Objective:To explore the clinical manifestations of IgG4-related diseases（IgG4-RD） complicated with moderately differentiated adenosquamous carcinoma of the parotid gland, the diagnostic criteria for IgG4-related diseases and parotid malignant tumors, treatment regimens, and the application of fine-needle aspiration in disease diagnosis, so as to reduce clinical misdiagnosis and missed diagnosis. Methods:A retrospective analysis was conducted on the case data of a patient with IgG4-related diseases（IgG4-RD） complicated with moderately differentiated adenosquamous carcinoma of the parotid gland admitted to our department in March 2024. The clinical characteristics, imaging findings, preoperative puncture results, and postoperative pathological features were analyzed, and relevant literatures on both diseases were reviewed and summarized. Results:The elderly male patient was admitted due to "a mass in the parotid area in front of the right ear for more than 3 months". Through clinical examination, imaging examination, laboratory examination, and preoperative needle biopsy, the diagnosis of "right parotid moderately differentiated adenosquamous carcinoma complicated with IgG4-related disease" was considered. It was also considered that IgG4-related disease did not involve other organs before surgery, so no systemic hormone therapy was given before or after surgery. After surgery combined with postoperative radiotherapy, follow-up showed that neither the parotid tumor nor IgG4-related disease recurred. Conclusion:"IgG4-related disease complicated with moderately differentiated adenosquamous carcinoma"is a rare clinical disease. Both lack typical clinical manifestations and specific imaging features, and the diagnosis is mostly unclear before surgery. Pathological examination is of great significance in the diagnosis of the disease, while fine-needle aspiration has limited value in the diagnosis, which should attract the attention of clinicians. In addition, for patients with both diseases, individualized treatment plans should be formulated.
Humans ; Parotid Neoplasms/pathology* ; Male ; Carcinoma, Adenosquamous/pathology* ; Immunoglobulin G4-Related Disease/complications* ; Parotid Gland/pathology* ; Retrospective Studies ; Aged ; Biopsy, Fine-Needle ; Immunoglobulin G

Dendrobium moniliforme (D. moniliforme) is a traditional medicinal herb widely cultivated in Asia. Flavonoids, one of the largest groups of secondary metabolites in plants, are significant medicinal components in Dendrobium species. Several subgroups of R2R3-MYB proteins have been validated to directly regulate flavonoid biosynthesis. Using PacBio sequencing technology, we assembled a high-quality chromosome-level D. moniliforme genome with a total length of 1.20 Gb and a contig N50 of 3.97 Mb. The BUSCO assessment of genome annotation was 91.4%. By integrating the genome and transcriptome, we identified biosynthesis pathway enzyme genes related to flavonoids, polysaccharides, carotenoids, and alkaloids. A total of 90 R2R3-MYBs were identified in D. moniliforme and classified into 21 subgroups. Studies on the functions of R2R3-MYB transcription factors revealed that R2R3-MYB in SG6 can up-regulate flavonoid biosynthesis. Various validation experiments, including subcellular localization, transient overexpression, UPLC-MS/MS, HPLC, yeast one-hybrid, and dual-luciferase assays, demonstrated that DMYB69 directly up-regulates the expression of enzyme genes involved in flavonoid biosynthesis, increasing the content of flavonoids such as anthocyanin, flavone, and flavonol. Additionally, DMYB44 was shown to directly up-regulate the expression of carotenoid biosynthesis enzyme genes, thereby increasing carotenoid content. This study provides an essential genome resource and theoretical basis for molecular breeding research in D. moniliforme.

