A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

OBJECTIVE To analyze the components migrating to blood and metabolites of Polygonum cuspidatum in rats with acute gouty arthritis （AGA）. METHODS SD rats were randomly divided into blank group， model group and P. cuspidatum group （10 g/kg， by raw material）， with 6 rats in each group. Except for blank group， AGA model was induced in the remaining groups by injecting potassium oxonate and sodium urate； meanwhile， they were administered corresponding drug solutions or water intragastrically， once a day， for 10 consecutive days. The histopathological morphology of the knee joint tissues in rats was observed；rat serum samples were collected， and the components migrating to blood and metabolites of P. cuspidatum were analyzed by using UPLC-Q-Exactive-Orbitrap-MS. RESULTS Following the intervention with P. cuspidatum， the histopathological morphology of the knee joint synovial tissue in AGA rats showed significant improvement， with reduced inflammatory cell infiltration and hyperplasia， and the preservation of the honeycomb-like structure integrity. In both positive and negative ion modes， a total of 67 chemical components were detected in the serum of rats from P. cuspidatum group， including 25 prototype components and 42 metabolites. The involved compound types encompassed stilbenes， anthraquinones， naphthols， and flavonoids， among others. The metabolic reactions identified included methylation， acetylation， sulfation， and glucuronidation. Notably， compounds such as polydatin， resveratrol and emodin were capable of entering the bloodstream in their prototype forms and undergoing in vivo metabolism. CONCLUSIONS Compounds such as polydatin， resveratrol and emodin are likely to be the active components responsible for the anti-AGA effects of P. cuspidatum.

In this study, high-performance liquid chromatography coupled with tantrum mass spectrometry (HPLC-MS/MS) technology was employed to determine milrinone nitrogen oxides in milrinone. An ACCHROM XCharge-C18 column (100 mm × 2.1 mm, 5 μm) was used with a mobile phase consisting of A phase (methanol) and B phase (5 mmol/L NH4FA, pH3 adjusted by formic acid). Agilent 6410B triple quadrupole mass spectrometer was used for HPLC-MS/MS analysis. Detection was performed using positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode to analyze the limit of milrinone nitrogen oxides in milrinone, and the quantitative transition for the ion pair was from m/z 228.01 to m/z 181.90. Experimental results showed that the method exhibited good specificity, and that neither blank solvent nor blank samples interfered with the determination of milrinone nitrogen oxides of milrinone. The method demonstrated high sensitivity, with a limit of quantitation (LOQ) of 0.0076 μg/mL and a limit of detection (LOD) of 0.0038 μg/mL. The linear range spanned from 20% to 200% of the LOQ concentration, and a good linear relationship between concentration and peak area was observed within this range. Additionally, the recovery rates were consistently within the range of 80% to 120%, and the RSD for repeatability tests was 12.0%. These results indicated that the precision and accuracy of this method meet the required standards. In summary, the method developed in this study can effectively and accurately determine the content of milrinone nitrogen oxides in milrinone.

