ObjectiveTo investigate the effects of Huanglian Jiedutang （HLJDT） on cognitive function in mice with ischemic stroke （IS） and to elucidate whether its neuroprotective effects are mediated by inhibition of the nuclear factor-κB （NF-κB） signaling pathway and subsequent suppression of NF-κB-regulated neuronal apoptosis. MethodsAn IS model was established using middle cerebral artery occlusion （MCAO）. Sixty C57BL/6J mice were randomly assigned to five groups （n =12 per group）， i.e.， sham operation， model， HLJDT low-dose （3.9 g·kg^-1·d^-1）， HLJDT high-dose （7.8 g·kg^-1·d^-1）， and Ginkgo biloba extract （GBE， 31.2 mg·kg^-1·d^-1）. Post-operatively， neurological deficit scores （Longa score）， cerebral infarct volume assessed by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and brain water content were evaluated. Learning and memory were assessed using new object recognition （NOR） and fear conditioning （FC） tests. Hippocampal pathology was examined via hematoxylin and eosin （HE） staining. Immunofluorescence detected expression of glial fibrillary acidic protein （GFAP， astrocyte marker）， cellular oncogene Fos （c-Fos， neuronal activation marker）， and glutamate decarboxylase 65 （GAD65）. Western blot measured nuclear factor-κB inhibitor protein α （IκBα）， phosphorylated IκBα （p-IκBα）， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， ionic calcium binding adapter molecule 1 （Iba-1）， tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and apoptosis-related proteins， such as cleaved cysteinyl aspartate-specific protease 3 （Caspase-3）， B-cell lymphoma 2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Real-time quantitative PCR （Real-time PCR） was used to assess mRNA levels of Iba-1， TNF-α， IL-1β， NF-κB p65， cleaved Caspase-3， Bax， and Bcl-2. ResultsCompared with the sham group， the model group exhibited significantly increased neurological deficit scores， brain water content， and cerebral infarct volume （P<0.01）. Hippocampal CA1 neurons were disorganized， showing nuclear pyknosis and karyolysis. NOR exploration time and FC freezing time were significantly reduced （P<0.01）. GFAP and c-Fos expression were increased， while GAD65 expression was decreased （P<0.01）. Cleaved Caspase-3 and Bax were upregulated， Bcl-2 was downregulated， and the Bax/Bcl-2 ratio was elevated （P<0.01）. Expression levels of p-IκBα， p-NF-κB p65， IL-1β， TNF-α， and Iba-1 were significantly increased （P<0.01）. Compared with the model group， HLJDT high-dose， low-dose， and GBE groups showed significant improvements in all parameters （P<0.01）. Among them， the HLJDT high-dose group showed the most pronounced neuronal structural recovery and superior performance in NOR and FC tests （P<0.01）. In this group， GFAP and c-Fos decreased， GAD65 increased （P<0.01）， apoptosis-related protein expression was reversed， and NF-κB signaling and related inflammatory factor expression were suppressed （P<0.01）. ConclusionHLJDT ameliorates cognitive dysfunction in mice after IS， potentially by inhibiting the NF-κB signaling pathway， thereby reducing neuroinflammation and hippocampal neuronal apoptosis.

Colorectal cancer （CRC） is a common malignant tumor of the digestive tract with high morbidity and mortality. Although existing treatments can prolong the survival of patients， problems such as low quality of life， obvious side effects， and unsatisfactory clinical efficacy still exist， which cannot fully satisfy the overall needs of patients. For this reason， it is crucial to explore the mechanism underlying the development of CRC and to identify new treatment strategies. In recent years， with the deepening of research， ferroptosis has been gradually proven to effectively inhibit the proliferation and metastasis of CRC cells， overcome tumor drug resistance， enhance anti-tumor efficacy， and prevent tumor progression and recurrence. Therefore， regulating ferroptosis is expected to become a new strategy for the treatment of CRC. Traditional Chinese medicine （TCM） has been widely used in CRC treatment due to its advantages of multiple components， multiple targets， low drug resistance， and few side effects， and has gradually become a current research hotspot. Extensive studies have shown that TCM active ingredients and compound formulae can regulate ferroptosis-related pathways， such as iron metabolism， lipid metabolism， the cystine/glutamate antiporter system X_c^- （System X_c^-）/glutathione （GSH）/glutathione peroxidase 4 （GPX4）， ferroptosis suppressor protein 1 （FSP1）/coenzyme Q₁₀ （CoQ₁₀）/nicotinamide adenine dinucleotide phosphate ［NAD（P）H］， tumor protein 53 （p53）， nuclear factor erythroid-2-related factor 2 （Nrf2）， and non-coding RNA pathways to inhibit the growth and proliferation of CRC， thereby exerting anti-tumor effects. This review systematically summarized the mechanisms of ferroptosis related to CRC， therapeutic targets and prognosis-related markers associated with ferroptosis in CRC， and research progress on TCM targeting and regulating ferroptosis for CRC intervention， aiming to provide new perspectives and a theoretical basis for the prevention and treatment of CRC with TCM.

