Highly integrated, self-powered and activatable bipedal DNA nanowalker for imaging of base excision repair in living cells.

DNA walkers have attracted considerable attention in biosensing and bioimaging. Compared with the conventional single leg-based DNA walker, the bipedal DNA walker has remarkable advantages, with improved sensitivity and fast kinetics, and can work efficiently in a crowded cellular environment. However, most reported bipedal DNA walkers are powered by exogenous supplementation, and elaborate DNA sequence designs, auxiliary additives or extra carriers are often needed. A highly integrated bipedal DNA walker that can address robustness, sensitivity and consistency issues in a single system is highly desirable but remains a great challenge. We herein report a novel bipedal DNA nanowalker system through simple assembly of a DNA substrate, hairpin functionalized-AuNPs (AuNPs-H2), and a blocked Mn2+-dependent DNAzyme hairpin (H1) on degradable MnO2 nanosheets, which holds great potential for living cell operation. Highly integrated features enable the simultaneous delivery of core components of the bipedal DNA walker, including a walking track (AuNPs-H2), a walking strand (H1 cleaved by APE1), and a driving force (Mn2+-dependent DNAzyme cleavage) as a whole, thereby enhancing the control of the spatiotemporal distribution of these components at the intracellular target sites. The redox reaction between the MnO2 nanosheets and GSH inside the cells not only consumed the intracellular GSH to improve the biostability of the walking track but also generated abundant Mn2+ as a cofactor of the DNAzyme. As a proof of concept, the developed nanowalker was demonstrated to work efficiently for monitoring base excision repair (BER)-related human apurinic/apyrimidinic endonuclease 1 (APE1) in living cells, highlighting the great potential of the bipedal DNA nanowalker in biological systems.

Contribution of gut microbiota to hepatic steatosis following F-53B exposure from the perspective of glucose and fatty acid metabolism.

Altered gut microbiota is a pathogenic mechanism of 6:2 Cl-PFESA (F-53B)-induced hepatic steatosis, indicated by correlations between gut microbiota and lipid indices. However, the detailed mechanism remains unknown. In this study, adult zebrafish were exposed to 0.25, 5 and 100 µg/L F-53B for 28 days to explore how microbiota regulate hepatic lipid metabolism from the perspective of glucose and fatty acid metabolism. Results showed glucose and fatty acids were transported from blood into liver after 100 µg/L F-53B exposure, in which glucose was further transformed into acetyl-CoA and fatty acid. The accumulated fatty acids were then converted into triglycerides (TGs), inducing hepatic steatosis. Changes in the abundances of certain gut microbiota contributed to the above processes, which was verified by the fact that the levels of g_Crenobacter, g_Shewanella, and g_Vibrio restored to control levels after Lactobacillus rhamnosus GG intervention, and the levels of their related lipid indicators recovered partially towards the control levels. 0.25 and 5 µg/L F-53B had no effect on the hepatic lipid profile due to the few changed TG synthesis related indicators. Our findings provide novel insights into lipid metabolic disorders caused by F-53B exposure, highlighting the health risks linked to gut microbial dysbiosis.

A unified evaluation descriptor for π-bridges applied to metalloporphyrin derivatives.

Establishing the structure of porphyrins with a A-π-D-π-A configuration is one of the effective strategies to maintain their dominance and compensate shortcomings through flexible changes in fragments. In this regard, π-bridges have attracted wide attention as a parameter affecting molecular backbones, electron transfer, energy levels, absorption, and other properties. However, the essence and influence of π-bridges have not yet been confirmed. In order to satisfy the requirements of intelligent application in molecular design, this study aimed to investigate the control effect of differences in π-bridge composition (thiophene and selenophene) and connection type (single bonds, ethylenic bonds and fused) on photoelectric performance. Y6 and PC61BM were used as acceptors to build donor/acceptor (D/A) interfaces and characterize the film morphology in three dimensions. Results showed that the essence of π-bridges involves a strong bridging effect (adjusting ability) between A and D fragments rather than highlighting its own nature. The large value could obtain high open circuit voltages (VOC), large separation and small recombination rates as well as stable and tight morphology. Therefore, adjusting ability is a unified descriptor for evaluating π-bridges, and it is an effective strategy to adjust material properties and morphology. This insight and discovery may provide a new evaluation descriptor for the screening and design of π-bridges.

