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Background Dyslipidemia is the most important and causal independent risk factor for atherosclerotic cardiovascular disease (ASCVD) . The prevalence of dyslipidemia in elderly residents in Guangdong Province is high, and it is urgent to analyze the specific prevalence of dyslipidemia and its influencing factors among the elderly, and to carry out targeted preventive and control measures for dyslipidemia. Objective To investigate the epidemiological status of dyslipidemia and its risk factors among elderly residents included in the national basic public health service in Yuexiu District, Guangzhou. Methods A total of 41 469 elderly residents aged 65 years and above with complete important variables were selected as subjects from the information system of community health service center in Yuexiu District, Guangzhou City in 2020, the 2020 health checkup data was used to describe the epidemiological characteristics of the included patients such as basic information, BMI and blood lipid levels. Restricted cubic spline (RCS) fitting Logistic regression model was used to analyze the relationship between age, BMI and the prevalence of dyslipidemia. Results The prevalence of dyslipidemia in 41 469 elderly residents was 53.65% (22 247/41 469) , with a standardized prevalence of 53.89%. The prevalence of hypercholesterolemia (HTC) , hypertriglyceridemia (HTG) , mixed hyperlipidemia and low high-density lipoprotein cholesterol was 21.43%, 16.50%, 14.51% and 3.80%, with the standardized prevalence of 21.57%, 16.53%, 14.61%, 3.78%, respectively. Multivariate Logistic regression analysis showed that gender, age, education level, exercise status, and BMI were all influencing factors for dyslipidemia in elderly residents, among which female, low age group, and high BMI were risk factors for dyslipidemia in elderly residents (P

Traditional diagnostic techniques including visual examination, ultrasound (US), and magnetic resonance imaging (MRI) have limitations of in-depth information for the detection of nail disorders, resolution, and practicality. This pilot study, for the first time, evaluates a dual-modality imaging system that combines photoacoustic tomography (PAT) with the US for the multiparametric quantitative assessment of human nail. The study involved a small cohort of five healthy volunteers who underwent PAT/US imaging for acquiring the nail unit data. The PAT/US dual-modality imaging successfully revealed the fine anatomical structures and microvascular distribution within the nail and nail bed. Moreover, this system utilized multispectral PAT to analyze functional tissue parameters, including oxygenated hemoglobin, deoxyhemoglobin, oxygen saturation, and collagen under tourniquet and cold stimulus tests to evaluate changes in the microcirculation of the nail bed. The quantitative analysis of multispectral PAT reconstructed images demonstrated heightened sensitivity in detecting alterations in blood oxygenation levels and collagen content within the nail bed, under simulated different physiological conditions. This pilot study highlights the potential of PAT/US dual-modality imaging as a real-time, noninvasive diagnostic modality for evaluating human nail health and for early detection of nail bed pathologies. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a complex inflammatory disease of colorectum that induces abnormal immune responses and severely affects the quality of life of the patients. Grape seed proanthocyanidin extract (GSPE) exerts anti‐inflammatory and antioxidant functions in many inflammatory diseases. The objective of this study was to investigate the potential therapeutic effects and underlying mechanisms of GSPE in UC using a dextran sodium sulfate (DSS)‐induced mouse UC model and a lipopolysaccharide (LPS)‐stimulated RAW264.7 macrophage model. In this study, we found that the GSPE markedly prevented DSS‐induced weight loss and colon length shortening in UC mice. Further investigations showed that GSPE significantly attenuated the expression of pro‐inflammatory cytokines TNF‐α, IL‐6, and IL‐1β, and elevated the expression of anti‐inflammatory cytokine IL‐10 in the colon tissues and serum of DSS‐induced colitis mice by suppressing NF‐κB signaling pathway. Furthermore, LPS‐induced inflammation in RAW264.7 cells was also reversed by GSPE. Taken together, our results confirm that GSPE can ameliorate inflammatory response in experimental colitis via inhibiting NF‐κB signaling pathway. This study advances the research progress on a potentially effective therapeutic strategy for inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging (PAI) is an emerging biomedical imaging modality, offering numerous advantages, including high resolution and high contrast. In its application to brain imaging, however, the photoacoustic (PA) signals from brain tissue weaken considerably due to the distortion effects of the skull. This attenuation reduces the resolution and contrast significantly. To address this issue, here we describe a Log-MSR algorithm that combines the logarithmic depth logarithmic enhancement (Log) algorithm and the multi-scale Retinex (MSR) algorithm. In this method, the Log algorithm performs local weighted compensation based on signal attenuation for different depths, while the MSR algorithm improves the contrast of the image. The proposed Log-MSR algorithm was tested and validated using several phantom and in vivo experiments. The enhanced images constructed by the Log-MSR algorithm were qualitatively and quantitatively analyzed in terms of brain structure and function. Our results show that the Log-MSR algorithm may provide a significant enhancement to photoacoustic imaging of deep brain tissue. [ABSTRACT FROM AUTHOR]

