Objective To retrospectively analyze multicenter data from domestic sources, aiming to explore the link between intrahepatic cholangiocarcinoma (ICC) tumor size and prognosis, establishing a classification system based on tumor size. Methods Between December 2011 and September 2018, 280 ICC patients from 13 hospitals were included. The tumor size prognosis cutoff was identified by the minimum P-value method, and the classification's overall survival related effectiveness was assessed by Kaplan-Meier analysis. Results All 280 patients were divided into the group of tumor maximum diameter ≤4 cm and >4 cm. Tumor size was confirmed as an independent prognosis factor by multivariate COX regression analysis (HR=2.110, 95% CI: 1.358-3.280). Conclusions The tumor size dichotomy classification system based on the Chinese patient group can expediently predict ICC prognosis and offers an important basis for selecting post-operative individualized adjuvant therapy and follow up plans.

The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To improve the isolation and culture method of seasonal influenza virus in embryonated chicken eggs (ECEs), and evaluate their isolation efficiency.Methods:We randomly selected 80 positive samples of H1N1 (H1N1pdm09) and seasonal H3N2 (H3N2snl) influenza virus nucleic acid, and inoculated them into the amniotic and urinary sac cavities of 10-day-old (traditional method) and 14-day-old (improved method) ECEs respectively to adapt the virus to the ECEs (E1-E2). Both method were used to inoculate 10-day-old urinary sac amplification virus (E2-E3), and the final virus isolation positive rates of the two method were compared; using fluorescence quantitative PCR method to detect viral nucleic acids in the improved amniotic and urinary sac cultures, and evaluate the viral proliferation at different inoculation sites; we analyzed the correlation between virus content and isolation positivity rate in the original specimen based on the CT value of nucleic acid testing and the final virus isolation positivity rate using the improved method.Results:The improved method obtained 42 strains of H1N1pdm09 strain, with a positive rate of 52.5% ( χ2=38.571, P<0.01); obtained 54 strains of H3N2snl strain, with a positive rate of 67.5% ( χ2=40.921, P<0.01). Significant differences were observed in the isolation efficiency of H1N1pdm09 samples when the improved method was applied to different inoculation sites of chicken embryos ( χ2=30.476, P<0.01), and similar differences were noted for H3N2snl samples ( χ2=4.928, P=0.026). There was no significant difference in the isolation rate of different CT value intervals of the original samples ( χH1N1pdm092=10.226, χH3N2snl2=3.764, P>0.05). Conclusions:The improved method of inoculating 14-day old ECEs adapted the virus, and the final number of strains obtained was significantly higher than the traditional method of inoculating 10 day old ECEs, which can significantly improve the positive isolation rate of H1N1pdm09 and H3N2snl influenza virus in ECEs. The amniotic cavity is more sensitive to H1N1pdm09 and H3N2snl influenza viruses, which helps the virus adapt in ECEs. There was no significant difference in the sample isolation rate and total positive rate of virus isolation among different CT value ranges, and further verification is needed.

Objective:To study the role of cadherin 1 (CDH1) gene DNA methylation in autoimmune thyroiditis (AIT) in population from different water-iodine regions.Methods:From May to June 2019, the information of AIT cases and healthy individuals in Shandong Province were collected in three types of water-iodine regions: iodine-fortification (IF) region, iodine-adequate (IA) region and iodine-excess (IE) region. A case-control study design was applied to match 176 AIT cases (case group) with age, gender, body mass index, and place of residence in a 1 ∶ 1 ratio to 176 healthy individuals (control group). Fasting urine and whole blood samples were collected to test the contents of urinary iodine, thyroid function indicators [serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid stimulating hormone (TSH)], and serum iodine. The DNA methylation levels of the target region of the CDH1 gene and its four CpG sites in whole blood were determined using methylation sequencing technology for target regions (MethylTarget TM). Results:The DNA methylation level of the target region of CDH1 gene in the case group was 0.832 ± 0.044, and that in the control group was 0.828 ± 0.049, there was no statistically significant difference between the two groups ( t = 0.76, P = 0.448). There was no statistically significant difference in DNA methylation levels of the four CpG sites in the target region of CDH1 gene between the case group and the control group ( P > 0.05). There was no statistically significant difference in the DNA methylation level of the CDH1 gene target region between the case group and the control group in IF, IA and IE regions ( P > 0.05). The detection results of DNA methylation levels at CpG sites in the target region of CDH1 gene in different water iodine regions showed that the DNA methylation level at site 83 in case group in IF region was higher than that in the control group ( t = 2.30, P = 0.023). However, there was no statistically significant difference in the DNA methylation levels of the four CpG sites between the case group and the control group in IA and IE regions ( P > 0.05). The DNA methylation level of CDH1 gene target region in AIT patients was not significantly correlated with urinary iodine, serum iodine, and serum FT 3, FT 4, and TSH contents ( P > 0.05), but was significantly negatively correlated with age ( r =-0.19, P = 0.014). Conclusions:The DNA methylation level at CpG site 83 of CDH1 gene in AIT patients in IF region is significantly higher than that in control population, indicating that DNA methylation at this locus may be involved in the occurrence and development of AIT after iodine fortification. The DNA methylation level of CDH1 gene is negatively correlated with age.

