Functional constipation （FC） is a clinically common functional bowel disorder characterized by a protracted course and associations with various chronic disorders and psychological abnormalities. Although not life-threatening， FC significantly impairs patients' quality of life. FC subtypes include slow-transit constipation （STC）， defecatory disorder （DD）， and normal-transit constipation （NTC）. The pathological mechanisms underlying FC have not been fully elucidated， and overall clinical efficacy remains unsatisfactory. Animal models of FC serve as essential tools for the study of disease mechanisms and the development of novel therapeutics. This article systematically reviews the current state of research on the animal models of FC and identifies that rodents， particularly rats and mice， are the most commonly used species. Dogs and pigs are also employed in complex intervention studies due to their physiological similarities to humans， though their use is limited by housing challenges and ethical considerations. Induction methods vary across different FC subtypes. STC models are primarily established with chemical agents such as loperamide or compound diphenoxylate. DD modeling often involves low-fiber diets combined with methylene blue injection or rectal narrowing. NTC modeling mainly relies on low-fiber dietary interventions. In addition， disease-syndrome combination models based on traditional Chinese medicine （TCM） theory have been developed， encompassing excess patterns such as heat accumulation， cold accumulation， and Qi stagnation， as well as deficiency patterns including Qi deficiency， blood deficiency， Yin deficiency， and Yang deficiency. These are achieved through an approach of disease model + syndrome induction， enabling the integration of mechanisms from both Western and TCM perspectives. Models are evaluated from two aspects： disease and syndrome manifestations （e.g.， colonic transit， secretory function， and TCM syndrome indicators such as mental state and body weight） and disease mechanisms （e.g.， enteric nervous system， interstitial cells of Cajal， smooth muscle cells， gut microbiota， and metabolites）. However， current research still faces challenges such as poor consistency in some models， non-specific interference in mechanism interpretation， insufficient studies on NTC， and lack of TCM tongue and pulse diagnosis in evaluation. Future efforts should focus on optimizing model stability and specificity to provide a more reliable experimental basis for investigating the pathological mechanisms of FC and developing therapeutic agents.

Objective:To investigate the correlation between mutations in KRAS, NRAS, BRAF, and PIK3 CA and the clinical characteristics of elderly colorectal cancer(CRC)patients. Methods:Paraffin-embedded tissue samples were obtained from 191 elderly CRC patients who consulted at Huadong Hospital, affiliated to Fudan University, between January 2022 and July 2023.Following deoxyribonucleic acid(DNA)extraction, the amplification refractory mutation system polymerase chain reaction(ARMS-PCR)was employed to detect the mutation profiles of KRAS, NRAS, BRAF, and PIK3 CA.Concurrently, serum samples collected prior to radical resection were analyzed for carcinoembryonic antigen(CEA), carbohydrate antigen 19-9(CA19-9), and carbohydrate antigen 72-4(CA72-4)using electrochemical luminescence.A comparative analysis of the clinical characteristics and preoperative serological tumor marker concentrations among patients with different gene mutations was conducted to elucidate their correlation. Results:A total of 191 elderly CRC patients were enrolled in the study, with ages ranging from 60 to 94 years(mean age 72.1±7.8 years), including 112 males.The mutation rate of KRAS, NRAS, BRAF, and PIK3 CA, as determined by combined detection, was found to be 49.21%(94/191)among elderly CRC patients. KRAS exhibited the highest mutation rate at 35.08%, with statistically significant differences observed in gender, primary site, degree of differentiation, and neurovascular invasion between patients with and without KRAS mutations( P<0.05 for all comparisons).The BRAF mutation rate was 8.90%, and significant differences in gender, age, primary site, and degree of differentiation were also noted between patients with and without BRAF mutations( P<0.05 for all).The mutation rates for NRAS and PIK3 CA were 2.62% and 5.24%, respectively, with no statistically significant differences in the clinical characteristics of patients across different groups( P>0.05 for all).Additionally, the proportion of patients over the age of 90 in the double mutation group was significantly higher( P<0.01).Significant differences in serum CA19-9 concentrations were observed among the various mutation types( P<0.05). Conclusions:There are notable differences in age, gender, primary site, degree of differentiation, and neurovascular invasion among elderly CRC patients with varying mutation statuses of KRAS, NRAS, BRAF, and PIK3 CA.Patients with double mutations exhibited higher concentrations of CA19-9 in preoperative serum.