This study aims to explore the feasibility of fine-needle aspiration biopsy (FNAB) under dual modal photoacoustic tomography(PAT)/ultrasound (US) imaging. A total of 25 patients who have thyroid nodules with thyroid imaging reporting and data system (TIRADS) 3 and 4 (malignant risk <85%) were recruited. The specimens obtained from the PAT/US-guided FNAB were collected for cytology analysis. Cytological diagnoses for the 25 patients were classified in perspective of the Bethesda system for reporting thyroid cytopathology diagnostic category (DC) I: 4%(1/25); DC II: 12% (3/25); DC III: 20% (5/25); DC IV: 8% (2/25); DC V: 32% (8/25); and DC VI: 24% (6/25). The DC I nodule exhibited inadequate cytology and had structural characteristic of predominant calcifications in PAT/US mapping. The DC V-VI nodules showed lower photoacoustic (PA) signals compared to the DC I-IV nodules. Regions with a high PA signal demonstrated a significant number of erythrocytes in FNAB cytology. Moreover, nodules with microcalcifications did not show a significant difference compared to their surroundings in the PA signal, while nodules with macrocalcifications gave higher PA signals compared to their surroundings. The conclusions are as follows: combining US with PAT can evaluate the structure and function of thyroid nodules in vivo. This study demonstrates that dual modal PAT/US imaging has the potential to be an effective clinical tool to guide FNAB of thyroid nodules. [ABSTRACT FROM AUTHOR]

BACKGROUND: Electrical conductivity directly correlates with tissue functional information such as blood and water contents, and quantitative extraction of tissue conductivity is of significant importance for disease detection and diagnosis using microwave-induced thermoacoustic tomography (TAT). OBJECTIVE: The existing quantitative TAT (qTAT) approaches capable of extracting tissue conductivity require two steps for the recovery of conductivity. Such two steps approaches depend on an accurate knowledge of the microwave energy loss distribution in tissue and offer a slow computational convergence rate. The purpose of this study is to develop a new algorithm to reconstruct tissue conductivity with higher reconstruction accuracy and greater computational efficiency. METHODS: We propose an improved qTAT method for direct recovery of tissue conductivity from thermoacoustic data measured along the boundary with only one step without the dependence of microwave energy loss information. The feasibility of our one-step qTAT method is validated in both simulated and tissue-mimicking phantom experiments with single-target and multi-target configurations with different contrast levels. RESULTS: Compared with the previous two-step methods, our one-step qTAT method improves the accuracy of conductivity recovery with approximately one-fold reduction in the mean absolute error (MAE) and root mean square error (RMSE) with p-values greater than 0.05. In addition, the convergence rate is improved by more than two folds for the one-step method. CONCLUSIONS: The study demonstrates that new method can quantitatively reconstruct conductivity of tissue more accurately and efficiently over the existing qTAT methods, leading to potentially enhanced accuracy for disease detection and diagnosis. [ABSTRACT FROM AUTHOR]

Background: Investigating adherence to the Atrial Fibrillation Better Care (ABC) pathway management and identifying gaps between the real world and established guidelines can lead to better integrated management of AF. Current data on adherence to ABC pathway management among community elderly patients with atrial fibrillation (AF) in Chinese communities is limited.Aim: To investigate the adherence to ABC pathway management among community elderly patients with AF in China.Methods: In this cross-sectional study, data were collected from the 2020 National Basic Public Health Service Program database that includes health examination information for all residents > 65 years of age in Yuexiu, Guangzhou, Guangdong Province. Demographic and clinical characteristics data from 197 community AF patients were obtained.Results: Among the 197 AF patients, 103 (52.3%) were male, 117 (59.4%) were ≥ 75 years of age, 127 (64.5%) had a senior middle school education or above, 84.3% were married, and 195 (99.0%) had medical insurance. The most common comorbidities were hypertension (72.1%, 142/197), dyslipidaemia (28.4%, 56/197), CAD (28.9%, 57/197), and diabetes (24.9%, 49/197). In terms of the ABC management pathway, 21.8% (43/197), 82.7% (163/197), and 31.5% (62/197) of AF patients were classified into the A-adherent group, B-adherent group, and C-adherent group, respectively. The level of adherence to ABC pathway management was very low (9.1%, 18/197) and independently associated with age and multimorbidity.Conclusion: The level of adherence to ABC pathway management in community elderly patients with AF was unsatisfactory. Further research is warranted to improve the integrated management of AF. [ABSTRACT FROM AUTHOR]