Eight previously undescribed lanostane triterpenoids, including five nortriterpenoids with 26 carbons, ganothenoids A-E (1-5), and three lanostanoids, ganothenoids F-H (6-8), along with 24 known ones (9-32), were isolated from the fruiting bodies of Ganodrma theaecolum. The structures of the novel compounds were elucidated using comprehensive spectroscopic methods, including electronic circular dichroism (ECD) and nuclear magnetic resonance (NMR) calculations. Compounds 1-32 were assessed for their neuroprotective effects against H₂O₂-induced damage in human neuroblastoma SH-SY5Y cells, as well as their inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. Compound 4 demonstrated the most potent neuroprotective activity against H₂O₂-induced oxidative stress by suppressing G₀/G₁ phase cell cycle arrest, reducing reactive oxygen species (ROS) levels, and inhibiting cell apoptosis through modulation of B-cell lymphoma 2 protein (Bcl-2) and Bcl-2 associated X-protein (Bax) protein expression. Compounds 26, 12, and 28 exhibited PTP1B inhibitory activities with IC₅₀ values ranging from 13.92 to 56.94 μmol·L^-1, while compound 12 alone displayed significant inhibitory effects on α-glucosidase with an IC₅₀ value of 43.56 μmol·L^-1. Additionally, enzyme kinetic analyses and molecular docking simulations were conducted for compounds 26 and 12 with PTP1B and α-glucosidase, respectively.
Humans ; Fruiting Bodies, Fungal/chemistry* ; Triterpenes/isolation & purification* ; Neuroprotective Agents/isolation & purification* ; Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism* ; Ganoderma/chemistry* ; Apoptosis/drug effects* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; alpha-Glucosidases/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Oxidative Stress/drug effects* ; Hydrogen Peroxide/toxicity* ; Molecular Docking Simulation

Objective To explore the application effect of the Mini-CEX evaluation model based on the OBE concept in the clinical Practice teaching of neurology.Methods We Selected 100 students who will Practice in the Department of Neurology from 2022 to 2023 as the research objects,and divided them into the experimental group(n=50)and the control group(n=50).Under the guidance of the OBE concept,the experimental group was guided by learning outcomes,refined the teaching objectives,and applied the Mini-CEX evaluation mode for evaluation and feedback.In contrast,the control group adopted the traditional teaching mode.Combined with the observation data,we analyzed and compared the data of various indicators of the two groups of students at the beginning and end of the internship.Results At the end of the internship,the scores of clinical consultation,Physical examination,humanistic medicine,clinical diagnosis,health consultation,organizational effect,and overall evaluation of the experimental group were significantly improved and were higher than those of the control group.After the Practice,in terms of skill test scores,the experimental group scored higher than the control group,the difference was statistically significant(P<0.05),and the experimental group also scored higher in satisfaction evaluation than the control group.Conclusion The Mini-CEX evaluation teaching model based on the concept of OBE is applied to the clinical practice teaching of the neurology department,which can enhance the training effect of students'clinical practice skills.

Objective:To explore the diagnosis and treatment of lymphoepithelioma-like intrahepatic cholangiocarcinoma(LEL-ICC).Methods:The retrospective and descriptive study was conducted. The data of 7 patients with pathological diagnosis of LEL-ICC after hepatectomy who were treated in Lishui Central Hospital in Zhejiang Province from December 1, 2009 to January 30, 2024 were collected. There were 2 males and 5 females. The age range was from 40 to 64 years old, with a median age of 52 years old. All 7 patients showed no obvious clinical symptoms.We analysed the imaging manifestations, pathological features, treatmentsand prognoses of patients.Postoperative follow-upswere conducted via telephone, with a focus on whether the patient had relapsed. The deadline was February 20, 2024.Results:Five cases underwent ultrasound examination, of which 4 cases showed hypoechogenicity and 1 case showed hyperechogenicity. 7 cases underwent MRI examination, showing low signal on T1WI, high signal on T2WI, and high signal on diffusion-weighted imaging. 2 cases had type A enhancement, 2 cases had type B enhancement, and 3 cases had type C enhancement. All 7 cases received surgical treatment, 2 cases were received prophylactic transarterial chemoembolization (TACE) after surgery, and 3 cases were received systemic chemotherapy after surgery; All 7 cases underwent postoperative follow-up, with a follow-up time of 1-166 months and a median follow-up time of 56 months. One case developed hilar and retroperitoneal lymph node metastasis after surgery for 6 months, and underwent surgical treatment. After surgery, chemotherapy was performed. 25 months later, right adrenal gland metastasis reappeared, and after combined treatment, the metastatic lesion was reduced and the patient received surgical treatment and chemotherapy, and there is currently no recurrence. The remaining 6 cases showed no recurrence.Conclusions:LEL-ICC lacks specific clinical symptoms and imaging manifestations, diagnosis relies on histopathological and immunohistochemical examinations. Comprehensive treatment with surgical intervention as the main approach can lead to better prognosis for patients.

