HER2-positive advanced biliary tract cancer responds to second-line pyrotinib therapy: a case report.

Biliary tract cancers are solid tumors with poor prognosis and over 70% of patients present in advanced stages. The efficacy of second-line treatment for patients who progressed on GC chemotherapy is limited. Median OS of these patients is less than 1 year with palliative treatment. Despite the success of anti-HER2 therapy in HER2-positive breast cancer, the targeted therapy of HER2 mutations in BTCs is still being explored. This case report is the first report suggesting a 15-month PFS and partial response of pyrotinib in HER2-positive BTC. We report a 64-year-old female with HER2-positive biliary tract cancer. She was diagnosed with AJCC clinical stage IV (cT3N1M1) intrahepatic biliary tract cancer and got PD after 3 cycles of systemic chemotherapy of gemcitabine plus cisplatin. Due to the HER2-positive signature, pyrotinib (400 mg daily in 21-day cycles), an oral irreversible pan-ErbB TKI was prescribed in September 2021, with her informed consent. The tumor shrank significantly after this treatment and imaging assessments conducted on 24 September 2022 showed PR. Until the writing of the case draft, the patient had achieved 15 months of PFS. The present case suggests that Pyrotinib might be a potential effective treatment for HER2-positive advanced BTC.

Combination anlotinib and toripalimab for an advanced biliary tract cancer patient with high Eastern Cooperative Oncology Group performance status: a case report.

Up to 80% of biliary tract cancer (BTC) patients relapse within 3 years after surgery and the efficacy of second-line treatment remains dismal for patients who progressed on gemcitabine and cisplatin chemotherapy. Median overall survival of patients with palliative chemotherapy is less than 1 year. The feasibility and safety of targeted therapies plus immunotherapies remain scanty currently, and patients with recurrent or advanced BTCs often experience a rapid decline in Eastern Cooperative Oncology Group (ECOG) performance status. This case report is the first report suggesting a 17-month progression-free survival (PFS), partial response, and another 11-month PFS after progressive disease of anlotinib plus toripalimab in advanced BTC with high ECOG performance status. We report a 67-year-old Chinese male with BTC. He was observed with progressive disease after surgical resection, adjuvant chemotherapy, palliative chemotherapy, and diagnosed with American Joint Committee on Cancer clinical stage IV (cT3N0M1) extrahepatic BTC. The patient experienced a rapid decline in performance status, and he received oral anlotinib and toripalimab with informed consent. MRI scans showed partial response on 22 June 2022. PET-CT showed that tumor activity has been inhibited on 8 March 2023. He achieved 17 months of PFS. Although the patient developed solitary lung metastasis, he had a continuous survival benefit from treatment of anlotinib plus toripalimab after lung radiotherapy. Until the writing of the case draft, he had achieved another 11 months of PFS. The present case suggests that anlotinib plus toripalimab might be a potential effective treatment for advanced BTCs patients with high ECOG performance status.

Trace photoacoustic SO2 gas sensor in SF6 utilizing a 266†nm UV laser and an acousto-optic power stabilizer.

A sulfur dioxide (SO2) gas sensor based on the photoacoustic spectroscopy technology in a sulfur hexafluoride (SF6) gas matrix was demonstrated for SF6 decomposition components monitoring in the power system. A passive Q-switching laser diode (LD) pumped all-solid-state 266 nm deep-ultraviolet laser was exploited as the laser excitation source. The photoacoustic signal amplitude is linear related to the incident optical power, whereas, a random laser power jitter is inevitable since the immature laser manufacturing technology in UV spectral region. A compact laser power stabilization system was developed for better sensor performance by adopting a photodetector, a custom-made internal closed-loop feedback controller and a Bragg acousto-optic modulator (AOM). The out-power stability of 0.04% was achieved even though the original power stability was 0.41% for ∼ 2 hours. A differential two-resonator photoacoustic cell (PAC) was designed for weak photoacoustic signal detection. The special physical constants of SF6 buffer gas induced a high-Q factor of 85. A detection limit of 140 ppbv was obtained after the optimization, which corresponds to a normalized noise equivalent absorption coefficient of 3.2 × 10-9 cm-1WHz-1/2.

Three-electrode germanium-on-silicon avalanche photodiode array.

