Objective To explore the role of neogambogic acid in the characteristics of colorectal cancer stem cells (CRC-CSCs) through the Wnt/β-catenin signaling pathway. Methods The colorectal cells SW480 and HCT166 were divided into control group and neogambogic acid groups (1.5, 3, 6, and 12 μmol/L). The viability of CRC-CSCs was determined by MTT method, and spheroid and clone formation assays were used to assess the capacity of spheroid formation and self-renewal ability of the cells. The effects of neogambogic acid on the apoptosis and cell cycle of CRC-CSCs were evaluated by flow cytometry assays. Real-time quantitative PCR was used to detect the mRNA expression levels of relative markers (CD133, CD44, ALDH1, Oct4, and Nanog) of CRC-CSCs, and the protein expression levels of the self-renewal marker (PCNA), apoptosis markers (cleaved caspase-3 and cleaved caspase-9), and Wnt/β-catenin signaling pathway markers (p-GSK3β, GSK3β, β-catenin, and Wnt) were analyzed using Western blot. Results Compared with the control group, after neogambogic acid treatment, the viability of SW480 and HCT116 cells decreased (P<0.05), the spheroid forming ability and the clone numbers of CRC-CSCs decreased (P<0.001, P<0.01) but the cell apoptosis rate increased (P<0.01), and cell cycle was arrested in G₀/G₁ phase. Moreover, neogambogic acid downregulated the mRNA and protein expression of relative markers of CRC-CSCs (CD133, CD44, ALDH1, Oct4, and Nanog), PCNA, p-GSK3β, β-catenin, and Wnt (P<0.05) and upregulated the expression of cleaved caspase-3, cleaved caspase-9, and GSK3β (P<0.01). Conclusion Neogambogic can inhibit the stem cell properties of colorectal cells via inhibition of Wnt/β-catenin signaling pathway. As a result, neogambogic acid may be an attractive agent against colorectal cancer.

Objective: To investigate the efficacy and incidence of adverse reactions of therapeutic erythrocytapheresis in high altitude polycythemia (HAPC) population. Methods: A retrospective study was conducted on 243 HAPC patients who were either native residents or long-term workers in Xizang and underwent therapeutic erythrocytapheresis in the Chengdu Office Hospital of the People's Government of Xizang Autonomous Region from 2021 to 2023. A comparative study was carried out on the changes in blood routine, vital signs, skin color, serum iron metabolism data, and the incidence of adverse reactions before and after the procedure. Results: After erythrocytapheresis, significant decreases were observed in red blood cell (RBC) count (7.06±0.89×10 vs 6.08±0.93×10 /L, P<0.001], hemoglobin (HGB, 211.59±17.99 vs 182.76±19.83 g/L, P<0.001), hematocrit (Hct) [(65.30±6.45)% vs (55.56±8.12)%, P<0.001], serum iron (14.46±4.38 vs 11.77±3.78 μmol/L, P=0.003), total iron-binding capacity (126.62±4.47 vs 123.73±3.77 μmol/L, P=0.002), transferrin (1.88±0.41 vs 1.77±0.12 g/L, P=0.023), transferrin saturation [(11.32±3.11)% vs (9.43±2.78)%, P=0.004], serum ferritin (832.4±295.6 vs 665.3±249.2 ng/mL, P<0.001), systolic blood pressure (123.86±14.43 vs 118.51±13.68 mmHg, P<0.001) and diastolic blood pressure (81.68±9.54 vs 74.28±7.61 mmHg, P<0.001). In contrast, platelet count (Plt, 137.21±46.21 ×10 vs 147.94±50.66 ×10 /L, P<0.001) and oxygen saturation [(93.97±3.29)% vs (95.84±2.27)%, P<0.001] increased. No significant differences were found in white blood cell (WBC) count [5.35 (4.59, 6.44)×10 /L vs 5.43 (4.54, 6.53) ×10 /L, P=0.690], unsaturated iron-binding capacity (112.15±0.50 vs 111.96±0.25 μmol/L, P=0.074) and pulse rate (73.42±11.28 vs 73.19±7.18 beats/min, P=0.750). Furthermore, skin color of the face (conjunctiva, lips) and palms mitigated after therapeutic erythrocytapheresis, changing from purplish-red to red. The total incidence of adverse reactions during erythrocytapheresis was 13.98% (34/243), including citrate toxicity 12.75% (31/243), puncture site hematoma 0.82% (2/243) and blood volume imbalance 0.41% (1/243). Conclusion: Therapeutic erythrocytapheresis could rapidly decrease HCT, Hb, serum iron, transferrin and transferrin saturation levels in HAPC patients, with a low incidence of adverse reactions. Therefore, therapeutic erythrocytapheresis has broad clinical application prospects in Xizang Autonomous Region.

