Search

Jian Jiang,1,2,* Xiaoyan Hou,1,* Lili Gu,3 Xian Liu,1 Huiting Lv,1 Jiaxin Xiong,1 Hongmei Kuang,1,2 Xiaofeng Jiang,1 Shunda Hong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China; 2Jiangxi Medical Imaging Research Institute, Nanchang, People’s Republic of China; 3Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shunda Hong, Department of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86-791-88693825, Email dyfy05441@ncu.edu.cnPurpose: This study aimed to explore the abnormal changes in short- and long-range functional connectivity density (FCD) in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN).Patients and Methods: Twenty HZ patients, 22 PHN patients, and 19 well-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scans. We used FCD mapping, a data-driven graph theory method, to investigate local and global functional connectivity patterns. Both short- and long-range FCD were calculated and compared among the PHN, HZ, and HC groups. Then, the abnormal regions were used to calculate seed-based functional connectivity. Finally, correlation analyses were performed between the altered FCD values and clinical datas.Results: Compared with HCs, HZ patients showed significantly increased long-range FCD of the bilateral cerebellum, thalamus, parahippocampal gyrus, superior temporal gyrus and lingual gyrus. HZ patients also displayed significantly decreased short-range FCD of the bilateral posterior cingulate gyrus, median cingulate/paracingulate gyri, and left precuneus. Compared with HCs, PHN patients displayed significantly decreased long-range FCD of the bilateral superior frontal gyrus and decreased short-range FCD in the bilateral posterior cingulate gyrus, median cingulate/paracingulate gyri, and precuneus. However, there was no significant difference in either long-range or short-range FCD between the PHN and HZ patients. Long-range FCD deficit areas and the right insula showed altered functional connectivity in PHN patients. Furthermore, pain duration in patients with PHN was correlated with abnormal long-range FCD.Conclusion: Herpes zoster pain widely affects intra- and inter-regional functional connectivity, leading to disrupted short-range FCD and increased long-range FCD during different stages of the disease. Long-term chronic pain in PHN patients may impair the pain emotion regulation pathway. These findings could improve our understanding of the pathophysiological mechanisms of HZ and PHN and offer neuroimaging markers for HZ and PHN.Keywords: functional connectivity density, herpes zoster, postherpetic neuralgia, pain, functional magnetic resonance imaging

The directional ecological filtering hypothesis posits that species in high-altitude environments typically exhibit broad environmental tolerance, influencing the colonization success of non-native species through niche overlap with natives. This study examines this hypothesis on Changbai Mountain, focusing on the encroachment of the herb Deyeuxia angustifolia from mountain birch forests into alpine tundra, where it competes with the endemic Rhododendron aureum. We established a permanent plot containing 10,000 continuous quadrats (2 × 2 m) in the summer of 2014, covering from treeline to the upper limit of alpine tundra. Each quadrat was divided into 40 × 40 cm resolution cells, totaling 250,000 cells. In 2014 we photographed and manually interpreted tundra plant species for all cells, assessing topographic and edaphic niche characteristics (the range of the factors) for both species. Findings reveal: (1) Over 50 % niche overlap between D. angustifolia and R. aureum, suggesting intense competition; (2) Broader niche width for R. aureum compared to D. angustifolia; and (3) The expansion of D. angustifolia is facilitated by available nitrogen, while R. aureum is uniquely adapted to low phosphorus levels at higher altitudes. These results demonstrate that ecological and environmental filtering jointly shape distribution patterns of R. aureum and D. angustifolia, supporting the idea that environmental filtering is critical in the colonization of invading plant species. Our research sheds light on the pivotal roles played by microenvironmental factors, notably topography and soil, in determining the composition and distribution of plant communities, and contributes valuable insights for understanding and forecasting future shifts in plant composition of alpine tundra.

Woody plant encroachment (WPE), a global phenomenon documented across various biomes and continents, has the potential to significantly impact ecosystem carbon and water cycling. However, the impacts of WPE on carbon and water cycling in wetland ecosystems of middle and high latitudes are still lacking. In this study, the interannual and seasonal impacts of WPE on gross primary production (GPP) and evapotranspiration (ET), as well as their underlying mechanisms, within boreal wetland ecosystems located in middle-high latitude regions, were examined using remote sensing datasets spanning the period 2001–2016. Our results demonstrated that WPE enhanced annual GPP, ET, Normalized Difference Vegetation Index (NDVI), and solar-induced chlorophyll fluorescence (SIF) in boreal wetlands with impacts increasing over time. The multi-year average GPP and ET in fully encroached wetland ecosystems were approximately 31% and 3% higher, respectively, compared to pure wetland ecosystems. Prominent increases in wetland GPP occurred during the early growing season, while an exacerbation of ET was observed during the peak growing season. The impacts of WPE on wetland GPP and ET were predominantly attributed to increased vegetation greenness followed by secondary contributions from climate change. Climate change not only directly influenced the responses of GPP and ET to WPE but also exerted indirect effects by regulating vegetation greenness and the degree of encroachment. Our findings offer valuable insights into the understanding of the interaction between WPE and climate change, highlighting the importance of considering WPE effects and their drivers for accurate predictions of carbon and water cycles, as well as atmosphere–biosphere feedbacks in boreal wetlands.

Global climate change has markedly influenced the structure and distribution of mid-high-latitude forests. In the forest region of Northeast China, the magnitude of climate warming surpasses the global average, which presents immense challenges to the survival and habitat sustainability of dominant tree species. We predicted the potential changes in aboveground biomass, dominant tree species composition, and distribution in the forest region of Northeast China over the next century under different climatic conditions encompassing the current scenario and future scenarios (RCP2.6, RCP4.5, and RCP8.5). Forest ecosystem process model LINKAGES 3.0 was used to simulate dynamic changes in species-level aboveground biomass under four climate scenarios at the homogeneous land-type unit level. The potential spatial distribution of tree species was investigated based on three indicators: extinction, colonization, and persistence. The results showed that LINKAGES 3.0 model effectively simulated the aboveground biomass of 17 dominant tree species in the forest region of Northeast China, achieving a high accuracy with R² = 0.88. Under the current, RCP2.6, and RCP4.5 climate scenarios, the dominant tree species presented gradual increases in aboveground biomass, whereas under RCP8.5, an initial increase and subsequent decline were observed. With increasing warming magnitude, cold-temperate coniferous tree species will gradually be replaced by other temperate broad-leaved tree species. Furthermore, a large temperature increase under RCP8.5 will likely produce a significant contraction in the potential distribution range of tree species like Larch, Scotch pine, Ribbed birch, Spruce and Fir, while most temperate broad-leaved tree species and Korean pine are expected to demonstrate a northward migration. These findings provide guidance for enhancing the adaptability and resilience of forest ecosystems in middle and high latitudes and addressing the threats posed by climate warming.

Shebin Hong,1– 3,* Weidong Jiang,1– 3,* Qinfeng Ding,1– 3,* Kaili Lin,1– 3 Cancan Zhao,1– 3 Xudong Wang1– 3 1Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2College of Stomatology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xudong Wang; Cancan Zhao, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, No. 639, Zhizaoju Road, Shanghai, 200011, People’s Republic of China, Tel +86-21-23271699, Fax +86-21-63136856, Email wang70@hotmail.com; cc.zhao@sjtu.edu.cnAbstract: Recently, programmable assembly technologies have enabled the application of DNA in the creation of new nanomaterials with unprecedented functionality. One of the most common DNA nanostructures is the tetrahedral DNA nanostructure (TDN), which has attracted great interest worldwide due to its high stability, simple assembly procedure, high predictability, perfect programmability, and excellent biocompatibility. The unique spatial structure of TDN allows it to penetrate cell membranes in abundance and regulate cellular biological properties as a natural genetic material. Previous studies have demonstrated that TDNs can regulate various cellular biological properties, including promoting cells proliferation, migration and differentiation, inhibiting cells apoptosis, as well as possessing anti-inflammation and immunomodulatory capabilities. Furthermore, functional molecules can be easily modified at the vertices of DNA tetrahedron, DNA double helix structure, DNA tetrahedral arms or DNA tetrahedral cage structure, enabling TDN to be used as a nanocarrier for a variety of biological applications, including targeted therapies, molecular diagnosis, biosensing, antibacterial treatment, antitumor strategies, and tissue regeneration. In this review, we mainly focus on the current progress of TDN-based nanomaterials for antimicrobial applications, bone and cartilage tissue repair and regeneration. The synthesis and characterization of TDN, as well as the biological merits are introduced. In addition, the challenges and prospects of TDN-based nanomaterials are also discussed.Graphical Abstract: Keywords: tetrahedral DNA nanostructure, carriers, antibacterial treatment, bone regeneration, cartilage regeneration