Puerarin, an isoflavonoid rich in Radix Puerariae , has been reported to be a broadly effective regulator in various biological processes and clinic conditions. However, the role of puerarin in sepsis-induced mortality with multiple-organ injury remains unknown. Herein, we showed that puerarin potently attenuated organ injury and increased survival rate in both lipopolysaccharides (LPS) and cecal ligation and puncture (CLP) induced mouse sepsis models. It greatly suppressed systemic inflammation, determined by the serum levels of proinflammatory factors TNF-α, IL-6, IL-1β, IL-10, as well as monocyte chemotactic protein-1 (MCP-1) and C-reactive protein (CRP). Flow cytometry analysis indicated that puerarin settled overall inflammation mainly by normalizing expanded macrophages with limited effects on dendritic cells and CD4+T cells in the circulation of sepsis mice. In the liver, puerarin inhibited the transcription of inflammatory factor TNF-α, IL-6, and IL-1β and protected hepatocyte apoptosis in sepsis mouse models. In vitro, puerarin inhibited LPS-induced inflammation in LO2 hepatocytes, prevented TNF-α-mediated cell apoptosis and promoted an M2 phenotype revealed by M2 marker IL-10 and Arginase-1 (Arg-1) in LPS challenged Raw 264.7 macrophages, through the inhibition of TLR4/NF-κB/JNK pathway. In conclusion, puerarin reduced systemic inflammation and protected organ injury in sepsis mice, thus, it might provide a new modality for a better treatment of sepsis. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a systemic granulomatous disease associated with Th1/ regulatory T cells (Treg) paradigm. PI3K/Akt signaling, critical for maintaining Treg's homeostasis, is aberrantly activated in sarcoidosis patients. Here we tested the role of the PI3K inhibitors, LY294002 and BKM120, in immune modulation in experimental pulmonary sarcoidosis, concerning Th1/Th17/Treg immune profile detected by fluorescence‐activated cell sorting analysis or quantitative polymerase chain reaction, as well as the effect on Treg's suppressive functions. Our investigation showed abnormal activation of PI3K/Akt signaling both in lung and Treg in pulmonary sarcoidosis, along with decreased frequency and damaged function of Treg. Blockage of PI3K suppressed this signaling in Treg, rebalanced Th1/Treg, inhibited the production of inflammatory cytokines, and enhanced Treg's function. These results demonstrate the key role of the PI3K/Akt signaling in regulating Th1/Th2 rebalances and indicates that PI3K/Akt signaling is critical for the optimal Treg responses in pulmonary sarcoidosis. Thus, PI3K inhibitors have potential for therapeutic translation, and can be candidate for add‐on drugs to treat pulmonary sarcoidosis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The therapeutic effects of bone marrow‐derived mononuclear cells (BMMNCs) transplantation in patients with nonischaemic dilated cardiomyopathy (DCM) are still under debate. Current randomized controlled trials (RCTs) reported conflicting results. The aim of this study was to assess the effects of BMMNCs transplantation on left ventricular ejection fraction (LVEF) in patients with nonischaemic DCM. Methods: A comprehensive search of PubMed, EMBASE and Cochrane Controlled Trials Register was performed. We included RCTs reporting data on LVEF in patients with nonischaemic DCM after BMMNCs transplantation. Results: Seven RCTs including 463 patients were included. BMMNCs transplantation significantly improved LVEF by 3.79% (95% CI: 0.56%‐7.03%; P = .007) and LVESV by −24.36 mL (95% CI: −46.36 to −2.36 mL; P = .03), while had no impact on the risk of all‐cause death (OR 0.92; 95% CI: 0.41 to 2.08%; P = .84). Subgroup analysis demonstrated a more significant improvement of LVEF in patients with longer follow‐up (~15 months to 5 years) than shorter ones (12 months). Moreover, using bone marrow mononuclear cells was more effective than using G‐CSF‐stimulated bone marrow/peripheral blood stem cells in the improvement of LVEF in patients with nonischaemic DCM. Conclusions: Bone marrow‐derived mononuclear cells transplantation is associated with a moderate, but significant, improvement in LVEF in patients with nonischaemic DCM. This meta‐analysis supports further RCT conductions using BMMNCs transplantation with larger patient's population and longer term follow‐up. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a multisystem inflammatory disease characterized by the development of Th1/Th17/regulatory T cells (Tregs)-related non-caseating granulomas. Phosphoinositide-3 kinases δ/γ (PI3Kδ/γ) play an important role in the maintenance of effective immunity, especially for Tregs homeostasis and stability. In the present study, superoxide dismutase A (SodA) stimulation was used to establish the sarcoidosis mouse model. The second immune stimulus was accompanied by CAL-101 (PI3Kδ inhibitor) or AS-605240 (PI3Kδ/γ inhibitor) treatment. To detect the effect of the PI3Kδ/γ inhibitor on the morphology of pulmonary granuloma and the activation of the PI3K signaling pathway, hematoxylin and eosin staining and immunofluorescence and western blotting was used, respectively. Fluorescence-activated cell sorting analysis and reverse transcription-quantitative PCR were adopted to detect the effect of the PI3Kδ/γ inhibitor on the SodA-induced sarcoidosis mouse model in respect to immune cell disorder and the function of Treg cells, with CD4+CD25- T cells and CD4+CD25+ T cells sorted by magnetic cell sorting. The results demonstrated that the inhibition of PI3Kδ/γ by transtracheal CAL-101/AS-605240 administration facilitated pulmonary granuloma formation. These therapeutic effects were associated with certain mechanisms, including suppressing the aberrantly activated PI3K/Akt signaling in both pulmonary granuloma and Tregs, particularly rescuing the suppressive function of Tregs. Notably, CAL-101 was more effective in immune modulation compared with AS-605240 and could overcome the aberrantly activated Akt in the lung and Tregs. These results suggest that PI3K/Akt signaling, especially the PI3Kδ subunit, can play a key role in optimal Tregs-mediated protection against pulmonary sarcoidosis. Therefore, transtracheal usage of PI3Kδ/γ inhibitors is an attractive therapy that may be developed into a new immune-therapeutic principle for sarcoidosis in the future. [ABSTRACT FROM AUTHOR]

