Antinociceptive C19-diterpenoid alkaloids from the root of Aconitum episcopale.

A chemical investigation on the roots of Aconitum episcopale afforded three undescribed aconitine-type C19-diterpenoid alkaloids, episcopalines A-C (1-3). The structures of the new compounds were elucidated by spectroscopic analysis (NMR, IR, UV, and MS). The isolated alkaloids were tested in vivo for their antinociceptive properties. As a result, episcopaline B (2) showed potent antinociceptive effect and its ID50 value (55.0 µmol/kg) was 2-fold less than those of the positive control drugs aspirin and acetaminophen.

Antinociceptive C19-diterpenoid alkaloids isolated from Aconitum pseudostapfianum.

Phytochemical investigation on the roots of Aconitum pseudostapfianum resulted in the isolation of three new aconitine-type C19-diterpenoid alkaloids, pseudostapines A-C (1-3). Their structures were determined by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, NOESY and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated alkaloids were tested in vivo for their antinociceptive potential. As a result, pseudostapine C (3) showed 2-fold more potent antinociceptive effect (ID50 = 60.3 µmol/kg) than the positive control drugs aspirin and acetaminophen.

Cytotoxic lycodine alkaloids from the aerial parts of Lycopodiastrum casuarinoides.

A phytochemical investigation on the 75% EtOH extract of the aerial parts of Lycopodiastrum casuarinoides resulted in the isolation of three new lycodine alkaloids, 16-hydroxy-9-oxo-lycocasuarinine D (1), 6α-hydroxy-16-dehydroxy-lycocasuarinine A (2), and 6α,16-dihydroxy-lycocasuarinine B (3). Structural elucidation of all the compounds was performed by spectral methods such as 1D- and 2D-NMR, infrared, ultraviolet, and HR-ESI-MS. The isolated alkaloids were tested in vitro for cytotoxic potential against six lung cancer cell lines. Consequently, alkaloid 1 exhibited cytotoxicity against all the tested tumor cell lines with IC50 values less than 20 µM.[Formula: see text].

Cytotoxic monoterpenoid indole alkaloids from the aerial parts of Kopsia officinalis.

Three new monoterpenoid indole alkaloids, kopsiaofficines A-D (1-3), were isolated from the 95% EtOH extract of the aerial parts of Kopsia officinalis. Their structures were established on the basis of spectroscopic data. The isolated alkaloids were tested in vitro for cytotoxic activity against seven lung cancer cell lines. Consequently, alkaloids 1 and 3 exhibited some cytotoxic activities against all the tested tumor cell lines with IC50 values less than 20 µM.[Formula: see text].

Cytotoxic monoterpenoid indole alkaloids from the aerial part of Kopsia arborea.

A phytochemical investigation on the 90% ethanol aqueous extract of the aerial part of Kopsia arborea led to the isolation of three new monoterpenoid indole alkaloids, kopsiarborines A-C (1-3). The new structures were elucidated by using spectroscopic data (NMR, IR, UV, and MS). The isolated alkaloids were tested in vitro for cytotoxic potentials against six human lung cancer cell lines (A549, ATCC, H446, H460, H292, and 95-D). As a result, alkaloids 1 and 2 exhibited significant cytotoxic activities against all the tested tumor cell lines with IC50 values less than 20 µM.

Predictive modeling for postoperative delirium in elderly patients with abdominal malignancies using synthetic minority oversampling technique.

BACKGROUND: Postoperative delirium, particularly prevalent in elderly patients after abdominal cancer surgery, presents significant challenges in clinical management. AIM: To develop a synthetic minority oversampling technique (SMOTE)-based model for predicting postoperative delirium in elderly abdominal cancer patients. METHODS: In this retrospective cohort study, we analyzed data from 611 elderly patients who underwent abdominal malignant tumor surgery at our hospital between September 2020 and October 2022. The incidence of postoperative delirium was recorded for 7 d post-surgery. Patients were divided into delirium and non-delirium groups based on the occurrence of postoperative delirium or not. A multivariate logistic regression model was used to identify risk factors and develop a predictive model for postoperative delirium. The SMOTE technique was applied to enhance the model by oversampling the delirium cases. The model's predictive accuracy was then validated. RESULTS: In our study involving 611 elderly patients with abdominal malignant tumors, multivariate logistic regression analysis identified significant risk factors for postoperative delirium. These included the Charlson comorbidity index, American Society of Anesthesiologists classification, history of cerebrovascular disease, surgical duration, perioperative blood transfusion, and postoperative pain score. The incidence rate of postoperative delirium in our study was 22.91%. The original predictive model (P1) exhibited an area under the receiver operating characteristic curve of 0.862. In comparison, the SMOTE-based logistic early warning model (P2), which utilized the SMOTE oversampling algorithm, showed a slightly lower but comparable area under the curve of 0.856, suggesting no significant difference in performance between the two predictive approaches. CONCLUSION: This study confirms that the SMOTE-enhanced predictive model for postoperative delirium in elderly abdominal tumor patients shows performance equivalent to that of traditional methods, effectively addressing data imbalance.

Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing.

OBJECTIVE: Autosomal recessive bestrophinopathy (ARB), a retinal degenerative disease, is characterized by central visual loss, yellowish multifocal diffuse subretinal deposits, and a dramatic decrease in the light peak on electrooculogram. The potential pathogenic mechanism involves mutations in the BEST1 gene, which encodes Ca2+-activated Cl- channels in the retinal pigment epithelium (RPE), resulting in degeneration of RPE and photoreceptor. In this study, the complete clinical characteristics of two Chinese ARB families were summarized. METHODS: Pacific Biosciences (PacBio) single-molecule real-time (SMRT) sequencing was performed on the probands to screen for disease-causing gene mutations, and Sanger sequencing was applied to validate variants in the patients and their family members. RESULTS: Two novel mutations, c.202T>C (chr11:61722628, p.Y68H) and c.867+97G>A, in the BEST1 gene were identified in the two Chinese ARB families. The novel missense mutation BEST1 c.202T>C (p.Y68H) resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1. Another novel variant, BEST1 c.867+97G>A (chr11:61725867), located in intron 7, might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators. CONCLUSION: Our findings represent the first use of third-generation sequencing (TGS) to identify novel BEST1 mutations in patients with ARB, indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes. The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.

Optic Neuritis Leading to Vision Loss: A Case of MOG-Associated Disease with Successful Immunotherapy.

BACKGROUND Myelin oligodendrocyte glycoprotein (MOG)-associated disease (MOGAD) is a recently described inflammatory demyelinating disease of the central nervous system (CNS), which needs to be distinguished from aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) and multiple sclerosis (MS). CASE REPORT A 42-year-old woman presenting with loss of vision due to optic neuritis was admitted to the Naval Medical Center in October 2022. She had optic disc edema, blurred visual margins, optic disc pallor, and deficient visual field in both eyes. Cranial magnetic resonance imaging (MRI) showed bilateral optic nerve thickening, tortuosity, and swelling, especially on the right side. Orbital MRI T2 sequence showed the typical "double track sign" change. The titers of MOG-IgG in CSF and serum were 1: 1 (+) and 1: 32 (+) separately, so MOGAD was diagnosed. The primary treatment was intravenous methylprednisolone for 2 weeks, after which the blurred vision improved and MRI showed the optic nerve lesions disappeared. She was discharged and oral corticosteroids were tapered gradually, and 1 month later, the symptom had vanished without recurrence, cranial MRI was normal, and MOG-IgG in CSF and serum were negative. Low-dose oral corticosteroids were continued for 6 months, with no relapse and normal cranial MRI, so we stopped corticosteroid therapy. At 1-year follow-up, the symptoms had not recurred. CONCLUSIONS A 42-year-old woman presented with loss of vision due to optic neuritis and positive antibody testing for MOG. MOGAD was diagnosed, and timely immunotherapy was effective.

Patients with MMAF induced by novel biallelic CFAP43 mutations have good fertility outcomes after intracytoplasmic sperm injection.

As a specific type of asthenoteratozoospermia, multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by composite abnormalities, including absent, short, coiled, angulation, and irregular-caliber flagella. Mutations in cilia- and flagella-associated protein 43 ( CFAP43 ) are one of the main causative factors of MMAF established to date. To identify whether there are other CFAP43 mutations related to MMAF and to determine the clinical outcomes of assisted reproductive technology for patients with MMAF harboring different mutations, we recruited and screened 30 MMAF-affected Chinese men using a 22-gene next-generation sequencing panel. After systematic analysis, seven mutations in CFAP43 , including five novel mutations and two previously reported mutations, were identified from four families and related to MMAF in an autosomal recessive pattern. Papanicolaou staining, immunofluorescence, and electronic microscopy further clarified the semen characteristics and abnormal sperm morphologies, including disorganized axonemal and peri-axonemal structures, of the CFAP43 -deficient men. The female partners of two patients were pregnant after undergoing assisted reproductive technology through intracytoplasmic sperm injection, and one of them successfully gave birth to a healthy boy. This study significantly expands the mutant spectrum of CFAP43 , and together with the available information regarding male infertility and MMAF, provides new information for the genetic diagnosis and counseling of MMAF in the future.