[Cardiac amyloidosis: pathological classification and clinical analysis of 48 cases].

Objective: To investigate the histological features and clinical manifestations in different types of cardiac amyloidosis to improve diagnostic accuracy. Methods: The histopathological features and clinical manifestations of 48 patients diagnosed with cardiac amyloidosis by Congo red stain and electron microscopy through endomyocardial biopsy were collected in West China Hospital of Sichuan University from January 2018 to December 2021. Immunohistochemical stains for immunoglobulin light chains (κ and λ) and transthyretin protein were carried out, and a review of literature was made. Results: The patients age ranged from 42 to 79 years (mean 56 years) and the male to female ratio was 1.1 to 1.0. The positive rate of endomyocardial biopsy was 97.9% (47/48), which was significantly higher than that of the abdominal wall fat (7/17). Congo red staining and electron microscopy were positive in 97.9% (47/48) and 93.5% (43/46), respectively. Immunohistochemical stains showed 32 cases (68.1%) were light chain type (AL-CA), including 31 cases of AL-λ type and 1 case of AL-κ type; 9 cases (19.1%) were transthyretin protein type (ATTR-CA); and 6 cases (12.8%) were not classified. There was no significant difference in the deposition pattern of amyloid between different types (P>0.05). Clinical data showed that ATTR-CA patients had less involvement of 2 or more organs and lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) than the other type patients (P<0.05). The left ventricular stroke volume and right ventricular ejection fraction of ATTR-CA patients were better than the other patients (P<0.05). Follow-up data of 45 patients was obtained, and the overall mean survival time was 15.6±2.0 months. Univariate survival analysis showed that ATTR-CA patients had a better prognosis, while cardiac amyloidosis patients with higher cardiac function grade, NT-proBNP >6 000 ng/L, and troponin T >70 ng/L had a worse prognosis (P<0.05). Multivariate survival analysis showed that NT-proBNP and cardiac function grade were independent prognostic factors for cardiac amyloidosis patients. Conclusions: AL-λ is the most common type of cardiac amyloidosis in this group. Congo red staining combined with electron microscopy can significantly improve the diagnosis of cardiac amyloidosis. The clinical manifestations and prognosis of each type are different and can be classified based on immunostaining profile. However, there are still a few cases that cannot be typed; hence mass spectrometry is recommended if feasible.

[Epithelioid glioblastoma with BRAF V600E mutation: a clinicopathological and molecular study].

Objective: To investigate the clinicopathological and molecular characteristics of the epithelioid glioblastoma (eGBM) with BRAF V600E mutation. Methods: Sixteen cases of eGBM with BRAF V600E mutation diagnosed at the West China Hospital of Sichuan University, China from 2012 to 2019 were collected. Their clinicopathological and molecular characteristics were analyzed. Results: The range of patients' age was from 7 to 61 years (median 31.5 years). There were 4 males and 12 females, with a male to female ratio of 1∶3. Eleven cases were newly diagnosed eGBM and five cases had a previous history of astrocytomas. Most of the tumors were located in the cerebral hemisphere, often in the frontal lobe, with an average diameter of 4.6 cm (2.0-8.0 cm). The tumors were composed of relatively uniform, closely packed epithelioid cells, some showing discohesion, with distinct cell membrane, eosinophilic cytoplasm, eccentric nuclei, distinct nucleoli and mitotic activity. Palisaded/coagulative necrosis was seen in all cases. Glomerular microvascular proliferation was seen in most of the cases, while mono-or multi-nucleated tumor giant cells were seen in some cases. Focal sarcomatoid area was seen in 2 cases, and focal pleomorphic xanthoastrocytoma (PXA)-like area was seen in 3 cases. Immunohistochemistry showed variable positivity for GFAP, Olig2 and p53. The median Ki-67 index was 30% (10%-50%). Only one case lost ATRX protein expression. Sanger sequencing identified the BRAF V600E mutation in all sixteen patients. Five cases also had mutations in the TERT gene promoter. No IDH1 (R132) or IDH2 (R172) mutation was detected. Surgical resection of the tumors was performed for all patients, and 3 patients also received adjuvant radiotherapy and chemotherapy. Follow-up data were available for 15 patients, with a follow-up time of 1-89 months (median 10 months). Among the 15 patients, 7 patients died of disease and another 5 patients had recurrences. The overall survival time of the patients under 35 years of age was significantly longer than that of the patients aged 35 years or older (P=0.014), but their progression-free survival was not statistically different (P=0.232). Conclusions: eGBM with BRAF V600E mutation is more commonly detected in young women than other the populations (i.e. elderly or male). The epithelioid morphology should include rhabdoid meningioma, anaplastic PXA, atypical teratoid/rhabdoid tumor, metastatic tumors, and melanoma in its differential diagnosis. PXA-like area is observed in some eGBM cases, suggesting a relationship of these two types of tumor. eGBM is a high-grade malignant tumor and most of the cases show recurrences or deaths in a short-period time. The younger patients have a relatively better prognosis than the older ones.

