Light on Alzheimer's disease: from basic insights to preclinical studies.

Alzheimer's disease (AD), referring to a gradual deterioration in cognitive function, including memory loss and impaired thinking skills, has emerged as a substantial worldwide challenge with profound social and economic implications. As the prevalence of AD continues to rise and the population ages, there is an imperative demand for innovative imaging techniques to help improve our understanding of these complex conditions. Photoacoustic (PA) imaging forms a hybrid imaging modality by integrating the high-contrast of optical imaging and deep-penetration of ultrasound imaging. PA imaging enables the visualization and characterization of tissue structures and multifunctional information at high resolution and, has demonstrated promising preliminary results in the study and diagnosis of AD. This review endeavors to offer a thorough overview of the current applications and potential of PA imaging on AD diagnosis and treatment. Firstly, the structural, functional, molecular parameter changes associated with AD-related brain imaging captured by PA imaging will be summarized, shaping the diagnostic standpoint of this review. Then, the therapeutic methods aimed at AD is discussed further. Lastly, the potential solutions and clinical applications to expand the extent of PA imaging into deeper AD scenarios is proposed. While certain aspects might not be fully covered, this mini-review provides valuable insights into AD diagnosis and treatment through the utilization of innovative tissue photothermal effects. We hope that it will spark further exploration in this field, fostering improved and earlier theranostics for AD.

Process quality, diagnosis quality, and patient satisfaction of primary care in Rural Western China: A study using standardized patients.

OBJECTIVES: Patient satisfaction is an essential indicator of the doctor-patient relationship. This study aimed to investigate the relationship between primary care quality and patient satisfaction for non-communicable diseases (NCDs) in rural western China. METHODS: The study utilized the standardized patients (SPs) approach to present typical symptoms of unstable angina and diabetes to rural healthcare providers. After the consultations, the SPs completed a satisfaction survey. Ordinary least squares and quantile regression were used to examine the association between quality of primary care and patient satisfaction. RESULTS: We examined 178 anonymous SPs visits. The results showed that higher process quality for angina SPs was correlated with stronger satisfaction for provider ability at a low quantile of ability satisfaction. For diabetes SPs, higher process quality increased overall satisfaction at a low quantile of overall satisfaction, whereas a correct diagnosis significantly contributed to communication satisfaction at a high quantile of communication satisfaction. CONCLUSIONS: The study found positive associations between process and diagnosis quality and SPs satisfaction. Notably, the influence of process quality was most significant among patients with lower satisfaction levels. PRACTICE IMPLICATIONS: Provider's process quality could be a key area of improving the satisfaction levels, especially for patients with lower levels of satisfaction.

Health Interventions May Have Divergent Impacts on Health and Economic Equity: A Case Study of the Community-Based Hypertension Improvement Project in Ghana.

BACKGROUND AND OBJECTIVE: Improving health and economic equity are key objectives in priority setting, particularly in low-income and middle-income countries. This study aims to assess the distributional impacts of the Community-based Hypertension Improvement Project (ComHIP) on health and economic outcomes across wealth quintiles in Ghana. METHODS: We developed a decision analytical model to simulate a 30 million cohort of Ghanaians aged 15-49 years. The study specified health outcomes as the prevention of stroke cases and averting deaths among those with hypertension. Furthermore, we explored economic impacts, including savings in out-of-pocket costs for stroke patients and government spending. Financial risk protection against catastrophic and impoverishing health expenditures was also examined. We assessed these outcomes across wealth quintiles, and the corresponding concentration indexes (CIXs) were determined. RESULTS: It was estimated that ComHIP could prevent 1450 stroke cases and 564 related deaths annually. Health benefits were observed to be more significant among the wealthier quintiles (CIX 0.217), mainly attributed to a higher occurrence of hypertension within these groups. ComHIP was also projected to result in an annual saving of USD 49,885 in individuals' out-of-pocket costs (CIX 0.262) and USD 37,578 in government spending (CIX 0.146). These savings correspond to the prevention of 335 catastrophic health expenditure cases (CIX - 0.239) and 11 impoverishing health expenditure cases (CIX - 0.600). CONCLUSIONS: While ComHIP provides greater health benefits to wealthier groups, it offers substantial financial risk protection for the less wealthy. This study highlights the importance of considering equity in both health and financial risk when making priority-setting decisions.

Free-moving-state microscopic imaging of cerebral oxygenation and hemodynamics with a photoacoustic fiberscope.

