Anti-LGI1 Antibody-Associated Encephalitis Misdiagnosed as Schizophrenia: A Case Report.

Anti-leucine-rich glioma-inactivated 1 (LGI1) antibody-associated encephalitis is a rare but clinically significant form of autoimmune encephalitis, predominantly affecting middle-aged men. Its heterogeneous clinical presentation often leads to misdiagnosis, commonly as other neurological or psychiatric disorders. This report details the case of a 46-year-old male who initially presented with depressive symptoms, personality changes, and visual hallucinations. Over time, his condition progressed to include memory impairment, disorganized behavior, and seizures. Initially misdiagnosed with schizophrenia, the correct diagnosis of LGI1 antibody-associated encephalitis was eventually established through positive serum and cerebrospinal fluid (CSF) tests for LGI1 antibodies. Neuroimaging findings revealed characteristic bilateral temporal lobe lesions. The patient demonstrated marked improvement following treatment with methylprednisolone and intravenous immunoglobulin, ultimately achieving significant recovery. This case highlights the critical importance of comprehensive antibody testing and neuroimaging in patients presenting with nonspecific psychiatric and neurological symptoms to prevent misdiagnosis and delays in appropriate treatment. The article also reviews the pathogenesis, clinical manifestations, diagnostic approaches, and therapeutic strategies for LGI1 antibody-associated encephalitis, aiming to enhance clinical awareness and optimize patient outcomes.

Synthesis and biological evaluation of 1-phenyl-tetrahydro-ß-carboline-based first dual PRMT5/EGFR inhibitors as potential anticancer agents.

Protein arginine methyltransferase 5 (PRMT5) and epidermal growth factor receptor (EGFR) are both involved in the regulation of various cancer-related processes, and their dysregulation or overexpression has been observed in many types of tumors. In this study, we designed and synthesized a series of 1-phenyl-tetrahydro-ß-carboline (THßC) derivatives as the first class of dual PRMT5/EGFR inhibitors. Among the synthesized compounds, 10p showed the most potent dual PRMT5/EGFR inhibitory activity, with IC50 values of 15.47 ± 1.31 and 19.31 ± 2.14 µM, respectively. Compound 10p also exhibited promising antiproliferative activity against A549, MCF7, HeLa, and MDA-MB-231 cell lines, with IC50 values below 10 µM. Molecular docking studies suggested that 10p could bind to PRMT5 and EGFR through hydrophobic, π-π, and cation-π interactions. Furthermore, 10p displayed favorable pharmacokinetic properties and oral bioavailability (F = 30.6%) in rats, and administrated orally 10p could significantly inhibit the growth of MCF7 orthotopic xenograft tumors. These results indicate that compound 10p is a promising hit compound for the development of novel and effective dual PRMT5/EGFR inhibitors as potential anticancer agents.

Discovery of tetrahydroisoquinolineindole derivatives as first dual PRMT5 inhibitors/hnRNP E1 upregulators: Design, synthesis and biological evaluation.

Protein arginine methyltransferase 5 (PRMT5) is an epigenetics related enzyme that has been validated as an important therapeutic target for treating various types of cancer. Upregulation of tumor suppressor hnRNP E1 has also been considered as an effective antitumor therapy. In this study, a series of tetrahydroisoquinolineindole hybrids were designed and prepared, and compounds 3m and 3s4 were found to be selective inhibitors of PRMT5 and upregulators of hnRNP E1. Molecular docking studies indicated that compounds 3m occupied the substrate site of PRMT5 and formed essential interactions with amino acid residues. Furthermore, compounds 3m and 3s4 exerted antiproliferative effects against A549 cells by inducing apoptosis and inhibiting cell migration. Importantly, silencing of hnRNP E1 eliminated the antitumor effect of 3m and 3s4 on the apoptosis and migration in A549 cells, suggesting a regulatory relationship between PRMT5 and hnRNP E1. Additionally, compound 3m exhibited high metabolic stability on human liver microsomes (T1/2 = 132.4 min). In SD rats, the bioavailability of 3m was 31.4%, and its PK profiles showed satisfactory AUC and Cmax values compared to the positive control. These results suggest that compound 3m is the first class of dual PRMT5 inhibitor and hnRNP E1 upregulator that deserves further investigation as a potential anticancer agent.

Arginine Methyltransferase 5 (PRMT5) Inhibitors with 3-(1H-benzo[d]imidazol- 2-yl)anilines Core Identified by Virtual Screening and Biological Evaluation.

BACKGROUND: PRMT5 is a major enzyme responsible for the post-translational symmetric demethylation of protein arginine residues, which has been validated as an effective therapeutic target for cancer. Thus, many nucleoside-based PRMT5 inhibitors have been reported in the past year. OBJECTIVE: To discover a novel series of non-nucleoside PRMT5 inhibitors through a molecular docking-based virtual screening approach. METHODS: Our in-house compound library was virtually screened using the Glide program, identifying a new PRMT5 inhibitor 1. Based on the structural similarity of hit 1, a series of structure-oriented derivatives, including 3a-3e, 7a-7g, and 12a-12f, were synthesized and selected for the inhibitory activity evaluation against PRMT5, as well as cytotoxicity against MV4-11 cell. RESULTS: The analogs 7a-7e with benzimidazole core exhibited potent PRMT5 inhibitory activities, with 7e displaying the most potent activity with an IC50 of 6.81 ± 0.12 µM. In the anti-proliferative assay, compound 7e showed a strong inhibitory effect on MV4-11 cell growth. Finally, the binding mode of 7e with PRMT5 was predicted to provide insights for further structural optimization. CONCLUSION: The newly discovered PRMT5 inhibitors have potential antitumor activity against MV4-11 cells. This work highlighted this series of 3-(1H-benzo[d]imidazol-2-yl)aniline derivatives as novel anti-cancer lead compounds targeting PRMT5, which were worthy of further investigation.