Forest cover change directly affects the surface energy balance by altering the radiative and non-radiative properties of the surface. These competing processes may yield considerable biophysical impacts on local and regional climate that depend on background climate and specific forest type. Here we compared the differences in land surface temperature (LST) between temperate forests and adjacent croplands/grasslands to quantify the potential biophysical effects of transitions from croplands/grasslands to forests in Northeast China, based on multiple satellite observation products from 2001 to 2016. Forests were found to show a slight lower daytime LST and strong higher nighttime LST than adjacent croplands or grasslands. As a result, the daily LST of forests was 0.15 ± 0.06 ℃ and 0.32 ± 0.04 ℃ higher than that of croplands and grasslands, respectively. On the seasonal scale, the warming effect of cropland/grassland-to-forest transition during non-growing season outweighed the cooling effect during growing season, and dominated the annual positive LST response. Moreover, the cooling effect of cropland-to-forest transition during growing season was stronger in the early growth stage than late growth stage (−1.65 ± 0.9 ℃ in May to June, −0.39 ± 0.5 ℃ in July to September). The net cooling effect of warm temperate broadleaved forests was found to shift toward net warming effect of cold temperate coniferous forests with increasing latitude. The daytime cooling effect of forests was mainly driven by increased non-radiative evapotranspiration. Overall, the radiative process related to the solar energy dominated the net warming effect of forest transitions over Northeast China. Estimating the climate feedback potential of forests could be useful to provide theoretical references for the adaptation and mitigation strategies for climate change.

Understanding the physiological adaptations of non-treeline trees to environmental stress is important to understand future shifts in species composition and distribution of current treeline ecotone. The aim of the present study was to elucidate the mechanisms of the formation of the upper elevation limit of non-treeline tree species, Picea jezoensis, and the carbon allocation strategies of the species on Changbai Mountain. We employed the 13C in situ pulse labeling technique to trace the distribution of photosynthetically assimilated carbon in Picea jezoensis at different elevational positions (tree species at its upper elevation limit (TSAUE, 1,700 ​m a.s.l.) under treeline ecotone; tree species at a lower elevation position (TSALE, 1,400 ​m a.s.l.). We analyzed 13C and the non-structural carbohydrate (NSC) concentrations in various tissues following labeling. Our findings revealed a significant shift in carbon allocation in TSAUE compared to TSALE. There was a pronounced increase in δ13C allocation to belowground components (roots, soil, soil respiration) in TSAUE compared to TSALE. Furthermore, the C flow rate within the plant-soil-atmosphere system was faster, and the C residence time in the plant was shorter in TSAUE. The trends indicate enhanced C sink activity in belowground tissues in TSAUE, with newly assimilated C being preferentially directed there, suggesting a more conservative C allocation strategy by P. jezoensis at higher elevations under harsher environments. Such a strategy, prioritizing C storage in roots, likely aids in withstanding winter cold stress at the expense of aboveground growth during the growing season, leading to reduced growth of TSAUE compared to TSALE. The results of the present study shed light on the adaptive mechanisms governing the upper elevation limits of non-treeline trees, and enhances our understanding of how non-treeline species might respond to ongoing climate change.

Alpine treeline ecotones are highly sensitive to climate warming. The low temperature-determined alpine treeline is expected to shift upwards in response to global warming. However, little is known about how temperature interacts with other important factors to influence the distribution range of tree species within and beyond the alpine treeline ecotone. Hence, we used a GF-2 satellite image, along with bioclimatic and topographic variables, to develop an ensemble suitable habitat model based on the species distribution modeling algorithms in Biomod2. We investigated the distribution of suitable habitats for B. ermanii under three climate change scenarios (i.e., low (SSP126), moderate (SSP370) and extreme (SSP585) future emission trajectories) between two consecutive time periods (i.e., current–2055, and 2055–2085). By 2055, the potential distribution range of B. ermanii will expand under all three climate scenarios. The medium and high suitable areas will decline under SSP370 and SSP585 scenarios from 2055 to 2085. Moreover, under the three climate scenarios, the uppermost altitudes of low suitable habitat will rise to 2,329 ​m a.s.l., while the altitudes of medium and high suitable habitats will fall to 2,201 and 2,051 ​m a.s.l. by 2085, respectively. Warming promotes the expansion of B. ermanii distribution range in Changbai Mountain, and this expansion will be modified by precipitation as climate warming continues. This interaction between temperature and precipitation plays a significant role in shaping the potential distribution range of B. ermanii in the alpine treeline ecotone. This study reveals the link between environmental factors, habitat distribution, and species distribution in the alpine treeline ecotone, providing valuable insights into the impacts of climate change on high-elevation vegetation, and contributing to mountain biodiversity conservation and sustainable development.

One-part alkali-activated materials (AAMs) can preserve natural resources and lower embodied carbon of the built environment by accommodating various wastes, industrial by-products, and end-of-life materials in their composition. This study investigates the feasibility of using end-of-life bricks in two physical states, powder and aggregate, to partially replace fly ash precursor and natural aggregate in AAMs, respectively. The mechanical characteristics, microstructure, water absorption, freeze-thaw and fire resistance of the modified AAMs were evaluated. The effect of adding different ratios of nano graphite platelets was also investigated. Results showed that brick-based one-part AAMs can achieve mechanical properties, pore structure, water absorption and freeze-thaw resistance comparable to fly ash-based AAM while having 65% better fire resistivity. Incorporating bricks as aggregate resulted in a maximum improvement of 17% and 27% in the AAMs' compressive and flexural strength levels, respectively, and a general enhancement in the freeze-thaw resistance with showing no reduction in compressive strength after exposure to elevated temperature. Incorporating 0.1 wt% nano-graphite further enhanced flexural strength by 30%, decreased water absorption by 18% and improved freeze-thaw resistance compared to the mix without nano-graphite. Moreover, adding up to 0.5% nano-graphite enhanced the fire resistivity of the composite, allowing it to exhibit 19% better strength performance than before exposure.

Alkaline-activated materials (AAM) are potentially low-carbon alternative binders for the cement industry. Most research studies related to AAM have been performed with high-purity laboratory-grade NaOH alkaline activators (Lab-grade). Gaining confidence in AAM beyond the laboratory scale in real applications remains a major challenge. To make this prospect more realistic, the viability of low-purity industrial-grade (Ind.-grade) and local no-grade alkaline activators was investigated. The strength results of Ind.-grade AAM were 15–20% lower than those of Lab-grade AAM. The purity of the Ind.-grade activator should be at least 98% to achieve the performance of Lab-grade AAM. The production cost of Ind.-grade AAM was 75–85% lower than that of Lab-grade AAM at the same activator concentration. It should be noted that the use of no-grade NaOH is not recommended for engineering purposes due to its uncertain quality and low purity. The combined benefits of low cost and high availability of Ind.-grade activators are expected to enhance the commercial viability of AAM as a sustainable alternative construction material for field applications.

Abstract Aortic aneurysm is a chronic aortic disease affected by many factors. Although it is generally asymptomatic, it poses a significant threat to human life due to a high risk of rupture. Because of its strong concealment, it is difficult to diagnose the disease in the early stage. At present, there are no effective drugs for the treatment of aneurysms. Surgical intervention and endovascular treatment are the only therapies. Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm, the specific mechanisms remain unclear. Researchers are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and treatment. To better understand aortic aneurysm, this review elaborates on the discovery history of aortic aneurysm, main classification and clinical manifestations, related molecular mechanisms, clinical cohort studies and animal models, with the ultimate goal of providing insights into the treatment of this devastating disease. The underlying problem with aneurysm disease is weakening of the aortic wall, leading to progressive dilation. If not treated in time, the aortic aneurysm eventually ruptures. An aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic wall. The disease is usually asymptomatic but leads to high mortality due to the risk of artery rupture.