Sucurchalasins A and B, Sulfur-Containing Heterodimers of a Cytochalasan and a Macrolide from the Endophytic Fungus Aspergillus spelaeus GDGJ-286.

Two sulfur-containing heterodimers of a cytochalasan and a macrolide, sucurchalasins A and B (1 and 2), and four known cytochalasan monomers (3-6), as well as four known macrolide derivatives (7-10), were obtained from the endophytic fungus Aspergillus spelaeus GDGJ-286. Sucurchalasins A and B (1 and 2) are the first cytochalasan heterodimers formed via a thioether bridge between cytochalasan and curvularin macrolide units. Their structures were elucidated by detailed analysis of NMR, LC-MS/MS, and X-ray crystallography. In bioassays, 1 and 2 exhibited cytotoxic effects on A2780 cells, with IC50 values of 3.9 and 8.3 µM, respectively. They also showed antibacterial activities against E. faecalis and B. subtilis with MIC values of 3.1 and 6.3 µg/mL, respectively.

A Visual Analysis of Patient-Reported Outcomes in Lung Cancer From 2013 to 2023.

BACKGROUND: Lung cancer is the most common cancer in the world and has become one of the malignancies with the highest incidence and mortality; more than half of patients die within one year of being diagnosed with lung cancer. In recent years, the concept of "patient-centered" service has gained popularity, and patients' subjective feelings have gradually been used in clinical decision-making. Therefore, this study determined the application of visual patient report outcomes in the field of lung cancer, in order to provide reference for specific clinical practice. METHODS: Using the Web of Science core collection as the main analysis content, Citespace and VOSviewer were used to conduct this scientometric study. RESULTS: A total of 499 literatures that met the inclusion criteria were retrieved. The most prolific institution was The University of Texas MD Anderson Cancer Center, and the United States dominates this field. CONCLUSION: The measurement of patient-reported outcomes is considered the gold standard for effectively evaluating patients' perceptions of clinical interventions or diseases. It is recommended that patient-reported outcomes be integrated into routine care for cancer patients in order to enhance communication between patients and healthcare providers. PATIENT OR PUBLIC CONTRIBUTION: Not applicable. All data in this paper are obtained from the web of science database.

Full-length GSDME mediates pyroptosis independent from cleavage.

Gasdermin (GSDM) family proteins, known as the executors of pyroptosis, undergo protease-mediated cleavage before inducing pyroptosis. We here discovered a form of pyroptosis mediated by full-length (FL) GSDME without proteolytic cleavage. Intense ultraviolet-C irradiation-triggered DNA damage activates nuclear PARP1, leading to extensive formation of poly(ADP-ribose) (PAR) polymers. These PAR polymers are released to the cytoplasm, where they activate PARP5 to facilitate GSDME PARylation, resulting in a conformational change in GSDME that relieves autoinhibition. Moreover, ultraviolet-C irradiation promotes cytochrome c-catalysed cardiolipin peroxidation to elevate lipid reactive oxygen species, which is then sensed by PARylated GSDME, leading to oxidative oligomerization and plasma membrane targeting of FL-GSDME for perforation, eventually inducing pyroptosis. Reagents that concurrently stimulate PARylation and oxidation of FL-GSDME, synergistically promoting pyroptotic cell death. Overall, the present findings elucidate an unreported mechanism underlying the cleavage-independent function of GSDME in executing cell death, further enriching the paradigms and understanding of FL-GSDME-mediated pyroptosis.

Effects of insonification on repairing the renal injury of diabetic nephropathy rats.