[Prognostic significance of combined TERT and IDH gene mutation analysis in diffusely infiltrating gliomas].

Objective: To investigate the status and prognostic significance of TERT and IDH1/2 genes mutations in diffusely infiltrating gliomas. Methods: Hot spot mutations of TERT and IDH1/2 genes were detected by DNA sequencing in 236 cases of gliomas at West China Hospital from 2012 to 2016, including pilocytic astrocytoma (WHO grade Ⅰ, 16 cases), diffuse astrocytoma and oligodendroglioma (WHO grade Ⅱ, 89 cases), anaplastic astrocytoma and oligodendroglioma (WHO grade Ⅲ, 72 cases) and glioblastoma (WHO grade Ⅳ, 59 cases). The prognostic significance of TERT and IDH1/2 hot spot mutations was evaluated. Results: No IDH or TERT mutations were detected in pilocytic gliomas. TERT promoter mutation frequency was higher in patients aged ≥40 years(60.8%, 93/153) than in patients aged <40 years (32.8%, 22/67; P<0.01). TERT promoter mutation rate was also significantly higher in oligodendroglioma (87.5% , 56/64) than that in astrocytoma(37.8%, 59/156; P<0.01). Young age (<40 years), oligodendroglioma and IDH1 mutation were favorable prognostic factors for diffusely infiltrating astrocytic and oligodendroglial tumors. TERT mutation alone was not of prognostic significance. Diffusely infiltrating astrocytic and oligodendroglial tumors were divided into four molecular subtypes according to TERT and IDH1 mutation status: IDH(+ )/TERT(+ ), IDH(+ )/TERT(-), IDH(-)/TERT(-) and IDH(-)/TERT(+ ). There was significant prognostic difference among the 4 subtypes. Conclusions: Combined IDH and TERT gene mutation analysis may be useful for prognostic subgrouping. Notably, IDH1 wild-type cases can be further subdivided into TERT(+ ) or (-) subgroups with significant prognostic difference.

[The relationship between non-alcoholic fatty liver disease and metabolic syndrome in patients with latent autoimmune diabetes in adults].

Objective: To investigate the relationship between non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in patients with latent autoimmune diabetes in adults (LADA). Methods: A total of 223 hospitalized patients were recruited between January 2007 and June 2009 in Department of Endocrinology and Metabolism of the Sixth People's Hospital Affiliated to Shanghai Jiaotong University. Finally, 142 patients with complete clinical data and without history of drinking were included in this study. According to the Chinese Medical Association's Guidelines of NAFLD, based on the result of ultrasound, all subjects were divided into two groups including patients with LADA and NAFLD (n=37) and patients with LADA but without NAFLD (n=105). Clinical data including diabetes duration, history of smoking and medications, height, weight, blood pressure, blood lipids, blood glucose, C-peptide, and liver and kidney function were collected. The prevalence and components of MetS were compared between two groups. The association between MetS and NAFLD was also explored. Results: After adjusting for age and sex, compared with the subjects without NAFLD, the subjects with NAFLD were older and had higher percentage of hypertension, and had higher body mass index[(26.5±3.7) kg/m(2) vs (21.9±3.1) kg/m(2)], waist-hip ratio(0.92±0.06 vs 0.86±0.07), low density lipoprotein cholesterol[(3.26±0.72) mmol/L vs (2.70±0.87) mmol/L], C-reactive protein, fasting C-peptide, 2 h postprandial C-peptide, systolic blood pressure, diastolic blood pressure, alanine aminotransferase and triglyceride (all P<0.05). But they had lower high-density lipoprotein cholesterol[(1.17±0.43) mmol/L vs (1.35±0.40) mmol/L]and HbA1c[(8.83±2.14) % vs (10.02±2.79)%](both P<0.05). In addition, after adjusting for age and sex, compared with the patients with LADA but without NAFLD, the prevalence of MetS in the patients with LADA and NAFLD was obviously higher (97.3% vs 47.6%, P<0.001), and the proportion of the patients with four (32.4% vs 16.2%, P<0.001) and five (43.2% vs 5.7%, P<0.001) components of MetS in the patients with LADA and NAFLD was also significantly increased than that in the patients with LADA but without NAFLD. Binary regression analysis showed that NAFLD was an independent factor associated with MetS in the patients with LADA after correcting other confounding factors (P<0.001). Conclusions: Compared with the patients with LADA but without NAFLD, the prevalence of MetS was obviously higher, and had more serious metabolic disorder in the patients with LADA and NAFLD. The presence of NAFLD was an independent factor associated with MetS in the patients with LADA.