Anseo Choi,1,* Kaila Javius-Jones,2,* Seungpyo Hong,2 Hansoo Park1 1School of Integrative Engineering, Chung-Ang University, Seoul, Republic of Korea; 2Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, WI, USA*These authors contributed equally to this workCorrespondence: Hansoo Park; Seungpyo Hong, School of Integrative Engineering, Chung-Ang University, Seoul, 06974, Republic of Korea, Tel +82-2 820 5804, Fax +82-2 813 8159, Email heyshoo@cau.ac.kr; seungpyo.hong@wisc.eduAbstract: Nanoparticle-based drug delivery systems have been designed to treat various diseases. However, many problems remain, such as inadequate tumor targeting and poor therapeutic outcomes. To overcome these obstacles, cell-based drug delivery systems have been developed. Candidates for cell-mediated drug delivery include blood cells, immune cells, and stem cells with innate tumor tropism and low immunogenicity; they act as a disguise to deliver the therapeutic payload. In drug delivery systems, therapeutic agents are encapsulated intracellularly or attached to the surface of the plasma membrane and transported to the desired site. Here, we review the pros and cons of cell-based therapies and discuss their homing mechanisms in the tumor microenvironment. In addition, different strategies to load therapeutic agents inside or on the surface of circulating cells and the current applications for a wide range of disease treatments are summarized.Keywords: drug delivery, homing ability, tumor microenvironment, drug loading

The rate, frequency and extent of forest disturbances decreased in China over 1986–2020 probably due to forest protection policies, but while they intensified in the southeast, they weakened in the northeast, according to 30 m resolution Landsat satellite data

Abstract Key message We propose a coupled framework to combine the strengths of the Weibull function in modeling diameter distributions and the ability of the k-nearest neighbor (kNN) method to impute spatially continuous forest stand attributes for the prediction of wall-to-wall tree lists (lists of stems per hectare by species and diameter at breast height (DBH)) at regional scales. The tree lists of entire Northeast China’s forests predicted by the above framework reasonably reflect the species-specific tree density and diameter distributions. Context Detailed tree lists provide information about forest stocks disaggregated by species and size classes, which are crucial for forest managers to accurately characterize the current forest stand state to formulate targeted forest management strategies. However, regional tree list information is still lacking due to limited forest inventory. Aims We aimed to develop a coupled framework to enable the prediction of wall-to-wall tree lists for the entire forest region of Northeast China, then analyze the species-specific diameter distributions and reveal the spatial patterns of tree density by species. Methods A two-parameter Weibull function was used to model the species-specific diameter distributions in the sample plots, and a maximum likelihood estimation (MLE) was used to predict the parameters of the Weibull distributions. The goodness-of-fit of the predicted species-specific Weibull diameter distributions in each plot was evaluated by Kolmogorov-Smirnov (KS) test and an error index. The kNN model was used to impute the pixel-level stand mean DBH. Results Weibull distribution accurately described the species-specific diameter distributions. The imputed stand mean DBH from the kNN model showed comparable accuracy with earlier studies. No difference was detected between predicted and observed tree lists, with a small error index (0.24–0.58) of diameter distributions by species. The fitted species-specific diameter distributions generally showed a right-skewed unimodal or reverse J-shaped pattern. Conclusion Overall, the coupled framework developed in this study was well-suited for predicting the tree lists of large forested areas. Our results evidenced the spatial patterns and abundance of tree species in Northeast China and captured the forest regions affected by disturbances such as fire.

Background and objectiveWhole body manipulation of the renin-angiotensin system (RAS) consistently exerts profound effects on experimental atherosclerosis development. A deficit in the literature has been a lack of attention to the effects of sex. Also, based on data with gene-deleted mice, the site of RAS activity that influences lesion formation is at an unknown distant location. Since angiotensin (AngII) concentrations are high in kidney and the major components of the RAS are present in renal proximal tubule cells (PTCs), this study evaluated the role of the RAS in PTCs in atherosclerosis development.Methods and resultsMice with an LDL receptor −/− background were fed Western diet to induce hypercholesterolemia and atherosclerosis. We first demonstrated the role of AT1 receptor antagonism on atherosclerosis in both sexes. Losartan, an AngII type 1 (AT1) receptor blocker, had greater blood pressure-lowering effects in females than males, but equivalent effects between sexes in reducing atherosclerotic lesion size. To determine the roles of renal AT1a receptor and angiotensin-converting enzyme (ACE), either component was deleted in PTCs after weaning using a tamoxifen-inducible Cre expressed under the control of an Ndrg1 promoter. Despite profound deletion of AT1a receptor or ACE in PTCs, the absence of either protein did not influence development of atherosclerosis in either sex. Conversely, mice expressing human angiotensinogen and renin in PTCs or expressing human angiotensinogen in liver but human renin in PTCs did not change atherosclerotic lesion size in male mice.ConclusionWhole-body AT1R inhibition reduced atherosclerosis equivalently in both male and female mice; however, PTC-specific manipulation of the RAS components had no effects on hypercholesterolemia-induced atherosclerosis.

Can Feng,1,&ast; Shihui Hong,1,&ast; Rong Fan,1,&ast; Xinjie Shi,2 Zhao Ma,3 Changgui Li,4 Chenghao Liu,5 Cong He,6 Min Fan,1 Ruiping Wang7,8 1Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 2Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 3Department of Acupuncture and Moxibustion, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 4Department of Hematology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 5Department of Endocrinology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 6Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 7Clinical Research Center, Shanghai Skin Diseases Hospital, Tongji University, Shanghai, People’s Republic of China; 8School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Fan; Ruiping Wang, Email fanminyueyang@outlook.com; w19830901@126.comBackground: An epidemic of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in March 2022, and over 600,000 cases were confirmed until early May 2022 in Shanghai, China. Data on Omicron infections are available in other countries, but the clinical features of patients in the Chinese population, especially in Shanghai, are still lacking. We collected data from a subset of asymptomatic and mildly ill patients to learn about the age and sex disparity of Omicron infection based on changes in cycle threshold values.Methods: The basic information of 325 patients who were consecutively admitted to the Shanghai Geriatrics Center was collected through medical records, and patients were tested for viral nucleic acid carriage using nasal swab samples during hospitalization. SAS 9.4 was used for data analysis, and a p value < 0.05% was considered statistically significant.Results: Among the 325 included patients, 58.8% were males, with a mean age of 47.2 years and 13.6 days of hospitalization on average. The average number of nucleic acid tests among female patients was 4.7, which was higher than that among male patients (4.1). The median value of the slope for cycle threshold (Ct) changes in the nucleic acid detection (NAD) test was 1.4. Logistic regression indicated that the proportion of slope for Ct changes > 1.5 was slightly higher among male patients than among female patients (odds ratio (OR) = 1.06, 95% confidence interval (CI): 0.68– 1.66), and patients aged < 45 years and 45– 59 years had a higher proportion of slope for Ct changes > 1.5 than patients aged ≥ 60 years. Ct values were more variable in the early stages of infection and stabilized in the later stages of infection.Conclusion: Among patients with mild illness or asymptomatic infection, the Ct value is a good, timely, and cost-effective method to reflect the recovery progress of patients. The slope of Ct changes was steeper among younger patients and male patients, which indicates faster disease recovery.Keywords: COVID-19, SARS-CoV-2, cycle threshold, Omicron, RT‒PCR, nucleic acid tests

Hyungsub Kim,1 Shi Hyang Lee,2 Jina Jung,3 Sunghee Hong,3 Hyeong-Seok Lim2 1Department of Emergency Medical Services, College of Health Sciences, Eulji University, Seongnam, Republic of Korea; 2Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea; 3Hanmi Pharmaceutical Co. Ltd., Seoul, Republic of KoreaCorrespondence: Hyeong-Seok Lim, Tel +82-2-3010-4613, Fax +82-2-3010-4623, Email mdlhs@amc.seoul.krPurpose: The combined administration of tadalafil, a phosphodiesterase-5 inhibitor, and amlodipine, a calcium channel blocker, can be a promising therapeutic option for hypertension patients with erectile dysfunction. This study aimed to examine the pharmacokinetic drug interaction between tadalafil and amlodipine and the tolerability of their combined administration in healthy male subjects.Subjects and Methods: Healthy volunteers (N = 24) were randomly assigned to one of the six sequences that consisted of three treatments: tadalafil (5 mg) alone, amlodipine (10 mg) alone, and tadalafil plus amlodipine. The study drugs were administered orally for 9 d, and the collected serial blood samples were analyzed up to 72 h after the last dosing. Pharmacokinetic parameters were calculated using non-compartmental analysis.Results: For tadalafil, geometric mean ratios (GMRs) (90% confidence interval (CI)) of the combined therapy over the monotherapy were 1.57 (1.46– 1.68) for AUCτ,ss and 1.34 (1.24– 1.45) for Cmax,ss. For amlodipine, the GMRs (90% CI) of AUCτ,ss and Cmax,ss were 0.93 (0.90– 0.97) and 0.95 (0.91– 0.99), respectively. The severity of all observed adverse events (AEs) related to the study drugs was mild, and the frequency of AEs of the combined administration was not significantly different from the monotherapy.Conclusion: A substantial pharmacokinetic drug interaction between tadalafil and amlodipine was observed with respect to the concentration of tadalafil when administered concomitantly. However, the dose range of the combined administration of tadalafil and amlodipine in the present study was well tolerated by the subjects.Keywords: drug interaction, tadalafil, amlodipine, pharmacokinetics, tolerability