Intestinal stem cells(ISCs),locating at the base of intestinal crypts and pivotal in orchestrating the homeostasis and damage repair of the intestinal epithelium,are characterized by their self-renewal and multipotential differentiation capabilities.With the continuous discoveries of new ISCs and related markers,the ISC migration and regeneration model has been further improved,greatly promoting the research in related fields.Diet can regulate ISC glycolipid and energy metabolism through influencing the stem cell niche,subsequently modulating overall metabolism.This paper summarizes the biological features of both classical and newly discovered ISCs,and analyzes the effects of common nutrients and different dietary patterns on ISCs,hoping to provide insights for the precise nutrition prevention and treatment of chronic intestinal diseases.

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.

Objective:To explore the genetic etiology of a child with Cowden syndrome 1 (CS1).Methods:A child who had visited the Ningbo Women and Children's Hospital on August 26, 2022 was selected as the study subject. Clinical information of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The child, a 13-year-old boy, had manifested with severe mental retardation, hyperactivity, autistic behavior, sparse and prominent teeth, macrocephaly, and skin freckles on the penis. His mother had presented with multiple papules, hamartomatous polyps, thyroid adenoma and macrocephaly. WES results revealed that the child has harbored a nonsense c. 781C>T (p.Q261*) variant of the PTEN gene, which was inherited from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.781C>T variant was classified as likely pathogenic (PVS1+ PM2_Supporting). Conclusion:The c. 781C>T variant of the PTEN gene probably underlay the pathogenesis in the child and his mother. Above finding has facilitated genetic counseling for this family.

Objective To explore the key targets and signaling pathways in the therapeutic mechanism of Semiliquidambar cathayensis Chang(SC)root against pancreatic cancer network pharmacology and molecular docking studies and cell experiments.Methods The targets of SC and pancreatic cancer were predicted using the network pharmacological database,the protein-protein interaction network was constructed,and pathways,functional enrichment and molecular docking analyses were performed.CCK-8 assay was used to test the inhibitory effect of the aqueous extract of SC root on 8 cancer cell lines,and its effects on invasion,migration,proliferation,and apoptosis of pancreatic cancer cells were evaluated.Western blotting was performed to verify the results of network pharmacology analysis.Results We identified a total of 18 active components in SC,which regulated 21 potential key targets in pancreatic cancer.GO and KEGG pathway enrichment analyses showed that these targets were involved mainly in the biological processes including protein phosphorylation,signal transduction,and apoptosis and participated in cancer signaling and PI3K-Akt signaling pathways.Among the 8 cancer cell lines,The aqueous extract of SC root produced the most obvious inhibitory effect in pancreatic cancer cells,and significantly inhibited the invasion,migration,and proliferation and promoted apoptosis of pancreatic cancer Panc-1 cells(P<0.05).Western blotting confirmed that SC significantly inhibited the phosphorylation levels of PI3K and AKT in Panc-1 cells(P<0.001).Conclusion The therapeutic effect of SC root against pancreatic cancer effects is mediated by its multiple components that act on different targets and pathways including the PI3K-Akt pathway.

Objective To compare the outcomes of transvaginal natural orifice transluminal endoscopic surgery(vNOTES)and laparoendoscopic single-site surgery(LESS)for total uterine excision in obese patients with benign uterine lesions,and to investigate the utility of vNOTES in this patient population.Methods A total of 100 obese patients(BMI>28.0 kg/m2)diagnosed with benign uterine lesions requiring total uterine and bilateral salpingectomy between January 2022 and January 2023 were included in this study.They were randomly assigned to two groups:the LESS group(n=51)and the vNOTES group(n=49).Patient demographics,surgical duration,intraoperative blood loss,changes in hemoglobin levels,pain scores,time to first flatus postoperatively,length of hospital stay,pelvic floor function,sexual quality of life,and postoperative complications were compared between the two groups.Results The two groups did not show any statistically significant differences in terms of blood loss,pre-and postoperative hemoglobin changes,pelvic floor function,sexual quality of life,or postoperative complications(P>0.05).However,the vNOTES group exhibited shorter surgical durations,time to first flatus postoperatively,and length of hospital stay compared to the LESS group(P<0.05).Additionally,the vNOTES group demonstrated lower intraoperative pain scores than the LESS group.(P<0.05).Conclusions In obese patients with benign uterine lesions,vNOTES total uterine excision surgery demonstrated shorter surgical durations and postoperative hospital stays,lower postoperative pain scores,and better adherence to the principles of en-hanced recovery after surgery(ERAS),indicating its potential for broader application.