INTRODUCTION: Prolonged hyperglycemia in diabetes mellitus can result in the development of diabetic nephropathy (DN) and increase the susceptibility to kidney failure. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive modality that has demonstrated effective tissue repair capabilities. The objective of this study was to showcase the reparative potential of LIPUS on renal injury at both animal and cellular levels, while also determining the optimal pulse length (PL). RESEARCH DESIGN AND METHODS: We established a rat model of DN, and subsequently subjected the rats' kidneys to ultrasound irradiation (PL=0.2 ms, 10 ms, 20 ms). Subsequently, we assessed the structural and functional changes in the kidneys. Additionally, we induced podocyte apoptosis and evaluated its occurrence following ultrasound irradiation. RESULTS: Following irradiation, DN rats exhibited improved mesangial expansion and basement membrane thickening. Uric acid expression increased while urinary microalbumin, podocalyxin in urine, blood urea nitrogen, and serum creatinine levels decreased (p<0.05). These results suggest that the optimal PL was 0.2 ms. Using the optimal PL further demonstrated the reparative effect of LIPUS on DN, it was found that LIPUS could reduce podococyte apoptosis and alleviate kidney injury. Metabolomics revealed differences in metabolites including octanoic acid and seven others and western blot results showed a significant decrease in key enzymes related to lipolysis (p<0.05). Additionally, after irradiating podocytes with different PLs, we observed suppressed apoptosis (p<0.05), confirming the optimal PL as 0.2 ms. CONCLUSIONS: LIPUS has been demonstrated to effectively restore renal structure and function in DN rats, with an optimal PL of 0.2 ms. The mechanism underlying the alleviation of DN by LIPUS is attributed to its ability to improve lipid metabolism disorder. These findings suggest that LIPUS may provide a novel perspective for future research in this field.

Unmasking Spatial Heterogeneity in Phytotoxicology Mechanisms Induced by Carbamazepine by Mass Spectrometry Imaging and Multiomics Analyses.

Previous studies have highlighted the toxicity of pharmaceuticals and personal care products (PPCPs) in plants, yet understanding their spatial distribution within plant tissues and specific toxic effects remains limited. This study investigates the spatial-specific toxic effects of carbamazepine (CBZ), a prevalent PPCP, in plants. Utilizing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), CBZ and its transformation products were observed predominantly at the leaf edges, with 2.3-fold higher concentrations than inner regions, which was confirmed by LC-MS. Transcriptomic and metabolic analyses revealed significant differences in gene expression and metabolite levels between the inner and outer leaf regions, emphasizing the spatial location's role in CBZ response. Notably, photosynthesis-related genes were markedly downregulated, and photosynthetic efficiency was reduced at leaf edges. Additionally, elevated oxidative stress at leaf edges was indicated by higher antioxidant enzyme activity, cell membrane impairment, and increased free fatty acids. Given the increased oxidative stress at the leaf margins, the study suggests using in situ Raman spectroscopy for early detection of CBZ-induced damage by monitoring reactive oxygen species levels. These findings provide crucial insights into the spatial toxicological mechanisms of CBZ in plants, forming a basis for future spatial toxicology research of PPCPs.

Enhanced recovery after surgery in elderly patients with non-small cell lung cancer who underwent video-assisted thoracic surgery.

BACKGROUND: This study was designed to investigate the clinical outcomes of enhanced recovery after surgery (ERAS) in the perioperative period in elderly patients with non-small cell lung cancer (NSCLC). AIM: To investigate the potential enhancement of video-assisted thoracic surgery (VATS) in postoperative recovery in elderly patients with NSCLC. METHODS: We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS (the ERAS group) and 327 elderly NSCLC patients who received routine care (the control group) after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017. After propensity score matching of baseline data, we analysed the postoperative stay, total hospital expenses, postoperative 48-h pain score, and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection. RESULTS: After propensity score matching, ERAS significantly reduced the postoperative hospital stay (6.96 ± 4.16 vs 8.48 ± 4.18 d, P = 0.001) and total hospital expenses (48875.27 ± 18437.5 vs 55497.64 ± 21168.63 CNY, P = 0.014) and improved the satisfaction score (79.8 ± 7.55 vs 77.35 ± 7.72, P = 0.029) relative to those for routine care. No significant between-group difference was observed in postoperative 48-h pain score (4.68 ± 1.69 vs 5.28 ± 2.1, P = 0.090) or postoperative complication rate (21.2% vs 27.1%, P = 0.371). Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection. CONCLUSION: ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.

