ObjectiveExisting artificial vision devices can be divided into two types: implanted devices and extracorporeal devices, both of which have some disadvantages. The former requires surgical implantation, which may lead to irreversible trauma, while the latter has some defects such as relatively simple instructions, limited application scenarios and relying too much on the judgment of artificial intelligence (AI) to provide enough security. Here we propose a system that has voice interaction and can convert surrounding environment information into tactile commands on head and neck. Compared with existing extracorporeal devices, our device can provide a larger capacity of information and has advantages such as lower cost, lower risk, suitable for a variety of life and work scenarios. MethodsWith the latest remote wireless communication and chip technologies, microelectronic devices, cameras and sensors worn by the user, as well as the huge database and computing power in the cloud, the backend staff can get a full insight into the scenario, environmental parameters and status of the user remotely (for example, across the city) in real time. In the meanwhile, by comparing the cloud database and in-memory database and with the help of AI-assisted recognition and manual analysis, they can quickly develop the most reasonable action plan and send instructions to the user. In addition, the backend staff can provide humanistic care and emotional sustenance through voice dialogs. ResultsThis study originally proposes the concept of “remote virtual companion” and demonstrates the related hardware and software as well as test results. The system can not only achieve basic guide functions, for example, helping a person with visual impairment to shop in supermarkets, find seats at cafes, walk on the streets, construct complex puzzles, and play cards, but also can meet the demand for fast-paced daily tasks such as cycling. ConclusionExperimental results show that this “remote virtual companion” is applicable for various scenarios and demands. It can help blind people with their travels, shopping and entertainment, or accompany the elderlies with their trips, wilderness explorations, and travels.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective To explore the correlation between diabetic retinopathy(DR)and five circuits and six qi of birthdate.Methods A questionnaire survey was carried out.The general clinical data and the birthdate five-circuit and six-qi data were collected from 1 227 patients with diabetes mellitus(DM)who were treated in clinic or hospitalized in the First Affiliated Hospital of Guangzhou University of Chinese Medicine and the Guangdong Second Traditional Chinese Medicine Hospital from May 22,2019 to September 13,2021.Univariate analysis and multivariate logistic regression analysis were performed to explore the correlation of DR with the general clinical data and the birthdate five-circuit and six-qi data.Results(1)The analysis of the general clinial data showed that DR patients had higher levels of uric acid(UA),serum creatinine(Scr)and urinary albumin-to-creatinine ratio(UACR)than the patients with simple DM,and the differences were statistically significant(P＜0.05 or P＜0.01).(2)The analysis of the birthdate five-circuit and six-qi data showed that DR patients were usually born in the year of earth phase with the dominant qi being yangming dry gold or taiyin damp earth,and with the guest qi being taiyin damp earth.Compared with the simple DM group,the proportion of sitian-zaiquan semiannual circuit qi being shaoyang ministerial fire-jueyin wind wood in the DR group was significantly increased,and the proportion of sitian-zaiquan semiannual circuit qi being shaoyin monarch fire-yangming dry gold was significantly decreased,the differences being statistically significant(P＜0.05 or P＜0.01).(3)The results of multivariate logistic regression analysis showed that the sitian-zaiquan semiannual circuit qi being shaoyin monarch fire-yangming dry gold in DM patients was the independent protective factor for DR,and Scr and UACR were the independent risk factors for DR,with statistically significant differences(P＜0.05 or P＜0.01).Conclusion The features of five circuits and six qi of birthdate in DM patients are correlated with the complication of DR to some extend;the DR patients are usually have the birthdate five circuits characterized by wood,earth and gold.

Gut microbiome and their metabolites are closely related to human diseases, which influence the development of diseases by interacting with receptors. G protein-coupled receptor (GPCR) is a receptor superfamily that exists on the surface of cell membrane, which is involved in a wide range of human physiological activities. GPCR is currently considered as important drug targets. Traditional Chinese medicines (TCM) are characterized by multi-components, multi-targets, and multi-pathways. More and more studies have demonstrated that TCM can ultimately intervene in diseases by modulating gut microbiome and their metabolites, affecting their interactions with GPCR. This review discusses the status of gut microbiome and human diseases, the interactions of gut microbiome and their metabolites with GPCR, and the status of GPCR drug development. Based on the above contents, a new model of "TCM-gut microbiome panel-GPCR-disease" is proposed. The interactions between active ingredients of TCM, gut microbiome panel, and GPCR and their effects on disease are elucidated through multi-omics techniques. This review will provide new ideas for analyzing the pharmacological mechanism of TCM efficacy and searching for new targets of TCM.

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

The epidemic of COVID-19 has brought great challenges to the global public health prevention and control system combined with clinical diagnosis and treatment system, and it makes the development of effective antiviral drugs an important task in current pharmaceutical research. Traditional Chinese medicine (TCM) has played an important role in the prevention and control of COVID-19. Due to its numerous chemical components and various structural types, TCM becomes a natural library for searching for lead compounds against SARS-CoV-2. In this study, a novel dual-target surface plasmon resonance (SPR) biosensor was developed for S protein receptor binding domain (SRBD) and angiotensin converting enzyme 2 (ACE2) which are two key proteins in the process of SARS-CoV-2 invading cells according to characteristics of synergistic effects of multiple components and comprehensive regulation of multiple targets of TCM. The SPR biosensor was applied to screen and identify active components from six TCMs, and daidzin from Puerariae Lobatae Radix was identified to bind with SRBD and ACE2. The affinity constant (K_D) of daidzin and ACE2 was 5.18 μmol·L^-1 through the SPR affinity assay. Competitive ELISA assay showed that daidzin could inhibit the binding of SRBD and ACE2, and the inhibition rate of daidzin (20 μmol·L^-1) was 38.6%. Molecular docking experiments further confirmed that daidzin had the best binding near the binding region of SRBD-ACE2 complex. This study shows that the dual-target SPR screening system is accurate and efficient, and is particularly suitable for screening of complex drug systems and effective substances study of TCM. It provides a material basis for exploring the mechanism of TCM active constituents against SARS-CoV-2, and provides a source of lead compounds for the development of anti-SARS-CoV-2 drugs.