[Combination of transrectal 125I seeds implantation brachytherapy and intermittent hormonal therapy for locally advanced prostate cancer].

OBJECTIVE: To evaluate the clinical efficacy of transrectal 125 I seeds implantation brachytherapy (BT) combined with intermittent hormonal therapy (IHT) in the treatment of locally advanced prostate cancer. METHODS: We treated 27 patients with locally advanced prostate cancer by transrectal 125I seeds implantation BT combined with IHT, and dynamically observed the changes in the PSA level, prostate volume, maximum urinary flow rate (Qmax) and International Prostate Symptoms Score (IPSS). RESULTS: All the implantation procedures were completed smoothly, lasting 20 to 35 minutes, with 40 to 58 seeds implanted. At 6 months after implantation, the PSA level was < 0.2 microg/L in all the patients (< 0.1 microg/L in 19 cases), the prostate volume was significantly reduced (P < 0.05), and Qmax and IPSS remarkably improved (P < 0.05). At 3 years after implantation, 19 cases were in the first cycle and the other 8 in the third cycle of IHT, of which 2 progressed to androgen-independent prostate cancer, and another 2 developed early bone metastasis. The rates of 3-year biochemically and clinically progression-free survival were 70.3% and 85.2%, respectively, and the rate of therapeutic effectiveness was 92.6%. No severe complications occurred in any of the cases. CONCLUSION: Transrectal 125I seeds implantation BT combined with IHT is a safe and minimally invasive procedure for locally advanced prostate cancer, which can effectively retard its clinical progression with no such complications as severe urethral, rectal or erectile dysfunction.

[Oral lichen planus: a retrospective study of 724 Chinese patients].

OBJECTIVE: To retrospectively analyze oral lichen planus (OLP) patients and to summarize the clinical characteristic of OLP in Chinese patients. METHODS: A total of 724 patients with histologically and clinically confirmed OLP were collected from department of oral mucosa in School of Stomatology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University between 1978 and 2006. RESULTS: The OLP patients were followed up from 1 month to 259 months (mean 21 months). Of the 724 patients, 68.23% were women and 31.77% were men. The buccal mucosa was the most common site of involvement in each form, followed by the dorsal tongue, ventral tongue, lip, gingiva, palate and the floor of mouth. The reticular form of the disease was the predominant type in 53.82% of patients at initial presentation. About 48.76% of the patients had multiple oral sites of involvement. Fifteen OLP lesions developed into carcinoma, the malignant transformation rate was 2.07%. CONCLUSIONS: Because OLP has potential of malignant change, a long time and periodical follow-up is of great importance for detection of malignant lesions.

[The application of 18F-fluorodeoxyglucose positron emission tomography in the diagnosis and staging of lung cancer].

OBJECTIVE: To study the clinical value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the diagnosis and staging of lung cancer. METHODS: Ninety-four patients with lung nodular changes were examined by CT, 18F-FDG PET and pathology, cytology. 18F-FDG PET images were analyzed by semi-quantitative standard uptake value (SUV) only and (or) SUV plus visual observation. Focuses with a SUV > 2.5 were judged as malignant changes, while SUV < or = 2.5 was judged as benign. SUV plus visual analysis, based on the focal SUV, the nodular size and shape, and clinical data, was carried out by two nuclear doctors. CT imaging was interpreted by two radiological doctors. The sensitivity, specificity, accuracy, positive predictive and negative predictive values of 18F-FDG PET and CT in the diagnosis, and in the evaluation of lymphatic metastasis and remote metastasis of lung lesions were calculated. The diagnostic efficiency of the two methods (SUV or visual plus SUV method) was compared. RESULTS: (1) 58 cases were confirmed to be malignant by surgery or pathological examination, while 36 cases were proved benign by pathology or empirical therapy. (2) The sensitivity, specificity, accuracy, positive and negative predictive values were 69%, 65%, 68%, 82% and 49% respectively for CT; and 91%, 89%, 90%, 93% and 87% respectively for SUV analysis; and 95%, 94%, 95%, 97% and 92% respectively for visual plus SUV methods. (3) Among 34 patients with mediastinal lymph node involvement confirmed by pathology, 18F-FDG PET detected 30 cases, while CT detected only 18 cases (P < 0.01). (4) 18F-FDG PET revealed 19 cases with distant metastases, while CT only discovered 8 cases with distant metastases. As a result, the therapy was modified by PET examination in 14 patients. CONCLUSION: 18F-FDG PET imaging is of important clinical value in the diagnosis of lung lesions and the staging of malignancy.