Objective:A model for predicting sentinel lymph node metastasis was established based on positron emission tomography(PET)-related metabolic parameters and clinicopathological characteristics.Methods:A retro-spective analysis was conducted on 211 patients diagnosed with breast cancer through surgical pathology from January 2016 to March 2023 in Meizhou People's Hospital,who underwent whole-body PET/CT examinations prior to surgery.Clinical,pathological,and PET-related metabolic parameters were collected.The study analyzed the association be-tween clinicopathological characteristics of the primary breast cancer lesion,PET metabolic parameters,and sentinel lymph node metastasis.A logistic regression predictive model was constructed using Broussonetia papyrifera.Results:Breast cancer primary lesion PET-suspicious axillary lymph nodes,vascular tumor thrombus,estrogen receptor(ER),and progesterone receptor(PR)showed statistically significant differences between the two groups(all P<0.05),while maxi-mum tumor diameter,SUVmax tumor location,maximum standardized uptake value(SUVmax),metabolic tumor volume(MTV),total lesion glycolysis(TLG),tumor location,number of lesions,pathological type,histological grade,neural inva-sion,Homo sapiens epidermal growth factor receptor 2(HER-2),and nuclear-associated antigen Ki-67(Ki-67)showed no statistically significant differences between the two groups(all P>0.05).Parameters with P<0.05 in the univariate analysis were subjected to multivariate logistic regression analysis,and the logistic regression model was established as Logit(P)=-0.437×vascular tumor thrombus+4.685×suspicious axillary lymph node metastasis.The predictive model AUC was 0.738(P<0.001,95%CI:0.664～0.812),with sensitivity and specificity of 63.4%and 74.4%,respectively.Con-clusion:PET findings of the primary breast cancer lesion regarding suspicious axillary lymph node metastasis,vascular tumor thrombus,ER and PR are associated with sentinel lymph node metastasis.The predictive model established based on PET-detected suspicious axillary lymph node metastasis and vascular tumor thrombus in primary breast cancer lesions has certain value in predicting sentinel lymph node metastasis,potentially providing a non-invasive examination modality for clinical practice.

This paper reports a 45-year-old female patient with lung squamous cell carcinoma who received chemotherapy for multiple systemic metastases,and then 171 mg of the immune checkpoint inhibitor serplulimab was added,ivd,d1(21 d as a cycle).After 2 cycles of treatment,the patient developed dizziness and nausea,and tumor brain metastasis was considered.The lung CT showed that the irregular mass shadow in the anterior segment of the upper lobe of the right lung was enlarged compared with the previous one,and MRI of the liver showed patchy abnormal signal in the liver segment Ⅳ.PET-CT showed that the lung,liver,adrenal gland,left groin and multiple bones were all progressed compared with the previous progress.It was considered to be tumor hyperprogression caused by serplulimab.Serplulimab was immediately discontinued and methylprednisolone was given for symptomatic treatment,but the patient still died due to overprogression.The Naranjo's Assessment Scale was used to evaluate the correlation between the tumor progression and serplulimab in this case,and the result was' likely to be related'.This case suggested that,the prognosis of tumor hyperprogression caused by immune checkpoint inhibitors has a poor prognosis,the clinical use of immune checkpoint inhibitors should be alert to this situation,and pay attention to early differential diagnosis and timely treatment to avoid serious consequences.

Objective:A model for predicting sentinel lymph node metastasis was established based on positron emission tomography(PET)-related metabolic parameters and clinicopathological characteristics.Methods:A retro-spective analysis was conducted on 211 patients diagnosed with breast cancer through surgical pathology from January 2016 to March 2023 in Meizhou People's Hospital,who underwent whole-body PET/CT examinations prior to surgery.Clinical,pathological,and PET-related metabolic parameters were collected.The study analyzed the association be-tween clinicopathological characteristics of the primary breast cancer lesion,PET metabolic parameters,and sentinel lymph node metastasis.A logistic regression predictive model was constructed using Broussonetia papyrifera.Results:Breast cancer primary lesion PET-suspicious axillary lymph nodes,vascular tumor thrombus,estrogen receptor(ER),and progesterone receptor(PR)showed statistically significant differences between the two groups(all P<0.05),while maxi-mum tumor diameter,SUVmax tumor location,maximum standardized uptake value(SUVmax),metabolic tumor volume(MTV),total lesion glycolysis(TLG),tumor location,number of lesions,pathological type,histological grade,neural inva-sion,Homo sapiens epidermal growth factor receptor 2(HER-2),and nuclear-associated antigen Ki-67(Ki-67)showed no statistically significant differences between the two groups(all P>0.05).Parameters with P<0.05 in the univariate analysis were subjected to multivariate logistic regression analysis,and the logistic regression model was established as Logit(P)=-0.437×vascular tumor thrombus+4.685×suspicious axillary lymph node metastasis.The predictive model AUC was 0.738(P<0.001,95%CI:0.664～0.812),with sensitivity and specificity of 63.4%and 74.4%,respectively.Con-clusion:PET findings of the primary breast cancer lesion regarding suspicious axillary lymph node metastasis,vascular tumor thrombus,ER and PR are associated with sentinel lymph node metastasis.The predictive model established based on PET-detected suspicious axillary lymph node metastasis and vascular tumor thrombus in primary breast cancer lesions has certain value in predicting sentinel lymph node metastasis,potentially providing a non-invasive examination modality for clinical practice.