Colorectal cancer （CRC） is a common malignant tumor of the digestive tract with high morbidity and mortality. Although existing treatments can prolong the survival of patients， problems such as low quality of life， obvious side effects， and unsatisfactory clinical efficacy still exist， which cannot fully satisfy the overall needs of patients. For this reason， it is crucial to explore the mechanism underlying the development of CRC and to identify new treatment strategies. In recent years， with the deepening of research， ferroptosis has been gradually proven to effectively inhibit the proliferation and metastasis of CRC cells， overcome tumor drug resistance， enhance anti-tumor efficacy， and prevent tumor progression and recurrence. Therefore， regulating ferroptosis is expected to become a new strategy for the treatment of CRC. Traditional Chinese medicine （TCM） has been widely used in CRC treatment due to its advantages of multiple components， multiple targets， low drug resistance， and few side effects， and has gradually become a current research hotspot. Extensive studies have shown that TCM active ingredients and compound formulae can regulate ferroptosis-related pathways， such as iron metabolism， lipid metabolism， the cystine/glutamate antiporter system X_c^- （System X_c^-）/glutathione （GSH）/glutathione peroxidase 4 （GPX4）， ferroptosis suppressor protein 1 （FSP1）/coenzyme Q₁₀ （CoQ₁₀）/nicotinamide adenine dinucleotide phosphate ［NAD（P）H］， tumor protein 53 （p53）， nuclear factor erythroid-2-related factor 2 （Nrf2）， and non-coding RNA pathways to inhibit the growth and proliferation of CRC， thereby exerting anti-tumor effects. This review systematically summarized the mechanisms of ferroptosis related to CRC， therapeutic targets and prognosis-related markers associated with ferroptosis in CRC， and research progress on TCM targeting and regulating ferroptosis for CRC intervention， aiming to provide new perspectives and a theoretical basis for the prevention and treatment of CRC with TCM.

Objective:To explore the safety and effectiveness of ileal bypass with stent to prevent anastomotic leakage in Da Vinci robot anus-preserving surgery for low rectal cancer.Methods:From Dec 2021 to Sep 2024, the clinical data of 55 patients undergoing robot anus-preserving surgery and stent ileal bypass for low rectal cancer in the First Affiliated Hospital of Ningbo University was analyzed retrospectively.Results:All the 55 patients successfully completed the operation. Among them, 47 patients underwent low anterior resection and 8 patients did sphincter resection. The total operation time was (207±37)min, the operation time of ileal bypass was (24±3)min, and the intraoperative blood loss was (32±18)ml. After operation, the time of stent disintegration was (23.93± 2.87) days, and the time of catheter removal was (29.55 ± 3.21) days. By postoperative TNM staging, there were 12 cases in T1 stage, 26 cases in T2 and 17 cases in T3. The number of lymph node dissection was (16.84±4.50), 15 cases being positive for lymph node metastasis, 40 cases being negtive for lymph node metastasis, 36 cases were stage Ⅰ, 4 cases were stage Ⅱ and 15 cases were stage Ⅲ. The median follow-up time was 20 (2-35) months. Delayed anastomotic leakage occurred in 1 patient and anastomotic stenosis occurred in 2 patients.Conclusion:Stent ileal bypass is safe and effective to prevent anastomotic leakage in Da Vinci robot anus-preserving surgery for low rectal cancer.

