Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

Purpose To investigate the value of MYB and Notch1 immunohistochemical staining in the differential diagno-sis of classic adenoid cystic carcinoma of the breast(C-AdCC)and solid-basaloid adenoid cystic carcinoma of the breast(SB-AdCC).Methods MYB and Notch1 immunohistochemical staining were performed in 20 cases of C-AdCC,6 cases of SB-AdCC and 65 cases of other breast lesions in the archives of pa-thology department.26 cases of AdCC were detected by FISH,and 6 cases of SB-AdCC were detected by NGS.Results MYB immunohistochemical staining showed that C-AdCC(20/20)was moderately or strongly positive,while SB-AdCC(4/6)was mod-erately or strongly positive.Collagenous spherulosis(5/5)showed focal or diffuse weak positivity;Malignant adenomyoepi-thelioma(3/3)was focally moderately or strongly positive;8 matrix-producing carcinomas and 9 secretory carcinomas and 40 non-specific triple-negative breast cancers were negative.Immu-nohistochemistry of Notch1 showed diffuse moderate positive for SB-AdCC(3/6)and negative for C-AdCC(20/20).3 cases of malignant adenomyoepithelioma,5 cases of collagenous spherulo-sis,8 cases of matrix-producing carcinoma,9 cases of secretory carcinoma and 40 cases of non-specific triple-negative breast cancer were negative.FISH showed MYB gene disruption in C-AdCC(12/19)and NGS showed SB-AdCC(3/6)Notch1 muta-tion.Conclusion Moderately or strongly diffuse expression of MYB and Notch1 by immunohistochemistry can assist in the dif-ferentiation of C-AdCC from SB-AdCC,and it can be further clarified by molecular detection when it is difficult to distinguish malignant adenomyoepithelioma.

Objective To establish a whole-body dynamic inhalation exposure system for toxicological studies on highly toxic chemicals, and to evaluate the safety and applicability of the system.Methods The safety and standardization of the laboratory were ensured after positive and negative pressure protection and airtight protection were finished.By modifying and optimizing the key technological units of the exposure chamber, the relationships between aerosol concentrations in the chamber and the push rate, exposure time and different monitoring points were investigated.Results and Conclusion Multi-protection was achieved, including the independent exposure chamber, negative pressure experiment and positive pressure protection under working conditions.The laboratory meets the demands of safety and specifications.The exposure aerosol concentrations in the chamber are uniform, stable and controllable while the air is dynamically flowing.The whole-body dynamic inhalation exposure system can meet the need for toxicological studies on highly toxic chemicals.

Three-electrode testing method was used to investigate the effect of temperature on electrode impedance, and the pH shifts in saline solution resulting from the electrical stimulation were also determined. Experiments in PBS (phosphate buffered solution) solution showed that the electrode impedance was almost invariable at the human body temperature range (35 degrees C-40 degrees C). And the experiments in unbuffered saline solution showed that pH shifts decreased from 0.03 to 0.005 when the frequency of biphasic charged-balanced pulses increased from 1 Hz to 100 Hz. Even stimulated by monophasic pulses (frequency is 15 Hz, amplitude is 50 microA), the stimulus-induced pH shift of electrode only varies 0.15 (anodic pulse current increased 0.15 and cathodic pulse current decreased 0.15).
Electrochemistry ; Eye, Artificial ; Materials Testing ; Microelectrodes ; Prostheses and Implants

The paper proposed a new method to design and fabricate a flexible neural microelectrode arrays (MEA) for retinal prosthesis, the ion-beam technology was introduced to decrease the width of conductive wires and the distances between wires, a high density MEA (120 microelectrodes with a matrix of 10 x 12) was fabricated on a single layer of polymer from this. The MEA was proved to possess a fine electrochemical property. In vitro test, the average impedance of MEA on 1 kHz was 16 k omega +/- 2 k omega and the average phase difference was -85 degrees +/-30 degrees.
Micro-Electrical-Mechanical Systems ; Microelectrodes ; Prosthesis Design ; Visual Prosthesis

The paper proposed a new method to design and fabricate a flexible neural microelectrode arrays(MEA) for retinal prosthesis, the Ion-Beam technology was intruduced to decrease the width of conductive wires and the distances between wires, a high density MEA(120 microelectrodes with a matrix of 10×12) was fabricated on a single layer of polymer from this. The MEA was proved to possess a fine electrochemical property. In vitro test, the average impedance of MEA on 1 kHz was 16 kΩ±2 kΩand the average phase difference was-85o±3o.

Implantable Neurostimulators ; Micro-Electrical-Mechanical Systems ; Microelectrodes

This paper proposed a new design on multi-layer flexible microelectrode arrays (MEA) of epiretinal prosthesis, as well as a set of automatic testing system to evaluate and analyze the MEA. Experiment results showed that the MEA was satisfying on both flexibility and impedance and the multi-layer design didn't introduce significant differences.
Microarray Analysis ; Microelectrodes ; Prostheses and Implants ; Prosthesis Design ; Prosthesis Implantation ; instrumentation ; Retina

This review paper presents the current research progress, challenges and future development on microelectrode array of retinal prosthesis, including epi-retinal and sub-retinal implants.
Microelectrodes ; Prosthesis Design ; Visual Prosthesis

Objective To investigate the electrophysiological and morphological properties of the single ventral neuron in the medial geniculate body (MGBv) in rats. Methods The basic electrophysiological properties and action potentials at different levels of membrane potentials were recorded by whole cell patch clamp technique. Morphological properties of ventral neurons in the medial geniculate body were studied by biocytin staining. Results Nissl and biocytin stainings indicated that MGBv neurons were composed of oval shaped cell bodies, and the dendritic branches were tufted. In current clamp recordings, the resting membrane potential was (-54.92?10.85) mV, the input resistance (945.67?507.80) M?, the membrane capacitance (5.37?1.98) pF, and the time constant (2 109 87 ?2 496 01) ?s. Action potentials under different current inputs were various. Spontaneous discharge could be recorded by voltage clamp and current clamp. Conclusion MGBv dendritic trees are fairly dense with bushy tufted neurons and variety of action potentials under different current inputs in ventral neurons of the medial geniculate body. Spontaneous activities recorded by current clamp are similar to the action potential, which may be the spontaneous action potential due to the exceeding of membrane potential over liminal value.