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.

OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. β-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. β-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.
Humans ; Microcirculation/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Stomach Neoplasms/physiopathology* ; Emulsions ; Male ; Plant Oils/administration & dosage* ; Brucea/chemistry* ; Middle Aged ; Female ; Drug Combinations ; Human Umbilical Vein Endothelial Cells/metabolism* ; Seeds/chemistry* ; Injections ; Vascular Endothelial Growth Factor A/metabolism* ; Aged ; Network Pharmacology

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 downregulated metabolites in sera of RLPS 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 [¹³C₅]-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.

Robotic surgery, as an increasingly widespread application in the treatment of gastric and colorectal cancer, still faces obvious discrepancies in recommendations, indications, and evidence strength across existing guidelines. This study systematically analyzed 31 relevant guidelines and consensus statements (retrieved from Chinese and English databases from January 2010 to May 2025) from two dimensions: feasibility (effectiveness, safety, etc.) and training quality control.The results showed that colorectal cancer guidelines had a higher proportion (4 guidelines) of "clear recommendations" for robotic surgery, while gastric cancer guidelines predominantly presented "conditional recommendations" or no recommendations. In the training and quality control dimension, although structured suggestions received positive recommendations, more than half were based on low or very low-quality evidence. Evidence mapping indicated insufficient matching between "case-specific recommendations" and evidence grades in the feasibility dimension, while training processes emphasized the importance of standardized systems and team collaboration.The study highlights the existing heterogeneity in evidence-based guidelines for robotic gastrointestinal surgery, with colorectal cancer demonstrating a more mature evidence base and gastric cancer showing notable evidence gaps. It is recommended that future guideline development should strengthen the consistency between recommendation grades and evidence levels, promote high-quality research in upper gastrointestinal surgery, and improve surgeon training and certification systems to facilitate standardized clinical translation of robotic gastrointestinal surgery.

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.

Robotic surgery, as an increasingly widespread application in the treatment of gastric and colorectal cancer, still faces obvious discrepancies in recommendations, indications, and evidence strength across existing guidelines. This study systematically analyzed 31 relevant guidelines and consensus statements (retrieved from Chinese and English databases from January 2010 to May 2025) from two dimensions: feasibility (effectiveness, safety, etc.) and training quality control.The results showed that colorectal cancer guidelines had a higher proportion (4 guidelines) of "clear recommendations" for robotic surgery, while gastric cancer guidelines predominantly presented "conditional recommendations" or no recommendations. In the training and quality control dimension, although structured suggestions received positive recommendations, more than half were based on low or very low-quality evidence. Evidence mapping indicated insufficient matching between "case-specific recommendations" and evidence grades in the feasibility dimension, while training processes emphasized the importance of standardized systems and team collaboration.The study highlights the existing heterogeneity in evidence-based guidelines for robotic gastrointestinal surgery, with colorectal cancer demonstrating a more mature evidence base and gastric cancer showing notable evidence gaps. It is recommended that future guideline development should strengthen the consistency between recommendation grades and evidence levels, promote high-quality research in upper gastrointestinal surgery, and improve surgeon training and certification systems to facilitate standardized clinical translation of robotic gastrointestinal surgery.