We report the development of a head-mounted photoacoustic fiberscope for cerebral imaging in a freely behaving mouse. The 4.5-gram imaging probe has a 9-µm lateral resolution and 0.2-Hz frame rate over a 1.2-mm wide area. The probe can continuously monitor cerebral oxygenation and hemodynamic responses at single-vessel resolution, showing significantly different cerebrovascular responses to external stimuli under anesthesia and in the freely moving state. For example, when subjected to high-concentration CO2 respiration, enhanced oxygenation to compensate for hypercapnia can be visualized due to cerebral regulation in the freely moving state. Comparative studies exhibit significantly weakened compensation capabilities in obese rodents. This new imaging modality can be used for investigating both normal and pathological cerebrovascular functions and shows great promise for studying cerebral activity, disorders and their treatments.

In vivo endoscopic ultrasound imaging with a rotational-scanning, all-optical ultrasound probe.

All-optical ultrasound manipulates ultrasound waves based on laser and photonics technologies, providing an alternative approach for pulse-echo ultrasound imaging. However, its endoscopic imaging capability is limited ex vivo by the multifiber connection between the endoscopic probe and the console. Here, we report on all-optical ultrasound for in vivo endoscopic imaging using a rotational-scanning probe that relies on a small laser sensor to detect echo ultrasound waves. The acoustically induced lasing frequency change is measured via heterodyne detection by beating the two orthogonally polarized laser modes, enabling a stable output of ultrasonic responses and immunity to low-frequency thermal and mechanical disturbances. We miniaturize its optical driving and signal interrogation unit and synchronously rotate it with the imaging probe. This specialized design leaves a single-fiber connection to the proximal end and allows fast rotational scanning of the probe. As a result, we used a flexible, miniature all-optical ultrasound probe for in vivo rectal imaging with a B-scan rate of 1 Hz and a pullback range of ∼7 cm. This can visualize the gastrointestinal and extraluminal structures of a small animal. This imaging modality offers an imaging depth of 2 cm at a central frequency of ∼20 MHz, showing promise for high-frequency ultrasound imaging applications in gastroenterology and cardiology.

Butyrate prevents the migration and invasion, and aerobic glycolysis in gastric cancer via inhibiting Wnt/ß-catenin/c-Myc signaling.

Gastric cancer (GC) remains a common cause of cancer death worldwide. Evidence has found that butyrate exhibited antitumor effects on GC cells. However, the mechanism by which butyrate regulate GC cell proliferation, migration, invasion, and aerobic glycolysis remains largely unknown. The proliferation, migration, and invasion of GC cells were tested by EdU staining, transwell assays. Additionally, protein expressions were determined by western blot assay. Next, glucose uptake, lactate production, and cellular ATP levels in GC cells were detected. Furthermore, the antitumor effects of butyrate in tumor-bearing nude mice were evaluated. We found, butyrate significantly prevented GC cell proliferation, migration, and invasion (p < .01). Additionally, butyrate markedly inhibited GC cell aerobic glycolysis, as shown by the reduced expressions of GLUT1, HK2, and LDHA (p < .01). Moreover, butyrate notably decreased nuclear ß-catenin and c-Myc levels in GC cells (p < .01). Remarkably, through activating Wnt/ß-catenin signaling with LiCl, the inhibitory effects of butyrate on the growth and aerobic glycolysis of GC cells were diminished (p < .01). Moreover, butyrate notably suppressed tumor volume and weight in GC cell xenograft nude mice in vivo (p < .01). Meanwhile, butyrate obviously reduced nuclear ß-catenin, c-Myc, GLUT1, HK2 and LDHA levels in tumor tissues in GC cell xenograft mice (p < .01). Collectively, butyrate could suppress the growth and aerobic glycolysis of GC cells in vitro and in vivo via downregulating wnt/ß-catenin/c-Myc signaling. These findings are likely to prove useful in better understanding the role of butyrate in GC.

Factors Influencing Adoption and Use of Telemedicine Services in Rural Areas of China: Mixed Methods Study.

