Gallbladder polypoid lesions (GPLs) refer to any elevated lesion of the mucosal surface of the gallbladder wall, and the prevalence is estimated to be between 0.9% and 12.1%. GPLs include benign polyps and malignant polyps. Benign polyps are further classified as non-neoplastic polyps and neoplastic polyps. Cholesterol polyps are the most common benign polyps and adenocarcinoma is the main type of malignant polyp. Hepatitis B virus infection, liver function abnormalities, dyslipidemia, and obesity are the main risk factors for GPLs. Studies of biological mechanisms have focused on malignant gallbladder polyps, the development of which is regulated by hormone levels in vivo, gut microbiota, inflammation, oxidative stress, Salmonella typhimurium, and related molecules. Diagnostic modalities include chemical examination and imaging examination, with imaging examination currently being the mainstay. Treatment of patients with GPLs is based on the presence or absence of symptoms, age, size of the polyps, tendency of the polyp to increase, and risk factors for symptomatic malignancy to determine whether surgery should be performed.

Aim To clarify the differential proteins of mammary tissues in Xihuang pills(XHP)against hy-perplasia of mammary glands(HMG)based on quanti-tative proteomics technology and validate them,and to explore the mechanism of action.Methods SD rats were randomly divided into blank group,model group and XHP group,with 10 rats in each group.Except for the blank group,estrogen and progesterone were injec-ted intramuscularly to establish a rat model of mamma-ry hyperplasia for 30 d.After XHP was administered for 14 d,the rats in each group were observed to have morphological changes in the apparent morphology of the mammary tissues,and pathological changes in the mammary tissues were stained with hematoxylin-eosin staining(HE),and the differentially expressed pro-teins(DEPs)in the groups were screened by quantita-tive proteomics technology and subjected to bioinforma-tics analysis,and Western blot to verify the key DEPs.Results Compared with the model group,the appar-ent pathological morphology of the XHP group was sig-nificantly improved,the diameter of the nipple height of the rats was significantly reduced(P＜0.01),and the degree of histopathology was significantly allevia-ted.Quantitative proteomics identified 4,299 DEPs in mammary tissue,and bioinformatics analysis of 14 DEPs with consistent changes between the XHP group and the blank group relative to the model group re-vealed that they were related to the regulation of mus-cular systemic processes,regulation of muscle contrac-tion,DNA replication,and pre-initiation of DNA repli-cation.Western blot results showed that,compared with the model group,rat mammary tissue of the XHP group showed significantly lower levels of ACLY and ALDOC protein expression levels were significantly re-duced and BIN1 protein expression levels were signifi-cantly increased(P＜0.01).Conclusions XHP may exert its anti-mammary hyperplasia effect through the regulation of BIN1,ACLY and ALDOC protein lev-els,the regulation of DNA replication,the regulation of pre-initiation of DNA replication and muscular sys-temic processes,and the regulation of muscle contrac-tion.

Objective To establish the ultra-high performance liquid chromatography(UPLC)chromatographic fingerprint of Notopterygii Rhizoma et Radix;To determine the contents of ferulic acid,nodakenin,ammijin,notopterol,isoimperatorin and volatile oil of Notopterygii Rhizoma et Radix from different producing areas;To provide reference for quality evaluation of Notopterygii Rhizoma et Radix.Methods Waters BEH C18 chromatographic column(2.1 mm×150 mm,1.7 μm)was used,with mobile phase acetonitrile-0.02%formic acid aqueous solution gradient elution,flow rate 0.25 mL/min,column temperature 25℃,detection wavelength 330 nm,injection volume 2 μL.UPLC fingerprints of 25 batches of Notopterygii Rhizoma et Radix were established,and the similarity analysis and chemometrics analysis were carried out.The contents of ferulic acid,nodakenin,ammijin,notopterol and isoimperatorin were determined simultaneously,and the contents of volatile oil was determined by steam distillation method.Results Totally 23 common fingerprint peaks were calibrated,11 known components were identified.According to the results of the cluster analysis and principal component analysis,25 batches of Notopterygii Rhizoma et Radix samples were divided into 3 categories,and the 6 potential differential components were screened out by orthogonal partial least squares-discriminant analysis(OPLS-DA).The results showed that the contents of notopterol and volatile oil from Sichuan Province were higher than those from Gansu Province and Qinghai Province.Conclusion The method established in the study is accurate and reliable,which can provide scientific basis and reference for the quality evaluation and control of Notopterygii Rhizoma et Radix.