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 determine the risk factors and prognostic survival of patients with para-aortic lymph node metastasis of advanced esophagogastric junction malignancy by comparing their general clinicopathological characteristics and regional lymph node metastasis status with those of patients with negative para-aortic lymph node metastasis. Methods This single-center retrospective case study collected the clinical and pathological data of 224 patients with esophagogastric junction malignant tumors undergoing radical resection. Single factor affecting lymph node metastasis in group 16 was analyzed by chi square test, and multiple factors were examined using logistic regression. Kaplan-Meier method was used for survival analysis, and Log rank test was used for survival rate comparison. Results Among the 224 patients with advanced esophagogastric junction malignant tumors, (1) Univariate analysis showed that Siewert classification, tumor diameter, pathological stage, T stage, and N stage were associated with positive para-aortic lymph node metastasis (P<0.05). Meanwhile, multivariate logistic analysis showed that Siewert type and tumor diameter were independent risk factors for positive metastasis (P<0.05); (2) Among the 17 groups of regional lymph nodes with para-aortic lymph node metastasis, univariate analysis revealed that No.5, No.6, No.111, and No.112 lymph nodes were not correlated with positive para-aortic lymph node metastasis (P>0.05). The remaining 13 groups of regional lymph nodes were all associated with para-aortic lymph node metastasis. Meanwhile, multivariate logistic analysis revealed that No.7, No.11p, and No.110 lymph nodes were independent risk factors for metastasis (P<0.05). When the regional lymph node metastasis in these three groups was negative, the positive rate of para-aortic lymph node metastasis was only 4.7%. When at least one of these groups had regional lymph node metastasis, the positive metastasis rate was up to 47.4%; (3) The 1- and 3-year cumulative survival rates of the patients with positive para-aortic lymph node metastasis after surgery were 76.5% and 8.1%, respectively, and those in negative patients were 98.3% and 76.8%, respectively. Log rank test showed a significant difference in overall survival rate between the patients with positive and negative para-aortic lymph node metastasis (P<0.001). Conclusion (1) Preoperative examination of patients with advanced esophagogastric junction malignant tumors should clarify the tumor type and maximum diameter. Patients with Siewert type Ⅱ and Ⅲ and maximum tumor diameter of >6 cm are recommended to undergo para-aortic lymph node dissection. (2) Frozen biopsy of lymph nodes of No.7 and No.11p is performed during the operation, and the para-aortic lymph nodes should be dissected if the metastasis is found to be positive, which is helpful for the clinical surgeon to judge the dissection of the para-aortic lymph nodes.

Objective:To analyze the status of respiratory pathogen detection and the clinical features in children with Mycoplasma pneumoniae pneumonia (MPP). Methods:A prospective, multicenter study was conducted to collect clinical data, including medical history, laboratory examinations and multiplex PCR tests of children diagnosed with MPP from 4 hospitals in China between November 15 th and December 20 th, 2023. The multiplex PCR results and clinical characteristics of MPP children in different regions were analyzed. The children were divided into severe and mild groups according to the severity of the disease. Patients in the severe group were further divided into Mycoplasma pneumoniae (MP) alone and Multi-pathogen co-detection groups based on whether other pathogens were detected besides MP, to analyze the influence of respiratory pathogen co-detection rate on the severity of the disease. Mann-Whitney rank sum test and Chi-square test were used to compare data between independent groups. Results:A total of 298 children, 136 males and 162 females, were enrolled in this study, including 204 children in the severe group with an onset age of 7.0 (6.0, 8.0) years, and 94 children in the mild group with an onset age of 6.5 (4.0, 7.8) years. The level of C-reactive protein, D-dimer, lactic dehydrogenase (LDH) were significantly higher (10.0 (5.0, 18.0) vs. 5.0 (5.0, 7.5) mg/L, 0.6 (0.4, 1.1) vs. 0.5 (0.3, 0.6) mg/L, 337 (286, 431) vs. 314 (271, 393) U/L, Z=2.02, 2.50, 3.05, all P<0.05), and the length of hospitalization was significantly longer in the severe group compared with those in mild group (6.0 (6.0, 7.0) vs. 5.0 (4.0, 6.0) d, Z=4.37, P<0.05). The time from onset to admission in severe MPP children was significantly shorter than that in mild MPP children (6.0 (5.0, 9.5) vs. 9.0 (7.0, 13.0) d, Z=2.23, P=0.026). All patients completed the multiplex PCR test, with 142 cases (47.7%) MPP children detected with 21 pathogens including adenovirus 25 cases (8.4%), human coronavirus 23 cases (7.7%), rhinovirus 21 cases (7.0%), Streptococcus pneumoniae 21 cases (7.0%), influenza A virus 18 cases (6.0%). The pathogens with the highest detection rates in Tianjin, Shanghai, Wenzhou and Chengdu were Staphylococcus aureus at 10.7% (8/75), adenovirus at 13.0% (10/77), adenovirus at 15.3% (9/59), and both rhinovirus and Haemophilus influenzae at 11.5% (10/87) each. The multi-pathogen co-detection rate in severe MPP children was significantly higher than that in mild MPP group (52.9% (108/204) vs. 36.2% (34/94), χ2=10.62, P=0.005). Among severe MPP children, there are 89 cases in the multi-pathogen co-detection group and 73 cases in the simple MPP group. The levels of LDH, D-dimer and neutrophil counts in the multi-pathogen co-detection group were significantly higher than those in the simple MPP group (348 (284, 422) vs. 307 (270, 358) U/L, 0.8 (0.5, 1.5) vs. 0.6 (0.4, 1.0) mg/L, 4.99 (3.66, 6.89)×10 9vs. 4.06 (2.91, 5.65)×10 9/L, Z=5.17, 4.99, 6.11, all P<0.05). Conclusions:The co-detection rate of respiratory pathogens, LDH and D-dimer in children with severe MPP were higher than those with mild MPP. Among severe MPP children the stress response of children in co-detection group was more serious than that of children with simple MPP.