Objective To investigate the curative effect of interventional therapy on postoperative multiple metastases of breast cancer.Methods A total of 15 patients with multiple metastases after breast cancer surgery were treated with interventional therapy.After comprehensive evaluation,all patients were treated with chemoembolization.The therapeutic regimen was docetaxel loaded on drug-eluting bead(DEB)combined with carboplatin,once in 1 d for 21 d,2 times in total,and then the regimen was changed to docetaxel and carboplatin combined with ordinary embolization microspheres,once in 1 d for 21 d,4 times in total.CT/MRI was performed on every 2 cycles and 1,3,and 6 months after interventional therapy to evaluate its efficacy and record adverse reactions.Results The overall remission rate(ORR)at 3 months after treatment was 75％,and the disease control rate(DCR)was 91.7％.The ORR and DCR at 6 months after treatment were 50％and 83.3％,respectively.Most of the common adverse reactions were below grade Ⅲ.Conclusion Interventional therapy for multiple metastases of breast cancer after operation has a definite short-term effect,with little adverse reactions.It is worthy of further promotion in the comprehensive treatment of postoperative metastases of breast cancer.

Background and purpose:Human epidermal growth factor receptor 2(HER2)is closely associated with drug efficacy and prognosis in urothelial carcinoma(UC).HER2 is a significant biomarker and therapeutic target in various tumors.In recent years,anti-HER2 antibody-drug conjugates have shown significant clinical efficacy in UC patients with HER2 overexpression.Therefore,an in-depth understanding of HER2 expression and its characteristics in Chinese UC patients is crucial to guide treatment decision-making,optimize treatment strategies and achieve personalized therapy.This study aimed to thoroughly investigate correlation of HER2 expression and clinicopathological characteristics in Chinese patients with UC.Methods:This study was a multicenter study that retrospectively included UC patients from urology departments of 8 tertiary hospitals in 5 geographical regions of China(North China,East China,South China,Central China and Northwest)whose tissue samples were collected from January 2023 to March 2024.Inclusion criteria:① age above 18 years;② UC diagnosed by histopathological or cytological examination;③ complete results of HER2 expression detection using immunohistochemistry(IHC)in the primary tumor site were required.Exclusion criteria:① diagnosed patients with tumors in other parts of the body;② physicians evaluated other situations that were not suitable for inclusion in this study.IHC results for HER2 expression and clinicopathological data were collected.HER2 expression was determined according to the criteria outlined in"Clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China",with HER2 2+and 3+defined as HER2 overexpression.The HER2 expression and clinicopathological features were analyzed.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical number:2301268-12)and was registered at China Clinical Trial Registry(registration number:ChiCTR2300069746).Results:A total of 1054 patients with UC were included.Most of the tumors were bladder UC(n=807,76.6%).The mean age of patients was(66.8±10.5)years,and the majority were male(78.5%).The HER2 overexpression rate was 58.4%(n=616),with an additional 23%of patients having HER2 1+expression(n=242),and a small proportion exhibiting negative HER2 expression(n=196,18.6%).HER2 expression was significantly associated with various clinical and pathological characteristics such as Eastern Cooperative Oncology Group(ECOG)performance status,history of cardiovascular disease,history of metabolic disorders,smoking,UC disease location,differentiation grade,pathological type,and tumor stage.Conclusion:Retrospective analysis of multi-center data shows that HER2 expression is frequently observed in Chinese UC patients,with an overexpression rate of up to 58.4%.Furthermore,HER2 expression is closely associated with various clinical and pathological features of UC patients.This study underscores the critical importance of accurately assessing HER2 expression in UC patient to guide personalized therapies.