Fungal-Bacterial Mutualism: Species and Strain-Dependent Simultaneous Modulation of Branched-Chain Esters and Indole Derivatives in Fermented Sausages through Metabolite Cross-Feeding.

The precise impact of species and strain diversity on fungal-bacterial interactions and the overall community functioning has remained unclear. First, our study revealed how Debaryomyces hansenii influences diverse bacteria to accumulate key metabolites in a simulated fermented food system. For flavor, D. hansenii promoted the accumulation of branched-chain esters in Staphylococcus xylosus by promoting growth and facilitating the precursor branched-chain acids transformations but hindered the accumulation of Staphylococcus equorum. Furthermore, fungal-bacterial interactions displayed diversity among S. equorum strains. For bioactive compounds, species and strain diversity of lactic acid bacteria (LAB) also influences the production of indole derivatives. Then, we investigated specific metabolic exchanges under reciprocal interaction. Amino acids, rather than vitamins, were identified as the primary drivers of the bacterial growth promotion. Moreover, precursor transformations by D. hansenii played a significant role in branched-chain esters production. Finally, a synthetic community capable of producing high concentrations of branched-chain esters and indole derivatives was successfully constructed. These results provide valuable insights into understanding and designing synthetic communities for fermented sausages.

Recent advances in functional nucleic acid decorated nanomaterials for cancer imaging and therapy.

Nanomaterials possess unusual physicochemical properties including unique optical, magnetic, electronic properties, and large surface-to-volume ratio. However, nanomaterials face some challenges when they were applied in the field of biomedicine. For example, some nanomaterials suffer from the limitations such as poor selectivity and biocompatibility, low stability, and solubility. To address the above-mentioned obstacles, functional nucleic acid has been widely served as a powerful and versatile ligand for modifying nanomaterials because of their unique characteristics, such as ease of modification, excellent biocompatibility, high stability, predictable intermolecular interaction and recognition ability. The functionally integrating functional nucleic acid with nanomaterials has produced various kinds of nanocomposites and recent advances in applications of functional nucleic acid decorated nanomaterials for cancer imaging and therapy were summarized in this review. Further, we offer an insight into the future challenges and perspectives of functional nucleic acid decorated nanomaterials.

Per- and polyfluoroalkyl substances induce lipid metabolic impairment in fish: Integration on field investigation and laboratory study.

The biotoxicity of perfluoroalkyl and polyfluoroalkyl substances (PFASs) to aquatic organisms has been widely concerned. However, studies on toxic effects of PFASs are usually evaluated directly by using laboratory exposure rather than laboratory validation based on data obtained in the field. In this study, wild catfish (Silurus meridinalis) was explored on the relationship between PFASs bioaccumulation and lipid disorders. Nine and thirteen lipid metabolites were significantly associated with perfluorooctane sulfonate (PFOS) and 6:2/8:2Cl-PFESA (trade name F-53B) exposures, respectively; and the correlated lipid metabolites were the fatty acid (FA) and conjugates, FA esters, steroids, and glycerophosphate subclasses. The effects of PFASs on lipid metabolism of fish and its mechanism were further analyzed through exposure experiments. Zebrafish (Danio rerio) of different sexes underwent PFOS and F-53B exposures for 21 days at 100 ng/L and 100 µg/L. By determining gene expression levels, hepatic lipid contents, and histopathological change, the adverse effects order on lipid metabolism in male or female was 100 µg/L F-53B > 100 µg/L PFOS > 100 ng/L F-53B > 100 ng/L PFOS; the stress response in male was more intensive than that in female. PFOS and F-53B activated the peroxisome proliferator-activated receptor pathway, promoting the processes of FA and total cholesterol (T-CHO) transport, FA ß-oxidation, FA synthesis, and finally induced FA and T-CHO transportation from blood into liver, then accelerated FA to FA ester transformation, and CHO into steroids. Laboratory experiments confirmed the field analysis. This study innovatively explored the adverse effects of PFOS and F-53B on lipid metabolism and their mechanisms at field and laboratory levels, highlighting concerns regarding PFASs health risks.