BACKGROUND:Immune cells are correlated with various metabolic bone diseases,yet the specific immunological mechanisms and causal relationships remain elusive.OBJECTIVE:To investigate the causal relationship between immune cells and the risk of metabolic bone diseases through two-sample Mendelian randomization.METHODS:Genome-wide association study(GWAS)data on 731 immune cells and metabolic bone diseases(osteonecrosis,osteomalacia,osteoporosis,and osteoporosis combined with pathological fracture)were obtained from publicly available databases.Genetic variants related to immune cells were employed as instrumental variables.The inverse variance weighting method was utilized as the primary analytical approach,while MR-Egger and weighted median methods were applied to assess the causal relationships between immune cells and the risk of metabolic bone diseases.In addition,MR-PRESSO,MR-Egger regression,Cochran's Q test,and the leave-one-out method were implemented to evaluate genetic polymorphisms and the heterogeneity of instrumental variables,and MR Steiger method was used to exclude reverse causality.RESULTS AND CONCLUSION:(1)The analysis revealed that IgD-CD38dim％B cells,HLA DR on CD14+CD16-monocytes,and HLA DR on CD14+monocytes were significantly and causally associated with an increased risk of osteoporosis(P＜6.8x10-5).Sensitivity analyses confirmed the reliability and stability of these results.Furthermore,among the immune cell types studied,28 demonstrated potential causal associations with osteonecrosis,23 with osteomalacia,46 with osteoporosis,and 45 with the combined condition of osteoporosis and pathologic fracture(P＜0.05).(2)This study provides a comprehensive assessment of the causal influence of immune cells on metabolic bone diseases,highlighting the significant role of immune factors in the pathogenesis of these conditions,particularly osteoporosis.The findings contribute valuable insights into the relationship between immune traits and bone metabolism,laying a foundation for future research in this domain.This study utilized an international database to analyze the European population,which offers a reference for Chinese biomedical research in the realm of metabolic bone diseases,and facilitates the conduction of relevant studies for the Chinese population,thereby promoting the enhancement of the prevention and treatment of metabolic bone diseases.

Objective To establish the reference interval of urine Alzheimer-associated neuronal thread protein(AD7c-NTP)for healthy adults in Mianyang area using the indirect method.Methods The detection results of urine AD7c-NTP from 5 093 healthy in-dividuals were collected from the information management database of Medical Laboratory Department of Sichuan Science City Hospital from March 2017 to March 2022.Skewness-kurtosis and Kolmogorov-Smirnov tests were used to determine whether the data followed a normal distribution.After removing outliers using the Box Plots method,the enrolled subjects were grouped by gender and age.The Mann-Whitney U or Kruska-Wallis H tests were used to analyze the between-group differences of urine AD7c-NTP in healthy individu-als with different genders and ages.The adjacent age groups without statistically significant difference(P＞0.05)were combined,and the indirect method(non-parametric test method)was used to calculate the reference intervals for different gender and age groups.Results Skewness-kurtosis and Kolmogorov-Smirnov tests showed that the data followed a non-normal distribution.After removing 293 outliers using the Box Plots method,a total of 4 800 subjects,including 3 199 males and 1 601 females,were enrolled.The enrolled subjects were grouped by gender and age,and the non-parametric test method were used to establish the reference intervals of urine AD7c-NTP in healthy populations with different genders.The Mann-Whitney U test confirmed that urine AD7c-NTP levels existed gen-der differences(Z=14.09,P＜0.01),and the reference intervals for males and females were≤1.10 ng/mL and≤1.40 ng/mL,re-spectively.There were also statistical differences in urine AD7c-NTP levels among different age groups of the same gender.After combi-ning adjacent age groups without statistically significant difference(P＞0.05),the reference intervals of urine AD7c-NTP in healthy populations with different genders and ages were established by the non-parametric test method,which were≤1.00 ng/mL for male 20-39 years old group,≤1.10 ng/mL for male 40-79 years old group,≤1.60 ng/mL for male≥80 years old group,≤1.30 ng/mL for female 20-69 years old group,and≤1.60 ng/mL for female≥70 years old group,respectively.The established reference intervals of urine AD7c-NTP were further verified by healthy individuals,and the results met the standards.Conclusion The reference intervals of urine AD7c-NTP in healthy populations with different genders and ages in Mianyang area are established successfully using the indi-rect method,which may help to predict the risk of Alzheimer's disease in clinical practice and provide support for the diagnosis and treatment of the disease.