Objective:To determine the motion detection uncertainty of the real-time CybeRay ? imaging system and patient intrafractional motion with thermoplastic mask-based immobilization. Methods:Real-time CybeRay ? imaging system was used for irradiation and treatment for head phantom and patients with brain tumors. All patients were immobilized with thermoplastic masks. Real-time imaging was delivered using kilovoltage projection images during radiotherapy. The detected patient motion data was collected from 5 head phantom measurements and 27 treatment fractions of 9 brain tumor patients admitted to Kaifeng Cancer Hospital. The accuracy and uncertainty of the motion monitoring system were determined. Results:The mean and standard deviation (SD) of the detected motion in the X, Y, and Z directions for phantom were (-0.02±0.41) mm, (-0.05±0.22) mm and (0.01±0.35) mm, respectively. The detected motion in the X, Y and Z directions for patents were (-0.13±0.48) mm, (-0.05±0.48) mm and (0.11±0.36) mm, respectively. After removing the motion detection uncertainty, the actual intrafractional motion of patients were (-0.11±0.25) mm, (0±0.43) mm and (0.10±0.08) mm in three directions, respectively. Conclusions:The uncertainty of real-time imaging-based motion monitoring system of CybeRay ? is less than 0.5 mm. It is feasible to apply thermoplastic masks for brain tumor patients in clinical practice, which can provide steady immobilization and limit the SD of patient intrafractional motion within 0.5 mm. Real-time imaging-based motion monitoring system of CybeRay ? is accurate for patient motion monitoring during frameless stereotactic radiosurgery/radiotherapy.

Objective To explore the current status and potential subtypes of frailty among family caregivers of patients with dementia,and to analyze the related influencing factors of different subtypes.Methods Dementia patients and their family caregivers in 8 community health service centers in Shanghai from June to October 2023 were recruited by convenience sampling.General information questionnaire,Tilburg Frailty Indicator(TFI),Pittsburgh Sleep Quality Index(PSQI),Self-Rating Depression Scale(SDS),Zarit Caregiver Burden Interview(ZBI),and Connor-Davidson Resilience Scale(CD-RISC)were conducted for investigation.Latent profile analysis was used to explore the potential subtypes of frailty among family caregivers of patients with dementia.The influencing factors associated with the potential subtypes were identified by univariate analysis and multivariate Logistic regression analysis.Results A total of 470 family caregivers of patients with dementia were surveyed,and 46.17％of them suffered from frailty.Frailty among family caregivers of patients with dementia can be classified into 3 potential subtypes:comprehensive-low frailty subtype(70.64％),psychosocial-medium frailty subtype(19.57％),and physical-high frailty subtype(9.79％).Family caregivers of patients with dementia who had poor sleep quality and suffered from 2 or more chronic diseases were more likely to be classified into the physical-high frailty subtype(P＜0.05).Family caregivers of patients with dementia who had higher levels of depression,lower mastery levels of caregiving knowledge and skills and spousal caregivers were more likely to be classified into the psychosocial-medium frailty subtype(P＜0.05).Family caregivers of patients with dementia who had higher levels of resilience were more likely to be classified into the comprehensive-low frailty subtype(P＜0.05).Conclusion The incidence of frailty among family caregivers of patients with dementia is at a high level with significant heterogeneity.It is suggested that medical staff should pay attention to the frailty of family caregivers,with a focus on family caregivers in the psychosocial-medium frailty subtype or physical-high frailty subtype,and take timely and targeted interventions according to the characteristics and influencing factors of different subtypes,so as to prevent or delay the occurrence and development of frailty.

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor with a poor prognosis and limited survival. Patients with GBM have a high demand for palliative care. In our present case, a 21-year-old female GBM patient received inpatient palliative care services including symptom management, mental and psychological support for the patient, psychosocial and clinical decision support for her family members, and pre- and post-death bereavement management for the family. Furthermore, we provided the family members with comprehensive psychological preparation for the patient's demise and assisted the patient's family throughout the mourning period.The aim of this study is to provide a reference and insights for the clinical implementation of palliative care for patients with malignant brain tumors.
Female ; Humans ; Young Adult ; Brain Neoplasms/therapy* ; Glioblastoma/therapy* ; Inpatients ; Palliative Care ; Terminal Care

