Anti-inflammatory discovery of sesquiterpenoids and a jasmonic acid derivative from Artemisia stolonifera.

Eleven previously undescribed sesquiterpenoids (8-18), one undescribed jasmonic acid derivative (35) and 28 known compounds were isolated from the leaves of Artemisia stolonifera. Undescribed compounds with their absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction and ECD calculation. Compound 8 was identified as a rare sesquiterpenoid featuring a rearranged 5/8 bicyclic ring system, whereas compound 17 was found to be an unprecedented monocyclic sesquiterpenoid with methyl rearrangement. Evaluation of biological activity showed that compounds 1-5 and 7 displayed cytotoxicity against six tumor cells. In the meantime, compounds 11, 12, 18 and 35 exhibited inhibitory effects against LPS-stimulated NO production in RAW 264.7 macrophage cells and reduced the transcription of IL-6 and IL-1ß in a dose-dependent manner at 25, 50 and 100 µM. Moreover, the anti-inflammatory-based network pharmacology and molecular docking analyses revealed potential target proteins of 11, 12, 18 and 35.

Hereditary transthyretin cardiac amyloidosis proven by endomyocardial biopsy: a single-centre retrospective study and literature review.

BACKGROUND: This study aimed to report the genotypes and phenotypes of hereditary transthyretin cardiac amyloidosis (hATTR-CA) in a Western Chinese cohort and review the genetic profiles of this disorder in the Chinese population. METHODS: Transthyretin (TTR) gene sequencing of probands diagnosed with TTR cardiac amyloidosis and their relatives was performed at West China Hospital of Sichuan University from January 2018 to December 2021. All patients underwent endomyocardial biopsy for light and electron microscopy examinations. Clinical and essential examination materials were retrospectively collected and analysed. RESULTS: TTR gene alteration was demonstrated in five probands and their two relatives. Three TTR variants were identified, namely, Ser23Asn, Glu54Leu and Thr60Ala. This study is the first to report Glu54Leu as pathogenic mutations in Chinese hATTR-CA patients. The Ser23Asn mutation was the most common mutation in this cohort. Five probands, including two males and three females, were all ethnic Han-Chinese. The median age at diagnosis and delay in diagnosis (interval from onset to diagnosis) was 56 years (range, 54-69 years) and 8 years (range, from 1 to 30 years), respectively. Three cases showed a defined family history of amyloidosis. Endomyocardial biopsies and TTR immunohistochemistry showed positive results in all patients. Two probands died 17.0 months and 21.0 months after diagnosis. CONCLUSIONS: We identified one novel TTR variants causing hATTR-CA in the West Han Chinese population. To avoid misdiagnosis or delayed diagnosis of hATTR-CA, TTR genotypic screening and endomyocardial biopsy should be performed as soon as possible in cases with heightened clinical suspicion.

Diffuse Midline Gliomas With Histone H3 K27M Mutation in Adults and Children: A Retrospective Series of 164 Cases.

Diffuse midline glioma, H3 K27M-mutant (H3 K27M-mt DMG), is a rare and highly aggressive tumor that is more common in children than in adults. Few studies have compared the differences between pediatric and adult patients with this rare tumor. We here report our retrospective study of 94 adult and 70 pediatric cases of diffuse midline glioma. Surgical tumor samples were analyzed by routine histopathology and immunohistochemistry for H3 K27M, IDH1 R132H, ATRX, p53, OLIG2, glial fibrillary acidic protein, and Ki-67; Sanger sequencing for hot mutation spots in genes including H3F3A, HIST1H3B, IDH1, IDH2, TERT, and BRAF; and methylation-specific polymerase chain reaction for O6-methylguanine DNA methyltransferase promoter methylation. The most frequent anatomic locations in adult and pediatric patients were the thalamus and brainstem, respectively. Molecular profiling revealed higher frequencies of ATRX loss and H3.3 mutation in adult than in pediatric H3 K27M-mt DMGs. TERT promoter mutations and O6-methylguanine DNA methyltransferase promoter methylation were not detected in pediatric patients but were present in a few adult patients. During the follow-up period, 93/122 patients (70.1%) died from the disease, with a median survival time of 10.5 months (range: 1 to 104 mo). Kaplan-Meier analyses demonstrated that the prognosis was better for adult patients than the pediatric cohort (P=0.0003). Multivariate analyses indicated that patient age, primary tumor size, status of ATRX expression, and Ki-67 index were independent prognosticators. The present study showed that there were differences between adult and pediatric H3 K27M-mt DMGs in terms of the anatomic location of tumor, molecular changes, and prognosis.