Effects of Low-Intensity Pulsed Ultrasound on the Regulation of Free Fatty Acid Release in 3T3-L1 Cells.

OBJECTIVES: To investigate the effects of low-intensity pulsed ultrasound (LIPUS) on the proliferation, differentiation, and tumor necrosis factor-α (TNF-α)-induced lipolysis of 3T3-L1 cells, and to explore the feasibility of regulating the release of free fatty acids (FFA) to prevent lipotoxicity. METHODS: Different intensities (30, 60, 90, and 120 mW/cm2) of LIPUS were applied to 3T3-L1 preadipocytes for different durations (5, 10, 15, 20, 25, and 30 minutes). Appropriate parameters for subsequent experiments were selected by assessing cell viability. The effect of LIPUS on the proliferation and differentiation of 3T3-L1 cells was evaluated by microscope observation, flow cytometry, and lipid content determination. After treated with LIPUS and TNF-α (50 ng/mL), the degree of lipolysis was assessed by measuring the extracellular FFA content. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of relevant genes. RESULTS: Different parameters of LIPUS significantly enhance the viability of 3T3-L1 cells (P < .05), with 20 minutes and 30 mW/cm2 as the most suitable settings. After LIPUS treatment, 3T3-L1 cell proliferation accelerated, apoptosis rate and G1 phase cell proportion decreased, the content of lipid droplets and TG was increased in differentiated cells, while FFA release decreased (P < .05). The expression of PCNA, PPARγ, C/EBPα, Perilipin A mRNA increased, and the expression of TNF-α, ATGL, HSL mRNA decreased (P < .05). CONCLUSIONS: LIPUS could promote the proliferation and differentiation of 3T3-L1 cells and inhibit TNF-α-induced lipolysis, indicating its potential as a therapy for mitigating lipotoxicity caused by decompensated adipocytes.

Bibliometric and visual analysis of photodynamic therapy for lung cancer from 2010 to 2022.

Background: A growing body of research shows that photodynamic therapy (PDT) has become an important mode of treatment in the field of lung cancer (LC) in recent years. Although numerous papers related to PDT in LC have been published, no bibliometric studies have been conducted to summarize the research prospects and highlight the research trends and hotspots in this field. This bibliometric analysis was conducted to investigate and provide a systematic understanding of the development of PDT research for LC over the past 13 years with the aim of providing a reference for new directions and strategies in the field of PDT for LC. Methods: In May 2023, relevant publications from the Web of Science Core Collection were downloaded, and CiteSpace and VOSviewer were used to conduct the scientometrics analysis in this study.Results: A total of 2,932 articles and reviews that met the inclusion criteria were retrieved, with China dominated the volume of publications from 2010 to 2022 and the most prolific institution was Shanghai Jiao Tong University. Conclusions: PDT can be utilized for the diagnosis and treat LC. Bronchoscopic fluorescence diagnosis using photosensitizers helps to detect tumor changes in the large bronchial mucosa. In the future, we should actively explore the use of new photosensitizers, including the development of nanomaterials, in addition, PDT combined with other treatments can significantly prolong survival. This combination therapy may also be the direction of future research.