Objective:To assess the safety and efficacy of thiotepa, busulfan, and etoposide (TBE) conditioning followed by autologous hematopoietic stem-cell transplantation (TBE auto-HSCT) in primary central nervous system lymphoma (PCNSL) patients.Methods:Clinical data from 27 PCNSL patients who received TBE auto-HSCT at the Fifth Medical Center of PLA General Hospital between November 1, 2021, and April 30, 2024, were retrospectively analyzed.Results:Twenty-seven patients [16 males, 11 females; median age 57 (23–72) years] were included, with 12 (44.4%, 12/27) over 60. Twenty-five had newly diagnosed PCNSL and 2 were relapsed. Median time from diagnosis to transplantation was 6.9 (5.0–10.0) months. TBE auto-HSCT increased complete remission (CR) rate from 63.0 to 96.3% ( P= 0.005), and 9 of 10 patients in partial remission achieving CR post-transplant. Median follow-up was 24.5 months (range 2.0–36.0). Two-year progress-free and OS rates were (87.2±6.9) % and (88.6±6.2) %, respectively. Common grade 3 nonhematologic adverse events were diarrhea (18.5%, 5/27) and bacterial infections (14.8%, 4/27). One patient (64 years old) died from carbapenem-resistant Enterobacteriaceae infection within 2 months post-transplant, yielding a 100-day treatment-related mortality of 3.7% (1/27) . Conclusion:TBE-conditioned high-dose chemotherapy with auto-HSCT is effective, safe, and well-tolerated in PCNSL patients, including the elderly.

Objective To explore the predictive value of ultra-sound(US)combined with multi-sequence MRI in a clinical-deep learning radiomics nomogram(DLRN)for the short-term efficacy of neoadjuvant chemotherapy(NAC)in patients with triple-negative breast cancer(TNBC).Methods A total of 122 TNBC patients from five hospitals were retrospectively analyzed,and divided into training group(72 cases)and validation group(50 cases).The clinical and pathological data,NAC regimens,and imaging data were collected.The lesions and its surrounding 10-unit voxels from US and MRI images were retained as the region of interest(ROI).Pyradiomics software and a ResNet152 convolutional neural network(CNN)framework were used to extract radiomics and deep learning features to construct a clinical-DLRN with outcome dimension fusion.The receiver operating characteristic(ROC)curve and calibration curve were plotted,and five-fold cross-validation decision curve were used to verify the model's clinical effec-tiveness.Results The clinical-DLRN constructed by US combined with multi-sequence MRI showed that area under the curve(AUC)was 0.967[95％confidence interval(CI)0.782-0.967]and accuracy(ACC)was 0.900,respectively.The five-fold cross-validation decision curve showed good generalization,with the highest clinical net benefit between risk thresholds of 0.72 and 0.96.Conclusion The clinical-DLRN integrating US and multi-sequence MRI has the best efficacy in predicting the short-term efficacy of NAC in TNBC patients,which offering potential guidance for personalized TNBC treatment.

Objective To assess the effects of “dual low” scanning technology in conjunction with an individualized injection protocol in enhancing the quality of abdominal contrast-enhanced CT images. Methods A total of 200 patients who underwent abdominal contrast-enhanced CT examinations at the Hainan Western Central Hospital between January 2022 and January 2024 were selected for the study. Using a random number table, participants were randomly assigned to either a control group (n = 100, sub-hypertonic contrast agent + conventional tube voltage + individualized injection protocol) or an observation group (n = 100, isotonic contrast agent + tube voltage of 100 kV + individualized injection protocol). The study compared the impact of these two methodologies on the quality of abdominal contrast-enhanced CT images. Results During the arterial phase, the CT value of the abdominal aorta was significantly higher in the observation group than that in the control group (P < 0.05), suggesting that isotonic contrast agent and low tube voltage more effectively enhanced vascular signal. During the portal vein phase, the CT value was higher and the liver parenchymal noise was lower in the observation group those in the control group (P < 0.05), further validating the advantages of the “dual low” approach during the portal venous phase. The radiation dose was significantly lower in the observation group than that in the control group (P < 0.05), indicating that the “dual low” protocol effectively reduced radiation dose while enhancing patient safety. During the arterial phase, both the abdominal aorta noise and liver parenchymal noise were lower in the observation group than those in the control group (P < 0.05), demonstrating that the “dual low” strategy effectively reduced image noise and enhanced image clarity. The image quality scores were significantly higher in the observation group than in the control group (P < 0.05), indicating that high image quality could be achieved even at reduced radiation doses and contrast agent concentrations. Conclusion The “dual low” scanning technology, combined with an individualized injection protocol, not only effectively enhances the contrast of arteries and veins, reduces image noise, and improves the overall image quality, but also decreases radiation dose and enhances patient safety. Therefore, this technology is worth being widely promoted.