Quantum dots (QDs), nanoscale semiconductor crystals, have emerged as a revolutionary class of nanomaterials with unique optical and electrochemical properties, making them highly promising for applications in disease diagnosis and treatment. Their tunable emission spectra, long-term photostability, high quantum yield, and excellent charge carrier mobility enable precise control over light emission and efficient charge utilization, which are critical for biomedical applications. This article provides a comprehensive review of recent advancements in the use of quantum dots for disease diagnosis and therapy, highlighting their potential and the challenges involved in clinical translation. Quantum dots can be classified based on their elemental composition and structural configuration. For instance, IB-IIIA-VIA group quantum dots and core-shell structured quantum dots are among the most widely studied types. These classifications are essential for understanding their diverse functionalities and applications. In disease diagnosis, quantum dots have demonstrated remarkable potential due to their high brightness, photostability, and ability to provide precise biomarker detection. They are extensively used in bioimaging technologies, enabling high-resolution imaging of cells, tissues, and even individual biomolecules. As fluorescent markers, quantum dots facilitate cell tracking, biosensing, and the detection of diseases such as cancer, bacterial and viral infections, and immune-related disorders. Their ability to provide real-time, in vivo tracking of cellular processes has opened new avenues for early and accurate disease detection. In the realm of disease treatment, quantum dots serve as versatile nanocarriers for targeted drug delivery. Their nanoscale size and surface modifiability allow them to transport therapeutic agents to specific sites, improving drug bioavailability and reducing off-target effects. Additionally, quantum dots have shown promise as photosensitizers in photodynamic therapy (PDT). When exposed to specific wavelengths of light, quantum dots interact with oxygen molecules to generate reactive oxygen species (ROS), which can selectively destroy malignant cells, vascular lesions, and microbial infections. This targeted approach minimizes damage to healthy tissues, making PDT a promising strategy for treating complex diseases. Despite these advancements, the translation of quantum dots from research to clinical application faces significant challenges. Issues such as toxicity, stability, and scalability in industrial production remain major obstacles. The potential toxicity of quantum dots, particularly to vital organs, has raised concerns about their long-term safety. Researchers are actively exploring strategies to mitigate these risks, including surface modification, coating, and encapsulation techniques, which can enhance biocompatibility and reduce toxicity. Furthermore, improving the stability of quantum dots under physiological conditions is crucial for their effective use in biomedical applications. Advances in surface engineering and the development of novel encapsulation methods have shown promise in addressing these stability concerns. Industrial production of quantum dots also presents challenges, particularly in achieving consistent quality and scalability. Recent innovations in synthesis techniques and manufacturing processes are paving the way for large-scale production, which is essential for their widespread adoption in clinical settings. This article provides an in-depth analysis of the latest research progress in quantum dot applications, including drug delivery, bioimaging, biosensing, photodynamic therapy, and pathogen detection. It also discusses the multiple barriers hindering their clinical use and explores potential solutions to overcome these challenges. The review concludes with a forward-looking perspective on the future directions of quantum dot research, emphasizing the need for further studies on toxicity mitigation, stability enhancement, and scalable production. By addressing these critical issues, quantum dots can realize their full potential as transformative tools in disease diagnosis and treatment, ultimately improving patient outcomes and advancing biomedical science.

Lipid droplets (LDs) are dynamic organelles that are ubiquitous across most organisms, including animals, plants, protists, and microorganisms. Their core consists of neutral lipids, surrounded by a phospholipid monolayer adorned with a specific set of proteins. As critical intracellular hubs of metabolic regulation, lipid droplets play essential roles in maintaining physiological homeostasis and contributing to the progression of various pathological processes. They store neutral lipids for energy production during periods of starvation or for membrane biosynthesis, and they sequester fatty acids to mitigate lipotoxicity. Clinically, dysregulation of lipid droplet function is associated with a wide range of diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD), obesity, type 2 diabetes mellitus (T2DM), neurodegenerative disorders, and cancer. Research into the biological functions of lipid droplets—as dynamic organelles and their links to multiple diseases—has emerged as a cutting-edge focus in cell biology. In recent years, significant advances have been made in understanding lipid droplet biogenesis. Researchers have developed a more refined framework that elucidates how LDs are assembled in the endoplasmic reticulum (ER). Triacylglycerols and sterol esters are synthesized between the inner and outer leaflets of the ER bilayer, and when they exceed the critical nucleation concentration (CNC), they coalesce to form neutral lipid lenses. These then bud from the ER under the coordinated action of key proteins such as Seipin, fat storage-inducing transmembrane protein 2 (FIT2), and the peroxisomal membrane protein Pex30. This budding process is driven by changes in membrane curvature and surface tension, induced by the asymmetric distribution of phospholipids. Nascent lipid droplets recruit lipid-synthesizing enzymes via ER-LD bridging structures, enabling localized lipid production and surface expansion, ultimately resulting in the formation of mature LDs. Biochemical and biophysical approaches have revealed important features of this process, underscoring the critical roles of ER membrane biophysical properties and specific phospholipids. Structural biology and proteomic studies have identified key regulators—particularly Seipin and FIT2—as central players in LD biogenesis. This review systematically summarizes recent advances in the molecular mechanisms of LD biogenesis. It delves into the processes of LD nucleation, membrane budding, and expansion in eukaryotic cells, with a special focus on how core factors such as Seipin and FIT2 dynamically regulate LD morphology. In addition, it examines the mechanisms and pathways by which class I and class II proteins are targeted to LDs, compares LD biogenesis involving different neutral lipid cores, and discusses the disease relevance of specific regulatory proteins. Finally, the review outlines critical unresolved questions in the field of LD biogenesis, offering clear directions for future research and providing a comprehensive framework for deepening our understanding of LD formation and its implications for disease intervention.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