In this Letter, we report a bridge-connected three-electrode germanium-on-silicon (Ge-on-Si) avalanche photodiode (APD) array compatible with the complementary metal-oxide semiconductor (CMOS) process. In addition to the two electrodes on the Si substrate, a third electrode is designed for Ge. A single three-electrode APD was tested and analyzed. By applying a positive voltage on the Ge electrode, the dark current of the device can be reduced, and yet the response of the device can be increased. Under a dark current of 100 nA, as the voltage on Ge increases from 0 V to 15 V, the light responsivity is increased from 0.6 A/W to 1.17 A/W. We report, for the first time to the best of our knowledge, the near-infrared imaging properties of an array of three-electrode Ge-on-Si APDs. Experiments show that the device can be used for LiDAR imaging and low-light detection.

Unidirectional large-scale waveguide grating with uniform radiation for optical phased array.

Two novel waveguide gratings for optical phased array transmitters are investigated. By offsetting the grating structures along the waveguide on the upper and lower surfaces of the silicon nitride (Si3N4) waveguide, the dual-level chain and dual-level fishbone structures can achieve 95% of unidirectional radiation with a single Si3N4 layer by design. With apodized perturbation along the gratings, both structures can achieve uniform radiation without compromising the unidirectional radiation performance. In experiment, both demonstrate ∼ 80-90% unidirectionality. With further analysis, it is found that the dual-level fishbone structure is more feasible and robust to process variations in uniform radiation.

Surface illuminated interdigitated Ge-on-Si photodetector with high responsivity.

To address the problem of traditional surface illuminated detectors being of low responsivity, this work proposes a large-size interdigitated "finger-type" germanium-on-silicon (Ge-on-Si) photodetector (PD) based on the surface illumination approach. For 1550 nm light with a surface incident power of -20 dBm at room temperature, the best responsivity of the PD achieved is ∼0.64 A/W at 0.5 V. At the same time, the optimal bandwidth reaches 1.537 MHz with 3.5 V applied voltage. In order to suppress the dark current induced noise, a Ge-on-Si avalanche photodiode (APD) with the interdigitated structure is designed. The avalanche voltage is designed ∼13.3 V at room temperature, and the dark current density in linear region is at mA/cm2 order. We believe this type of device can be applied in weak light detection condition.

Wavelength-modulated photoacoustic spectroscopic instrumentation system for multiple greenhouse gas detection and in-field application in the Qinling mountainous region of China.

We present a sensitive and compact quantum cascade laser-based photoacoustic greenhouse gas sensor for the detection of CO2, CH4 and CO and discuss its applicability toward on-line real-time trace greenhouse gas analysis. Differential photoacoustic resonators with different dimensions were used and optimized to balance sensitivity with signal saturation. The effects of ambient parameters, gas flow rate, pressure and humidity on the photoacoustic signal and the spectral cross-interference were investigated. Thanks to the combined operation of in-house designed laser control and lock-in amplifier, the gas detection sensitivities achieved were 5.6 ppb for CH4, 0.8 ppb for CO and 17.2 ppb for CO2, signal averaging time 1 s and an excellent dynamic range beyond 6 orders of magnitude. A continuous outdoor five-day test was performed in an observation station in China's Qinling National Botanical Garden (E longitude 108°29', N latitude 33°43') which demonstrated the stability and reliability of the greenhouse gas sensor.

On-chip generation of Bessel-Gaussian beam via concentrically distributed grating arrays for long-range sensing.

Bessel beam featured with self-healing is essential to the optical sensing applications in the obstacle scattering environment. Integrated on-chip generation of the Bessel beam outperforms the conventional structure by small size, robustness, and alignment-free scheme. However, the maximum propagation distance (Zmax) provided by the existing approaches cannot support long-range sensing, and thus, it restricts its potential applications. In this work, we propose an integrated silicon photonic chip with unique structures featured with concentrically distributed grating arrays to generate the Bessel-Gaussian beam with a long propagation distance. The spot with the Bessel function profile is measured at 10.24 m without optical lenses, and the photonic chip's operation wavelength can be continuously performed from 1500 to 1630 nm. To demonstrate the functionality of the generated Bessel-Gaussian beam, we also experimentally measure the rotation speeds of a spinning object via the rotational Doppler Effect and the distance through the phase laser ranging principle. The maximum error of the rotation speed in this experiment is measured to be 0.05%, indicating the minimum error in the current reports. By the compact size, low cost, and mass production potential of the integrated process, our approach is promising to readily enable the Bessel-Gaussian beam in widespread optical communication and micro-manipulation applications.