BACKGROUND: The shortage of medical resources in rural China reflects the health inequity in resource-limited settings, whereas telemedicine could provide opportunities to fill this gap. However, evidence of patient acceptance of telemedicine services from low- and middle-income countries is still lacking. OBJECTIVE: We aimed to understand the profile of patient end-user telemedicine use and identify factors influencing telemedicine service use in rural China. METHODS: Our study followed a mixed methods approach, with a quantitative cross-sectional survey followed by in-depth semistructured interviews to describe telemedicine use and its associated factors among rural residents in Guangdong Province, China. In the quantitative analysis, explanatory variables included environmental and context factors, household-level factors, individual sociodemographic factors, access to digital health care, and health needs and demand factors. We conducted univariate and multivariate analyses using Firth logistic regression to examine the correlations of telemedicine uptake. A thematic approach was used, guided by the Social Cognitive Theory for the qualitative analysis. RESULTS: A total of 2101 households were recruited for the quantitative survey. With a mean age of 61.4 (SD 14.41) years, >70% (1364/2101, 72.94%) of the household respondents were male. Less than 1% (14/2101, 0.67%) of the respondents reported experience of using telemedicine. The quantitative results supported that villagers living with family members who had a fever in the past 2 weeks (adjusted odds ratio 6.96, 95% CI 2.20-21.98; P=.001) or having smartphones or computers (adjusted odds ratio 3.71, 95% CI 0.64-21.32; P=.14) had marginally higher telemedicine uptake, whereas the qualitative results endorse these findings. The results of qualitative interviews (n=27) also supplemented the potential barriers to telemedicine use from the lack of knowledge, trust, demand, low self-efficacy, and sufficient physical and social support. CONCLUSIONS: This study found extremely low use of telemedicine in rural China and identified potential factors affecting telemedicine uptake. The main barriers to telemedicine adoption among rural residents were found, including lack of knowledge, trust, demand as well as low self-efficacy, and insufficient physical and social support. Our study also suggests strategies to facilitate telemedicine engagement in low-resource settings: improving digital literacy and self-efficacy, building trust, and strengthening telemedicine infrastructure support.

Optical-resolution functional gastrointestinal photoacoustic endoscopy based on optical heterodyne detection of ultrasound.

Photoacoustic endoscopy shows promise in the detection of gastrointestinal cancer, inflammation, and other lesions. High-resolution endoscopic imaging of the hemodynamic response necessitates a small-sized, high-sensitivity ultrasound sensor. Here, we utilize a laser ultrasound sensor to develop a miniaturized, optical-resolution photoacoustic endoscope. The sensor can boost the acoustic response by a gain factor of ωo/Ω (the frequency ratio of the signal light and measured ultrasound) by measuring the acoustically induced optical phase change. As a result, we achieve a noise-equivalent pressure density (NEPD) below 1.5 mPa·Hz-1/2 over the measured range of 5 to 25 MHz. The heterodyne phase detection using dual-frequency laser beams of the sensor can offer resistance to thermal drift and vibrational perturbations. The endoscope is used to in vivo image a rat rectum and visualize the oxygen saturation changes during acute inflammation, which can hardly be observed with other imaging modalities.

Evaluation of a village-based digital health kiosks program: A protocol for a cluster randomized clinical trial.

Background: To address disparities in healthcare quality and access between rural and urban areas in China, reforms emphasize strengthening primary care and digital health utilization. Yet, evidence on digital health approaches in rural areas is lacking. Objective: This study will evaluate the effectiveness of Guangdong Second Provincial General Hospital's Digital Health Kiosk program, which uses the Dingbei telemedicine platform to connect rural clinicians to physicians in upper-level health facilities and provide access to artificial intelligence-enabled diagnostic support. We hypothesize that our interventions will increase healthcare utilization and patient satisfaction, decrease out-of-pocket costs, and improve health outcomes. Methods: This cluster randomized control trial will enroll clinics according to a partial factorial design. Clinics will be randomized to either a control arm with clinician medical training, a second arm additionally receiving Dingbei telemedicine training, or a third arm with monetary incentives for patient visits conducted through Dingbei plus all prior interventions. Clinics in the second and third arm will then be orthogonally randomized to a social marketing arm that targets villager awareness of the kiosk program. We will use surveys and Dingbei administrative data to evaluate clinic utilization, revenue, and clinician competency, as well as patient satisfaction and expenses. Results: We have received ethical approval from Guangdong Second Provincial General Hospital (IRB approval number: GD2H-KY IRB-AF-SC.07-01.1), Peking University (IRB00001052-21007), and the University of North Carolina at Chapel Hill (323385). Study enrollment began April 2022. Conclusions: This study has the potential to inform future telemedicine approaches and assess telemedicine as a method to address disparities in healthcare access.Trial registration number: ChiCTR2100053872.

Terahertz wave modulation properties of graphene with different excitation laser power.

The terahertz wave modulation properties of graphene were investigated using an external 975 nm continuous wave laser with different power. Upon excitation laser, the transmission and modulation depth was measured using terahertz time-domain spectroscopy. The experimental results showed that the modulation depth of monolayer graphene and 3-layer graphene was 16% and 32% under the 1495 mW excitation power. Further, we analyzed the graphene modulation mechanism based on the Drude model and the thin-film approximation. Both theoretical analysis and calculation results showed that the terahertz wave could be modulated using graphene with different excitation laser power.