Objective:To evaluate the effects of sequential immunotherapy with radiotherapy on survival time and immune function in patients with unresectable stage III non-small cell lung cancer (NSCLC) in a real-world study.Methods:Data of 84 patients with unresectable stage III NSCLC who were treated at the Affiliated Hospital of Inner Mongolia Medical University from January 2021 to December 2022 (retrospective cohort) and from January 2023 to December 2023 (prospective cohort) were collected. The patients were divided into the combination group ( n=40) and radiotherapy group ( n=44) based on whether they received sequential immunotherapy or not. The progression-free survival (PFS) and overall survival (OS) between two groups were compared using standardized mortality ratio weighting (SMRW). Univariate Cox proportional hazards model, multivariate regression analysis, multi-model comparison of propensity score matching and subgroup analysis were emploed to analyze the robustness of clinical efficacy between two groups. E-value analysis was used to analyze the sensitivity of unmeasured confounding factors in observational studies. Additionally, the percentage of CD4 +T cells, CD8 +T cells and natural killer (NK) cells, and CD4 +/CD8 + T cell ratio before and after treatment between two groups were compared using analysis of covariance. Results:Among 84 patients, 77 (92%) cases were male and 7 (8%) were female. Among them, 42 (50%) were aged 65 years or older. The variables showed high homogeneity after SMRW, with a standardized mean difference of less than 0.1. In the combination group, the median PFS [17.0 months vs. 7.0 months, HR=0.260, 95% CI: 0.130-0.490, P<0.001] and OS [not reached vs. 24.0 months, HR=0.210, 95% CI: 0.070-0.590, P=0.002] were significantly longer compared to that in the radiotherapy group, with statistically significant differences. The study results were confirmed by robustness and sensitivity analyses. After treatment, patients in the combination group showed a statistically significant increase in the percentage of CD4 + T cells and NK cells, and CD4 +/CD8 + T cell ratio, as well as a decrease in the percentage of CD8 + T cells compared to those in the radiotherapy group (all P<0.05). Conclusions:Sequential immunotherapy following radiotherapy can significantly improve survival and prognosis of unresectable stage III NSCLC patients. The survival benefit is even greater when combined with chemotherapy. The main mechanism of the survival benefit may be the improvement of anti-tumor immune function.

Objective To establish the reference interval of urine Alzheimer-associated neuronal thread protein(AD7c-NTP)for healthy adults in Mianyang area using the indirect method.Methods The detection results of urine AD7c-NTP from 5 093 healthy in-dividuals were collected from the information management database of Medical Laboratory Department of Sichuan Science City Hospital from March 2017 to March 2022.Skewness-kurtosis and Kolmogorov-Smirnov tests were used to determine whether the data followed a normal distribution.After removing outliers using the Box Plots method,the enrolled subjects were grouped by gender and age.The Mann-Whitney U or Kruska-Wallis H tests were used to analyze the between-group differences of urine AD7c-NTP in healthy individu-als with different genders and ages.The adjacent age groups without statistically significant difference(P＞0.05)were combined,and the indirect method(non-parametric test method)was used to calculate the reference intervals for different gender and age groups.Results Skewness-kurtosis and Kolmogorov-Smirnov tests showed that the data followed a non-normal distribution.After removing 293 outliers using the Box Plots method,a total of 4 800 subjects,including 3 199 males and 1 601 females,were enrolled.The enrolled subjects were grouped by gender and age,and the non-parametric test method were used to establish the reference intervals of urine AD7c-NTP in healthy populations with different genders.The Mann-Whitney U test confirmed that urine AD7c-NTP levels existed gen-der differences(Z=14.09,P＜0.01),and the reference intervals for males and females were≤1.10 ng/mL and≤1.40 ng/mL,re-spectively.There were also statistical differences in urine AD7c-NTP levels among different age groups of the same gender.After combi-ning adjacent age groups without statistically significant difference(P＞0.05),the reference intervals of urine AD7c-NTP in healthy populations with different genders and ages were established by the non-parametric test method,which were≤1.00 ng/mL for male 20-39 years old group,≤1.10 ng/mL for male 40-79 years old group,≤1.60 ng/mL for male≥80 years old group,≤1.30 ng/mL for female 20-69 years old group,and≤1.60 ng/mL for female≥70 years old group,respectively.The established reference intervals of urine AD7c-NTP were further verified by healthy individuals,and the results met the standards.Conclusion The reference intervals of urine AD7c-NTP in healthy populations with different genders and ages in Mianyang area are established successfully using the indi-rect method,which may help to predict the risk of Alzheimer's disease in clinical practice and provide support for the diagnosis and treatment of the disease.