The steroid Na+/K+-ATPase blocker ouabain has been shown to exhibit cytotoxic effects in various tumor cell systems. This study aimed to determine the effects of ouabain on Burkitt’s lymphoma Raji cells. Ouabain treatment of Raji cells significantly inhibited cell proliferation in a dose-dependent manner and increased the morphological changes associated with apoptosis. Additionally, increased numbers of both early and late apoptotic cells were observed by annexin V-FITC/PI flow cytometry assay. Increased levels of caspase-3 and cleaved-caspase-3, higher Bax activity and decreased expression of the anti-apoptotic protein Bcl-2 were detected in ouabain-treated Raji cells. Vacuole accumulation was also observed in transmission electron microscope (TEM) images of ouabain-treated Raji cells, indicating that these cells were undergoing autophagy. Expression of the autophagy-related proteins LC3-II and Beclin-1 was upregulated in ouabain-treated Raji cells. These results suggest that ouabain may promote cell death in Raji cells by inducing pathways associated with apoptosis and autophagy. Our study also provides novel evidence that ouabain may be an effective agent for treating Burkitt’s lymphoma. [ABSTRACT FROM AUTHOR]

Purpose: Hematopoietic stem cell transplantation (HSCT) has been proposed as a novel therapy for multiple sclerosis (MS). CD4 + CD25 + regulatory T cells (Tregs) expressing Foxp3 play an important role in the maintenance of immune tolerance to self. Our study was conducted to confirm the efficiency of nonmyeloablative conditioning and syngeneic bone marrow transplantation (BMT) on experimental autoimmune encephalomyelitis (EAE) mice and to determine whether Tregs plays a role in the underlying mechanism. Methods: EAE were induced in C57BL/6 mice and were randomly divided into 4 groups: the Conditioning group received the conditioning regimen, the Normal-EAE BMT group received conditioning and bone marrow (BM) grafts from normal mice, the EAE-EAE BMT group received conditioning and BM grafts from EAE mice and the EAE control group received no further therapy. The cumulative clinical score was used to assess the efficacy of the different treatments, and the proportion of Tregs in the spleen was measured by flow cytometry on day 40, 80 and 120 after BMT. Foxp3 mRNA expression was assessed by real-time PCR, and the expression of Foxp3 protein was tested by western blot on day 120 after BMT. Results: Conditioning and conditioning with BMT led to a significant clinical improvement on day 80 after BMT compared with EAE without further treatment. On day 120 after BMT, the clinical score of the Conditioning group showed no significant difference from that of the EAE control group, whereas BMT led to a further amelioration of the disease score. On day 80 and day 120 after BMT, the proportions of Tregs of the two BMT groups were significantly higher than that in EAE control group, whereas no statistically significant difference was found between the Conditioning group and the EAE control group. On day 120 after BMT, the Foxp3 mRNA level and Foxp3 protein expression was higher in the two BMT groups than in EAE control group or Conditioning group. Conclusions: Nonmyeloablative conditioning could temporarily reverse already established EAE, but it was not sufficient for the induction of long-term EAE remission. Transplantation by BM cells from healthy or diseased donors was necessary and responsible for complete and long-time remission of EAE, and these beneficial effects may be the result of the induction of Tregs and the Treg-related factor Foxp3. [ABSTRACT FROM AUTHOR]

Abstract: Autologous hematopoietic stem cell transplantation (HSCT) has recently been performed as a novel strategy to treat patients with new-onset type 1 diabetes (T1D). However, the mechanism of autologous HSCT-induced remission of diabetes remains unknown. In order to help clarify the mechanism of remission-induction following autologous HSCT in patients with T1D, mice treated with multiple low doses of streptozotocin to induce diabetes were used as both donors (n =20) and recipients (n =20). Compared to streptozocin-treated mice not receiving transplantation, syngeneic bone marrow transplantation (syn-BMT) from a streptozocin-treated diabetic donor, if applied during new-onset T1D (day 10 after diabetes onset), can reverse hyperglycemia without relapse (P <0.001), maintain normal blood insulin levels (P <0.001), and preserve islet cell mass. Compared to diabetic mice not undergoing HSCT, syn-BMT, results in restoration of Tregs in spleens (P <0.01), increased Foxp3 mRNA expression (P <0.01) and increased Foxp3 protein expression (P <0.05). This diabetic-remission-inducing effect occurred in mice receiving bone marrow from either streptozocin-treated diabetic or non-diabetic normal donors. We conclude that autologous HSCT remission of diabetes is more than transient immune suppression, and is capable of prolonged remission-induction via regeneration of CD4+CD25+FoxP3+ Tregs. [Copyright &y& Elsevier]