A novel promoter-associated non-coding small RNA paGLI1 recruits FUS/P65 to transactivate GLI1 gene expression and promotes infiltrating glioma progression.

Glioma-associated oncogene homolog 1 (GLI1) is a core component of the Hedgehog (HH) signalling pathway and is a transcription activator of numerous oncogenes, such as SOX9, VEGFA, BCL2, and CDK2. The complex regulation of GLI1 involves numerous pathways and molecules, including HH-dependent and independent, epigenetic and post-transcriptional mechanisms. Here, we report the discovery, characterization and function of a novel sense promoter-associated ncRNA, paGLI1 that is overexpressed in infiltrating glioma. We show that paGLI1 promotes GLI1 gene transcription through binding to and recruitment of the transcription factor complex FUS/P65 by interacting with paGLI1 DNA sequence. This interaction facilitates FUS/P65 binding to the GLI1 promoter to activate GLI1 transcription and hence its downstream oncogenes, which results in enhancement of glioma cell proliferation and invasiveness. Importantly, over-expression of paGLI1 is a significant unfavorable prognosticator for both disease-specific and progression-free survival in glioma patients, with relative risks being 2.932 (95% confidence interval: 1.280 to 6.713) (P < 0.05) and 2.284 (95% confidence interval: 1.051 to 4.966) (P < 0.05), respectively. The novel paGLI1/FUS/P65 regulatory mechanisms play important roles in infiltrating glioma progression and may serve as potential targets for future therapeutics.

Case report: Amphiphysin-IgG autoimmunity: a paraneoplastic presentation of appendiceal goblet cell carcinoma.

Background: Appendiceal goblet cell carcinoma (aGCC) is a rare neoplasm with mixed endocrine and exocrine features. No paraneoplastic neurological syndromes or autoantibodies have been identified in cases of aGCC or even appendiceal tumors. Amphiphysin-immunoglobulin G (IgG) autoimmunity was first described in stiff-person syndrome with breast cancer. We firstly described the clinical course and pathological findings of a patient with aGCC-associated amphiphysin-IgG autoimmunity. Case presentation: A 54-year-old man who developed aGCC was admitted for acute disturbance of consciousness, psychiatric symptoms, cognitive impairment, seizure and hypotension. Amphiphysin-IgG was detected in the patient's serum and CSF by immunoblotting and tissue-based indirect immunofluorescence assay confirming the diagnosis of definite paraneoplastic amphiphysin-IgG-positive encephalitis. Histopathology revealed amphiphysin protein expression and accompanying immune cell infiltration (predominantly CD20+ B cells, CD3+ and CD8+ T cells) within the tumor tissue, suggesting a possible paraneoplastic origin of amphiphysin-associated paraneoplastic neurological syndromes (PNSs) in this case. Although the patient's symptoms resolved after high-dose corticosteroid therapy, he experienced recurrence 6 months later, manifesting as paraneoplastic cerebellar dysfunction. Despite treatment with IV cyclophosphamide and oral mycophenolate mofetil, no improvement was noted. Conclusions: This case suggests that aGCC may trigger amphiphysin-IgG autoimmunity.

Case Report: Extra-Articular Diffuse Tenosynovial Giant Cell Tumor of the Temporomandibular Joint.