Xianglian Pill combined with 5-fluorouracil enhances antitumor activity and reduces gastrointestinal toxicity in gastric cancer by regulating the p38 MAPK/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Perioperative or postoperative adjuvant chemotherapy based on 5-fluorouracil (5-FU) is a common first-line adjuvant therapy for gastric cancer (GC). However, drug resistance and the side effects of 5-FU have reduced its efficacy. Among these side effects, gastrointestinal (GI) toxicity is one of the most common. Xianglian Pill (XLP) is a Chinese patent medicine that is commonly used for the treatment of diarrhoea. It can reduce inflammation and has a protective effect on the intestinal mucosa. Recent studies have shown that many components of XLP can inhibite tumor cell growth. However, the therapeutic effect of XLP in combination with 5-FU on GC is unclear. AIM OF THE STUDY: To investigate whether the combination of XLP and 5-FU can enhance anti-GC activity while reducing GI toxicity. MATERIALS AND METHODS: XLP was administered orally during intraperitoneal injection of 5-FU in GC mice model. Mice were continuously monitored for diarrhea and xenograft tumor growth. After 2 weeks, the mice were sacrificed and serum was collected to determine interleukin-6 levels. Pathological changes, the expression of pro-inflammatory factors and p38 mitogen-activated protein kinase (MAPK) in GI tissue were determined by Western blot analysis. Pathological changes, apoptosis levels and p38 MAPK expression levels in xenograft tissues were also determined. RESULTS: The results showed that XLP could alleviate GI mucosal injury caused by 5-FU, alleviated diarrhea, and inhibited the expression of nuclear factor (NF)-κB and myeloid differentiation primary response-88. Besides, XLP could promote the 5-FU-induced apoptosis of GC cells and enhance the inhibitory effect of 5-FU on tumor xenografts. Further study showed that XLP administration could regulate the expression of p38 MAPK. CONCLUSIONS: XLP in combination with 5-FU could alleviate its GI side effects and enhance its inhibitory effect on xenograft tumor. Moreover, these effects were found to be related to the regulation of the p38 MAPK/NF-κB pathway.

Evaluation of biomass sources on the production of biofuels from lignocellulosic waste over zeolite catalysts.

Catalytic fast pyrolysis (CFP) is a promising method to convert biomass waste into sustainable bio-oils. However, the relationship gap between biomass characteristics and bio-oil quality has hindered the development of CFP technology. This study investigated the pyrolysis and CFP of ten biomass sources over zeolites, and showed that biomass sources and zeolites played important roles in bio-oil production. For noncatalytic trials, the bio-oil yield was positively related to holocellulose (R2 = 0.75) and volatiles content (R2 = 0.62) but negatively to ash content (R2 = -0.65). The bio-oil quality was dramatically improved after catalyst addition. For CFP over ZSM-5, hydrocarbons selectivity of bio-oils was increased by 1.6∼79.3 times, which was closely related to H/C ratio (R2 = 0.79). For ZSM-5@SBA-15 trials, the dependency of hydrocarbons selectivity on biomass characteristics was less clear than that in ZSM-5 counterparts, although undesirable PAHs were inhibited for most biomass sources. This study demonstrated the influence mechanism of biomass characteristics on bio-oil compositions.

Azvudine for the Treatment of COVID-19 in Pre-Existing Cardiovascular Diseases: A Single-Center, Real-World Experience.

COVID-19 can lead to adverse outcomes in patients with pre-existing diseases. Azvudine has been approved for treating COVID-19 in China, but the real-world data is limited. It is aimed to investigate the efficacy of Azvudine in patients with COVID-19 and pre-existing cardiovascular diseases. Patients with confirmed COVID-19 and pre-existing cardiovascular diseases are retrospectively enrolled. The primary outcome is all-cause death during hospitalization. Overall, 351 patients are included, with a median age of 74 years, and 44% are female. 212 (60.6%) patients are severe cases. Azvudine is used in 106 (30.2%) patients and not in 245 (69.8%). 72 patients died during hospitalization. After multivariate adjustment, patients who received Azvudine a lower risk of all-cause death (hazard ratio: 0.431; 95% confidence interval: 0.252-0.738; p = 0.002) than controls. Azvudine therapy is also associated with lower risks of shock and acute kidney injury. For sensitivity analysis in the propensity score-matched cohort (n = 90 for each group), there is also a significant difference in all-cause death between the two groups (hazard ratio: 0.189; 95% confidence interval: 0.071-0.498; p < 0.001). This study indicated that Azvudine therapy is associated with better outcomes in COVID-19 patients with pre-existing cardiovascular diseases.

Prevalence of thalassemia-carrier couples and fertility risk assessment.