The sonographic and histopathologic features of a rare case of left ventricular aneurysm are reported, detailing the method of prenatal diagnosis and suggesting possible etiology of congenital ventricular aneurysm. [ABSTRACT FROM AUTHOR]

Abstract The feature of pulmonary sarcoidosis is characterized by a Th1/Th17/regulatory T cells (Tregs) -driven inflammatory process in lung, resulting in noncaseating granulomas containing CD4+ T cells. Tregs increase in both lung and peripheral blood, with damaged immunoregulatory function. The current study investigated the effects of IL33 or anti-IL23 antibody on restoring the homeostasis and functions of Tregs in mycobacterial superoxide dismutase A (SodA)-induced pulmonary sarcoidosis. IL33 or anti-IL23 antibody was administered to mice with late-stage pulmonary sarcoidosis. The levels of Th1/Th17/Tregs and Tregs' suppressive functions were detected by fluorescence activated cell sorting (FACS) analysis or qPCR. The expressions of key proteins in PI3K/Akt/mTOR and TGF-β/Smad2/Smad3 signaling pathways were tested by western blot. IL33 administration was associated with the rebalance of Th1/Th2 and Tregs, as well as a superior suppressor activity of Tregs on effector T cells in sarcoidosis, probably through increasing ST2 expressions on Tregs, along with the suppression of PI3K/Akt/mTOR and TGF-β/Smad2/Smad3 signaling pathways. Small dose of anti-IL23 antibody independently improved Th1/Th2 bias, but had limited effects on the homeostasis and ST2 expressions on Tregs. These results suggested a major anti-inflammatory ability of IL33 to ameliorate the disturbance of Th1/Th2 and Tregs in pulmonary sarcoidosis, and provided rationales for further strategies of targeting the IL33/ST2 signals in the treatment of pulmonary sarcoidosis. Highlights • Disturbance of Tregs in SodA-induced sarcoidosis was ameliorated by IL33. • Tregs' function may be sustained through IL33/ST2 regulation. • PI3K/Akt pathway was suppressed along with the sustained Tregs' function. [ABSTRACT FROM AUTHOR]

Photoacoustic tomography (PAT) is an emerging biomedical imaging modality that combines optical and ultrasonic imaging, providing overlapping fields of view. This hybrid approach allows for a natural integration of PAT and ultrasound (US) imaging in a single platform. Due to the similarities in signal acquisition and processing, the combination of PAT and US imaging creates a new hybrid imaging for novel clinical applications. Over the recent years, particular attention is paid to the development of PAT/US dual-modal systems highlighting mutual benefits in clinical cases, with an aim of substantially improving the specificity and sensitivity for diagnosis of diseases. The demonstrated feasibility and accuracy in these efforts open an avenue of translating PAT/US imaging to practical clinical applications. In this review, the current PAT/US dual-modal imaging systems are discussed in detail, and their promising clinical applications are presented and compared systematically. Finally, this review describes the potential impacts of these combined systems in the coming future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wen, Guo, Zhang, Liu, Liu, Li, Jiang, Wu and Jiang.)

Detailed insight into the radiation-induced changes in tumor microvasculature is crucial to maximize the efficacy of radiotherapy against breast cancer. Recent advances in imaging have enabled precise targeting of solid lesions. However, intratumoral heterogeneity makes treatment planning and monitoring more challenging. Conventional imaging cannot provide high-resolution observation and longitudinal monitoring of large-scale microvascular in response to radiotherapy directly in deep tissues. Herein, we report on an emerging non-invasive imaging assessment method of morphological and functional tumor microvasculature responses with high spatio-temporal resolution by means of optoacoustic imaging (OAI). In vivo imaging of 4T1 breast tumor response to a conventional fractionated radiotherapy at varying dose (14 × 2 Gy and 3 × 8 Gy) has been performed after 2 weeks following treatment. Remarkably, optoacoustic images can generate richful contrast for the tumor microvascular architecture. Besides, the functional status of tumor microvasculature and tumor oxygenation levels were further estimated using OAI. The results revealed the differential (size-dependent) nature of vascular responses to radiation treatments at varying doses. The vessels exhibited an decrease in their density accompanied by a decline in the number of vascular segments following irradiation, compared to the control group. The measurements further revealed an increase of tumor oxygenation levels for 14 × 2 Gy and 3 × 8 Gy irradiations. Our results suggest that OAI could be used to assess the response to radiotherapy based on changes in the functional and morphological status of tumor microvasculature, which are closely linked to the intratumor microenvironment. OAI assessment of the tumor microenvironment such as oxygenation status has the potential to be applied to precise radiotherapy strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Xu, Xie, Shen, Fu, Liu, Chi, Lu, Xiang, Wen, Yang and Jiang.)

Online supplemental material is available for this article.

