[Clinical and molecular pathological features of bronchopulmonary large cell neuroendocrine carcinoma].

Objective: To investigate the clinical manifestations, imaging, pathological and molecular features of bronchopulmonary large-cell neuroendocrine carcinoma (LCNEC). Methods: The clinical data of 216 LCNEC patients in the First Affiliated Hospital of Zhengzhou University from 2011 to 2021 were analyzed retrospectively. The clinical manifestations, tumor location and size, characteristics of CT images, immunohistochemical and molecular pathological features were analyzed and compared with 115 cases of mixed small cell carcinoma (M-SCLC) diagnosed in the same period. Results: Among the 216 LCNEC patients, there were 190 males and 26 females, with a median age of 65 years. The first symptoms of the patients were mainly cough (106 cases, 49.1%) and bloody sputum (48 cases, 22.2%). The median tumor length were 4.7cm, including 55 cases of nodular type (25.5%) and 161 cases of mass-forming type (74.5%). CT imaging results showed that LCNEC lesions had soft tissue density, and the proportion of slight enhancement lesions was significantly lower than that in M-SCLC group (52.3% vs 74.8%, P<0.001). In contrast, the proportion of necrosis (87.0% vs 58.3%, P<0.001) and calcification (26.9% vs 2.6%, P<0.001) in LCNEC patients was significantly higher than that in M-SCLC group. Immunohistochemical results showed that the positive rate of CK in LCNEC was significantly higher than that in M-SCLC (99.0 % vs 90.5%, P<0.05), while the positive rate of TTF-1 was significantly lower than that in M-SCLC (51.6% vs 67.0%, P<0.05). In LCNEC group, the proportion of patients with Ki-67 positive index between 50% and 80% was significantly higher than that of M-SCLC (41.2% vs 25.2%), while the proportion between 80% and 100% was lower than that of M-SCLC (51.9% vs 72.2%). There was no significant difference in the positive rates of CD56 (91.7% vs 94.6%, P=0.336), Syn (83.8% vs 84.7%, P=0.838) and CgA (54.8% vs 50.0%, P=0.632) in both tumor types. Molecular pathology results showed that frequent mutatios were TP53 (54.5%), RB1 (36.4%), KEAP1 (18.2%), MYC(18.2%), and PTEN (14.3%), and the rate of tumor mutation burden which is more than 25 mutation/Mb was 27.3%. Conclusions: LCNEC lacks specific clinical manifestations. CT imaging is powerful in distinguishing LCNEC from M-SCLC. LCNEC contains a specific mutation spectrum. Pathology combined with immunohistochemical staining is still the gold standard for LCNEC diagnosis, and the differentiation from M-SCLC mainly depends on cell size and nuclear chromatin pattern with light microscopy.

Design of an electric-driven nonvolatile low-energy-consumption phase change optical switch.

Traditional optical switches relying on the weak, volatile thermo-optic or electro-optic effects of Si or SiN waveguides show a high consumption and large footprint. In this paper, we reported an electric-driven phase change optical switch consisting of a Si waveguide, Ge2Sb2Te5(GST) thin film and graphene heater suitable for large-scale integration and high-speed switching. The reversible transition between the amorphous and crystalline states was achieved by applying two different voltage pulses of 1.4 V (SET) and 4 V (RESET). The optical performance of the proposed switch showed a high extinction ration of 44-46 dB in a wide spectral range (1525-1575 nm), an effective index variation of Δneff = 0.49 and a mode loss variation of Δα = 15 dBµm-1at the wavelength of 1550 nm. In thermal simulations, thanks to the ultra-high thermal conductivity of graphene, the proposed switch showed that the consumption for the SET process was only 3.528 pJ with a 1.4 V pulse of 5 ns, while a 4 V pulse of 1.5 ns was needed for RESET process with a consumption of 1.05 nJ. Our work is helpful to analyze the thermal-conduction phase transition process of on-chip phase change optical switches, and the design of the low-energy-consumption switch is conducive to the integrated application of photonic chips.