Alcohol Consumption and Risk of Liver Fibrosis in People Living With HIV: A Systematic Review and Meta-Analysis.

Objectives: It is unclear if a high level of alcohol consumption is a risk factor for liver fibrosis for people living with HIV (PLWH). This study systematically summarizes the risk relationship between different alcohol consumption and the incidence of liver fibrosis among PLWH. Methods: We identified potential studies by searching the PubMed, Embase, Web of Science Library, and CNKI databases up to September 26th, 2021. Observation studies in PLWH that evaluated the relationship between alcohol consumption and the risk of liver fibrosis and estimated the effect of alcohol with pooled odds ratios (pooled ORs) and 95% confidence intervals (CIs) were included. Results: There were total 15 studies included in data analysis. Three studies were set up as cohort studies and the other twelve were cross-sectional studies. Our study was based on 22,676 individuals and 2,729 liver fibrosis cases from 15 studies. Alcohol abuse is a significant risk factor of liver fibrosis (pooled OR = 2.25, 95% CI: 1.59-3.17, p < 0.05) among PLWH. Daily alcohol consumption > 50 g can elevate the risk of liver fibrosis (pooled OR = 3.10, 95% CI: 2.02-4.73, p < 0.05) among PLWH. However, high-risk alcohol consumption determined by AUDIT-C (AUDIT-C ≥ 4) had little or no effect on subsequent liver fibrosis risk. Further, alcohol consumption > 50 g is also a risk factor to liver fibrosis in PLWH co-infected with HCV (pooled OR = 2.48, 95% CI: 1.62-3.80, p < 0.05) and in HIV mono-infected (pooled OR = 1.85, 95% CI: 1.00-3.43, p < 0.05). Conclusion: Alcohol consumption is associated with an increased risk of liver fibrosis in PLWH. HCV co-infection with alcohol abuse could possibly induce a higher risk of liver fibrosis than HIV mono-infected patients. Systematic Review Registration: PROSPERO, identifier (CRD42021272604).

High spatiotemporal resolution optoacoustic sensing with photothermally induced acoustic vibrations in optical fibres.

Optoacoustic vibrations in optical fibres have enabled spatially resolved sensing, but the weak electrostrictive force hinders their application. Here, we introduce photothermally induced acoustic vibrations (PTAVs) to realize high-performance fibre-based optoacoustic sensing. Strong acoustic vibrations with a wide range of axial wavenumbers kz are photothermally actuated by using a focused pulsed laser. The local transverse resonant frequency and loss coefficient can be optically measured by an intra-core acoustic sensor via spectral analysis. Spatially resolved sensing is further achieved by mechanically scanning the laser spot. The experimental results show that the PTAVs can be used to resolve the acoustic impedance of the surrounding fluid at a spatial resolution of approximately 10 µm and a frame rate of 50 Hz. As a result, PTAV-based optoacoustic sensing can provide label-free visualization of the diffusion dynamics in microfluidics at a higher spatiotemporal resolution.

Fiber laser technologies for photoacoustic microscopy.

Fiber laser technology has experienced a rapid growth over the past decade owing to increased applications in precision measurement and optical testing, medical care, and industrial applications, including laser welding, cleaning, and manufacturing. A fiber laser can output laser pulses with high energy, a high repetition rate, a controllable wavelength, low noise, and good beam quality, making it applicable in photoacoustic imaging. Herein, recent developments in fiber-laser-based photoacoustic microscopy (PAM) are reviewed. Multispectral PAM can be used to image oxygen saturation or lipid-rich biological tissues by applying a Q-switched fiber laser, a stimulated Raman scattering-based laser source, or a fiber-based supercontinuum source for photoacoustic excitation. PAM can also incorporate a single-mode fiber laser cavity as a high-sensitivity ultrasound sensor by measuring the acoustically induced lasing-frequency shift. Because of their small size and high flexibility, compact head-mounted, wearable, or hand-held imaging modalities and better photoacoustic endoscopes can be enabled using fiber-laser-based PAM.

Compact polarimetric heterodyning DBR fiber laser sensor with high temperature resistance.