Objective:To investigate the active ingredients and targets of Compound Gastritis Mixture(CGM)in the treatment of chronic atrophic gastritis(CAG)by network pharmacology method,and to validate the potential mechanism combined with molecular docking technology and cellular experiments.Methods:The Traditional Chinese Medicine System Analysis Platform(TCMSP)and Swiss Target Prediction databases were used to select the herbal ingredients of CGM and the corresponding targets;the GeneCards and Online Mendelian Inheritance in Man(OMIM)database were used to screen the targets of CAG;the common targets of CGM and CAG were analyzed from the Venny2.1.0 platform;STRING online platform was used to construct protein-protein interaction(PPI)networks for common drug-disease targets and screen the core targets.Cytoscape 3.9.1 software was used to construct the drug-disease-target network and screen the drug core components;Gene Ontology(GO)fuctional,Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were used to analyze the common targets of CGM and CAG;and AutoDock analysis software was used to perform molecular docking analysis of predicted main components of the drugs and core targets.The gastric mucosal epithelial cells GES-1 were induced by lipopolysaccharide(LPS)to construct CAG cell model.The GES-1 cells were divided into blank group(10%serum complete medium),model group(10 mg·L-1 LPS),and different concentrations of CGM groups(50,100,200,400,800 and 1 600 g·L-1 CGM+10 mg·L-1 LPS),and cells were incubated for 12,24,and 48 h.The cell counting kit-8(CCK-8)assay was used to detect the proliferation activities of GES-1 cells.The GES-1 cells were divided into blank group(10%serum complete medium),model group(10 mg·L-1 LPS)and CGM group(1 600 g·L-1 CGM+10 mg·L-1 LPS).Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of interleukin(IL)-6,tumor necrosis factor(TNF),serine/threonine protein kinase 1(AKT1),IL-1β,and epidermal growth factor receptor(EGFR)mRNA in the cells in various groups.Results:A total of 198 ingredients of CGM were screened,and 128 common targets with CAG were identified.The main herbal ingredients of CGM in treatment of CAG were quercetin,kaempferol,and lluteolin,which mainly acted on the core targets of IL-6,TNF,AKT1,IL-1β,and EGFR.The GO function enrichment analysis results showed that the top 15 targets mainly focused on biological processes(BP)such as apoptosis,inflammatory response and cell proliferation,mainly included cellular components(CC)such as cytoplasm,cell surface and macromolecular complexes,and mainly exerted molecular functions(MF)such as proteins,enzymes and ubiquitin-protein ligases.A total of 158 pathways were obtained from KEGG signaling pathway enrichment analysis,mainly involved cancer-related pathways,TNF signaling pathways,viral infection,programmed cell death-ligand 1(PD-L1)/programmed cell death protein-1(PD-1)pathways,apoptosis,NOD-like receptor signaling pathways,Toll-like receptor signaling pathways,EGFR,and IL-17 signaling pathways.The binding energies of the core targets IL-6,TNF,IL-1β,AKT1,and EGFR with main herbal ingredients quercetin,kaempferol,and luteolin were<-5 kcal·mol-1.The CCK-8 assay results showed that compared with blank group,after 24 and 48 h of cell culture,the proliferation activities of the cells in model group were significantly decreased(P<0.01),and the inhibition of the proliferation activity was more obvious after 48 h;therefore,48 h was selected for the modeling time;compared with model group,the proliferation activities of cells in 800 and 1 600g·L-1 GCM groups were significantly decreased(P<0.01),and the promotion of cell proliferation activity was more obvious in 1 600g·L-1 GCM group,so the intervening concentration of this drug was selected for the subsequent experiments.The RT-qPCR method results showed that compared with blank group,the expression levels of IL-6,TNF,IL-1β,AKT1,and EGFR mRNA in the cells in model group were significantly increased(P<0.01);compared with model group,the expression levels of IL-6,IL-1β,AKT1 and EGFR mRNA in the cells in CGM group were significantly decreased(P<0.01).Conclusion:CGM may play a role in the prevention and treatment of CAG through multiple ingredients such as quercetin,kaempferol and lignocerol,acting on the multiple target proteins such as IL-6,TNF,AKT1,IL-1β,and EGFR,as well as involving a variety of"inflammatory-cancer-related"pathways.