Xian Liu,1,&ast; Lili Gu,2,&ast; Jiaqi Liu,3 Shunda Hong,1 Qing Luo,1 Ying Wu,1 Jiaojiao Yang,1 Jian Jiang1 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Radiology, The Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Jiang, Department of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, People’s Republic of China, Tel +86 791 8869 3825, Email jij2002cn@126.comObjective: To measure the changes in cerebral cortical thickness in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN) by surface-based morphometry (SBM) and further estimate its correlation with clinical scores.Materials and Methods: Twenty-nine HZ patients, 30 PHN patients and 30 well-matched healthy controls (HCs) were included. Magnetic resonance imaging (MRI) data from all subjects were collected and then analyzed by SBM. The changes in cortical thickness among the HZ, PHN and HC groups were analyzed by ANOVA and correlated with clinical scores.Results: The thickness of the bilateral primary visual cortex (V1, V2) and right primary visual cortex (V3), left somatosensory cortex (L3A), right anterior cingulate gyrus and medial prefrontal cortex (RS32) increased in PHN group, and the thickness the left insular and frontal opercular cortex (LFOP4), left motor cortex (L3B), and right superior temporal visual cortex (RSTV) were decreased in the HZ and PHN groups compared to the HC group. The thickness measurements of RS32, LFOP4, and (L3B) in HZ and PHN patients were correlated with the duration of disease. In HZ and PHN patients, the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores were significantly positively correlated.Conclusion: Changes in cortical thickness in the areas related to sensory, motor, and cognitive/emotional changes in patients with PHN affect the neuroplasticity process of the brain, which may be the reason for the transformation of HZ into PHN and provide a possible explanation for the neuropathological mechanism of pain persistence in PHN patients.Keywords: postherpetic neuralgia, PHN, neuropathic pain, cortical thickness, surface-based morphometry, SBM

The mechanistic basis for the formation of aortic aneurysms and dissection needs to be elucidated to facilitate the development of effective medications. β-Aminopropionitrile administration in mice has been used frequently to study the pathologic features and mechanisms of aortic aneurysm and dissection. This mouse model mimics several facets of the pathology of human aortic aneurysms and dissection, although many variables exist in the experimental design and protocols that must be resolved to determine its application to the human disease. In the present brief review, we have introduced the development of this mouse model and provided insights into understanding its pathologic features.

Vascular smooth muscle cells (vSMCs) exert a critical role in sensing and maintaining vascular integrity. These cells abundantly express the low-density lipoprotein receptor–related protein 1 (LRP1), a large endocytic signaling receptor that recognizes numerous ligands, including apolipoprotein E–rich lipoproteins, proteases, and protease-inhibitor complexes. We observed the spontaneous formation of aneurysms in the superior mesenteric artery (SMA) of both male and female mice in which LRP1 was genetically deleted in vSMCs (smLRP1–/– mice). Quantitative proteomics revealed elevated abundance of several proteins in smLRP1–/– mice that are known to be induced by angiotensin II–mediated (AngII-mediated) signaling, suggesting that this pathway was dysregulated. Administration of losartan, an AngII type I receptor antagonist, or an angiotensinogen antisense oligonucleotide to reduce plasma angiotensinogen concentrations restored the normal SMA phenotype in smLRP1–/– mice and prevented aneurysm formation. Additionally, using a vascular injury model, we noted excessive vascular remodeling and neointima formation in smLRP1–/– mice that was restored by losartan administration. Together, these findings reveal that LRP1 regulates vascular integrity and remodeling of the SMA by attenuating excessive AngII-mediated signaling.

Dennd5b plays a pivotal role in intestinal absorption of dietary lipids in mice and is associated with body mass index in humans. This study examined the impact of whole-body Dennd5b deletion on plasma lipid concentrations, atherosclerosis, and hepatic lipid metabolism in mice. Hypercholesterolemia was induced in Dennd5b−/− mice by infection with an adeno-associated virus expressing the proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) gain-of-function mutation (PCSK9D377Y) and feeding a Western diet for 12 weeks. Body weight and plasma lipid concentrations were monitored over 12 weeks, and then aortic atherosclerosis and hepatic lipid content were quantified. Compared to Dennd5b+/+ mice, Dennd5b−/− mice were resistant to diet-induced weight gain and PCSK9-induced hypercholesterolemia. Atherosclerosis quantified by en face analysis and in aortic root sections, revealed significantly smaller lesions in Dennd5b−/− compared to Dennd5b+/+ mice. Additionally, Dennd5b−/− mice had significantly less hepatic lipid content (triglyceride and cholesterol) compared to Dennd5b+/+ mice. To gain insight into the basis for reduced hepatic lipids, quantitative PCR was used to measure mRNA abundance of genes involved in hepatic lipid metabolism. Key genes involved in hepatic lipid metabolism and lipid storage were differentially expressed in Dennd5b−/− liver including Pparg, Cd36, and Pnpla3. These findings demonstrate a significant impact of Dennd5b on plasma and hepatic lipid concentrations and resistance to PCSK9-induced hypercholesterolemia in the absence of Dennd5b.

Climate change has increased the severity, frequency, and impact of fire disturbance on boreal forests worldwide. Unusual fire events can trigger a shift from needle-leaf dominated forests to broad-leaf dominated forests, altering the original succession trajectory. Thus, it is necessary to identify how altered fire regimes affect boreal forest resilience or capacity to recover after fire disturbance. In this study, we used the post-fire tree recruitment density, the aboveground biomass, the understory shrub cover, and the herb cover as indicators of forest resilience. We explored the links between patterns of resilience and burn severity across topographic positions in two post-fire forests with different time since fire. We quantified how burn severity, time since fire, and topographic position affect resilience indicators related to post-fire overstory and understory recruitment in the Great Xing’an Mountains of Northeastern China. We found that burn severity and topographic position exhibited strong influences on post-fire overstory tree recruitment and aboveground biomass. Severe fire promoted deciduous needle-leaf tree (larch) recruitment in lowland sites by removing a thick organic layer. In contrast, severe fire promoted broad-leaf tree (birch and aspen) recruitment in south-facing upland sites with relatively warmer and drier microclimates. Therefore, severe fire disturbance may trigger a post-fire species shift from larch dominated forest to broad-leaf forest, especially in south-facing upland sties. We also found that the understory may be more resilient to high severity fire than the overstory, because severity had short-term effects on post-fire understory recruitment. Our study suggested that burn severity was a crucial factor that affects boreal forest resilience through substantially altering resilience indicators related to post-fire overstory tree recruitment.

Chunyan Wang,1,2,&ast; Zhengyun Chen,1,&ast; Xianlei Zhao,2,&ast; Cuicui Lin,2 Shenghui Hong,3 Yuhan Lou,2 Xiaomeng Shi,1 Mengdan Zhao,1 Xiaohang Yang,1,2 Min-Xin Guan,2 Yongmei Xi1,2 1The Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, People’s Republic of China; 2Institute of Genetics, Zhejiang University; Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang Provincial Key Laboratory of Genetic & Developmental Disorders, Hangzhou, Zhejiang, 310058, People’s Republic of China; 3Laboratory Animal Center of Zhejiang University, Hangzhou, Zhejiang, 310001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongmei Xi; Min-Xin Guan Tel +86-0571-88206623; +86-0571-88981371Email xyyongm@zju.edu.cn; gminxin88@zju.edu.cnIntroduction: Endometriosis (EMs) is associated with severe chronic pelvic pain and infertility and the development of improved EMs treatment options is an ongoing focus. In this study, we investigated the effects of resveratrol on EMs and analyzed transcriptional changes in the lesions of model rats before and after resveratrol treatment.Methods: We established arat model of endometriosis through the trans-implantation of endometrial fragments to the peritoneal wall and then used resveratrol as treatment. We then analyzed the results using RNA sequencing of the lesion tissues of each of the model rats before resveratrol treatment and the reduced lesion tissues after the treatment. Examinations of anatomy, biochemistry, immunohistochemical staining and flow cytometry examinations were also conducted. Other trans-implanted rats were also given sham treatments as sham-treatment control and other untrans-implanted rats served as sham-operation controls.Results: In addition to the obvious lesions observed in the model rats, there were significant differences in the glucose tolerance, macrophage M1/M2 polarization, and adipocyte sizes between the treated model rats and sham (control) rats. Resveratrol treatment in the model rats showed significant efficacy and positive therapeutic effect. Transcriptional analysis showed that the effects of resveratrol on the endometriosis model rats were manifested by alterations in the PPAR, insulin resistance, MAPK and PI3K/Akt signaling pathways. Correspondingly, changes in PPARγ activation, M1/M2 polarization and lipid metabolism were also detected after resveratrol treatment.Discussion: Our study revealed that resveratrol treatment displayed efficient therapeutic effects for EMs model rats, probably through its important roles in anti-inflammation, immunoregulation and lipid-related metabolism regulation.Keywords: endometriosis, resveratrol, RNA-seq, glucose tolerance, PPAR&#x03B3

Abstract Primary pulmonary meningioma (PPM) is a very rare and mostly benign disease. Although PPM is incidentally detected as a solitary pulmonary nodule on X‐ray or chest computed tomography, it does not have unique radiological characteristics; thus, it is difficult to differentiate it from other lung tumors. A healthy 54‐year‐old man visited our hospital because of multiple variable‐sized lung nodules. He had no contributive medical history and no abnormality that was suggestive of extrapulmonary malignancy. Video‐assisted thoracoscopic wedge resection was undertaken for diagnosis, and the tumor cells were histopathologically confirmed as PPM. Brain magnetic resonance imaging revealed no intracranial tumor. The patient has been well and without any progression of the remaining lesions over 24 months. Here, we present the clinicopathological features of this case in which the patient's nodules were mistaken for multiple metastatic lung nodules.