BACKGROUND:For dislocation of acromioclavicular joint induced by coracoclavicular ligament fracture,single EndoButton Plate reconstruction and double EndoButton Plates reconstruction are common repair methods.Further study on the stress distribution and fracture risk of the two repair methods is of great significance. OBJECTIVE:To study the biomechanical properties of the coracoclavicular ligament,and compare the fixation effect,stress distribution and failure mode of single and double EndoButton Plates reconstruction. METHODS:(1)Finite element simulation analysis:Mimics,Wrap and SolidWorks were used to establish normal coracoclavicular ligament,single EndoButton Plate reconstruction and double EndoButton Plates reconstruction.Ansys software was used to analyze the stress and deformation of the scapula and clavicle of each model under vertical load.(2)Sample experiment:Fifteen intact scapular-clavicle specimens were randomly grouped into five groups,with three specimens in each group.In group A,the acromioclavicular ligament was severed and the coracoclavicular ligament remained intact.In group B,acromioclavicular ligaments and trapeoid ligaments were severed,leaving intact conical ligaments.In group C,acromioclavicular ligaments and conical ligaments were cut off,and the intact traprex ligaments were retained.In group D,acromioclavicular and coracoclavicular ligaments were severed,and coracoclavicular ligaments were repaired by single EndoButton Plate reconstruction.In group E,acromioclavicular and coracoclavicular ligaments were severed,and the coracoclavicular ligaments were repaired by double EndoButton Plates reconstruction.The mechanical experiment was carried out by a mechanical testing machine to analyze the biomechanical status,stress distribution and failure patterns of the scapular-clavicle and clavicle. RESULTS AND CONCLUSION:(1)Finite element simulation analysis:The average stress of coracoclavicular ligament attached specimens was the lowest,and the risk of coracoclavicular fracture was less than that of single and double EndoButton Plates reconstruction.The mean stress of the coracoid process was similar in single and double EndoButton Plates reconstruction,and the fracture risk was similar.(2)Sample experiment:In groups A,B,C,D and E,the stiffness of specimens was(26.4±3.5),(19.8±2.8),(21.3±3.2),(57.7±4.1),and(46.2±2.8)N/mm,respectively;the ultimate loads were(545.5±53.7),(360.1±42.1),(250.9±44.4),(643.5±39.1),and(511.9±31.7)N,respectively;global stiffness in groups D and E was higher than that in group A(P=0.000 06,0.000 3);ultimate load in group D was higher than that in group A(P<0.05);the ultimate load was not significantly different between the group E and group A(P>0.05).Ligament fracture was observed in groups A,B and C and coracoid process fracture was found in groups D and E.(3)These results suggest that from the biomechanical analysis,Single EndoButton Plate reconstruction and double EndoButton Plates reconstruction are effective treatment techniques for coracoclavicular ligament fracture in acromioclavicular joint dislocation,but increase the risk of fracture.The double EndoButton Plates reconstruction dispersed the stress of the steel plate and reduced the contact force between the steel plate and bone,but slightly reduced the ultimate bearing capacity.Single and double EndoButton Plates reconstruction should be selected according to the actual clinical situation.