Objective To observe the value of artificial neural network(ANN)model based on recursive feature elimination-support vector machine(RFE-SVM)for differentiating ductal carcinoma in situ(DCIS)and DCIS complicated with microinvasion(DCISM).Methods Totally 296 female patients with single breast cancer(244 cases of DCIS and 52 cases of DCISM)were retrospectively collected as training set.Then 120 female patients with single breast cancer(87 cases of DCIS and 33 cases of DCISM)were prospectively enrolled as validation set.The general data,mammography and MRI findings were compared between sets.The optimal feature subsets for establishing ANN model were screened.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of ANN model for differentiating DCIS and DCISM.Results Ki-67 index,the minimum apparent diffusion coefficient(ADCmin),nuclear grade,ADCheterogeneity,maximum diameter of lesion,patient's age,P63,lesion enhancement type,calcification status and necrosis were the selected top 10 optimal feature subsets.The accuracy,sensitivity,specificity,positive predictive,negative predictive and AUC of ANN model for differentiating DCIS and DCISM was 91.55％,63.46％,97.54％,84.62％,92.61％and 0.950 in training set,respectively,while was 80.00％,69.70％,83.91％,62.16％,87.95％and 0.896 in validation set,respectively.The calibration curves of ANN model were consistent with the ideal curves in both training and validation set(P=0.355,0.480),which also expressed high clinical net benefit.Conclusion ANN model based on SVM-RFE could be used to differentiate DCIS and DCISM effectively.

Objective To investigate the impact of overweight on the prognosis of patients with acute mild ischemic stroke or moderate-high risk transient ischemic attack (TIA). Methods A total of 366 patients with acute mild ischemic stroke or moderate-high risk TIA who carried CYP2C19 loss-of-function alleles were included in the study. Baseline data were collected at admission, and clinical outcomes were collected within 3 months post-onset (primary outcomes: stroke recurrences within 3 months post-onset; secondary outcomes: composite outcome of stroke recurrence or death within 3 months post-onset, vascular events, and quality of life within 3 months). Kaplan-Meier method was used to plot the cumulative incidence curve of outcomes. Multivariate Cox proportional hazards model and multivariate Logistic regression model were used to evaluate the relationship between overweight and clinical outcomes within 3 months post-onset in patientswith ischemic stroke or TIA. The integrated discrimination improvement index (IDI) and net reclassification improvement index (NRI) were calculated to assess the predictive value of adding body mass index (BMI, whether overweight or not) based on traditional models for predicting the prognosis of acute ischemic stroke or TIA. Results After 3 months of follow-up, 28 patients had stroke recurrence, 1 patient died, and 31 patients had vascular events. The Kaplan-Meier cumulative incidence curve showed that the cumulative incidences of stroke recurrence, stroke recurrence or death, and vascular events after 3 months of onset were lower in overweight patients compared with non-overweight patients (Log-rank P < 0.05). Multivariate analysis showed that compared with non-overweight patients, overweight patients had significantly reduced risks of stroke recurrence within 3 months (HR=0.24; 95%CI, 0.08 to 0.71), composite outcome of stroke recurrence or death (HR=0.24; 95%CI, 0.08 to 0.69), and vascular events (HR=0.22; 95%CI, 0.07 to 0.63), and significantly improved quality of life within 3 months (OR=0.39; 95%CI, 0.20 to 0.76). The IDI and NRI calculations showed that compared with traditional models, the new model adding BMI (whether overweight) had significantly improved predictive ability for the prognosis of acute ischemic stroke or TIA. Conclusion Overweight may be a protective factor for the prognosis of TIA patients with acute mild ischemic stroke or moderate-high risk who carry CYP2C19 loss-of-function alleles. Compared with non-overweight patients, overweight patients have reduced risks of stroke recurrence, composite outcome of stroke recurrence or death, and vascular events within 3 months post-onset, and improved quality of life within 3 months post-onset.