Background A single dose of small interfering RNA (siRNA) targeting liver angiotensinogen eliminates hepatic angiotensinogen and lowers blood pressure. Angiotensinogen elimination raises concerns for clinical application because an angiotensin rise is needed to maintain perfusion pressure during hypovolemia. Here, we investigated whether conventional vasopressors can raise arterial pressure after angiotensinogen depletion. Methods and Results Spontaneously hypertensive rats on a low‐salt diet were treated with siRNA (10 mg/kg fortnightly) for 4 weeks, supplemented during the final 2 weeks with fludrocortisone (6 mg/kg per day), the α‐adrenergic agonist midodrine (4 mg/kg per day), or a high‐salt diet (all groups n=6–7). Pressor responsiveness to angiotensin II and norepinephrine was assessed before and after siRNA administration. Blood pressure was measured via radiotelemetry. Depletion of liver angiotensinogen by siRNA lowered plasma angiotensinogen concentrations by 99.2±0.1% and mean arterial pressure by 19 mm Hg. siRNA‐mediated blood pressure lowering was rapidly reversed by intravenous angiotensin II or norepinephrine, or gradually reversed by fludrocortisone or high salt intake. Midodrine had no effect. Unexpectedly, fludrocortisone partially restored plasma angiotensinogen concentrations in siRNA‐treated rats, and nearly abolished plasma renin concentrations. To investigate whether this angiotensinogen originated from nonhepatic sources, fludrocortisone was administered to mice lacking hepatic angiotensinogen. Fludrocortisone did not increase angiotensinogen in these mice, implying that the rise in angiotensinogen in the siRNA‐treated rats must have depended on the liver, most likely reflecting diminished cleavage by renin. Conclusions Intact pressor responsiveness to conventional vasopressors provides pharmacological means to regulate the blood pressure–lowering effect of angiotensinogen siRNA and may support future therapeutic implementation of siRNA.

Current increases in not only the intensity and frequency but also the duration of drought events could affect the growth, physiology, and mortality of trees. We experimentally studied the effects of drought duration in combination with fertilization on leaf water potential, gas exchange, growth, tissue levels of non-structural carbohydrates (NSCs), tissue NSC consumption over-winter, and recovery after drought release in oak (Quercus petraea) and beech (Fagus sylvatica) saplings. Long drought duration (>1 month) decreased leaf water potential, photosynthesis, and NSC concentrations in both oak and beech saplings. Nitrogen fertilization did not mitigate the negative drought effects on both species. The photosynthesis and relative height increment recovered in the following rewetting year. Height growth in the rewetting year was significantly positively correlated with both pre- and post-winter root NSC levels. Root carbon reserve is critical for tree growth and survival under long-lasting drought. Our results indicate that beech is more sensitive to drought and fertilization than oak. The present study, in a physiological perspective, experimentally confirmed the view that the European beech, compared to oak, may be more strongly affected by future environmental changes.

Zhenkun Yan,1 Sen Hong,2 Yumei Song,3 Miaomiao Bi4 1Department of Endoscopy Center, The Third Hospital of Jilin University, Changchun, Jilin, 130022, People’s Republic of China; 2Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130022, People’s Republic of China; 3Department of Thoracic Oncology, Tumor Hospital of Jilin Province, Changchun, Jilin, 130022, People’s Republic of China; 4Department of Ophthalmology, The Third Hospital of Jilin University, Changchun, Jilin, 130022, People’s Republic of ChinaCorrespondence: Sen HongDepartment of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130022, People’s Republic of ChinaEmail hongsen@jlu.edu.cnZhenkun YanDepartment of Endoscopy Center, The Third Hospital of Jilin University, Changchun, Jilin, 130022, People’s Republic of ChinaEmail yanzhenkun@jlu.edu.cnIntroduction: Dysregulation of microRNAs (miRNAs), which represented a critical level of gene expression modulation, regulated the development of colorectal cancer. However, the functions of numerous miRNAs remain unclear in colorectal cancer.Methods: The microarray data of GSE115513 were retrieved; subsequently, the differentially expressed miRNAs between 411 colon tumors and 381 normal colon mucosa were analyzed. Real-time PCR (RT-qPCR) and bioinformatic analysis were applied to examine the expression of miR-4449 in collected colorectal tumors and published microarray data. The activity of signal transducer and activator of transcription 3 (STAT3) signaling was detected by Western blotting and RT-qPCR. Dual-Luciferase assay and bioinformatic analysis were used to confirm the interaction between suppressor of cytokine signaling 3 (SOCS3) and miR-4449. Loss of function and rescue assays were performed to study the involvement of miR-4449 and SOCS3 in cell proliferation and apoptosis of colorectal cancer.Results: Herein, we identified miR-4449 as a novel upregulated miRNA in colorectal cancer. Our data suggested that miR-4449 downregulation blocked the proliferation of colorectal cancer cells accompanied with the elevation of cell apoptosis. Decreased expression of miR-4449 led to inactivation of STAT3 pathway as indicated by dephosphorylation of STAT3 and downregulation of STAT3 target genes, including vascular endothelial growth factor (VEGF), c-Myc, baculovirus inhibitor of apoptosis containing 5 (BIRC5). Furthermore, SOCS3, a negative regulator of STAT3 pathway, was found to be a target gene of miR-4449. The data also showed that the inactivation of STAT3 pathway by miR-4449 inhibitor was realized by targeting SOCS3. Moreover, the biological function of miR-4449 downregulation was reversed by SOCS3 knockdown in colorectal cancer cells.Conclusion: The current study revealed that miR-4449 promoted cell proliferation of colorectal cancer and was a promising potential therapeutic target for colorectal cancer.Keywords: STAT3, microR-4449, colorectal cancer, SOCS3

The poor natural regeneration of Pinus koraiensis is a key limitation for restoring the primary mixed Pinus koraiensis forests. Seed harvesting and climate change are the important factors that influence the natural regeneration of Pinus koraiensis; however, it is hard to illustrate how, in synergy, they affect its regeneration at the landscape scale. In this study, we coupled an ecosystem process model, LINKAGES, with a forest landscape model, LANDIS PRO, to evaluate how seed harvesting and climate change influenced the natural regeneration of Pinus koraiensis over large temporal and spatial scales. Our results showed that seed harvesting decreased the abundance of Pinus koraiensis juveniles by 1, 14, and 18 stems/ha under the historical climate, and reduced by 1, 17, and 24 stems/ha under the future climate in the short- (years 0–50), medium- (years 60–100), and long-term (years 110–150), respectively. This indicated that seed harvesting intensified the poor regeneration of Pinus koraiensis, irrespective of climate change. Our results suggested that seed harvesting diminished the generation capacity of Pinus koraiensis over the simulation period. Seed harvesting reduced the abundance of Pinus koraiensis at the leading edge and slowed down its shift into high-latitude regions to adapt to climate change. Our results showed that the effect magnitudes of seed harvesting, climate change, their interaction and combination at the short-, medium- and long-term were −61.1%, −78.4%, and −85.7%; 16.5%, 20.9%, and 38.2%; −10.1%, −16.2% and −32.0%; and −54.7%, −73.8%, and −79.5%, respectively. Seed harvesting was a predominant factor throughout the simulation; climate change failed to offset the negative effect of seed harvesting, but the interactive effect between seed harvesting and climate change almost overrode the positive effect of climate change. Seed harvesting, climate change, and their interaction jointly reduced the natural regeneration of Pinus koraiensis. We suggest reducing the intensity of seed harvesting and increasing silvicultural treatments, such as thinning and artificial plantation, to protect and restore the primary mixed Pinus koraiensis forests.

