Objective To establish a cell bank of extrahepatic cholangiocarcinoma (ECC)-derived organoids and investigate the key factors influencing the organoids generation. Methods The tumor samples from patients with portal cholangiocarcinoma (pCCA) and distal cholangiocarcinoma (dCCA) were used to isolate cells, and these cells were cultured using three-dimensional (3D) technique to establish ECC organoids. Histological characteristics of the organoids were evaluated and identified through hematoxylin-eosin (HE) and immunohistochemistry stainings. The success rates of organoids generation from different tumor types were compared. And clinical characteristics of patients between successful and failure culture groups were compared. Results The success rates of organoids establishment from pCCA and dCCA were all low, with 42.4% (14/33), 51.9% (14/27), respectively. The tumor was larger in successful group than that in failure group (P＜0.001); there was no statistical difference in tumor differentiation status, microvascular invasion, and perineural invasion between the two groups. Conclusions The successful rate of ECC-derived organoids establishment is low, and larger tumor has higher successful culture rate.

Objective Establish a relationship model between the outcome of inpatient rehabilitation treatment and the influencing factors of rehabilitation effect,explore the evaluation method of inpatient rehabilitation service effect.Methods Using a neural network model to construct a functional relationship model between the outcomes of inpatient rehabilitation treatment and the factors affecting rehabilitation effectiveness,in order to predict the expected rehabilitation outcomes of patients receiving inpatient treatment.Compare the distribution of the difference between the actual discharge ICF total score and the predicted ICF total score to determine the effectiveness of rehabilitation treatment.Results As a result,a total of 1 334 hospitalized rehabilitation cases of brain injury patients were included in this study for analysis.Based on the evaluation indicators and standards of prediction accuracy,the optimal model was selected and the rehabilitation effect was evaluated.Conclusion Based on the ICF-RS-17 measurement of patient entry and exit function scores,the functional status of hospitalized rehabilitation patients themselves,and related possible influencing factors,a relationship model between inpatient rehabilitation treatment outcomes and influencing factors is constructed.It provides a certain scientific basis for establishing an effective evaluation method for the actual clinical rehabilitation effect,and also provides reference suggestions for the realization of value-based payment of rehabilitation medical insurance.

The study aims to investigate the effects of adding different proportions of Codonopsis radix compound crude extracts to the rabbit diet on growth performance,immune status,intesti-nal enzyme activity,structure,and microbial composition.A total of 96 5-week-old New Zealand White rabbits were randomly divided into 4 groups,with 6 replicates per group.The control group(BC)was fed a basal diet,while the experimental groups(CM-H and CM-L)were fed a basal diet supplemented with 1 000 mg/kg and 500 mg/kg of Codonopsis radix compound crude extracts,re-spectively.The antibiotic group(CK)was fed a basal diet supplemented with 300 mg/kg of keto-tifen.The experimental period was 42 days.Blood samples were collected at days 21 and 42,and se-rum biochemical and immune markers were determined.Intestinal segments and contents were col-lected at day 42 for analysis of intestinal health.The results showed that compared with the BC group,the average daily gain,feed-to-gain ratio,and diarrhea rate were significantly higher(P＜0.05)in the CM-H and CM-L groups.The total cholesterol(Tchol)content in the serum was sig-nificantly lower in the CM-H group at day 21 and the CM-L group at day 42(P＜0.05).The high-density lipoprotein(HDL)was significantly higher in the CM-H and CM-L groups than in the CK group at day 42(P＜0.05),and the total protein(TP)in the serum was significantly higher in the CM-H and CM-L groups than in the BC group(P＜0.05).The IgG and IgM levels in the serum were significantly higher in the CM-H and CM-L groups than in the BC group(P＜0.05).In the CM-H and CM-L groups,the content of acetic acid in the colon was significantly higher than that in the BC group(P＜0.05).The content of propionic acid in the colon of the CM-L group was also significantly higher than that in the BC group(P＜0.05).The content of α-amylase in the duode-num,the content of trypsin in the duodenum,the pancreas,and the ileum of the CM-H group were significantly higher than those in the BC group(P＜0.05),and the content of trypsin in the duode-num of the CM-H group was significantly higher than those in the BC group and the CM-L group(P＜0.05).Compared with the BC group,the content of GPX1 in the ileum and jejunum of the CM-L group and the ileum of the CM-H group was significantly increased(P＜0.05),and the length of the villi in the duodenum of the CM-H group was significantly increased(P＜0.05).Compared with the BC group,the expression level of ZO-1 in the ileum of the CM-H group was significantly upregulated(P＜0.05),and the expression level of Claudin in the jejunum of the CM-H group and the CM-L group was significantly higher than that in the CK group(P＜0.05).The high-throughput sequencing results showed that the Sob index was significantly higher in the CM-L group compared to the BC group(P＜0.05).At the phylum level,the Firmicutes and Bacteroid-ota phyla were the main phyla.At the genus level,Akkermansia and Ruminococcus were the main genera.The relative abundance of Papillibacter and Eubacterium_ruminantium_group in the CM-L group was significantly higher than that in the CK group(P＜0.05).In summary,adding a Codonopsis radix compound crude extract to the diet can improve the growth performance,immu-nity,antioxidant capacity,integrity of intestinal mucosal structure,enzyme activity in the intestine,and increase the diversity of microorganisms in the blind intestine when the diet is supplemented with 500 mg/kg of Codonopsis radix compound crude extract.