Numerical investigation of the transverse instability on the radiation-pressure-driven foil.

The development of transverse instability in the radiation-pressure-acceleration dominant laser-foil interaction is numerically examined by two-dimensional particle-in-cell simulations. When a plane laser impinges on a foil with modulated surface, the transverse instability is incited, and periodic perturbations of the proton density develop. The growth rate of the transverse instability is numerically diagnosed. It is found that the linear growth of the transverse instability lasts only a few laser periods, then the instability gets saturated. In order to optimize the modulation wavelength of the target, a method of information entropy is put forward to describe the chaos degree of the transverse instability. With appropriate modulation, the transverse instability shows a low chaos degree, and a quasi-monoenergetic proton beam is produced.

Gamma-aminobutyric acid type A receptors modulate cAMP-mediated long-term potentiation and long-term depression at monosynaptic CA3-CA1 synapses.

cAMP induces a protein-synthesis-dependent late phase of long-term potentiation (LTP) at CA3-CA1 synapses in acute hippocampal slices. Herein we report cAMP-mediated LTP and long-term depression (LTD) at monosynaptic CA3-CA1 cell pairs in organotypic hippocampal slice cultures. After bath application of the membrane-permeable cAMP analog adenosine 3',5'-cyclic monophosphorothioate, Sp isomer (Sp-cAMPS), synaptic transmission was enhanced for at least 2 h. Consistent with previous findings, the late phase of LTP requires activation of cAMP-dependent protein kinase A and protein synthesis. There is also an early phase of LTP induced by cAMP; the early phase depends on protein kinase A but, in contrast to the later phase, does not require protein synthesis. In addition, the cAMP-induced LTP is associated with a reduction of paired-pulse facilitation, suggesting that presynaptic modification may be involved. Furthermore, we found that Sp-cAMPS induced LTD in slices pretreated with picrotoxin, a gamma-aminobutyric acid type A (GABA(A)) receptor antagonist. This form of LTD depends on protein synthesis and protein phosphatase(s) and is accompanied by an increased ratio of failed synaptic transmission. These results suggest that GABA(A) receptors can modulate the effect of cAMP on synaptic transmission and thus determine the direction of synaptic plasticity.

A directed search for quantitative trait loci on chromosomes 4 and 7 in pigs.

Improvements in the porcine genetic map and availability of resource families to study performance traits in pigs have made it possible to re-examine previous findings that linked certain traits to genes or chromosomal regions. Previous studies suggested that chromosomes 4 and 7 may be associated with growth and performance traits. To confirm these previous results, an interval mapping-regression approach was used to determine whether quantitative trait loci (QTL) exist in the Iowa State University reference/resource families. Traits measured were birth weight; body weight at 21 d; weaning weight (weight at 42 d); average daily gain; backfat at the first, 10th, lumbar, and last ribs and average backfat thickness; loin eye area; meat color; marbling; and firmness. The total number of F2 pigs used ranged from 241 to 330 and came from five Chinese x American resource families. Five markers (S0001, SW871, S0175, S0214, and SW445) were genotyped and mapped on chromosome 4, and so were 10 markers (S0064, tumor necrosis factor alpha [TNFalpha], S0102, S0078, S0158, S0066, SW304, SW1083, S0101, and S0212) on chromosome 7. Data were analyzed for each family (breed cross) separately and were also pooled. Experiment-wise thresholds were used to determine significance. Suggestive evidence of QTL on chromosomes 4 and 7 was observed for several traits in pooled and individual family analyses. Suggestive evidence of a QTL with a relatively large effect for average daily gain was detected on chromosome 4 in the pooled analysis. Significant (P < .05) evidence for QTL was seen on chromosome 7 for 10th-rib, last-rib, and average backfat thickness in the pooled data set in a region of the chromosome that was near TNFalpha. These results verify in part that chromosomes 4 and 7 contain QTL for growth and carcass traits.