To respond to the NIH's policy for rigor and reproducibility in preclinical research, many journals have implemented guidelines and checklists to guide authors in improving the rigor and reproducibility of their research. Transparency in developing detailed prospective experimental designs and providing raw data are essential premises of rigor and reproducibility. Standard peer reviews and journal-specific technical and statistical reviews are critical factors for enhancing rigor and reproducibility. This brief review also shares some experience from Arteriosclerosis, Thrombosis, and Vascular Biology, an American Heart Association journal, that has implemented several mechanisms to enhance rigor and reproducibility for preclinical research.

Category: Ankle; Basic Sciences/Biologics Introduction/Purpose: The treatment of syndesmotic injuries with ankle fractures is controversial. The purpose of this study was to compare the biomechanical properties of suture-button fixation with suture-tape augmentation with those of screw fixation. Methods: Ten matched pairs of human cadaver specimens were subjected to suture-button fixation with suture-tape augmentation or screw fixation. Each specimen underwent initial intact physiologic loading, consisting of 10 cycles of axial loading with peak of 750N, 10 cycles of external torsional loading with peak of 7.5Nm, and 10 cycles of combined axial and external torsional loading with peak of 750N and 7.5Nm at 0.05 Hz. Injuries of the anterior inferior tibiofibular ligament, tibiofibular interosseous membrane, posterior tibiofibular ligament and medial malleolar fracture were applied to each specimen. Postfixation cyclic loading consisted of 50 cycles of combinedaxial and external rotation loading with peak torques of 750 N and 7.5 Nm at a rate of 0.05 Hz. After postfixation loading, each specimen underwent failure loading by external rotation at 0.25 degrees/second. Failure torque and failure angle were measured. Results: Mean failure torques were 15.99 +- 8.88 Nm in the suture-button fixation with suture-tape augmentation and 17.10 +- 10.38 Nm in the screw group. There was no significant difference in average failure torque between two groups (p-value = 0.669)Average failure angle in screw-fixation group (39.37 +- 10.19 deg) was significantly lower than average failure angle suture- button fixation with suture-tape augmentation (56.64 +- 9.64 deg) (p-value = 0.001).Average rotational stiffness in screw-fixation group (0.53 +- 0.24 Nm/deg) was significantly higher than average rotational stiffness in suture-button fixation with suture-tape augmentation group (0.35 +- 0.19 Nm/deg) (p-value = 0.033). Conclusion: Suture-button fixation with suture-tape augmentation for ankle syndesmotic injury provides similar torsional strength to that of screw fixation and has lower stiffness than screw fixation. Therefore, Suture-button fixation with suture-tape augmentation can be considered as an alternative treatment option for syndesmosis injury.

Bin Zhu,1 Binhua Dong,2 Simei Hong,3 Meihua Wang,1 Weichao Dai,4 Qingzhu Zheng,1 Dan Wu,5 Yingping Cao1 1Department of Clinical Laboratorial Examination, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 2Department of Gynecology, Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Pathology, Fujian Provincial Cancer Hospital, Fuzhou, People’s Republic of China; 4Department of Gynecology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 5Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of ChinaCorrespondence: Yingping CaoDepartment of Clinical Laboratorial Examination, Fujian Medical University Union Hospital, NO. 29, Xinquan Road, Fuzhou City, Fujian Province, People’s Republic of ChinaTel +86-591-86218678Email caoyingping@aliyun.comBinhua DongDepartment of Gynecology, Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, NO. 18, Daoshan Road, Fuzhou, Fujian 350001, People’s Republic of ChinaTel +86-591-87558732Fax +86-591-87551247Email dbh18-jy@126.comPurpose: Cervical cancer (CC) is a common malignancy in women. Squamous cell carcinoma antigen (SCC-Ag) and cancer antigen (CA)-125 are widely used to help diagnose CC, but novel tumour markers with superior sensitivity and specificity are needed. α-Actinin 4(ACTN4) is overexpressed in CC, though its diagnostic value for CC is unclear. This study examined the diagnostic value of ACTN4 and SCC-Ag as biomarkers for cervical intraepithelial neoplasia (CIN) 3 or worse.Methods: Women screened for CC at Fujian Medical University Union Hospital were recruited from 2017.1 to 2018.5. Cervical tissues and blood were collected at the same time. Patients pathologically diagnosed as CIN3+ or NILM/CIN1/CIN2 were classified into the case and control groups, respectively. ACTN4 mRNA and protein levels were detected through quantitative PCR and immunohistochemistry, respectively, and ACTN4 and SCC-Ag concentrations were analysed by ELISA. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood rate (PLR), negative likelihood rate (NLR), and Youden index (YI) of ACTN4 and SCC-Ag were evaluated. The optimum cut-off points for ACTN4 and SCC-Ag were determined by receiver operating characteristic (ROC) curve analysis, and accuracy was evaluated by the area under the ROC curve.Results: In total, 105 patients were classified as CIN3+ cases and 106 as controls. The median ACTN4 levels in case and control tissues were 10.6 and 4.15, respectively. The ACTN4 and SCC-Ag concentrations were significantly higher in cases than controls (PACTN4=0.0007; PSCC-Ag=0.0067). The sensitivity, specificity, PPV, NPV, PLR, NLR and YI of ACTN4 were 68.6%, 76.3%, 76.3%, 72.5%, 2.89, 0.41 and 44.9, respectively; SCC-Ag had a similar diagnostic value (P> 0.05), and ACTN4 combined with SCC-Ag had a superior diagnostic value (75.6%, 87.5%, 88.6%, 73.7%, 6.05, 0.28, and 63.1, respectively).Conclusion: Combined ACTN4 and SCC-Ag detection is a promising serological biomarker for patients with CIN3 or worse.Keywords: ACTN4, SCC-Ag, CIN3 or worse, serological biomarker

Chen Chen,1,2,* Xuanye Zhang,2,3,* Yixin Zhou,2,4,* Sha Fu,5 Zuan Lin,2,6 Shaodong Hong,2,3 Li Zhang2,3 1Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 3Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 4Department of VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 5Pathology Department, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 6Department of Clinical Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaodong Hong; Li ZhangSun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, People’s Republic of ChinaTel +86-15920527656; +86-13902282893Fax +862087342480; +862087343392Email hongshd@sysucc.org.cn; zhangli6@mail.sysu.edu.cnPurpose: The purpose of this study was to evaluate the anti-tumor activity and safety of anti-epidermal growth factor receptor (EGFR) monoclonal antibody combined with gemcitabine plus platinum (GP) as a first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC).Patients and Methods: This retrospective study analyzed RM-NPC patients at Sun Yat-sen University Cancer Center who received anti-EGFR antibody plus GP as a first-line treatment between July 2007 and November 2018. Survival analyses were performed using the Kaplan–Meier method with Log rank test. Cox proportional hazards model was used for the multivariate analysis.Results: A total of 84 patients were enrolled. The median progression-free survival (PFS) was 10.3 months (95% CI, 6.9– 13.6 months), and the median overall survival (OS) was 42.8 months (95% CI, 24.6– 60.9 months). The objective response rate and disease control rate were 67.9% and 92.9%, respectively. The multivariate analysis identified a higher baseline EBV DNA level as a risk factor for both PFS (P=0.025) and OS (P=0.013). Additionally, age≥ 44 years (P =0.003), non-cisplatin (P= 0.009), and poor KPS (≤ 80) (P =0.034) were other risk factors for OS. The most common adverse events were leukopenia (n=73, 86.9%). The most common grade 3– 4 AEs were leukopenia (n=30, 35.7%) and thrombocytopenia (n=22, 26.2%).Conclusion: Anti-EGFR monoclonal antibody plus GP achieved promising antitumor activity with a tolerable toxicity profile in RM-NPC as a first-line treatment. Randomized clinical trials are warranted to compare the efficacy of GP with or without anti-EGFR antibody in these patients.Keywords: advanced cancer, chemotherapy, oncology, targeted therapy

A colorimetric chemosensor for hydrogen peroxide (H2O2) and biosensor for cholesterol is developed in this work following a ‘label-free and reagentless’ concept. In this strategy, silver nanoparticles (AgNPs) are used as a bifunctional probe, namely, a chemical capture probe for H2O2 recognition and a signal probe for displaying detection results. The working principle of these colorimetric sensors is based on the redox reaction between AgNPs and H2O2. This reaction converts AgNPs into Ag+ ions, which can induce a visible color change from yellow to pinkish or colorless depending on the amount of H2O2. Therefore, H2O2 concentration can be measured. The developed colorimetric H2O2 chemosensor exhibits a highly selective and sensitive property towards H2O2 with a limit of detection (LOD) of 3.5 μM. Subsequently, a colorimetric biosensor is developed for cholesterol detection by combining AgNPs and cholesterol oxidase (ChOx) enzyme. Here, ChOx oxidizes cholesterol into cholest-4-en-3-one and H2O2. Then, the detected as-generated H2O2 concentration reflects the cholesterol level in the sample. This cholesterol biosensor exhibits high selectivity and sensitivity for cholesterol detection with a LOD of 40 μM. The developed sensor is successfully applied to the detection of cholesterol levels in serum samples. Our results show that the AgNP–based colorimetric method is cost-effective, sensitive and selective. It has potential applications in H2O2 and cholesterol detection and in clinical and medical diagnoses.

