(P<0.05),increased swimming speed and target quadrant time(P<0.05),and elevated levels of exosomal miR-126a-5p(P<0.001).Morphological staining revealed a de-crease in the expression and proportion of NeuN in hippocampal neurons and an increase in the expression and proportion of glial cells in the CA1 and CA3 regions of DM group mice compared to CON group mice(P<0.05),while DE group mice showed increased fluorescence intensity and proportion of neurons(P<0.05).Western blotting analysis revealed that the DM group also showed significant upregulation of amy-loid β(Aβ),high mobility group box 1(Hmgb1),and NF-κB in the hippocampus(P<0.05),which were reduced after exercise(P<0.05).Moreover,exosomal miR-126a-5p overexpression greatly de-creased the levels of Hmgb1,NF-κB,and amyloid precursor protein(APP)in HT22 cells and TNF-α,IL-1β in supernatant exposed to HG(P<0.05),while inhibition of miR-126a-5p led to increased levels of these proteins(P<0.05).In conclusion,eight weeks of treadmill exercise improved cognitive function in db/db mice,likely through the EXs-miR-126/HMGB1/NF-κB pathway to reduce inflammation in hip-pocampal tissue.

Objective:To observe the intervention effect of personalized nutrition program combined with rehabilitation training in stroke rehabilitation patients.Methods:86 stroke rehabilitation patients who were admitted to our hospital from January 2023 to June 2024 were prospectively selected,they were divided into control group and study group according to the random number table method,with 43 cases in each group,the control group received rehabilitation training,while the study group received personalized nutrition program combine with rehabilitation training.Simple Fugl Meyer motor function(FMA)score,immune function indicators[immunoglobulin(Ig)A,IgG,complement C3,IgM,complement C4],National Institutes of Health Stroke Scale(NIHSS),nutritional status indicators[albumin(ALB),prealbumin(PA),total protein(TP),hemoglobin(HB)],Stroke Specific Quality of Life Scale(SS-QOL),Barthel Index(BI)score were compared between the two groups.Results:NIHSS score in the study group at 8 weeks after intervention was lower than that in the control group,and SS-QOL score,BI score,FMA score,IgM,IgA,IgG,complement C3,complement C4,ALB,HB,TP and PA were higher than those in the control group(P＜0.05).Conclusion:Personalized nutrition program combined with rehabilitation training in stroke rehabilitation patients,can reduce neurological damage,improve limb motor function,enhance nutritional status,immunity,and quality of life.

Objective:To evaluate the efficacy and safety of combining third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) with brain radiotherapy in patients with newly diagnosed EGFR mutation-positive non-small cell lung cancer (NSCLC) with brain metastases. Methods:A retrospective analysis was performed on the clinical data of patients with newly diagnosed EGFR-mutant NSCLC with brain metastases who received first-line treatment with third-generation EGFR-TKI with or without brain radiotherapy at the Fourth Affiliated Hospital of Guangxi Medical University between January 2018 and December 2022. Patients treated with EGFR-TKI plus brain radiotherapy were assigned to the combination group, while those treated with EGFR-TKI alone were assigned to the monotherapy group. Intracranial progression-free survival (iPFS), progression-free survival (PFS), overall survival (OS), intracranial disease control rate (iDCR), intracranial objective response rate (iORR), and adverse events were compared between groups. Subgroup analyses were performed according to EGFR exon 19 deletion (19del) and exon 21L858R mutation status. Survival was estimated using the Kaplan-Meier method, with the log-rank test applied for group comparisons and univariate analysis, while multivariate analysis was conducted using Cox proportional hazards regression model. Results:A total of 107 patients were included: 57 (53%) in the monotherapy group and 50 (47%) in the combination group. The combination therapy significantly improved iORR (80% vs. 60%, P=0.023), prolonged median OS (37.7 vs. 31.6 months, P=0.004), and extended median iPFS (21.8 vs. 16.7 months, P=0.018). The iDCR was 100% in both groups, and the difference in median PFS was not statistically significant (18.6 vs. 15.2 months, P=0.086). In the 19del subgroup ( n=53), patients in the combination group had longer OS ( P=0.028) and iPFS ( P=0.028). In the 21L858R subgroup ( n=54), the median OS was also longer in the combination group ( P=0.050). Multivariate analysis identified TKI monotherapy and an Eastern Cooperative Oncology Group (ECOG) performance status score=2 as independent adverse prognostic factors for iPFS, while TKI monotherapy, age ≥65 years, ECOG score=2, and >3 brain metastases were the independent adverse prognostic factors for OS. The incidence of adverse events did not differ significantly between groups (all P>0.05). Conclusions:First-line combination therapy with third-generation EGFR-TKI and cranial radiotherapy provides superior efficacy and acceptable safety compared with EGFR-TKI monotherapy in patients with EGFR-mutant lung adenocarcinoma and brain metastases. Both EGFR 19del and 21L858R mutation subgroups benefit from the combined treatment approach.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) .Methods:In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed.Results:A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively ( P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively ( P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively ( P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively ( P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively ( P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively ( P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively ( P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively ( P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively ( P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion:There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.