Diffuse tenosynovial giant cell tumor (D-TSGCT) is a benign but locally destructive tumor of synovium that may involve joints, tendon sheaths, and bursae. Its occurrence in the temporomandibular joint (TMJ) is extremely rare. The authors reported a case of 48-year-old man with an extra-articular D-TSGCT in the TMJ with medial cranial fossa extension. computed tomography (CT) and magnetic resonance imaging (MRI) features are described. The lesion was a cystic-solid mass centered at the temporal bone without involvement of the condylar head, and its solid component presented high-density on CT and hypointensity on MRI. No signs of recurrence or metastasis was observed during 12-months of follow-up. The present report suggested the potential characteristics of radiologic imaging of D-TSGCT in TMJ.

Partial resection of large congenital left ventricular diverticulum in an infant: a case report.

BACKGROUND: Congenital left ventricular diverticulum is a rare cardiac malformation usually requiring total resection. CASE PRESENTATION: This report describes an infant presenting with a large apical diverticulum with a wide ventricle connection. Given the vicinity of the left anterior descending coronary artery to the diverticulum and its wide ventricular connection, partial resection was undertaken. The patient remained asymptomatic with good heart function 8 months after surgery. The last follow-up echocardiography did not demonstrate any significant left ventricular outpouching. CONCLUSIONS: We advocate early treatment of left ventricular diverticulum in children given the risk of spontaneous rupture of diverticulum, sudden death, and other serious complications if left untreated. For small patients with a wide connection of diverticulum to ventricle, partial resection is a safe option with favorable short-term outcomes.

[Characteristics of CMR Appearance in a Case of Cardiac Metastatic Melanoma].

A 53-year-old woman was found "an occupant in the left ciliary body" two years ago and underwent the surgery of "left eye ball removal". Pathological results confirmed the diagnosis of malignant melanoma. The patient was admitted to our hospital again due to newly found heart murmur. With the combination of cardiac magnetic resonance (CMR) imaging characteristics, including high signals on T1-weighted and fat-suppressed T1-weighted images, the high signal on T2-weighted images, uneven first-pass perfusion and late gadolinium enhancement (LGE), as well as PET signal characteristics, the diagnosis of malignant melanoma cardiac metastasis was made. This case suggests that multimodality CMR, including T1-weighted, T2-weighted, first-pass perfusion, late gadolinium enhancement, and cine imaging, can be used to monitor and detect cardiac metastasis of melanoma in a relatively early stage. Therefore, we recommend a routine echocardiography screening for patients diagnosed with melanoma. In addition, CMR examinations and PET/CT may help early detection and timely intervention of melanoma cardiac metastasis, as for their good specificity in detecting, this disease in clinical practice.

Mixed adenoneuroendocrine carcinoma of the liver: A rare case report.

A 55-year-old woman presented with chest and back pain of unknown cause. Contrast-enhanced computed tomography revealed two low-density tumors, sized 4.6 and 4.4 cm, in the hepatic caudate and left inner lobes, respectively. There are multiple enlarged lymph nodes around the abdominal aorta, hepatogastric ligament and gastrosplenic ligament. At the same time, there were multiple enlarged lymph nodes between the portal vein and the vena cava. Upper gastrointestinal endoscopy revealed chronic non-atrophic gastritis and esophagitis (grade B). Endoscopic examination of the lower digestive tract revealed polyps of the colon, diagnosed as tubular adenomas following biopsy and histopathological examination. The patient underwent left three hepatic resection (including left inner lobe, left outer lobe and right anterior lobe resection), abdominal lymph node dissection, right liver tumor radiofrequency ablation, hepatic caudate lobe resection, intestinal adhesion release, vena cava formation, portal vein repair and hilar cholangioplasty. The pathological examination of the resected specimens revealed intrahepatic bile duct carcinoma and hepatic parenchymal neuroendocrine tumor (NET). In addition, liver solid portions consisted of tumor cells with characteristic salt-and-pepper nuclei. Immunohistochemical examination revealed expression of the neuroendocrine marker synaptophysin in this solid component, confirming the diagnosis of NET. Furthermore, the MIB-1 proliferation index of the NET was higher compared with that of the adenocarcinoma, and lymph node invasion by the NET component was detected, indicating a neuroendocrine carcinoma (NEC, or NET G3). The diagnosis of mixed adenoneuroendocrine carcinoma of the liver was confirmed based on the World Health Organization 2010 criteria. Taking into consideration the patient's poor general condition, only symptomatic supportive treatment was administered postoperatively, without chemotherapy. Contrast-enhanced computed tomography at 45 days postoperatively revealed disease progression, with metastases in the liver stump, abdominal lymph nodes, spine and pelvis. The patient remained on symptomatic supportive treatment and succumbed to disease progression 3 months after surgery.

