Perihilar cholangiocarcinoma(PHC)is a common malignancy of biliary tract,for which surgery is the most effective treatment.However,its prognosis is not satisfactory even after surgical resection.In recent years,there have been some new advances in the surgical treatment of PHC.In this paper,we reviewed the existing literatures,demonstrated the current situation of preoperative biliary drainage,liver hyperplasia,hepatic resection,liver transplantation and minimally invasive surgery in the treatment of PHC,and prospected the future research direction.

Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is one of the most common complications after endoscopic retrograde cholangiopancreatography(ERCP).Numerous PEP prediction models have been established based on different statistical methods at home and abroad.The PEP prediction model,as a tool for evaluating and screening high-risk populations,can provide a basis for medical staff to find high-risk PEP patients early and take effective preventive measures.In recent years,new PEP prediction models have appeared one after another,but there is still a lack of recognized reliable prediction models in clinic.This article reviews the research status of PEP risk prediction models,aim to provide a direction for establishing a more reliable,accurate,and practical PEP risk prediction model in the later period.

Humans ; Atrial Fibrillation ; Atrial Flutter ; Lung Transplantation/adverse effects*

Endocrine-resistance remains a major challenge in estrogen receptor α positive (ERα⁺) breast cancer (BC) treatment and constitutively active somatic mutations in ERα are a common mechanism. There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrine-resistance. Given aberrant ERα activity, we herein report the identification of novel covalent selective estrogen receptor degraders (cSERDs) possessing the advantages of both covalent and degradation strategies. A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERα⁺ breast cancer cell lines including mutant ERα. Crystal structure of ERα‒ 29c complex alongside intact mass spectrometry revealed that 29c disrupted ERα protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11, thus enforcing a unique antagonist conformation and driving the ERα degradation. These significant effects of the cSERD on ERα homeostasis, unlike typical ERα degraders that occur directly via long side chains perturbing the morphology of H12, demonstrating a distinct mechanism of action (MoA). In vivo, 29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity. This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To explore the effect of joint segmentation model of myocardial-fibrotic region based on deep learning in quantitative analysis of myocardial fibrosis in patients with dilated cardiomyopathy(DCM).Methods:The data of 200 patients with confirmed DCM and myocardial fibrosis in the left ventricle detected by cardiac MR-late gadolinium enhancement (CMR-LGE) in Xuzhou Central Hospital from January 2015 to April 2022 were retrospectively analyzed. Using a complete randomized design, the patients were divided into training set ( n=120), validation set ( n=30) and test set ( n=50). The left ventricle myocardium was outlined and the normal myocardial region was selected by radiologists. Fibrotic myocardium was extracted through calculating the threshold with standard deviation (SD) as a reference standard for left ventricle segmentation and fibrosis quantification. The left ventricular myocardium was segmented by convex prior U-Net network. Then the normal myocardial image block was recognized by VGG image classification network, and the fibrosis myocardium was extracted by SD threshold. The myocardial segmentation effect was evaluated using precision, recall, intersection over union (IOU) and Dice coefficient. The consistency of myocardial fibrosis ratio in left ventricle obtained by joint segmentation model and manual extraction was evaluated with intra-class correlation coefficient (ICC). According to the median of fibrosis rate, the samples were divided into mild and severe fibrosis, and the quantitative effect of fibrosis was compared by Mann-Whitney U test. Results:In the test set, the precision of myocardial segmentation was 0.827 (0.799, 0.854), the recall was 0.849 (0.822, 0.876), the IOU was 0.788 (0.760, 0.816), and the Dice coefficient was 0.832 (0.807, 0.857). The consistency of fibrosis ratio between joint segmentation model and manual extraction was high (ICC=0.991, P<0.001). No statistically significant difference was found in the ratio error between mild and severe fibrosis ( P>0.05). Conclusions:The joint segmentation model realizes the automatic calculation of myocardial fibrosis ratio in left ventricle, which is highly consistent with the results of manual extraction. Therefore, it can accurately realize the automatic quantitative analysis of myocardial fibrosis in patients with dilated cardiomyopathy.

Objective: To investigate the association of blood lead and blood selenium with serum high-sensitivity C-reactive protein (hs-CRP) among Chinese adults aged 19 to 79 years. Methods: The participants were enrolled from the first wave of China National Human Biomonitoring (CNHBM) conducted from 2017 to 2018. 10 153 participants aged 19 to 79 years were included in this study. Fasting blood samples were obtained from participants. Lead and selenium in whole blood and hs-CRP in serum were measured. Individuals with hs-CRP levels above 3.0 mg/L were defined as elevated hs-CRP. Generalized linear mixed models and restricted cubic spline models were used to analyze the association of blood lead and blood selenium with elevated hs-CRP. Logistic regression models were used to analyze the multiplicative scale and additive scale interaction between blood lead and blood selenium on elevated hs-CRP. Results: The age of participants was (48.91±15.38) years, of which 5 054 (61.47%) were male. 1 181 (11.29%) participants were defined as elevated hs-CRP. After multivariable adjustment, results from generalized linear models showed that compared with participants with the lowest quartile of blood lead, the OR (95%CI) of elevated hs-CRP for participants with the second, third, and highest quartiles were 1.14 (0.94-1.37), 1.25 (1.04-1.52) and 1.38 (1.13-1.68), respectively. When compared with participants with the lowest quartile of blood selenium, the OR (95%CI) of elevated hs-CRP for participants with the second, third and highest quartiles were 0.86 (0.72-1.04), 0.91 (0.76-1.11), and 0.75 (0.61-0.92), respectively. Results from the interaction analysis showed no significant interaction between lead and selenium on elevated hs-CRP. Conclusion: Blood concentration of lead was positively associated with elevated serum hs-CRP, and blood concentration of selenium was inversely related to elevated hs-CRP, while blood lead and selenium did not present interaction on elevated hs-CRP.
Adult ; Aged ; Asians ; Biomarkers ; C-Reactive Protein/analysis* ; China/epidemiology* ; Humans ; Male ; Middle Aged ; Risk Factors ; Selenium ; Young Adult