Even sampling designs generation by charges repulsion simulation.

Evenly distributed sampling design is generally considered as an efficient sampling design. It is widely used in sampling for the environmental survey. In this paper, we present a novel method for generating N evenly distributed samples within a given irregular polygon via simulating the movements of some ideal homogeneous point charges. Initially, charges are randomly put into the sampling region; then, they are freed and held orderly; and after enough runs, the charges will finally reach a stable state with all of them having a zero resultant force and velocity; and so they distribute evenly within the region. Their layout can thus be considered as an evenly distributed sampling design. The main advantages of this method are: (1) it is easy to understand and implement; (2) it is efficient in both running and generating better designs. Analysis and experimental results indicate that this method is an efficient and robust method for generating even sampling designs for 2D polygonal sampling region.

Clone-derived human AF-amniotic fluid stem cells are capable of skeletal myogenic differentiation in vitro and in vivo.

Stem cell-based therapy may be the most promising method to cure skeletal muscle degenerative diseases such as Duchenne muscular dystrophy (DMD) and trauma in the future. Human amniotic fluid is enriched with early-stage stem cells from developing fetuses and these cells have cardiomyogenic potential both in vitro and in vivo. In the present study, we investigated the characteristics of human amniotic fluid-derived AF-type stem (HAF-AFS) cells by flow cytometry, immunofluorescence staining, reverse-transcription polymerase chain reaction, and osteogenic and adipogenic differentiation analysis. After confirming the stemness of HAF-AFS cells, we tested whether HAF-AFS cells could differentiate into skeletal myogenic cells in vitro and incorporate into regenerating skeletal muscle in vivo. By temporary exposure to the DNA demethylation agent 5-aza-2'-deoxycytidine (5-Aza dC) or co-cultured with C2C12 myoblasts, HAF-AFS cells differentiated into skeletal myogenic cells, expressing skeletal myogenic cell-specific markers such as Desmin, Troponin I (Tn I) and α-Actinin. Four weeks after transplantation into cardiotoxin-injured and X-ray-irradiated tibialis anterior (TA) muscles of NOD/SCID mice, HAF-AFS cells survived, differentiated into myogenic precursor cells and fused with host myofibres. The findings that HAF-AFS cells differentiate into myogenic cells in vitro and incorporate in skeletal muscle regeneration in vivo hold the promise of HAF-AFS cell-based therapy for skeletal muscle degenerative diseases.

Tissue engineering of bladder using vascular endothelial growth factor gene-modified endothelial progenitor cells.

PURPOSE: This study assessed the use of vascular endothelial growth factor (VEGF) gene-modified endothelial progenitor cells (EPCs) seeded onto bladder acellular matrix grafts (BAMGs), to enhance the blood supply in tissue-engineered bladders in a porcine model. METHODS: Autologous porcine peripheral EPCs were isolated, cultured, expanded, characterized, and modified with the VEGF gene using an adenovirus vector. The expression of VEGF was examined using reverse transcriptase polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA). VEGF gene modified EPCs were seeded onto BAMG and cultured for 3 days before implantation into pigs for bladder tissue engineering. A partial bladder cystectomy was performed in 12 pigs. The experimental group (6 pigs) received VEGF gene-modified EPC-seeded BAMG. The control group (6 pigs) received BAMG without seeded EPCs. The resulting tissue-engineered bladders were subject to a general and histological analysis. Microvessel density (MVD) was assessed using immunohistochemistry. RESULTS: The ex vivo transfection efficiency of EPCs was greater than 60%-70% when concentrated adenovirus was used. The genetically modified cells expressed both VEGF and green fluorescent protein (GFP). Scanning electron microscopy (SEM) and Masson's trichrome staining of cross sections of the cultured cells seeded to BAMG showed cell attachment and proliferation on the surface of the BAMG. Histological examination revealed bladder regeneration in a time-dependent fashion. Significant increases in MVD were observed in the experimental group, in comparison with the control group. CONCLUSIONS: VEGF-modified EPCs significantly enhanced neovascularization, compared with BAMG alone. These results indicate that EPCs, combined with VEGF gene therapy, may be a suitable approach for increasing blood supply in the tissue engineering of bladders. Thus, a useful strategy to achieve a tissue-engineered bladder is indicated.