ObjectiveTo investigate the role of the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway in intestinal mucosal barrier damage in ulcerative colitis， as well as the intervention mechanism of Shaoyaotang. MethodsSixty SD rats were allocated into a blank group， a model group， a mesalazine （0.42 g·kg^-1） group， and low-， medium-， and high-dose （11.1， 22.2， 44.4 g·kg^-1， respectively） Shaoyaotang groups. A model of ulcerative colitis was induced by 2，4，6-trinitrobenzenesulfonic acid （TNBS）. After successful modeling， rats were administrated with corresponding agents via gavage for 7 days. Changes in colon length and colon weight were observed. Hematoxylin-eosin staining was performed to examine the pathological changes of the colon， and immunohistochemistry was employed to detect the expression of the inflammatory cytokine interleukin-8 （IL-8）， cyclooxygenase-2 （COX-2）， junction adhesion molecule-1 （JAM-1）， and claudin-1 in the colon. Western blot analysis was performed to determine the protein levels of TLR4， MyD88， and NF-κB in the colon. ResultsCompared with the blank group， the model group showed elevated DAI score （P<0.01）， reduced colon length and colon weight （P<0.01）， down-regulated protein levels of JAM-1 and claudin-1 （P<0.01）， and up-regulated protein levels of IL-8， COX-2， TLR4， MyD88， and NF-κB p65 （P<0.01） in the colon tissue. Compared with the model group， each treatment group showed decreased DAI score （P<0.05， P<0.01）， increased colon length and colon weight （P<0.05， P<0.01）， up-regulated protein levels of JAM-1 and claudin-1 （P<0.01）， and down-regulated protein levels of IL-8， COX-2， TLR4， MyD88， and NF-κB p65 （P<0.01） in the colon tissue. ConclusionShaoyaotang alleviates intestinal inflammation and intestinal mucosal damage to protect intestinal barrier integrity by regulating the TLR4/MyD88/NF-κB signaling pathway.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective:To analyze intestinal microecological differences and their correlation with psychological status in patients with constipated irritable bowel syndrome(IBS-C)and functional constipation(FC).Methods:A total of 160 patients with IBS-C and FC attending the outpatient and inpatient departments of the Department of Gastroenterology at the General Hospital of Ningxia Medical University from January 2021 to January 2024 were selected and grouped according to the type of disease into the IBS-C group(80 patients)and the FC group(80 patients),and 80 patients who had a health checkup during the same period were selected as the control group.Fresh fecal specimens were taken from all subjects,and 16S rRNA sequencing was used to detect the intestinal flora,and the indices of intestinal microecological diversity(Ace index,Chao index,Shannon index,and Sobs index)were detected,and the psychological state of the subjects was assessed by using the Self-Assessment Scale for Anxiety(SAS)and the Self-Depression Scale(SDS).Pearson's correlation method was used to analyze the correlation between intestinal microecology and correlation with psychological state in IBS-C and FC patients.Result:Bifidobacteria and Lactobacillus levels were lower in both the FC and IBS-C groups compared with the control group,and the decrease was more pronounced in the IBS-C group(P＜0.05).Enterobacteriaceae and Enterococci contents were higher in patients in the FC and IBS-C groups(P＜0.05),with the greatest increase in the IBS-C group(P＜0.05);Microbial diversity analysis showed that there were differences in Ace,Chao,Shannon and Sobs indices among the three groups(P＜0.05).All diversity indices were lower in the FC and IBS-C groups than in the control group,and the degree of reduction was more pronounced in the IBS-C group than in the FC group(P＜0.05);The SAS and SDS scores of both FC and IBS-C groups were higher than those of the control group,and the scores of the IBS-C group were higher than those of the FC group(P＜0.05);correlation analysis showed that,in the IBS-C and FC groups,Bifidobacterium and Lactobacillus,Ace index,Chao index,Shannon index,and Sobs index were negatively correlated with SAS and SDS scores.Enterobacteriaceae and Enterococci were positively correlated with SAS and SDS scores(P＜0.05).Conclusion:There are possible differences in the gut microbiota between IBS-C and FC patients.The imbalance of gut microbiota is more significant in IBS-C patients,and gut microbiota is closely related to psychological status.Clinical treatment of IBS-C and FC should pay attention to the regulation of gut microbiota and intervention of psychological status.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

The Masquelet technique, also known as the induced membrane technique, is a surgical technique for repairing large bone defects based on the use of a membrane generated by a foreign body reaction for bone grafting. This technique is not only simple to perform, with few complications and quick recovery, but also has excellent clinical results. To better understand the mechanisms by which this technique promotes bone defect repair and the factors that require special attention in practice, we examined and summarized the relevant research advances in this technique by searching, reading, and analysing the literature. Literature show that the Masquelet technique may promote the repair of bone defects through the physical septum and molecular barrier, vascular network, enrichment of mesenchymal stem cells, and high expression of bone-related growth factors, and the repair process is affected by the properties of spacers, the timing of bone graft, mechanical environment, intramembrane filling materials, artificial membrane, and pharmaceutical/biological agents/physical stimulation.
Humans ; Bone Transplantation/methods* ; Membranes, Artificial ; Bone Regeneration ; Animals