Objective This study investigated feasible cases and their significance in promoting the"generalized"development of inspection through digital-intelligent equipment.Methods A qualitative research approach was used,involving interviews conducted between February 2025 and March 2025 with experts in traditional Chinese medicine diagnostics,clinical research methodology,medical engineering integration,and related disciplines,using both online and offline methods.In accordance with the Consolidated Criteria for Reporting Qualitative Research,feasible cases involving the specific application of digital equipment in various parts of observation were collected through item enrichment.The significance of extending observation capabilities via these cases was analyzed,along with the overall implications of integrating digital technologies with traditional inspection method.Results Interviews were completed with 11 experts from domestic universities and research institutes in the fields of traditional Chinese medicine diagnosis,medical engineering integration,and related disciplines.A total of 78 feasible cases of digital-intelligent inspection were identified,along with 69 insights regarding the significance of enhancing the inspection capabilities.These insights were synthesized into two dimensions and 23 holistic meanings.The first dimension is to expand the scope of inspection,including obtaining internal environmental characteristics,observing external environmental characteristics,expanding thermodynamic characteristic data,and crossing time and space.The second dimension is to improve the quality of observation and diagnosis information collection and analysis,including 19 specific meanings,such as standardized collection environment,objective quantification,and refined observation.Conclusion Digital-intelligent equipment plays a significant role in expanding the scope of inspection content and achieving high-quality acquisition and analysis of extensive inspection information.These advancements extend and enrich the capabilities of traditional inspection method in traditional Chinese medicine.

Objective:It analyzes the flow characteristics and spatial distribution patterns of intra-provincial cross-regional medical patients in Guangdong,while comparing hospitalization cost differences between local and non-local care.Methods:Based on 2022-2023 cross-regional medical data from Guangdong,spatial visualization and descriptive analysis were conducted combined with Mann-Whitney U test to compare the cost burden.Results:Cross-Regional patients in Guangdong primarily flow to Guangzhou,accounting for 77.8％of the total intra-provincial cross-regional hospitalizations.Cross-regional medical expenses were significantly higher than the insured locations,with notable differences in mean total hospitalization costs and personal out-of-pocket payment ratios.Conclusion:Refining pre-approval procedures for cross-regional care,enhancing specialized medical departments in under-resourced regions,and strengthening coordination between healthcare insurance systems and primary healthcare strengthening initiatives are needed to promote balanced medical resource allocation and reduce the cost burden on patients.

Objective:It analyzes the flow characteristics and spatial distribution patterns of intra-provincial cross-regional medical patients in Guangdong,while comparing hospitalization cost differences between local and non-local care.Methods:Based on 2022-2023 cross-regional medical data from Guangdong,spatial visualization and descriptive analysis were conducted combined with Mann-Whitney U test to compare the cost burden.Results:Cross-Regional patients in Guangdong primarily flow to Guangzhou,accounting for 77.8％of the total intra-provincial cross-regional hospitalizations.Cross-regional medical expenses were significantly higher than the insured locations,with notable differences in mean total hospitalization costs and personal out-of-pocket payment ratios.Conclusion:Refining pre-approval procedures for cross-regional care,enhancing specialized medical departments in under-resourced regions,and strengthening coordination between healthcare insurance systems and primary healthcare strengthening initiatives are needed to promote balanced medical resource allocation and reduce the cost burden on patients.