Category: Diabetes Introduction/Purpose: Some patients with below knee (BK) amputation for treatment of ischemic and/or infectious foot disease eventually further progress to above knee (AK) amputation. We aimed to analyze predictors for sequential AK amputation after BK amputation. Methods: We retrospectively reviewed medical records and find 55 patients with BK amputation for surgical treatment of ischemic and/or infectious foot from 2013 to 2018. Twelve patients with sequential AK amputation after BK amputation were designated as group I, and 43 patients successfully treated with BK amputation only were designated as group II. Two groups were compared for various demographic, laboratory and physical state. Then, multivariate logistic regression analysis was done to find predictors for sequential AK amputation after BK amputation. Results: In univariate analysis between two groups, only 'knee contracture' showed significant difference between two groups (p= 0.003). In multivariate logistic regression analysis performed with variables showing p

Adequate seed provenance is an important guarantee for the restoration of the mixed Korean pine (Pinus koraiensis) and broadleaf forest (MKPBF). However, the commercial harvest exclusion in natural forests has led to a sharp decline in economic income from timber. Given the economic value of Korean pine seeds, predatory seed harvesting (PSH) has become increasingly serious in the past 20 years and has significantly reduced the seed and seedling bank, which might seriously threaten the restoration and sustainable management of the MKPBF. How the historical PSH has affected the future of the MKPBF is unclear at the landscape scale. In this study, we quantified the effects of seed harvesting at the landscape scale by a forest landscape model LANDIS PRO, and then assessed the legacy effects of the historical PSH on the composition and structure of the MKPBF in the Xiaoxing’an Mountains, Northeast China. Our results showed that the historical PSH decreased the Korean pine basal area of all age cohorts, with an average decrease of 0.06 to 0.19 m2 ha−1 but insignificantly altered the age structure diversity of Korean pine throughout the simulation. Our results indicated that the historical PSH remarkably decreased the dominance of Korean pine by 11.1%, but significantly increased the dominance of spruce (Picea koraiensis and Picea jezoensis) and fir (Abies nephrolepis) by 3.8% and 4.5%, respectively, and had an insignificant effect on the other tree species over the simulation. We found that the historical PSH evidently changed the succession trajectories of the disturbed stands, which would result in the transition from the succession pattern dominated by Korean pine to that dominated by spruce and fir. The historical PSH decreased the importance value of Korean pine by 12.2% on average but increased it by 5.1% and 6.0% for spruce and fir, respectively, and resulted in an average 33.2% increase in the dissimilarity index compared with the initial state during the whole simulation period. Future forest management should strictly limit the intensity and rotation of seed harvesting to protect the seed provenance of Korean pine and consider how to ensure the recovery and sustainable management of the MKPBF through direct seeding or seedling planting.

Nonalcoholic fatty liver disease (NAFLD) is considered as a liver manifestation of metabolic disorders. Previous studies indicate that the renin-angiotensin system (RAS) plays a complex role in NAFLD. As the only precursor of the RAS, decreased angiotensinogen (AGT) profoundly impacts RAS bioactivity. Here, we investigated the role of hepatocyte-derived AGT in liver steatosis. AGT floxed mice (hepAGT+/+) and hepatocyte-specific AGT-deficient mice (hepAGT−/−) were fed a Western diet and a normal laboratory diet for 12 weeks, respectively. Compared with hepAGT+/+ mice, Western diet-fed hepAGT−/− mice gained less body weight with improved insulin sensitivity. The attenuated severity of liver steatosis in hepAGT−/− mice was evidenced by histologic changes and reduced intrahepatic triglycerides. The abundance of SREBP1 and its downstream molecules, acetyl-CoA carboxylase and FASN, was suppressed in hepAGT−/− mice. Furthermore, serum derived from hepAGT+/+ mice stimulated hepatocyte SREBP1 expression, which could be diminished by protein kinase B (Akt)/mammalian target of rapamycin (mTOR) inhibition in vitro. Administration of losartan did not affect diet-induced body weight gain, liver steatosis severity, and hepatic p-Akt, p-mTOR, and SREBP1 protein abundance in hepAGT+/+ mice. These data suggest that attenuation of Western diet-induced liver steatosis in hepAGT−/− mice is associated with the alternation of the Akt/mTOR/SREBP-1c pathway.

Permeable pavements are used to mitigate urban flooding. However, conventional concrete permeable pavements have low compressive strength and are prone to clogging, which degrades performance and reduces service life. A new type of permeable pavement, high-strength clogging resistant permeable pavement (CRP), has recently been developed that overcomes many limitations of conventional permeable pavements. This paper presents a new design methodology for CRP that takes into account both structural and hydrological considerations. This is used in 12 case studies which compare CRP with conventional permeable pavements. The results highlight several advantages of CRP and demonstrate that CRP with low porosity (∼5%) can cope with severe rainfall run-off volumes. The suitability of using CRP in both light and heavy load bearing applications is demonstrated. The research also shows that the use of CRP allows considerable reductions in pavement depth compared to conventional permeable pavements with reduced material costs.

Objective: Elevated plasma cholesterol concentrations contributes to ischemic cardiovascular diseases. Recently, we showed that inhibiting hepatic (pro)renin receptor [(P)RR] attenuated diet-induced hypercholesterolemia and hypertriglyceridemia in low-density lipoprotein receptor (LDLR) deficient mice. The purpose of this study was to determine whether inhibiting hepatic (P)RR could attenuate atherosclerosis.Approach and Results: Eight-week-old male LDLR−/− mice were injected with either saline or N-acetylgalactosamine-modified antisense oligonucleotides (G-ASOs) primarily targeting hepatic (P)RR and were fed a western-type diet (WTD) for 16 weeks. (P)RR G-ASOs markedly reduced plasma cholesterol concentrations from 2,211 ± 146 to 1,128 ± 121 mg/dL. Fast protein liquid chromatography (FPLC) analyses revealed that cholesterol in very low-density lipoprotein (VLDL) and intermediate density lipoprotein (IDL)/LDL fraction were potently reduced by (P)RR G-ASOs. Moreover, (P)RR G-ASOs reduced plasma triglyceride concentrations by more than 80%. Strikingly, despite marked reduction in plasma lipid concentrations, atherosclerosis was not reduced but rather increased in these mice. Further testing in ApoE−/− mice confirmed that (P)RR G-ASOs reduced plasma lipid concentrations but not atherosclerosis. Transcriptomic analysis of the aortas revealed that (P)RR G-ASOs induced the expression of the genes involved in immune responses and inflammation. Further investigation revealed that (P)RR G-ASOs also inhibited (P)RR in macrophages and in enhanced inflammatory responses to exogenous stimuli. Moreover, deleting the (P)RR in macrophages resulted in accelerated atherosclerosis in WTD fed ApoE−/− mice.Conclusion: (P)RR G-ASOs reduced the plasma lipids in atherosclerotic mice due to hepatic (P)RR deficiency. However, augmented pro-inflammatory responses in macrophages due to (P)RR downregulation counteracted the beneficial effects of lowered plasma lipid concentrations on atherosclerosis. Our study demonstrated that hepatic (P)RR and macrophage (P)RR played a counteracting role in atherosclerosis.

Aortic aneurysms and dissections (AAD) are devastating aortic diseases with high risks for aortic rupture, leading to uncontrolled bleeding and death [...]