Objective:To compare the clinical outcomes and prognosis of transabdominal opening of the left diaphragm and traditional thoracoabdominal combination approach for Siewert type II adenocarcinoma of the esophagogastric junction.Methods:A retrospective cohort study was conducted. The clinical data of 59 patients with Siewert type Ⅱ adenocarcinoma of the esophagogastric junction who underwent radical total gastrectomy in Shanxi Provincial People's Hospital from January 2018 to March 2020 were retrospectively analyzed, and all patients were divided into the transabdominal opening of the left diaphragm group (30 cases) and the thoracoabdominal combination group (29 cases) according to surgical access. The general data, perioperative indexes, postoperative complications and postoperative survival of patients in the two groups were compared. Factors influencing the overall survival were analyzed by using Cox proportional hazards model.Results:The differences in terms of gender, age, tumor diameter, pT staging, and pN staging between the two groups were not statistically significant (all P > 0.05). The length of esophageal invasion was (3.5±1.1) cm and (3.7±1.1) cm, respectively in the transabdominal opening of the left diaphragm group and the thoracoabdominal combination group, and the difference was not statistically significant ( t = -0.70, P = 0.486). Compared with the thoracoabdominal combination group, the transabdominal opening of the left diaphragm group had less operative time, intraoperative bleeding, postoperative bedtime, chest tube extraction time and postoperative hospitalization days, and the differences were statistically significant (all P < 0.05); the differences in the number of lymph nodes cleared, the number of positive lymph nodes, the number of thoracic lymph node dissection, and the number of positive thoracic lymph node were not statistically significant in the two groups (all P > 0.05). The total incidence of postoperative complications in the transabdominal opening of the left diaphragm group and the thoracoabdominal combination group were 53.3% (16/30) and 72.4% (21/29), respectively, and the difference was not statistically significant ( χ2 = 2.30, P = 0.130), while the incidence of lung infection and pleural effusion in the thoracoabdominal combination group was higher than that in the transabdominal opening of the left diaphragm group (both P<0.05). The 1- and 3-year postoperative overall survival rates were 80.0%, 63.3% in the transabdominal opening of the left diaphragm group, and 79.3%, 62.1% in the thoracoabdominal combination group, respectively, and the difference in overall survival between the two groups was not statistically significant ( χ2 = 0.01, P = 0.934). Multivariate analysis showed that pT staging ( HR = 4.009, 95% CI: 1.851-8.683, P < 0.001) and pN staging ( HR = 2.338, 95% CI: 1.435-3.811, P = 0.001) were the independent influencing factors of overall survival. Conclusions:For patients with Siewert type Ⅱ adenocarcinoma of the esophagogastric junction with esophageal invasion length > 3 cm, transabdominal opening of the left diaphragm approach can reduce intraoperative bleeding and postoperative chest complications, and it has the advantages of shorter operation, hospitalization time, and less trauma, which can help to accelerate the recovery of the patients; pT and pN staging are the independent factors influencing the prognosis of patients.