Objective:To explore the time variations of the influence of the ultra-high dose rate irradiation (FLASH irradiation, FLASH-IR) and conventional dose rate irradiation (CONV-IR) of electron beams under different doses on the energy metabolism of triple-negative breast cancer cells MDA-MB-231.Methods:The basal metabolism of the MDA-MB-231 cells and normal breast epithelial cells MCF-10A was compared using a Seahorse XF Pro Metabolic Analyzer. Based on an irradiation platform with a thermionic cathode electron accelerator (6 MeV), the MDA-MB-231 cells were exposed to FLASH-IR (106 Gy/s) and CONV-IR (0.1 Gy/s) at 2 and 14 Gy, respectively. Meanwhile, a sham irradiation group was established under identical culture conditions. The mitochondrial metabolism and glycolytic metabolism of the cells at 4, 24, and 48 h post-irradiation were analyzed.Results:Compared to the MCF-10A cells, the MDA-MB-231 cells exhibited a greater reliance on glycolytic metabolism. Compared to those of the sham irradiation group, MDA-MB-231 cells in the 2 Gy CONV-IR group showed up-regulated ATP-linked respiration at 4, 24, and 48 h post-irradiation ( t = 2.69-3.70, P < 0.05). Their glycolytic level and glycolytic capacity were up-regulated only at 4 h post-irradiation and were down-regulated at 48 h ( t = 2.79, -4.44, P < 0.05). In contrast, there was no statistically significant difference in these indicators between the FLASH-IR and CONV-IR groups ( P > 0.05). However, the proton leak of the MDA-MB-231 cells in the FLASH-IR group was relatively down-regulated at 4 h post-irradiation and was significantly up-regulated at 24 h and 48 h post-irradiation compared with the CONV-IR group ( t = -2.45, 3.19, 6.51, P < 0.05). At 14 Gy, the MDA-MB-231 cells in the CONV-IR group showed progressively increased mitochondrial and glycolytic metabolism across all time points ( t = 2.48-12.14, P < 0.05). Notably, compared with the CONV-IR group, the MDA-MB-231 cells in the FLASH-IR group exhibited more significantly up-regulated basal respiration, ATP-linked respiration, and non-mitochondrial oxygen consumption ( t = 2.56-6.51, P < 0.05), as well as a higher glycolytic capacity at 24 h post-irradiation ( t = 2.86, P < 0.05). Conclusions:Low-dose (2 Gy) FLASH-IR induces relatively up-regulated proton leak in breast cancer cells MDA-MB-231 at 24 h post-irradiation. In contrast, under high-dose (14 Gy) FLASH-IR, the MDA-MB-231 cells show more pronounced mitochondrial metabolic stress and a higher demand for energy metabolism.

Objective Establish a relationship model between the outcome of inpatient rehabilitation treatment and the influencing factors of rehabilitation effect,explore the evaluation method of inpatient rehabilitation service effect.Methods Using a neural network model to construct a functional relationship model between the outcomes of inpatient rehabilitation treatment and the factors affecting rehabilitation effectiveness,in order to predict the expected rehabilitation outcomes of patients receiving inpatient treatment.Compare the distribution of the difference between the actual discharge ICF total score and the predicted ICF total score to determine the effectiveness of rehabilitation treatment.Results As a result,a total of 1 334 hospitalized rehabilitation cases of brain injury patients were included in this study for analysis.Based on the evaluation indicators and standards of prediction accuracy,the optimal model was selected and the rehabilitation effect was evaluated.Conclusion Based on the ICF-RS-17 measurement of patient entry and exit function scores,the functional status of hospitalized rehabilitation patients themselves,and related possible influencing factors,a relationship model between inpatient rehabilitation treatment outcomes and influencing factors is constructed.It provides a certain scientific basis for establishing an effective evaluation method for the actual clinical rehabilitation effect,and also provides reference suggestions for the realization of value-based payment of rehabilitation medical insurance.

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

Objective:Investigate the clinical characteristics of patients with coronary artery disease (CAD) and moderate-to-severe coronary calcification lesions confirmed by intravascular ultrasound (IVUS), and to compare the prevalence of moderate-to-severe calcification lesions among different clusters of patients with CAD.Methods:This cross-sectional study enrolled patients with coronary artery disease who underwent coronary angiography and IVUS at the General Hospital of Northern Theater Command from June 2016 to June 2023. Patients with mild calcification were excluded, and the remaining cohort was divided into moderate-to-severe calcification and non-calcification groups. The least absolute and selective operator logistic regression was used to identify baseline variables associated with mederate-to-severe calcification. Hierarchical cluster analysis was used to identify similarities in clinical baseline data among patients, and the prevalence of moderate-to-severe coronary calcification was compared across different clusters of patients with CAD.Results:A total of 1 406 patients with CAD were enrolled (age (60.7±10.0) years; 963 males (68.5%)). A total of 563 patients were assigned in the moderate-to-severe calcification group and 843 patients were assigned in the non-calcification group. The least absolute and selective operator logistic regression identified 23 baseline variables associated with moderate-to-severe coronary artery calcification. Hierarchical cluster analysis based on these 23 variables divided all patients into Cluster 1 (500 cases) and Cluster 2 (906 cases). Patients in Cluster 1 were characterized by high age, high body mass index, high diastolic blood pressure, elevated mean arterial pressure, history of hypertension, history of diabetes, low endogenous creatinine clearance, high fasting blood glucose, low high-density lipoprotein cholesterol (HDL-C), high lipoprotein(a), high alkaline phosphatase, high glycated hemoglobin, low serum albumin, high triglycerides/HDL-C ratio, high HbA1c/HDL-C ratio, and high triglyceride glucose index. Cluster 1 (49.6%, 248/500) exhibited a significantly higher prevalence of moderate-to-severe coronary artery calcification compared to Cluster 2 (34.8%, 315/906, P=0.002). Conclusions:Patients with moderate-to-severe coronary artery calcification exhibited clinical heterogeneity compared to those without calcification. A subgroup characterized by high age, elevated body mass index, high diastolic blood pressure, elevated mean arterial pressure, history of hypertension, history of diabetes, low endogenous creatinine clearance, and high fasting blood glucose levels demonstrated a higher prevalence of moderate-to-severe coronary artery calcification.