Objective: Photoacoustic tomography (PAT) and multispectral optoacoustic tomography (MSOT) are evolving technologies that are capable of delivering real-time, high-resolution images of tissues. The purpose of this study was to evaluate the feasibility of using PAT and MSOT for detecting histology in a rabbit tracheal stenosis model.
 Method: A total of 12 rabbits (9 stenosis and three control) were randomly divided into four groups (A, B, C and D). Each group consisted of three rabbits, which were staged at the first, fourth, and eighth weeks of stenosis progression, respectively. PAT/MSOT images and corresponding histology from these experimental animals were compared, for analyzing the morphologic features and quantitative tracheal measurements in different tracheal stenosis stage. Result: Both the PAT images and corresponding histology indicated the most severe degree of stenosis in group C. MSOT images indicated notable differences in tracheal contents of group B and D. Conclusion: This study suggests that PAT/MSOT are potentially valuable non-invasive modality which are capable of evaluating tracheal structure and function in vivo ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wen, Wu, Zhang, Jiang, Xiong, Guo, Chi, Chen, Li, Yang, Liu and Jiang.)

Background: Type 1 diabetes (T1D) is a multiple factor autoimmune disease characterized by T cell-mediated immune destruction of islet β cells. Autologous hematopoietic stem cell transplantation (AHSCT) has been a novel strategy for patients with new-onset T1D, but not for those with a later diagnosis. Disturbance of regulatory T cells (Tregs) likely contributes to poor response after transplantation in later-stage T1D. Inhibition of phosphoinositide 3-kinases (PI3K)/Akt signaling maintains Tregs' homeostasis., Methods: We built a later-stage streptozotocin (STZ)-induced T1D mouse model. Syngeneic bone marrow transplantation (syn-BMT) was performed 20 days after the onset of diabetes in combination with BKM120 (a PI3K inhibitor). Meanwhile, another group of STZ-diabetic mice were transplanted with bone marrow cells cocultured with BKM120 in vitro for 24 h. Fasting glucose and glucose tolerance were recorded during the entire experimental observation after syn-BMT. Samples were collected 126 days after syn-BMT. Hematoxylin and eosin (H&E) staining was used to detect the effect of PI3K inhibitor combined with syn-BMT on morphology of the T1D pancreas. CD4 + CD25 - T cells and CD4 + CD25 + T cells were sorted by magnetic cell sorting (MACS), then fluorescence activated cell sorting (FACS) and quantitative real-time PCR (qPCR) were used to detect the effect of PI3K inhibitor on modulating immune disorder and restoring the function of Treg cells., Results: Our investigation showed syn-BMT in combination with BKM120 effectively maintained normoglycemia in later-stage T1D. The disease remission effects may be induced by the rebalance of Th17/Tregs dysregulation and restoration of Tregs' immunosuppressive function by BKM120 after syn-BMT., Conclusions: These results may reveal important connections for PI3K/Akt inhibition and Tregs' homeostasis in T1D after transplantation. AHSCT combining immunoregulatory strategies such as PI3K inhibition may be a promising therapeutic approach in later-stage T1D., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-3329). SL, Y Wang, YZ, Y Wen received funding from the Independent and Open Grant of Jiangsu Key Laboratory of Molecular Medicine and Innovation and Entrepreneurship Training Program for College Students (G201910284011). DC, NZ, Y Wen received funding from the Independent and Open Grant of Jiangsu Key Laboratory of Molecular Medicine and Innovation and Entrepreneurship Training Program for College Students (202010284016Z). JD received funding from the National Natural Science Foundation of China (81400046). Y Wen received funding from the National Natural Science Foundation of China (81100386). The other authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: Birt-Hogg-Dubé Syndrome (BHDS) characterised by skin fibrofolliculomas, kidney tumour and pulmonary cysts/pneumothorax is caused by folliculin (FLCN) germline mutations. The pathology of both neoplasia and focused tissue loss of BHDS strongly features tissue-specific behaviour of the gene. Isolated cysts/pneumothorax is the most frequent atypical presentation of BHDS and often misdiagnosed as primary spontaneous pneumothorax (PSP). Deferential diagnosis of BHDS with isolated pulmonary presentation (PSP-BHD) from PSP is essential in lifelong surveillance for developing renal cell carcinoma., Methods: The expression profiles of microRNAs (miRNAs) in cystic lesions of PSP-BHD and PSP were determined via microarray. The selected upregulated miRNAs were further confirmed in the plasma of an expanded cohort of PSP-BHD patients by reverse transcription quantitative PCR (RT-qPCR). Their diagnostic accuracy was evaluated. Moreover, the cellular functions and targeted signalling pathways of FLCN-regulated miRNAs were assessed in various cell lines and in the lesion tissue contexts., Results: Cystic lesions of PSP-BHD and PSP showed different miRNAs profiles with a significant upregulation of miR-424-5p and let-7d-5p in PSP-BHD. The combination of the two effectively predicted BHDS patients. In vitro studies revealed a suppressive effect of FLCN on miR-424-5p and let-7d-5p expressions specifically in lung epithelial cells. The ectopic miRNAs triggered epithelial apoptosis and epithelial transition of mesenchymal cells and suppressed the reparative responses in cells and tissues with FLCN deficiency., Conclusion: The upregulation of miR-424-5p and let-7d-5p by FLCN deficiency occurred in epithelial cells and marked the PSP-BHD condition, which contributed to a focused degenerative pathology in the lung of PSP-BHD patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: S1PR1-STAT3 inter-regulatory loop was initially suggested to be oncogenic in several cancer cells. However, the clinical relevance of this mechanism in tumor progression, disease prognosis and drug response was not established., Methods: The correlations between S1PR1 transcription, overall survival and chemotherapy response of GC patients were tested using a large clinical database. The relevance of S1PR1 expression and STAT3 activation in both tumor tissues and cancer cell lines was also tested. The effect of S1PR1 high expression achieved by persistent STAT3 activation on tumor cell drug resistance was investigated in vitro and in vivo., Findings: An enhanced S1PR1 expression was highly related with a reduced overall survival time and a worse response to chemotherapy drug and closer correlation to STAT3 in gastric cancer patients. The issue chip analysis showed that the expressions of S1PR1 and STAT3 activation were increased in higher graded gastric cancer (GC) tissues. Cellular studies supported the notion that the high S1PR1 expression was responsible for drug resistance in GC cells through a molecular pattern derived by constitutive activation of STAT3. The disruption of S1PR1-STAT3 signaling significantly re-sensitized drug resistance in GC cells in vitro and in vivo., Interpretation: S1PR1-STAT3 signaling may participate drug resistance in GC, thus could serve as a drug target to increase the efficacy of GC treatment. FUND: This work was supported by the National Natural Science Foundation of China (No. 81570775, 81471095), the grant from the research projects in traditional Chinese medicine industry of China (No. 201507004-2)., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The present study is planned to discuss the clinical value of prenatal 3D ultra-sonic diagnosis on fetus hemivertebra deformity through the retrospective analysis of clinical data of fetus hemivertebra deformity., Methods: Selected 9 fetus hemivertebra deformity cases, which have been admitted to our hospital during the period from January, 2010 to January, 2016 as study samples, and analyzed their 2D and 3D ultrasonic examination data., Results: 4 cases of the fetus hemivertebra deformity occurred at lumbar vertebra, 3 cases at thoracic vertebra, and 2 cases at thoracolumbar vertebra. There were scoliosis and opened spine bifida (OSB). In 7 cases, there was absence of ribs in fetus. The 2D ultrasonic image showed that: The echo at the center of fetus vertebral arch lesion was blurred or lost. The coronal section showed the deformity of the spine. There was obvious loss of the ossification center. From the cross section, we could see that the vertebral body of the fetus was shrinking and the edges were relatively blurred. The 3D ultrasonic image showed that: the echo at the ossification center of the fetus vertebra was relatively blurred, or even lost. The image also indicated scoliosis deformity of the spine. The vertebral body lesion could be accurately located., Conclusion: 9 cases of fetus hemivertebra deformity have been detected through examination. Labor inductions have been carried out after getting the permission from the family members. The X-ray examination of the fetus after labor induction showed that the diagnosis was correct. Prenatal ultra-sonic examination holds strong potential for the diagnosis of fetus hemivertebra deformity quite early and deserves further clinical evaluation with large sample size.