BACKGROUND:Immune cells are correlated with various metabolic bone diseases,yet the specific immunological mechanisms and causal relationships remain elusive.OBJECTIVE:To investigate the causal relationship between immune cells and the risk of metabolic bone diseases through two-sample Mendelian randomization.METHODS:Genome-wide association study(GWAS)data on 731 immune cells and metabolic bone diseases(osteonecrosis,osteomalacia,osteoporosis,and osteoporosis combined with pathological fracture)were obtained from publicly available databases.Genetic variants related to immune cells were employed as instrumental variables.The inverse variance weighting method was utilized as the primary analytical approach,while MR-Egger and weighted median methods were applied to assess the causal relationships between immune cells and the risk of metabolic bone diseases.In addition,MR-PRESSO,MR-Egger regression,Cochran's Q test,and the leave-one-out method were implemented to evaluate genetic polymorphisms and the heterogeneity of instrumental variables,and MR Steiger method was used to exclude reverse causality.RESULTS AND CONCLUSION:(1)The analysis revealed that IgD-CD38dim％B cells,HLA DR on CD14+CD16-monocytes,and HLA DR on CD14+monocytes were significantly and causally associated with an increased risk of osteoporosis(P＜6.8x10-5).Sensitivity analyses confirmed the reliability and stability of these results.Furthermore,among the immune cell types studied,28 demonstrated potential causal associations with osteonecrosis,23 with osteomalacia,46 with osteoporosis,and 45 with the combined condition of osteoporosis and pathologic fracture(P＜0.05).(2)This study provides a comprehensive assessment of the causal influence of immune cells on metabolic bone diseases,highlighting the significant role of immune factors in the pathogenesis of these conditions,particularly osteoporosis.The findings contribute valuable insights into the relationship between immune traits and bone metabolism,laying a foundation for future research in this domain.This study utilized an international database to analyze the European population,which offers a reference for Chinese biomedical research in the realm of metabolic bone diseases,and facilitates the conduction of relevant studies for the Chinese population,thereby promoting the enhancement of the prevention and treatment of metabolic bone diseases.

Objective:To explore the safety and effectiveness of ileal bypass with stent to prevent anastomotic leakage in Da Vinci robot anus-preserving surgery for low rectal cancer.Methods:From Dec 2021 to Sep 2024, the clinical data of 55 patients undergoing robot anus-preserving surgery and stent ileal bypass for low rectal cancer in the First Affiliated Hospital of Ningbo University was analyzed retrospectively.Results:All the 55 patients successfully completed the operation. Among them, 47 patients underwent low anterior resection and 8 patients did sphincter resection. The total operation time was (207±37)min, the operation time of ileal bypass was (24±3)min, and the intraoperative blood loss was (32±18)ml. After operation, the time of stent disintegration was (23.93± 2.87) days, and the time of catheter removal was (29.55 ± 3.21) days. By postoperative TNM staging, there were 12 cases in T1 stage, 26 cases in T2 and 17 cases in T3. The number of lymph node dissection was (16.84±4.50), 15 cases being positive for lymph node metastasis, 40 cases being negtive for lymph node metastasis, 36 cases were stage Ⅰ, 4 cases were stage Ⅱ and 15 cases were stage Ⅲ. The median follow-up time was 20 (2-35) months. Delayed anastomotic leakage occurred in 1 patient and anastomotic stenosis occurred in 2 patients.Conclusion:Stent ileal bypass is safe and effective to prevent anastomotic leakage in Da Vinci robot anus-preserving surgery for low rectal cancer.