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*

Objective: To explore the concordance and causes of different mismatch repair (MMR) and microsatellite instability (MSI) detection results in endometrial carcinoma (EC) molecular typing. Methods: A total of 214 EC patients diagnosed from January 2021 to April 2023 were selected at the Department of Pathology, Peking University Third Hospital. The immunohistochemistry (IHC) results of MMR protein were reviewed. Tumor specific somatic mutations, MMR germline mutations, microsatellite scores and tumor mutation burden (TMB) were detected by next-generation sequencing (NGS) with multi-gene panel. Methylation-specific PCR was used to detect the methylation status of MLH1 gene promoter in cases with deficient MLH1 protein expression. In cases with discrepant results between MMR-IHC and MSI-NGS, the MSI status was detected again by PCR (MSI-PCR), and the molecular typing was determined by combining the results of TMB and MLH1 gene promoter methylation. Results: (1) In this study, there were 22 cases of POLE gene mutation subtype, 55 cases of mismatch repair deficient (MMR-d) subtype, 29 cases of p53 abnormal subtype, and 108 cases of no specific molecular profile (NSMP). The median age at diagnosis of MMR-d subtype (54 years old) and the proportion of aggressive histological types (40.0%, 22/55) were higher than those of NSMP subtype [50 years old and 12.0% (13/108) respectively; all P<0.05]. (2) Among 214 patients, MMR-IHC test showed that 153 patients were mismatch repair proficient (MMR-p), 49 patients were MMR-d, and 12 patients were difficult to evaluate directly. MSI-NGS showed that 164 patients were microsatellite stable (MSS; equal to MMR-p), 48 patients were high microsatellite instability (MSI-H; equal to MMR-d), and 2 patients had no MSI-NGS results because the effective sequencing depth did not meet the quality control. The overall concordance between MMR-IHC and MSI-NGS was 94.3% (200/212). All the 12 discrepant cases were MMR-d or subclonal loss of MMR protein by IHC, but MSS by NGS. Among them, 10 cases were loss or subclonal loss of MLH1 and (or) PMS2 protein. Three discrepant cases were classified as POLE gene mutation subtype. In the remaining 9 cases, 5 cases and 3 cases were confirmed as MSI-H and low microsatellite instability (MSI-L) respectively by MSI-PCR, 6 cases were detected as MLH1 gene promoter methylation and 7 cases demonstrated high TMB (>10 mutations/Mb). These 9 cases were classified as MMR-d EC. (3) Lynch syndrome was diagnosed in 27.3% (15/55) of all 55 MMR-d EC cases, and the TMB of EC with MSH2 and (or) MSH6 protein loss or associated with Lynch syndrome [(71.0±26.2) and (71.5±20.1) mutations/Mb respectively] were significantly higher than those of EC with MLH1 and (or) PMS2 loss or sporadic MMR-d EC [(38.2±19.1) and (41.9±24.3) mutations/Mb respectively, all P<0.01]. The top 10 most frequently mutated genes in MMR-d EC were PTEN (85.5%, 47/55), ARID1A (80.0%, 44/55), PIK3CA (69.1%, 38/55), KMT2B (60.0%, 33/55), CTCF (45.5%, 25/55), RNF43 (40.0%, 22/55), KRAS (36.4%, 20/55), CREBBP (34.5%, 19/55), LRP1B (32.7%, 18/55) and BRCA2 (32.7%, 18/55). Concurrent PTEN, ARID1A and PIK3CA gene mutations were found in 50.9% (28/55) of MMR-d EC patients. Conclusions: The concordance of MMR-IHC and MSI-NGS in EC is relatively high.The discordance in a few MMR-d EC are mostly found in cases with MLH1 and (or) PMS2 protein loss or MMR protein subclonal staining caused by MLH1 gene promoter hypermethylation. In order to provide accurate molecular typing for EC patients, MLH1 gene methylation, MSI-PCR, MMR gene germline mutation and TMB should be combined to comprehensively evaluate MMR and MSI status.
Female ; Humans ; Middle Aged ; Class I Phosphatidylinositol 3-Kinases/metabolism* ; Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis* ; DNA Mismatch Repair/genetics* ; Endometrial Neoplasms/pathology* ; Microsatellite Instability ; Mismatch Repair Endonuclease PMS2/genetics* ; Molecular Typing

ObjectiveTo investigate the prognostic value of the enhancement pattern in arterial phase of preoperative Gd-EOB-DTPA enhanced magnetic resonance imaging （MRI） in evaluating the disease-free survival （DFS） and overall survival （OS） in patients undergoing curative resection for intrahepatic cholangiocarcinoma （ICC）. MethodsA retrospective analysis was done on the clinical， preoperative MRI findings and postoperative follow-up results of 93 pathologically confirmed ICC patients undergoing surgery in our hospital between January 2018 and December 2021. Kaplan-Meier survival curves and log-rank test were used to compare the DFS and OS of three groups with different arterial enhancement patterns. Cox regression analysis was used to identify the factors affecting DFS and OS. ResultsThere were significant differences in DFS and OS among the 3 groups （log-rank test， P < 0.05）. The arterial enhancement pattern was an independent predictive factor for DFS （using diffuse hyperenhancement as a reference， peripheral rim enhancement： HR = 3.550； 95%CI： 1.16 ~ 10.8； P = 0.026；diffuse hypoenhancement： HR = 3.430； 95%CI： 1.04 ~ 11.3； P = 0.042）. The arterial enhancement pattern and tumor location were predictive factors for OS （（using diffuse hyperenhancement as a reference， diffuse hypoenhancement， HR = 8.500； 95%CI： 1.09-66.3； P = 0.041； using tumor distal location as a reference， tumor perihilar location HR=2.583，95%CI： 1.14-5.83， P =0.022）. The AUC of arterial enhancement patterns in predicting 1-， 2-， and 3- year DFS were 0.722， 0.748， and 0.617， respectively； in OS， 0.720， 0.704， and 0.730， respectively， which showed better prognostic efficacy than AJCC-TNM staging system. ConclusionArterial-phase enhancement pattern of preoperative Gd-EOB-DTPA enhanced MRI is an independent predictive factor for DFS and OS of ICC patients， with a better prognostic value than AJCC-TNM staging system， and can be used for the clinical management of ICC patients.