To explore the digital manufacturing process of distal extension removable partial denture. From November 2021 to December 2022, 12 patients (7 males and 5 females) with free-ending situation were selected from the Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University. Three-dimensional model of the relationship between alveolar ridge and jaw position was obtained by intraoral scanning technique. After routine design, manufacturing and try-in of metal framework for removable partial denture, the metal framework was located in the mouth and scanned again to obtain the composite model of dentition, alveolar ridge and metal framework. The free-end modified model is obtained by merging the digital model of free-end alveolar ridge with the virtual model with the metal framework. The three-dimensional model of artificial dentition, and base plate was designed on the free-end modified model, and the resin model were made by digital milling technology. The removable partial denture was made by accurately positioning the artificial dentition and base plate, bonding metal framework with injection resin, grinding and polishing the artificial dentition and resin base. Compared with the design data after clinical trial, the results showed that there was an error of 0.4-1.0 mm and an error of 0.03-0.10 mm in the connection between the resin base of artificial dentition and the connecting rod of the in-place bolt and the connection between artificial dentition and resin base. After denturen delivery, only 2 patients needed grinding adjustment in follow-up visit due to tenderness, and the rest patients did not find any discomfort. The digital fabrication process of removable partial denture used in this study can basically solve the problems of digital fabrication of free-end modified model and assembly of artificial dentition with resin base and metal framework.

Objective To investigate the effect of silencing E6-associated protein(E6AP)on the level of p53 protein in human papilloma virus(HPV)negative cervical cancer cells(C33A cells).Methods The siRNA sequence silencing E6AP(siE6AP)and silencing control disordered siRNA sequence(siControl)were transfected into C33A cells with the mediation of LipofectamineTM2000 transfection reagent respectively.The silencing effect of siRNA on E6AP and the expression of p53and cleaved-caspase-3 proteins were detected by Western blot.Results The levels of E6AP protein in C33A cells of siE6AP group were significantly lower(t =-4.597,P<0.05),while the levels of p53 and cleaved-caspase-3 proteins were significantly higher than those of siControl group(t = 4.533 and 7.099 respectively,each P<0.05).Conclusion Silencing of E6AP significantly increased the expression of p53 protein in C33A cells,indicating that silencing of E6AP may restore the activity and function of p53 protein in C33A cells.

BACKGROUND: Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown. METHODS: In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot. RESULTS: The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC. CONCLUSIONS These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.

Objective:To observe the clinical and multimodal imaging features of eyes with acute macular neuroretinopathy (AMN) associated with the coronavirus disease 2019 (COVID-19).Methods:A retrospective study. From December 20, 2022 to January 17, 2023, a total of 29 patients (58 eyes) with COVID-19-associated AMN admitted to Department of Ophthalmology of Eye and ENT Hospital, Shanghai Medical College were included in the study. All the affected eyes underwent the best corrected visual acuity, color fundus photography, infrared fundus photography (IR), short-wavelength autofluorescence (SW-AF), near-infrared autofluorescence (NIL-AF), optical coherence tomography (OCT), and OCT angiography (OCTA). All patients were administered microcirculation-improving oral medication with 12 cases receiving adjunctive low-dose corticosteroid therapy. Follow-ups were conducted 1 to 3 months after the initial diagnosis, with a total of 19 cases (38 eyes) completing the one-month follow-up.Results:Out of the 29 cases, there were 9 males (18 eyes) and 20 females (40 eyes), all of whom experienced bilateral eye involvement. The age of the patients ranged from 12 to 47 years, with an average age of (29.9±9.5) years. The time from the onset of fever to the appearance of ocular symptoms was (2.52±2.01) days. Among the 58 affected eyes, there were 5 cases with retinal cotton wool spots, 2 cases with optic disc edema, and 1 case with parafoveal branch retinal vein occlusion. All affected eyes exhibited deep reddish-brown macular dark spots. IR revealed wedge-shaped, wedge-like, or "petaloid-like" dark areas involving the fovea and parafovea. SW-AF examination showed no obvious abnormality in 39 eyes. Weak autofluorescence dark area were consistent with IR in 19 eyes. NIR-AF examination showed spot-like or flaky self-fluorescent dark areas. OCT examination showed strong reflex lesions spreading vertically upward from the retinal pigment epithelium (RPE) layer in the macular area in the acute stage, showing typical "bean seedling" sign. OCTA revealed reduced blood flow density in the deep capillary plexus (DCP) of 50 eyes. Enface OCT displayed lesion areas that corresponded to the dark areas seen in IR. One month after the initial diagnosis, the condition improved in 18 eyes (47.4%, 18/38). Among the 5 eyes with cotton wool spots, regression of these spots was accompanied by loss of nerve fiber layer in 4 eyes. In cases with optic disc edema, the edema subsided. The "bean sprout" sign disappeared in all affected eyes, and the lesions became localized. The ellipsoid zone and/or interdigitation zone in the lesion areas were discontinuous.Conclusions:COVID-19-related AMN is characterized by distinctive features. IR fundus reveals wedge-shaped, wedge-like, or petaloid dark areas involving the fovea and parafovea. OCT displays strongly reflective lesions with vertical spread above the RPE. OCTA shows reduced blood flow density in the DCP of the retina.