IDH1 status is significantly different between high-grade thalamic and superficial gliomas.

BACKGROUND: While major progress has been made in diagnosis and treatment of gliomas based on molecules, molecular features of thalamic glioma have rarely been reported till now. OBJECTIVE: IDH1 mutation is important for prognosis of gliomas and represents a distinctive category of glioma. We intended to survey specific molecular abnormalities in high-grade thalamic gliomas (WHO III-IV). METHODS: We collected data of 50 and 93 newly diagnosed high-grade thalamic and superficial glioma patients respectively and conducted a comparative analysis of molecular characteristics between them. We analyzed expressions of molecules as follow: IDH1/2, P53, Ki-67, ATRX, PTEN, MMP9 and MGMT by Immunohistochemistry (IHC). Direct gene sequencing was performed to test the IDH1(R 132H) mutation. RESULTS: We found a significant difference of IDH1 mutation between those high-grade gliomas, with 92% (46/50) of the thalamic tumors and 71% (66/93) of the superficial gliomas showing IDH1 wild-type (p= 0.004). It also showed that IDH1 mutation in superficial glioblastomas 18.6% (13/70) occurred more than thalamic glioblastomas 2.6% (1/39) (p= 0.017). As to high-grade superficial gliomas, there were 26 patients with IDH1 mutation, which contained 7, 13, and 6 high, moderate and low Ki-67 expression gliomas, respectively. The IDH1 wild-type group (62 patients), was composed of 29, 30, and 3 high, moderate and low Ki-67 expression gliomas, respectively. There was a significant distinction between the IDH1 mutation and Ki-67 expressions (p= 0.024). We also noted that the occurrence of low Ki-67 expressions 23.1% (6/26) in IDH1 mutation group was outnumbered than IDH1 wild-type group 4.8% (3/62) (p= 0.018). In addition, we found PTEN negative correlated with MMP9 negative in thalamic high-grade gliomas, whereas no such difference was found in superficial gliomas (p= 0.016). CONCLUSION: The rare occurrence of IDH1 mutant high-grade thalamic gliomas strongly suggested that the high-grade thalamic glioma is another distinct tumor entity as compared to the high-grade superficial gliomas.

[The research of SurgiCase CMF software in surgical simulation and prediction for mandibular asymmetry].