Objective:To investigate the different clinical characteristics and prognosis of patients with diabetic nephropathy (DN) accompanied by IgA deposition diagnosed by renal biopsy.Methods:The study was a retrospective cohort study. Clinical and pathological data of patients diagnosed with DN through renal biopsy in Beijing Anzhen Hospital affiliated to Capital Medical University from January 1, 2010 to March 31, 2023 were retrospectively collected. The clinical and pathological characteristics and prognosis of DN patients with IgA deposition and DN control group patients without IgA deposition were compared. Immunofluorescence staining was used to detect the intensity of galactose-deficient IgA1 (Gd-IgA1) staining in renal tissue of DN patients with DN IgA deposition, and grouping was performed according to whether the staining intensity was≥2+. Enzyme linked immunosorbent assay was used to detect the serum level of Gd-IgA1 in patients. A 50% decrease in estimated glomerular filtration rate (eGFR) from baseline or progression to end-stage renal disease within 5 years was defined as a renal endpoint event, and Kaplan-Meier survival analysis and Log-rank test were used to compare the difference in cumulative incidence of renal endpoint events between two groups of patients.Results:A total of 101 DN patients were enrolled in this study, including 68 males (67.3%) and 33 females (32.7%), with age of (52.2±10.3) years and a median follow-up time of 13.5(4.8, 26.3) months. There were 44 patients with IgA deposition (43.6%) and 57 patients without IgA deposition (56.4%). Compared with DN control group, Kaplan-Meier analysis showed that DN patients with IgA deposition had a higher cumulative incidence of renal endpoint within 5 years ( χ2=6.473, P=0.011). The proportion of positive glomerular Gd-IgA1 (KM55) staining in the DN patients with IgA deposition was 54.5% (24/44), and immunofluorescence examination showed consistent distribution of Gd-IgA1 and IgA in the glomerular mesangial and capillary regions. The serum level of Gd-IgA1 in the glomerular Gd-IgA1 positive patients was significantly higher than that in those negative patients [(6 296.4± 1 535.4) μg/L vs. (4 057.4±1 082.0) μg/L, t=-3.037, P=0.010]. In DN patients with IgA deposition, the age of the subgroup with endpoint events was younger [(42.8±6.9) years vs. (53.3±9.4) years, t=-3.440, P=0.002], the duration of proteinuria was shorter [6.0(1.0, 22.0) months vs. 12.0(10.0, 36.0) months, Z=-2.150, P=0.032], and the proportion of patients with glomerular Gd-IgA1 staining intensity ≥2+ was higher [Fisher'exact test, 30.8%(4/13) vs. 0(0/20), P=0.017]. Kaplan-Meier survival analysis showed that patients with glomerular Gd-IgA1 staining intensity≥2+ had a significantly higher cumulative incidence of renal endpoint events ( χ2=4.846, P=0.028). Conclusion:DN patients with glomerular IgA deposition and Gd-IgA1 positivity may be associated with worse prognosis.

Objective To explore the predictive value of ultra-sound(US)combined with multi-sequence MRI in a clinical-deep learning radiomics nomogram(DLRN)for the short-term efficacy of neoadjuvant chemotherapy(NAC)in patients with triple-negative breast cancer(TNBC).Methods A total of 122 TNBC patients from five hospitals were retrospectively analyzed,and divided into training group(72 cases)and validation group(50 cases).The clinical and pathological data,NAC regimens,and imaging data were collected.The lesions and its surrounding 10-unit voxels from US and MRI images were retained as the region of interest(ROI).Pyradiomics software and a ResNet152 convolutional neural network(CNN)framework were used to extract radiomics and deep learning features to construct a clinical-DLRN with outcome dimension fusion.The receiver operating characteristic(ROC)curve and calibration curve were plotted,and five-fold cross-validation decision curve were used to verify the model's clinical effec-tiveness.Results The clinical-DLRN constructed by US combined with multi-sequence MRI showed that area under the curve(AUC)was 0.967[95％confidence interval(CI)0.782-0.967]and accuracy(ACC)was 0.900,respectively.The five-fold cross-validation decision curve showed good generalization,with the highest clinical net benefit between risk thresholds of 0.72 and 0.96.Conclusion The clinical-DLRN integrating US and multi-sequence MRI has the best efficacy in predicting the short-term efficacy of NAC in TNBC patients,which offering potential guidance for personalized TNBC treatment.