Background: Sarcoidosis is a systemic inflammatory disorder characterized by granulomas. Not enough evidences correlate the derangement of CD4+ T subsets, which have an impact on the therapeutic effects of corticosteroids, with the radiographical staging of sarcoidosis. Here we show the disturbance of CD4+ T subsets in newly diagnosed stage II pulmonary sarcoidosis, which is the most common stage in which corticosteroids treatment is used., Materials and Methods: 39 newly diagnosed and treatment-naïve patients and 9 subjects after corticosteroids treatment were included. CD4+ CD45RA+/ CD45RO+ cells, CCR4+ CCR6+ cells, and T regulatory cells (Tregs) were tested by Flow Cytometry Analysis. Th1/Th2, Tregs/Th17 related cytokines and mRNAs, SAA and CCL20 were also measured. The activation of PI3K/PTEN/Akt signaling pathway was detected., Results: Percentages of CD4+CD45RO+ memory T cells and Tregs, serum levels of IL-17A, TGF-β1, IL-6, IFN-γ, IL-10, SAA and CCL20, copies of T-bet, FoxP3, IL-17 and RORc in the periphery were elevated in newly diagnosed stage II pulmonary sarcoidosis patients. Additionally, PI3K/Akt signaling pathway was activated in bronchoalveolar lavage fluid cells., Conclusions: Disturbance of T memory cells, Th1/Th2, and Tregs/Th17 cells, and activation of PI3K/Akt signaling were seen in newly diagnosed stage II pulmonary sarcoidosis, which can be partly ameliorated by corticosteroids treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Objective: This meta-analysis aimed to assess whether bone marrow-derived mononuclear cells (BMMNCs) therapy may improve cardiac functional parameters in patients with ischemic heart disease (IHD) or ischemic heart failure (IHF)., Methods: Relevant randomized controlled trials (RCTs) were searched from web databases. Weighted mean difference was calculated for changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volumes by using a random effects model., Results: 13 RCTs met inclusion criteria. Compared with controls, BMMNCs therapy improved LVEF by 3.83% (95% confidence interval (CI): 2.10 - 5.56%; p < 0.0001) in patients with ischemic heart conditions. Notably, in patients with IHF, a more severe clinical condition when compared with IHD, BMMNCs therapy appeared more effective in LVEF improvement. While LVEF increased by 5.67% (95% CI: 3.65 - 7.69%; p < 0.00001) in IHF patients, it only increased by 2.19% (95% CI: 0.37 - 4.00%; p = 0.02) in patients with IHD., Conclusions: BMMNCs therapy is associated with moderate but significant improvement over regular therapy in LVEF in patients with IHD and IHF. This observation, therefore, supports further RCTs conducting safety and efficiency of BMMNCs therapy with longer-term follow-up.