OBJECTIVE: To evaluate the predictive accuracy of the SurgiCase CMF software in surgical simulation and prediction for mandibular asymmetry with 3-dimensional simulation and measurement. METHODS: CBCT data of 27 patients with mandibular asymmetry were observed in CMF, and postoperative soft tissue physiognomy were predicted by simulating sagittal ramus osteotomy with or without genioplasty. The measurement parameters representing the symmetry of soft tissue were selected and the horizontal, coronal and sagittal planes were established. The results were analyzed by SPSS 19. 0. The overlap compared color grading charts were observed. RESULTS: Angles between cheilions and the horizonta plane (Ch-Ch-FH) in the simulation and postoperative soft tissues are (2. 35 ± 1. 81)° and (1. 44 ± 1. 13)°. The angles constructed among subnasale, upper lip and lower lip (Sn-UL-LL) are (4. 02 ± 3. 05)° and (2. 59 ± 1. 64)°, showing statistically different (P < 0. 01, P < 0. 05), which means that predictive accuracy of the lip canting and lip vertical deviation is relatively low. Distance between gonioi and sagittal plane (Go'-MS), distance between gonion and pogonion (Go'-Pog') and angle betweer subnasale to menton and the horizontal plane (Sn-Me'-MS) are not statistically different, which mean! high predictive accuracy of mandibular angle and chin. By observing the overlap compared color gradin-) charts, the predictive accuracy is not good in the cheek, especially in the deviate side. CONCLUSIONS: The predictive accuracy of CMF system for patients with mandibular asymmetry is relatively high, but it is not good in the lip and cheek. The software improvement is still necessary.

Evaluation of the mandibular split patterns in sagittal split ramus osteotomy.

PURPOSE: To evaluate the split patterns of the mandibular ramus in sagittal split ramus osteotomy (SSRO) using cone-beam computed tomography (CBCT) and examine the related anatomic features that may be associated with these split patterns. PATIENTS AND METHODS: The authors designed and implemented a retrospective cohort study and enrolled a sample composed of consecutive patients with different maxillofacial deformities who underwent an SSRO from July 2011 through October 2012 at the Department of Orthognathic Surgery at the Tianjin Stomatological Hospital of Nankai University. The split patterns, which were selected at random at 1 side per patient, were evaluated by CBCT as the outcome variable 1 month after the operation. The predictor variable was composed of a set of heterogeneous anatomic variables that could be associated with the split patterns. Type I split was defined as a split at the lingual side near the mylohyoid sulcus. Type II split was defined as a split at the posterior border of the mandibular ramus. Appropriate bivariate and regression statistics were computed, and the level of statistical significance was set at a P value less than .05. RESULTS: One hundred thirty patients with different maxillofacial deformities (62 male and 68 female; mean age, 23 yr) underwent an SSRO. Two types of split patterns of the mandibular ramus were observed in SSRO: a split at the lingual side near the mylohyoid sulcus, which occurred in 75.38% of patients, and split at the posterior border region of the mandibular ramus, which occurred in 24.62% of patients. No fracture lines were observed through the mandibular canal. The thickness of the lingual cortical bone between the mandibular canal and the posterior border of the ramus was significantly associated with the split patterns (P < .05). The thickness of the cortical bone in the posterior border of the ramus, the degree of the mandibular angle, and the shapes of the mandibular ramus in the axial plane also were found to influence these split patterns. There was no meaningful association between the split patterns and a patient's age and gender. CONCLUSION: The split patterns of the mandibular ramus during SSRO were influenced by some anatomic features of the mandibular ramus. Therefore, examining the anatomy of the mandible with CBCT before surgery may play an important role in predicting the split patterns of the mandibular ramus during SSRO.

[Study of biomechanical properties of mucosa scars after cleft palate surgery].

OBJECTIVE: To explore biomechanical properties and stress-strain of mucosa scars after cleft palate surgery. METHODS: After the model of mucosa scars was made, the mucosa scars and normal mucosa were excised and examined immediately by tensionometry. RESULTS: The mucosa scars after cleft palate surgery were compared with normal mucosa. The Poisson's ratio of mucosa scars and normal mucosa was 0.5 and 0.49, respectively, showing no significant difference between the two groups. The ultimate Young's modulus of mucosa scars was about 24.22 MPa, however, it declined to 3.32 Mpa in normal mucosa. CONCLUSIONS: The mucosa scars after cleft palate surgery are biomechanically weaker than normal mucosa. It can be used for further research, such as maxillary orthognathic surgery, distraction osteogenesis, and orthodontic treatment.