Objective:To investigate the different clinical characteristics and prognosis of patients with diabetic nephropathy (DN) accompanied by IgA deposition diagnosed by renal biopsy.Methods:The study was a retrospective cohort study. Clinical and pathological data of patients diagnosed with DN through renal biopsy in Beijing Anzhen Hospital affiliated to Capital Medical University from January 1, 2010 to March 31, 2023 were retrospectively collected. The clinical and pathological characteristics and prognosis of DN patients with IgA deposition and DN control group patients without IgA deposition were compared. Immunofluorescence staining was used to detect the intensity of galactose-deficient IgA1 (Gd-IgA1) staining in renal tissue of DN patients with DN IgA deposition, and grouping was performed according to whether the staining intensity was≥2+. Enzyme linked immunosorbent assay was used to detect the serum level of Gd-IgA1 in patients. A 50% decrease in estimated glomerular filtration rate (eGFR) from baseline or progression to end-stage renal disease within 5 years was defined as a renal endpoint event, and Kaplan-Meier survival analysis and Log-rank test were used to compare the difference in cumulative incidence of renal endpoint events between two groups of patients.Results:A total of 101 DN patients were enrolled in this study, including 68 males (67.3%) and 33 females (32.7%), with age of (52.2±10.3) years and a median follow-up time of 13.5(4.8, 26.3) months. There were 44 patients with IgA deposition (43.6%) and 57 patients without IgA deposition (56.4%). Compared with DN control group, Kaplan-Meier analysis showed that DN patients with IgA deposition had a higher cumulative incidence of renal endpoint within 5 years ( χ2=6.473, P=0.011). The proportion of positive glomerular Gd-IgA1 (KM55) staining in the DN patients with IgA deposition was 54.5% (24/44), and immunofluorescence examination showed consistent distribution of Gd-IgA1 and IgA in the glomerular mesangial and capillary regions. The serum level of Gd-IgA1 in the glomerular Gd-IgA1 positive patients was significantly higher than that in those negative patients [(6 296.4± 1 535.4) μg/L vs. (4 057.4±1 082.0) μg/L, t=-3.037, P=0.010]. In DN patients with IgA deposition, the age of the subgroup with endpoint events was younger [(42.8±6.9) years vs. (53.3±9.4) years, t=-3.440, P=0.002], the duration of proteinuria was shorter [6.0(1.0, 22.0) months vs. 12.0(10.0, 36.0) months, Z=-2.150, P=0.032], and the proportion of patients with glomerular Gd-IgA1 staining intensity ≥2+ was higher [Fisher'exact test, 30.8%(4/13) vs. 0(0/20), P=0.017]. Kaplan-Meier survival analysis showed that patients with glomerular Gd-IgA1 staining intensity≥2+ had a significantly higher cumulative incidence of renal endpoint events ( χ2=4.846, P=0.028). Conclusion:DN patients with glomerular IgA deposition and Gd-IgA1 positivity may be associated with worse prognosis.

Objective:To investigate the correlation between mutations in KRAS, NRAS, BRAF, and PIK3 CA and the clinical characteristics of elderly colorectal cancer(CRC)patients. Methods:Paraffin-embedded tissue samples were obtained from 191 elderly CRC patients who consulted at Huadong Hospital, affiliated to Fudan University, between January 2022 and July 2023.Following deoxyribonucleic acid(DNA)extraction, the amplification refractory mutation system polymerase chain reaction(ARMS-PCR)was employed to detect the mutation profiles of KRAS, NRAS, BRAF, and PIK3 CA.Concurrently, serum samples collected prior to radical resection were analyzed for carcinoembryonic antigen(CEA), carbohydrate antigen 19-9(CA19-9), and carbohydrate antigen 72-4(CA72-4)using electrochemical luminescence.A comparative analysis of the clinical characteristics and preoperative serological tumor marker concentrations among patients with different gene mutations was conducted to elucidate their correlation. Results:A total of 191 elderly CRC patients were enrolled in the study, with ages ranging from 60 to 94 years(mean age 72.1±7.8 years), including 112 males.The mutation rate of KRAS, NRAS, BRAF, and PIK3 CA, as determined by combined detection, was found to be 49.21%(94/191)among elderly CRC patients. KRAS exhibited the highest mutation rate at 35.08%, with statistically significant differences observed in gender, primary site, degree of differentiation, and neurovascular invasion between patients with and without KRAS mutations( P<0.05 for all comparisons).The BRAF mutation rate was 8.90%, and significant differences in gender, age, primary site, and degree of differentiation were also noted between patients with and without BRAF mutations( P<0.05 for all).The mutation rates for NRAS and PIK3 CA were 2.62% and 5.24%, respectively, with no statistically significant differences in the clinical characteristics of patients across different groups( P>0.05 for all).Additionally, the proportion of patients over the age of 90 in the double mutation group was significantly higher( P<0.01).Significant differences in serum CA19-9 concentrations were observed among the various mutation types( P<0.05). Conclusions:There are notable differences in age, gender, primary site, degree of differentiation, and neurovascular invasion among elderly CRC patients with varying mutation statuses of KRAS, NRAS, BRAF, and PIK3 CA.Patients with double mutations exhibited higher concentrations of CA19-9 in preoperative serum.