DNA genetic markers have always played important roles in individual identification, kinship analysis, ancestry inference and phenotype characterization in the field of forensic medicine. DNA methylation has unique advantages in biological age inference, body fluid identification and prediction of phenotypes. The majority of current studies independently examine DNA and DNA methylation markers using various workflows, and they use various analytical procedures to interpret the biological information these two markers present. Integrated methods detect DNA and DNA methylation markers simultaneously through a single experimental workflow using the same preparation of sample. Therefore, they can effectively reduce consumption of time and cost, streamline experimental procedures, and preserve valuable DNA samples taken from crime scenes. In this paper, the integrated detection approaches of DNA and DNA methylation markers on different detection platforms were reviewed. In order to convert methylation modifications to detectable forms, several options were available for pretreatment of genomic DNA, including digestion with methylation-sensitive restriction enzyme, affinity enrichment of methylated fragments, conversion of methylated or unmethylated cytosine. Multiplexed primers can be designed for DNA markers and converted DNA methylation markers for co-amplification. The schemes of using capillary electrophoresis platform for integrated detection add the pretreatment of genomic DNA on the basis of detecting DNA genetic markers. DNA and DNA methylation markers are then integrated by co-amplification. But the limited number of fluorescent options available and the length of amplicons restrict the type and quantity of markers that can be integrated into a panel. Pyrophosphate sequencing also supports integrated detection of DNA and DNA methylation markers. On this platform, due to the conversion of unmethylated cytosine to thymine after treatment with bisulfite, the methylation level of CpG site can be directly calculated using the peak height ratio of cytosine bases and thymine bases. Therefore, the methylation levels and SNP typing can be simultaneously obtained. However, due to the limited read length of sequencing, the detection of markers with longer amplicons is restricted. It is not conducive to fully interpret the complete information of the target sequence. Next-generation sequencing also supports integrated detection of DNA and DNA methylation markers. A preliminary experimental process including DNA extraction, pretreatment of genomic DNA, co-preparation of DNA and DNA methylation library and co-sequencing, has been formed based on the next-generation sequencing platform. It confirmed the feasibility of next-generation sequencing technology for integrated detection of DNA and DNA methylation markers. In field of biomedicine, various integrated detection schemes and corresponding data analysis approaches of DNA and DNA genetic markers developed based on the above detection process.Co-analysis can simultaneously obtain the genomic genetic and epigenetic information through a single analytic process. These schemes suggest that next-generation sequencing may be an effective method for achieving more accurate and highly integrated detection, helping to explore the potential for application in forensic biological samples. We finally explore the impact of interactions between sites and different pretreatment methods on the integrated detection of DNA and DNA methylation markers, and also propose the challenge of applying third-generation sequencing for integrated detection in forensic samples.

Non-alcoholic fatty liver disease (NAFLD) is a pathological syndrome characterized by the excessive deposition of lipids in hepatocytes but not caused by alcohol and other definite liver damage factors. The pathogenesis of NAFLD is complex. When the liver is damaged, a large amount of lipids deposited in hepatocytes will induce oxidative stress injury, endoplasmic reticulum stress and metabolic disorders in hepatocytes, and immune cells further secrete inflammatory cytokines and release them into the blood, causing systemic inflammation. In the process of NAFLD, the inflammatory response plays an important role. Macrophages are the most abundant non-parenchymal cells in the liver and play an important role in liver inflammatory injury. Hepatic macrophages include liver-native and monocyte-derived macrophages, and their activation and polarization processes are involved in the different development stages of NAFLD. Traditional Chinese medicine (TCM) compound and its active compounds have been found to regulate macrophages to participate in the process of inflammation, injury and recovery of NAFLD. Based on the existing research reports, this paper elaborates the relationship between the source, activation and polarization of macrophages and NAFLD as the breakthrough point, and systematically reviews the mechanism of TCM in the prevention and treatment of NAFLD by regulating the activation, recruitment and polarization of macrophages. This paper aims to provide new ideas for the discovery of novel NAFLD candidate drugs from TCM via targeting macrophages.

Objective By analyzing relevant literature of long COVID,we aimed to understand the current research status,hotspots and trends in this field.Methods Based on Web of Science core collection data,bibliometric analysis was used as the main research method.The results were visualized with VOSviewer.A comprehensive analysis was performed from various perspectives including trends in publication,journal distribution,highly cited papers,international research collaboration networks,and clusters of keywords,etc.Results The field of long COVID has garnered significant global academic attention.A total of 7 877 related articles were retrievable,with a total citation count of 103 389 and an average citation count of 13.13 per article.Among them,the United States published the most articles(1 780 articles,22.59%),while China ranked fifth in publication volume(686 articles,8.71%).The international scientific cooperation network reflected the close collaborative relationships between countries in long COVID research,predominantly involving the United States,the United Kingdom,Italy,India,and China.Keywords clustering indicated that the current main research focuses in the long COVID field include:clinical manifestations,epidemiological characteristics,risk factors,and mechanisms of occurrence,treatment and rehabilitation measures of long COVID,and its impact on public and social life.Conclusion This article reveals the current state,research hotspots and trends in the long COVID field,providing valuable references for related research institutions,scholars as well as health administrative office.