Objective To analyze the relationships of the expression of retinoid X receptor alpha (RXRA) and nuclear receptor interaction protein 1(NRIP1) in colorectal cancer tissues with the features of clinical pathology and prognosis. Methods A total of 106 specimens from colorectal cancer tissues of patients during surgery were included in colorectal cancer group (n=106), and corresponding paracancer tissue specimens were included in paracancer group (n=106). The expressions of RXRA and NRIP1 in colorectal cancer tissues were detected by immunohistochemistry. Multivariate Cox regression analysis was used to investigate th4e effects of RXRA and NRIP1 expressions on the prognosis of patients with colorectal cancer. Results The positive expression rates of RXRA and NRIP1 in colorectal cancer group were 66.04%, 69.81%, which were significantly higher than 33.96% and 30.19% in the para-cancer group (P < 0.05). The positive expression rates of RXRA and NRIP1 in patients with pathological stage Ⅲ, low differentiation, serous infiltration and lymph node metastasis were higher than those in patients with pathological stage Ⅱ, medium and high differentiation, no serous infiltration and lymph node metastasis (P < 0.05). The 3-year overall survival rates of patients with pathological stage Ⅱ, low differentiation, no serous infiltration, no lymph node metastasis, negative RXRA and NRIP1 were higher than those of patients with pathological stage Ⅲ, medium and high differentiation, serous infiltration, lymph node metastasis, positive RXRA and NRIP1 (P < 0.05). Multivariate Cox regression analysis showed serous membrane infiltration (HR=2.687; 95%CI, 1.531 to 3.156), positive RXRA (HR=3.743; 95%CI, 2.217 to 5.992), positive NRIP1 (HR=2.641; 95%CI, 1.124 to 4.757) were influencing factors for prognosis in patients with colorectal cancer (P < 0.05). Conclusion RXRA and NRIP1 are highly expressed in colorectal cancer, which are closely related to pathological stage, differentiation degree and metastasis, which can be used as biomarkers to assist in evaluating the prognosis of patients.

The goal of Medical Immunology is to enable students to pay attention to integration of immunology theory with clini-cal practice,be familiar with professional English,consciously pay attention to cutting-edge knowledge,and can learn independently and lifelong.However,existing teaching models lack explanation of clinical disease related events,and arrangement of experimental content and projects is seriously disconnected from clinical practice,scientific research on solving clinical problems is clearly insuffi-cient.We established a"B to B"cycle model for immunology teaching by starting from clinical practical problems(Bedside),return to basic research(Bench),and then solve clinical problem(Bedside),which will comprehensively cultivate senior medical profession-als with clinical competence,scientific research thinking ability,innovative spirit,and international perspective.

Objective:To construct and validate a nomogram model for predicting the risk of 28-day mortality in sepsis patients.Methods:A retrospective cohort study was conducted. 281 sepsis patients admitted to the department of intensive care unit (ICU) of the 940th Hospital of the Joint Logistics Support Force of PLA from January 2017 to December 2022 were selected as the research subjects. The patients were divided into a training set (197 cases) and a validation set (84 cases) according to a 7∶3 ratio. The general information, clinical treatment measures and laboratory examination results within 24 hours after admission to ICU were collected. Patients were divided into survival group and death group based on 28-day outcomes. The differences in various data were compared between the two groups. The optimal predictive variables were selected using Lasso regression, and univariate and multivariate Logistic regression analyses were performed to identify factors influencing the mortality of sepsis patients and to establish a nomogram model. Receiver operator characteristic curve (ROC curve), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to evaluate the nomogram model.Results:Out of 281 cases of sepsis, 82 cases died with a mortality of 29.18%. The number of patients who died in the training and validation sets was 54 and 28, with a mortality of 27.41% and 33.33% respectively. Lasso regression, univariate and multivariate Logistic regression analysis screened for 5 independent predictors associated with 28-day mortality. There were use of vasoactive drugs [odds ratio ( OR) = 5.924, 95% confidence interval (95% CI) was 1.244-44.571, P = 0.043], acute physiology and chronic health evaluation Ⅱ (APACHEⅡ: OR = 1.051, 95% CI was 1.000-1.107, P = 0.050), combined with multiple organ dysfunction syndrome (MODS: OR = 17.298, 95% CI was 5.517-76.985, P < 0.001), neutrophil count (NEU: OR = 0.934, 95% CI was 0.879-0.988, P = 0.022) and oxygenation index (PaO 2/FiO 2: OR = 0.994, 95% CI was 0.988-0.998, P = 0.017). A nomogram model was constructed using the independent predictive factors mentioned above, ROC curve analysis showed that the AUC of the nomogram model was 0.899 (95% CI was 0.856-0.943) and 0.909 (95% CI was 0.845-0.972) for the training and validation sets respectively. The C-index was 0.900 and 0.920 for the training and validation sets respectively, with good discrimination. The Hosmer-Lemeshoe tests both showed P > 0.05, indicating good calibration. Both DCA and CIC plots demonstrate the model's good clinical utility. Conclusions:The use of vasoactive, APACHEⅡ score, comorbid MODS, NEU and PaO 2/FiO 2 are independent risk factors for 28-day mortality in patients with sepsis. The nomogram model based on these 5 indicators has a good predictive ability for the occurrence of mortality in sepsis patients.