Kiyoung Lee,1,2 Ie Byung Park,1,2 Seung Hee Yu,2 Soo-Kyung Kim,3 So Hun Kim,4 Da Hea Seo,4 Seongbin Hong,4 Ja Young Jeon,5 Dae Jung Kim,5 Soo Wan Kim,6 Cheol Soo Choi,1,2 Dae Ho Lee1,21Department of Internal Medicine, Gachon University College of Medicine, Incheon, Republic of Korea; 2Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea; 3Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea; 4Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea; 5Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea; 6Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of KoreaAim: We aimed to evaluate the clinical utility of blood ketone measurement and to test the performance of the diagnostic criteria for diabetic ketoacidosis (DKA) issued by the American Diabetes Association, the Joint British Diabetes Societies, and the American Association of Clinical Endocrinologists and the American College of Endocrinology.Methods: This retrospective analysis included 278 patients with suspected DKA who were hospitalized at 4 university hospitals and aged ≥16 years with a blood glucose level of >200 mg/dL and a blood ketone level of ≥1.0 mmol/L as well as other biochemical data. The patients were categorized into four subgroups (ketosis, typical DKA, atypical DKA, and DKA + lactic acidosis). Atypical DKA in each analysis was defined by our supplementary criteria if the biochemical data did not meet each set of diagnostic criteria from the aforementioned societies.Results: Blood ketone levels in patients with diabetic ketosis and those with DKA varied widely, 1.05–5.13 mmol/L and 1.02–15.9 mmol/L, respectively. Additionally, there were significant discrepancies between the guidelines in the diagnosis of DKA. Thus, the proportion of patients with atypical DKA ranged from 16.5% to 42.4%. Notably, the in-hospital mortality was comparable between patients with typical and atypical DKA, with a very high mortality in patients with DKA + lactic acidosis (blood lactate >5 mmol/L).Conclusions: Our results showed that considering variable presentations of DKA, blood ketone data need to be interpreted cautiously along with other biochemical data and suggested that a new system is required to better characterize DKA.Keywords: Diabetic ketoacidosis, ketone bodies, diagnosis, lactic acidosis, acid base imbalance

Jiaqi Liu,1,* Lili Gu,2,* Qing Huang,1 Shunda Hong,1 Xianjun Zeng,1 Daying Zhang,2 Fuqing Zhou,1 Jian Jiang1 1Department of Radiology, 2Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to measure brain alterations in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN) and compare their differences using a voxel-based morphometry (VBM) technique. Materials and methods: Thirty-three patients with HZ, 22 patients with PHN, and 28 well-matched healthy controls (HCs) were recruited. Magnetic resonance imaging data were acquired for all subjects and analyzed using the VBM method. The changes in gray matter volume (GMV) in HZ and PHN groups were compared with those in HC group, and the GMV differences were also compared between the PHN and HZ groups. Further correlation analysis and receiver operating characteristic curves were used to confirm the significance of GMV changes in various brain regions. Results: Compared with HCs, decreased GMV was found in the bilateral insular lobes and increased GMV was found in the bilateral thalamus in the HZ group. In the PHN group, GMV decreased in the bilateral insula lobes, right middle frontal gyrus, bilateral precentral gyrus, and left postcentral gyrus and increased in the left cerebellar posterior lobe, right parahippocampal gyrus, and right lentiform nucleus. In addition, the PHN group exhibited increased GMV in the left cerebellar tonsil, culmen, and left lentiform nucleus and decreased GMV in the right precentral gyrus compared with the HZ group. Further correlation analysis and receiver operating characteristic curves revalidate the significance of most of these abnormal brain regions. Conclusion: The VBM method revealed widespread GMV abnormalities in HZ and PHN patients. The brains of PHN patients have broader abnormalities in nonpain-related regions, suggesting the complexity of a central mechanism. When PHN patients were compared with HZ patients, the left cerebellar tonsil, culmen, and left lentiform nucleus corresponded to greater area under the curve, suggesting that abnormalities in these regions are risk factors for HZ patients’ transformation to PHN. Keywords: chronic pain, neuroimaging, ROC, fMRI, VBM

Angiotensin II (AngII) infusion in mice has been used widely to investigate mechanisms of abdominal aortic aneurysms (AAAs). To achieve a high incidence of AngII-induced AAAs, mice should be hypercholesterolemic. Therefore, either low-density lipoprotein receptor (LDLR) or apolipoprotein E deficiency have been used as a hypercholesterolemic background. However, it is a time-consuming and expensive process to generate compound deficient strains that have either an LDLR or apolipoprotein E deficient background. Proprotein convertase subtilisin/kexin type 9 (PCSK9) facilitates the degradation of LDL receptors. Previous studies demonstrated profound increases of plasma cholesterol concentrations after a single intraperitoneal injection of adeno-associated viruses (AAV) expressing a gain-of-function mutation of mouse PCSK9 (AAV.mPCSK9D377Y) in C57BL/6J mice fed a Western diet. Of note, injection of AAV.mPCSK9D377Y augmented AngII-induced AAA formation in C57BL/6J mice that had comparable severity of AAAs to LDLR deficient mice. Thus, AAV.mPCSK9D377Y infection greatly expedites studies on a gene of interest using AngII-induced AAAs. This commentary provides a brief technical guide of this approach and discusses the pros and cons of its use in AAA research.

Background and Objective: In an experiment designed to explore the mechanisms of fludrocortisone-induced high blood pressure, we serendipitously observed aortic aneurysms in mice infused with fludrocortisone. The purpose of this study was to investigate whether fludrocortisone induces aortic pathologies in both normocholesterolemic and hypercholesterolemic mice. Methods and Results: Male adult C57BL/6J mice were infused with either vehicle (85% polyethylene glycol 400 (PEG-400) and 15% dimethyl sulfoxide (DMSO); n = 5) or fludrocortisone (12 mg/kg/day dissolved in 85% PEG-400 and 15% DMSO; n = 15) for 28 days. Fludrocortisone-infused mice had higher systolic blood pressure, compared to mice infused with vehicle. Fludrocortisone induced aortic pathologies in 4 of 15 mice with 3 having pathologies in the ascending and aortic arch regions and 1 having pathology in both the ascending and descending thoracic aorta. No pathologies were noted in abdominal aortas. Subsequently, we infused either vehicle (n = 5/group) or fludrocortisone (n = 15/group) into male ApoE −/− mice fed a normal laboratory diet or LDL receptor −/− mice fed either normal or Western diet. Fludrocortisone increased systolic blood pressure, irrespective of mouse strain or diet. In ApoE −/− mice infused with fludrocortisone, 2 of 15 mice had ascending aortic pathologies, but no mice had abdominal aortic pathologies. In LDL receptor −/− mice fed normal diet, 5 had ascending/arch pathologies and 1 had pathologies in the ascending, arch, and suprarenal aortic regions. In LDL receptor −/− mice fed Western diet, 2 died of aortic rupture in either the descending thoracic or abdominal region, and 2 of the 13 survived mice had ascending/arch aortic pathologies. Aortic pathologies included hemorrhage, wall thickening or thinning, or dilation. Only ascending aortic diameter in LDLR −/− mice fed Western diet reached statistical significance, compared to their vehicle. Conclusion: Fludrocortisone induces aortic pathologies independent of hypercholesterolemia. As indicated by the findings in mouse studies, people who are taking or have taken fludrocortisone might have an increased risk of aortic pathologies.

Lili Gu,1,* Shunda Hong,2,* Jian Jiang,2 Jiaqi Liu,2 Xintian Cao,1 Qing Huang,2 Xianjun Zeng,2 Fuqing Zhou,2 Daying Zhang1 1Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China 2Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Purpose: Postherpetic neuralgia (PHN) detrimentally affects brain function. Recent studies have suggested that frequency-dependent changes in electroencephalography in chronic pain patients and blood oxygenation level dependent (BOLD) fluctuations can reflect neuronal activity in different frequencies. The current study aimed to investigate PHN-related brain oscillatory activity in a specific frequency band by using the amplitude of low-frequency fluctuation (ALFF) method.Materials and methods: ALFF changes were analyzed across different frequencies (slow-4 band: 0.027–0.073 Hz; slow-5 band: 0.01–0.027 Hz; and typical band: 0.01–0.08 Hz) in the brains of PHN patients and compared with those in the brains of healthy controls (HCs) during resting-state fMRI. Eighteen HCs and PHN patients underwent fMRI scanning.Results: In the typical band, compared with HCs, PHN patients showed prominently decreased ALFF in the right prefrontal cortex (Brodmann area 10/46) and increased ALFF in the bilateral brain stem/cerebellum anterior lobe (BS/CAL). In the slow-4 band, PHN patients exhibited significantly decreased ALFF in the bilateral cuneus/lingual gyrus and the right prefrontal cortex. In the slow-5 band, PHN patients presented significantly increased ALFF in the bilateral BS/CAL and left parieto-occipital cortex. Moreover, the increased ALFF in the left parieto-occipital cortex in the slow-5 band was positively correlated with VAS scores (P=0.022), and the increased ALFF in the bilateral BS/CAL in the slow-5 band was positively correlated with disease duration (P=0.020).Conclusion: Our results suggested that the intrinsic brain activity of PHN patients was abnormal and frequency dependent, especially the bidirectional alteration in ALFF across the slow-4 and slow-5 frequencies in the brains of PHN patients. Keywords: amplitude of low-frequency fluctuation, postherpetic neuralgia, functional magnetic resonance imaging, resting state, pain