Objective: Early-phase clinical trials suggest that autologous bone-marrow-derived cells (BMCs) may have a positive effect on patients with severe peripheral arterial disease (PAD). However, the therapeutic effects of BMCs treatment in various aspects remain controversial., Research Design and Methods: We conducted a meta-analysis using data from randomized controlled trials (RCTs) by comparing autologous BMCs therapy with controls in patients with severe PAD. Pubmed, EMBASE, EBSCO and the Cochrane Central Register of Controlled Trials ( to approximately April 2011) were searched., Results: Seven RCTs with 276 patients were included. Pooled comparisons of studies found that BMCs therapy significantly improved ankle-brachial index (ABI) by 0.10 (95% CI, 0.07 to 0.14; p < 0.00001), transcutaneous oxygen tension (TcO(2)) by 13.39 mmHg (95% CI, 6.69 to 20.1 mmHg; p < 0.0001) and pain-free walking distance by 119.91 m (95% CI, 90.71 to 149.11 m; p < 0.00001). BMCs therapy significantly decreased scale of rest pain by 1.13 (95% CI, -1.71 to -0.54, p = 0.0002) and helped heal ulcers (OR, 7.17; 95% CI, 2.66 to 19.32; p < 0.0001)., Conclusions: Our analysis based on seven RCTs suggests that autologous BMCs therapy, has a beneficial effect on physiologic and anatomic parameters in patients with severe PAD.

Objective: Previous evaluation of intracoronary autologous bone marrow-derived stem cell (BMSCs) therapy following ischemic heart disease (IHD) suggested improvement of cardiac functional parameters. We performed a meta-analysis to provide systematic assessment of the safety and efficacy of direct (intramyocardial or endomyocardial) BMSCs transplantation in patients with IHD., Research Design and Methods: Randomized controlled Trials (RCTs) were identified in the MEDLINE (approximately Oct. 2010), the Cochrane Central Register of Controlled Trials (Central) (approximately Oct. 2010), EMBASE (approximately Oct. 2010), and EBSCO (approximately Oct. 2010), reviews, and reference lists of relevant articles. Weighted mean difference (WMD) was calculated for changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV) by using a fixed effects model., Results: Eight RCTs with 307 participants were eligible. Compared with controls, direct BMSCs transplantation improved LVEF (8.4%, 95% CI, 6.49 to 10.31%; p < 0.01), reduced LVESV and LVEDV (-14.85 ml, 95% CI, -27.29 to -2.41 ml, p = 0.02 and -12.79 ml, 95% CI, -24.94 to -0.65 ml, p = 0.04, respectively)., Conclusions: This meta-analysis suggests that direct BMSCs transplantation is associated with moderate but significant improvements over regular therapy in cardiac functional parameters in patients with IHD, and supports conducting further RCTs of a higher quality.

Treatment with autologous bone marrow transplantation (ABMT) can change the natural history of diabetes in patients with new-onset Type 1 diabetes (T1D). Effects of syngeneic bone marrow transplantation (syn-BMT) on diabetic nephropathy were studied in streptozotocin-induced diabetic mice. Diabetic mice received sibling's bone marrow on days 3, 10, 20, or 40 after T1D onset, respectively. Renal pathology, levels of oxidative stress, and the expressions of angiotensinogen (AGT), monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor beta 1 (Tgf-beta1) mRNA were investigated. Treatment with syn-BMT when disease was early-onset reduced mesangial area expansion and kidney enlargement; besides, if it is given on day 10, syn-BMT attenuated glomerular hypertrophy. Oxidative stress factors such as catalase (CAT) and superoxide radical anion O(2-) (O(2-)) were markedly maintained by syn-BMT compared to mice without treatment. In diabetic mice without treatment, renal AGT and MCP-1 mRNA were increased, while they were effectively suppressed by syn-BMT. But it showed no changes or even increment in Tgf-beta1 mRNA after syn-BMT. Syn-BMT, if applied when disease was early-onset, ameliorated diabetic renal injury. These preventive effects could be partly via maintaining oxidative stress and expression of AGT and MCP-1 in kidney in streptozotocin-diabetic mice., (Copyright 2009 Elsevier B.V. All rights reserved.)