This paper reports a 45-year-old female patient with lung squamous cell carcinoma who received chemotherapy for multiple systemic metastases,and then 171 mg of the immune checkpoint inhibitor serplulimab was added,ivd,d1(21 d as a cycle).After 2 cycles of treatment,the patient developed dizziness and nausea,and tumor brain metastasis was considered.The lung CT showed that the irregular mass shadow in the anterior segment of the upper lobe of the right lung was enlarged compared with the previous one,and MRI of the liver showed patchy abnormal signal in the liver segment Ⅳ.PET-CT showed that the lung,liver,adrenal gland,left groin and multiple bones were all progressed compared with the previous progress.It was considered to be tumor hyperprogression caused by serplulimab.Serplulimab was immediately discontinued and methylprednisolone was given for symptomatic treatment,but the patient still died due to overprogression.The Naranjo's Assessment Scale was used to evaluate the correlation between the tumor progression and serplulimab in this case,and the result was' likely to be related'.This case suggested that,the prognosis of tumor hyperprogression caused by immune checkpoint inhibitors has a poor prognosis,the clinical use of immune checkpoint inhibitors should be alert to this situation,and pay attention to early differential diagnosis and timely treatment to avoid serious consequences.

Objective:To investigate the impact of circumferential tumor location (anterior wall, nonanterior wall, or circumferential) on circumferential resection margin (CRM) status, local recurrence, and survival in patients with mid-low rectal cancer.Methods:A retrospective cohort study was conducted using data from 696 patients with mid-low rectal adenocarcinoma who underwent surgery in the Department of Colorectal Surgery at the First Affiliated Hospital of Naval Medical University between December, 2018 and December, 2019. Based on MRI or contrast-enhanced CT findings, the rectal wall was divided into four quadrants: anterior, posterior, left, and right. Tumors were classified into three groups: anterior wall group ( n = 245), nonanterior wall group ( n = 286, tumors predominantly located on the posterior or lateral walls), and circumferential group ( n = 165, tumors involving ≥ 3/4 of the circumference). Propensity score matching (PSM) was used to balance baseline characteristics. Outcomes included pathological CRM positivity, local recurrence rate (LRR), overall survival (OS), and disease-free survival (DFS). Cox regression analysis was performed to identify risk factors for recurrence, and subgroup analysis was conducted in patients who did not receive neoadjuvant therapy. Results:After PSM, both the anterior and circumferential groups had significantly higher pathological CRM positivity rates compared to the nonanterior wall group ( P=0.040 and P=0.039, respectively). The median follow-up time was 64 months (range: 1-71 months). Compared to the nonanterior wall group, the anterior wall group also had a significantly higher 5-year LRR (8.8% vs. 2.3%, P=0.003), and significantly lower 5-year OS (80.7% vs. 91.6%, P=0.001) and DFS (76.6% vs. 84.6%, P=0.029). The circumferential group had a significantly higher 5-year LRR than the nonanterior wall group (11.4% vs. 3.8%, P=0.020), but no significant differences were observed in 5-year OS (81.8% vs. 89.5%, P=0.100) or DFS (70.7% vs. 78.3%, P=0.101). No significant differences were found between the anterior and circumferential groups in 5-year LRR (11.1% vs. 9.7%), OS (76.3% vs. 83.7%), or DFS (69.8% vs. 74.1%) either (all P>0.05). Cox univariate analysis and multivariate analysis identified anterior wall tumors (HR=3.751, 95%CI: 1.373-10.215, P=0.010), circumferential tumors (HR=3.240, 95%CI: 1.109-9.466, P=0.032), pathological CRM positivity (HR=3.071, 95%CI: 1.144-8.245, P=0.026), and lymph node metastasis (HR=2.584, 95%CI: 1.192-5.601, P=0.016) as independent risk factors for LRR. Conversely, a greater distance from tumor to the anal verge (per 1 cm increase, HR=0.831, 95%CI: 0.712-0.970, P=0.019), and neoadjuvant therapy (HR=0.442, 95%CI: 0.204-0.957, P=0.038) were identified as independent protective factors against LRR. In patients who did not receive neoadjuvant therapy, locally advanced nonanterior wall tumors exhibited markedly low LRR (1.3% for pathological stage II-III, 1.6% for pT3-4 stage). Conclusion:Rectal tumors located in the anterior wall or involving the circumference are associated with higher CRM positivity rates, increased local recurrence, and poorer survival. These patients should be prioritized for neoadjuvant therapy. In contrast, nonanterior wall tumors have a low recurrence rate, and selective omission of neoadjuvant therapy may be considered for these cases.