OBJECTIVE: To analyze the changes in psychological distress and quality of life of patients with advanced liver cancer after transformation therapy. METHODS: This study was conducted among 60 patients with advanced liver cancer undergoing transformation therapy from July, 2019 to March, 2022. Before and after 2-10 cycles of treatment, the patients were assessed for psychological distress and quality of life using a psychological stress thermometer and the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep). RESULTS: The patients showed significantly lowered scores for psychological distress after transformation therapy (P < 0.01) with decreased psychological stress, emotional factors, tension, worry, sleep problems, memory decline and inattention, physical factors, pain, fatigue, eating problems and dyspepsia (P < 0.05). The total score of quality of life and the scores for physical status, social and family status, emotional status, functional status and hepatobiliary-specific items were all significantly lowered after the treatment (P < 0.05). CONCLUSION In patients with advanced liver cancer, the psychological distress involves mainly the emotional factors and physical factors. Transformation therapy can significantly relieve psychological distress of the patients and improve their quality of life.
Humans ; Quality of Life/psychology* ; Surveys and Questionnaires ; Psychological Distress ; Fatigue/psychology* ; Stress, Psychological ; Neoplasms ; Liver Neoplasms

Purpose: Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC. Materials and Methods: Three hundred fifty-three patients with resectable PC and 807 patients with locally advan-ced or metastatic PC were recruited in this study. These patients were classified into a training set (n=758) and a validation set (n=402). Kaplan-Meier survival plots and Cox proportional hazards regression models were used to analyze prognosis. Results: Overall survival (OS) was significantly better for patients with resectable PC with low preoperative PLR (p=0.048) and MLR (p=0.027). Low FAR, MLR, NLR (p < 0.001), and PLR (p=0.003) were significantly associated with decreased risk of death for locally advanced or metastatic PC patients. FAR (hazard ratio [HR], 1.522; 95% confidential interval [CI], 1.261 to 1.837; p < 0.001) and MLR (HR, 1.248; 95% CI, 1.017 to 1.532; p=0.034) were independent prognostic factors for locally advanced or metastatic PC. Conclusion The prognostic roles of FAR, MLR, NLR, and PLR in resectable PC and locally advanced or metastatic PC were different. FAR showed the most prognostic power in locally advanced or metastatic PC. Low FAR was positively correlated with OS in locally advanced or metastatic PC, which could be used to predict the prognosis.

Objective:To investigate the influence of environmental factors on body mass index of children and adolescents in China.Methods:Using data from the China Health and Nutrition Survey, the research object to 7 - 17 years old children and adolescents who participated in 2000, 2006, 2011, and 2015 round of survey with complete data, a total of 6 626 children and adolescents (male 3 473, female 3 153) were investigated under univariate analysis for each environmental factor variable before using Partial Least Square Regression fitting a linear model for further screening. Finally, we fitted a three-level linear mixed-effects model distinct by urban and rural area for analysis.Results:The three-level null model, log likelihood=-17 034.68, χ 2=483.06, P<0.001. Intern-class correlation coefficient ( ICC) showed that community-level was 9.97%, and both community and individual were 39.38%. The three-level model also showed that urban model's urbanization index ( β=-0.05, 95% CI: -0.09--0.01, P<0.05), the park location ( β=-0.88, 95% CI: -1.72 - -0.04, P<0.05), 15 - 17 age group ( β=-1.04, 95% CI:-1.78 - -0.30, P<0.05) were negatively correlated with BMI. The distance to the gym ( β=0.12, 95% CI: 0.02 - 0.22, P<0.05), the number of home TV sets ( β=0.50, 95% CI: 0.08 - 0.92, P<0.05) and the frequency of parents' alarm of fiction TV program contents ( β=1.85, 95% CI: 0.70 - 3.00, P<0.05) were correlated with BMI. Rural urbanization index ( β=-0.04, 95% CI:-0.07 - -0.01, P<0.05). Rural per capita income ( β=-7.29e -4, 95% CI:-1.00e -3 - -6.77e -5, P<0.05), parents' restricted frequency of watching TV ( β=-1.29, 95% CI:-2.36 - -0.21, P<0.05), adipo-energy ratio ( β=-0.03, 95% CI:-0.06 - -1.00e -3, P<0.05) were negatively correlated with the BMI. Factors as the frequency of parents' alarm of fiction TV program contents ( β=3.01, 95% CI: 0.03 - 6.00, P<0.05), the survey time was 2015 ( β=4.83, 95% CI: 1.96 - 7.69, P<0.05) were correlated with BMI. Conclusions:Environmental factors could indirectly influence the change of BMI of children and adolescents to different degrees and various aspects. Urbanization index and rural per capita income had a slight protective effect on increasing BMI of children and adolescents. At the community level, attention should be paid to the setting of activity places around the living environment of children and adolescents. Family members should also guide their children and adolescents to develop nice behavior in watching TV.