We report on a short-cavity polarization beat-frequency distributed Bragg reflector (DBR) fiber laser that can operate in an unprecedentedly wide range of temperatures from -200∘ C to 500°C. The beat-frequency signal inherited by the intrinsic fiber birefringence enables implementation of the laser as an eligible temperature or hydrostatic pressure sensor. Furthermore, type-IIa Bragg reflectors allow the annealing of high temperature on the laser cavity to suppress the phase noise of the lasing signal effectively. This research will guide future attempts to achieve high-precision sensing and high-performance signal generation using polarized beat-frequency DBR fiber lasers in harsh environments.

Tumor mutation burden associated with miRNA-gene interaction outcome mediates the survival of patients with liver hepatocellular carcinoma.

Tumor mutation burden (TMB) is associated with immunogenic responses and the survival of cancer patients. This study demonstrates how TMB levels impact the immune-related cells, genes, and miRNAs, and how miRNA/gene interactions respond to variations in the survival rate of patients with liver hepatocellular carcinoma (LIHC). LIHC patients were divided into two groups, either a low TMB (< median) or a high TMB (≥ median) group. We found that high TMB plays a positive role in immune-mediated infiltration, generating more CD4 T-cells and memory B cells. Among the 21 immune genes that altered significantly, only C9orf24 and CYP1A1 were expected to up-regulate in LIHC patients with high TMB. A total of 19 miRNAs, which regulate various functional pathways, were significantly altered in patients with LIHC. One of the miRNA/gene pair, hsa-miR-33a/ALDH1A3 was significantly associated with the survival rate of LIHC patients. Our results suggest that LIHC patients with high TMB can be treated more effectively with immunotherapy.

Wide-field polygon-scanning photoacoustic microscopy of oxygen saturation at 1-MHz A-line rate.

We report wide-field polygon-scanning functional OR-PAM that for the first time achieves 1-MHz A-line rate of oxygen saturation in vivo. We address two technical challenges. The first is a 1-MHz dual-wavelength pulsed laser that has sufficient pulse energy and ultrafast wavelength switching. The second is a polygon-scanning imaging probe that has a fast scanning speed, a large field of view, and great sensitivity. The OR-PAM system offers a B-scan rate of 477.5 Hz in a 12-mm range and a volumetric imaging rate of ∼1 Hz over a 12 × 5 mm2 scanning area. We image microvasculature and blood oxygen saturation in a 12 × 12 mm2 scanning area in 5 s. Dynamic imaging of oxygen saturation in the mouse ear is demonstrated to monitor fast response to epinephrine injection. The new wide-field fast functional imaging ability broadens the biomedical application of OR-PAM.

Photoacoustic computed tomography by using a multi-angle scanning fiber-laser ultrasound sensor.

Photoacoustic computed tomography (PACT) can ultrasonically image optical absorbers in biological tissues by using a linear piezoelectric transducer array, but some features can not be visualized as a result of the limited acceptance angle. The optical ultrasound sensors for photoacoustic imaging have received great interests, because of their compact sizes, comparable sensitivities to their electric counterparts, as well as the extended field/angle-of-view. In this work, we have developed a PACT system based on a fiber-laser based ultrasound sensor. Two-dimensional imaging was performed by horizontally scanning the sensor and image reconstruction via back projection, and three-dimensional imaging was further achieved by repeating such scanning process at multiple angles, based on inverse Radon transform. The axial and lateral resolutions are 93 and 220 µm in three-dimensional imaging. The fiber-based PACT can resolve more features than that with a piezoelectric transducer array, taking advantage of the dual-60-degree vision angles of the sensor.

Acoustic-spectrum-compensated photoacoustic microscopy.

Photoacoustic microscopy (PAM) can label-free image oxy- and deoxy-hemoglobin (${{\rm HbO}_2}$HbO2 and Hb) concentrations in vivo, providing useful information for metabolic researches and diagnostic applications. Conventional PAM assumes a linear relationship between the photoacoustic amplitude and the absorption coefficient. However, many factors, including absorber size, laser pulse width, and frequency response of the ultrasound transducer, may affect the measured acoustic spectrum and the shape of the temporal photoacoustic signal. The ultrasound transducer may weigh the blood vessels differently according to their diameters. In addition, the pulse width also affects the photoacoustic signal amplitude. These factors may cause inaccurate measurement of Hb and ${{\rm HbO}_2}$HbO2 concentrations. To address this issue, we develop an acoustic-spectrum-compensated optical-resolution PAM (OR-PAM) that corrects the nonuniform acoustic spectrum and makes the quantitative results to be independent of the vessel diameter and pulse width. In dual-wavelength OR-PAM, we demonstrate that the acoustic spectrum compensation can improve the accuracy of oxygen saturation imaging by $\sim{15}\% $∼15%.