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*

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 compare the prognostic impact of complete mesocolic excision (CME) versus D2 lymphadenectomy in patients with stage III right-sided colon cancer.Methods:A retrospective cohort study was conducted. Clinical data of 263 patients with stage III colon cancer undergoing right hemicolectomy in the Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital (January 1, 2016 to August 8, 2023) were included. Of the 263 patients, 152 underwent CME and 111 received D2 dissection. Propensity score matching (PSM) was employed to balance baseline characteristics between the two groups. Continuous variables were compared using the Mann-Whitney U test or Student's t-test; categorical variables were compared using the χ2 test or Fisher exact test. Survival curves were constructed using the Kaplan-Meier method, and the Log-Rank test was used to compare disease-free survival (DFS) and overall survival (OS) between groups. Cox proportional hazards models were utilized to analyze prognostic factors, with subgroup analyses performed.Results:Patients undergoing CME surgery were younger (proportion >75 years: 4.6% vs. 25.2%, P<0.001), had a lower burden of comorbidities (Charlson comorbidity index ≥ 1: 25.0% vs. 36.9%, P=0.045), The rates of open surgery and converted open surgery were lower [0.6% (1/152) vs. 4.5% (5/111) and 0.6% (1/152) vs. 2.7% (3/111), respectively; P=0.040].They also had a higher rate of receiving adjuvant therapy (92.7% vs. 76.0%, P<0.001). In terms of short-term postoperative outcomes, the CME group had a greater number of harvested lymph nodes (median: 30 vs. 25, P<0.001) and less blood loss (median: 20 ml vs. 20 ml, P=0.041). There were no significant differences between the groups in terms of the number of metastatic lymph nodes, operation time, and the incidence of postoperative complications. Survival analysis demonstrated significantly longer DFS in the CME group both before and after PSM. CME was an independent favorable prognostic factor for DFS (pre-PSM: HR=0.53, 95%CI: 0.31-0.91, P=0.022; post-PSM: HR=0.50, 95%CI: 0.26-0.97, P=0.042). No significant difference in OS was detected between the two groups across models. The subgroup analysis based on clinicopathological features revealed DFS benefits associated with CME in patients with tumor deposits (HR=0.41, 95%CI: 0.18-0.94, P=0.035), moderately-to-well-differentiated adenocarcinoma(HR=0.48, 95%CI: 0.26-0.90, P=0.023), proficient mismatch repair tumors (HR=0.55, 95%CI: 0.32-0.94, P=0.030), and pN2 stage disease (HR=0.43, 95%CI: 0.19-0.95, P=0.036). Conclusion:An extended lymph node dissection, as exemplified by CME, may confer a DFS advantage in patients with stage III right-sided colon cancer, especially those exhibiting a substantial burden of lymph node metastases.

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 compare the prognostic impact of complete mesocolic excision (CME) versus D2 lymphadenectomy in patients with stage III right-sided colon cancer.Methods:A retrospective cohort study was conducted. Clinical data of 263 patients with stage III colon cancer undergoing right hemicolectomy in the Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital (January 1, 2016 to August 8, 2023) were included. Of the 263 patients, 152 underwent CME and 111 received D2 dissection. Propensity score matching (PSM) was employed to balance baseline characteristics between the two groups. Continuous variables were compared using the Mann-Whitney U test or Student's t-test; categorical variables were compared using the χ2 test or Fisher exact test. Survival curves were constructed using the Kaplan-Meier method, and the Log-Rank test was used to compare disease-free survival (DFS) and overall survival (OS) between groups. Cox proportional hazards models were utilized to analyze prognostic factors, with subgroup analyses performed.Results:Patients undergoing CME surgery were younger (proportion >75 years: 4.6% vs. 25.2%, P<0.001), had a lower burden of comorbidities (Charlson comorbidity index ≥ 1: 25.0% vs. 36.9%, P=0.045), The rates of open surgery and converted open surgery were lower [0.6% (1/152) vs. 4.5% (5/111) and 0.6% (1/152) vs. 2.7% (3/111), respectively; P=0.040].They also had a higher rate of receiving adjuvant therapy (92.7% vs. 76.0%, P<0.001). In terms of short-term postoperative outcomes, the CME group had a greater number of harvested lymph nodes (median: 30 vs. 25, P<0.001) and less blood loss (median: 20 ml vs. 20 ml, P=0.041). There were no significant differences between the groups in terms of the number of metastatic lymph nodes, operation time, and the incidence of postoperative complications. Survival analysis demonstrated significantly longer DFS in the CME group both before and after PSM. CME was an independent favorable prognostic factor for DFS (pre-PSM: HR=0.53, 95%CI: 0.31-0.91, P=0.022; post-PSM: HR=0.50, 95%CI: 0.26-0.97, P=0.042). No significant difference in OS was detected between the two groups across models. The subgroup analysis based on clinicopathological features revealed DFS benefits associated with CME in patients with tumor deposits (HR=0.41, 95%CI: 0.18-0.94, P=0.035), moderately-to-well-differentiated adenocarcinoma(HR=0.48, 95%CI: 0.26-0.90, P=0.023), proficient mismatch repair tumors (HR=0.55, 95%CI: 0.32-0.94, P=0.030), and pN2 stage disease (HR=0.43, 95%CI: 0.19-0.95, P=0.036). Conclusion:An extended lymph node dissection, as exemplified by CME, may confer a DFS advantage in patients with stage III right-sided colon cancer, especially those exhibiting a substantial burden of lymph node metastases.

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 investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.

OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.

Karyotype analysis is the basic method in cytogenetics, and is also recognized as the "gold standard" for diagnosing chromosomal disorders. The teaching and training for traditional karyotyping analysis is time-consuming and even boring. The individual's ability for mastering the chromosome morphology can vary greatly. Therefore, it is necessary to improve the teaching method. On the basis of the traditional method, we have added auxiliary analysis software during the teaching. This type of splicing karyotype teaching has increased the students' interest and improved their ability for karyotyping, allowing them to quickly remember the characteristic bands of chromosomes. Through enhanced memory of a large number of karyotypic images, the students' ability to recognize individual chromosomes has improved.
Humans ; Karyotyping ; Karyotype ; Cytogenetics ; RNA Splicing ; Software

Circadian rhythm refers to the daily rhythmic variations in an organism. The irregular lifestyles of modern humans have led to a high incidence of chronic diseases, highlighting an inseparable relationship between disrupted circadian rhythm and disease development. TCM has long discussed rhythmic variations, with records dating back to the Yellow Emperor's Inner Canon(Huang Di Nei Jing), which laid a rich theoretical foundation for the research on circadian rhythm. Modern medical research has provided a more comprehensive explanation of its molecular mechanisms. This article integrated the current understanding of circadian rhythm in both Chinese and western medicine, emphasizing the crucial relationship between rhythm regulation and disease treatment. By highlighting the interdisciplinary nature of the two fields, it offers new directions for exploring the field of chronomedicine.
Humans ; Medicine, Chinese Traditional ; Acupuncture Therapy ; Circadian Rhythm ; Biomedical Research ; Polygonatum