Thalassemia is a highly prevalent hematologic disease in Guizhou, China. This study aimed to determine the epidemiological characteristics of thalassemia in couples at childbearing age and assess the neonatal risk of thalassemia in this subpopulation. A cohort of 4481 couples at childbearing age were recruited for thalassemia carrier screening by both traditional hematological tests and next-generation sequencing. Of them, 1314 (14.66%) thalassemia carriers were identified, including 857 (9.76%) α-thalassemia, 391 (4.36%) ß-thalassemia, and 48 (0.54%) composite α and ß-thalassemia. A total of 12 α-globin gene alterations and 16 ß-globin mutations were detected, including four novel thalassemia mutations. SEA was the most common α-thalassemia genotype (26.86%), CD41-42 the most common ß-thalassemia genotype (36.57%), and αα/- α3.7 + CD41-42 the most common composite α- and ß-thalassemia genotype (18.75%). Ethnically, the Zhuang had the highest rate of thalassemia gene carriers among the ethnic groups. Geographically, Qiannan had the highest rate of thalassemia gene carriers. In addition, 38 of the 48 couples with composite α- and ß-thalassemia were high-risk thalassemia carriers, and 4 carrying the -SEA/αα gene needed fertility guidance.

Blood-based biomarkers of cerebral small vessel disease.

Age-associated cerebral small vessel disease (CSVD) represents a clinically heterogenous condition, arising from diverse microvascular mechanisms. These lead to chronic cerebrovascular dysfunction and carry a substantial risk of subsequent stroke and vascular cognitive impairment in aging populations. Owing to advances in neuroimaging, in vivo visualization of cerebral vasculature abnormities and detection of CSVD, including lacunes, microinfarcts, microbleeds and white matter lesions, is now possible, but remains a resource-, skills- and time-intensive approach. As a result, there has been a recent proliferation of blood-based biomarker studies for CSVD aimed at developing accessible screening tools for early detection and risk stratification. However, a good understanding of the pathophysiological processes underpinning CSVD is needed to identify and assess clinically useful biomarkers. Here, we provide an overview of processes associated with CSVD pathogenesis, including endothelial injury and dysfunction, neuroinflammation, oxidative stress, perivascular neuronal damage as well as cardiovascular dysfunction. Then, we review clinical studies of the key biomolecules involved in the aforementioned processes. Lastly, we outline future trends and directions for CSVD biomarker discovery and clinical validation.

Pathological diagnosis and immunohistochemical analysis of giant retrosternal goiter in the elderly: A case report.

BACKGROUND: Elderly giant retrosternal thyroid goiter is a rare yet significant medical condition, often presenting clinical symptoms that can be confused with other diseases, posing diagnostic and therapeutic challenges. This study aims to delve into the characteristics and potential mechanisms of this ailment through pathological diagnosis and immunohistochemical analysis, providing clinicians with more precise diagnostic and treatment strategies. CASE SUMMARY: A 77-year-old male, was admitted to hospital with the chief complaint of finding a goiter in the semilunar month during physical examination, accompanied by dyspnea. Locally protruding into the superior mediastinum, the adjacent structure was compressed, the trachea was compressed to the right, and the local lumen was slightly narrowed. The patient was diagnosed with giant retrosternal goiter. Considering dyspnea caused by trachea compression, our department planned to perform giant retrosternal thyroidectomy. Immunohistochemical results: Tg (+), TTF-1 (+), Calcitonin (CT) (I), Ki-67 (+, about 20%), CD34 (-). Retrosternal goiter means that more than 50% of the volume of the thyroid gland is below the upper margin of the sternum. As retrosternal goiter disease is a relatively rare disease, once the disease is diagnosed, it should be timely surgical treatment, and the treatment is more difficult, the need for professional medical team for comprehensive treatment. CONCLUSION: The imaging manifestations of giant retrosternal goiter are atypical, histomorphology and immunohistochemistry can assist in its diagnosis. This article reviews the relevant literature of giant retrosternal goiter immunohistochemistry and shows that giant retrosternal goiter is positive for Tg, TTF-1, and Ki-67.