Co-infection of hepatitis D virus （HDV） and hepatitis B virus （HBV） is the most severe form of viral hepatitis and is associated with accelerated progression of liver disease and a significant increase in the risk of liver cirrhosis and hepatocellular carcinoma. Nucleo（s）tide analogues for HBV treatment are ineffective against HDV infection， necessitating the urgent need for developing specific and effective antiviral therapies for HDV. In recent years， significant advances have been made in the research and development of specific antiviral drugs against HDV， including entry inhibitors targeting viral entry （Bulevirtide） and monoclonal antibody drugs （Libevitug）， which bring ground-breaking advances in the treatment of HDV infection. This article briefly reviews the latest research advances in therapeutic drugs for HDV， introduces the mechanism of action and clinical research data of new drugs recently approved for the treatment of HDV， and discusses the challenges that need to be solved in the field of HDV treatment， in order to provide a reference for understanding the current status of hepatitis D treatment.

Myelodysplastic syndrome (MDS) is a chronic hematologic disorder characterized by ineffective hematopoiesis, dysplasia of one or more cell lines with or without definite genetic changes. Its diagnosis requires a comprehensive analysis combining morphology, immunology, cytogenetics, and molecular biology findings. In recent years, the development of second-generation sequencing (NGS) has provided great assistance in exploring the molecular pathogenesis of hematological malignancies and guidance for clinical practice. Mutations of a series of gene involved in RNA splicing, DNA methylation, transcriptional regulation, signal transduction, chromatin modification and cohesin complex have been identified as important mechanisms for the development of MDS, among which some mutations have been found to play important roles in the diagnosis, treatment, and prognosis of MDS. This article has provided a comprehensive review the the common molecular genetic abnormalities involved in MDS.
Humans ; Myelodysplastic Syndromes/diagnosis* ; Mutation ; DNA Methylation ; RNA Splicing ; High-Throughput Nucleotide Sequencing

Sixteen compounds were isolated from the solid rice culture of the endophytic fungus Alternaria alstroemeriae WZ-419 derived from Pseudostellariae Radix, using silica gel, ODS, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were elucidated based on physicochemical properties and comprehensive spectroscopic analyses, and identified as alterpenoid A (1), tricycloalternarene A (2), altenusin (3), 4'-epialtenuene (4), altenuene (5), alternariol (6), altenuisol (7), 3-hydroxyalternariol-5-O-methylether (8), alternariol-9-methyl ether (9), alternariol 1′-hydroxy-9-methyl ether (10), stemphyperylenol (11), dihydroalterperylenol (12), alterinone A (13), 4-hydroxy-3-methoxy-5-(2E,6E-3,7,11-trimethyldodeca-2,6,10-trien-1-yl) benzoic acid (14), hexylitaconic acid (15), and altechromone A (16). Among them, compound 1 and 13 were new, and compounds 14 and 15 were isolated from the genus Alternaria for the first time. The antibacterial activities of compounds 1–16 were evaluated in vitro. Compounds 3, 6–8, 10, 11, 13, and 14 exhibited notable inhibitory effects against Gram-positive bacteria, with minimal inhibitory concentrations ranging from 8 to 64 µg/mL.This study isolated a series of antimicrobial metabolites from the endophytic fungi of Pseudostellariae Radix, providing new insights into their bioactive constituents and laying a foundation for further pharmacological investigations.

ObjectiveTo investigate the role of interleukin （IL）-17A in acute inhalational pneumonia induced by the highly drug-resistant and hypervirulent Staphylococcus aureus strain USA300-R in mice. MethodsAn acute inhalational pneumonia model was established in mice using an aerosolized pulmonary delivery technique. RNA sequencing （RNA-seq） and enzyme-linked immunosorbent assay （ELISA） were employed to examine the expression dynamics of Il17a mRNA and IL-17A protein， respectively， in the lungs of infected mice. Il17a knockout （Il17a^-/-） mice were generated using CRISPR/Cas9 gene editing technology. The survival rate， body weight， bacterial load in lung tissue， and histopathological changes were compared between Il17a^-/- and wild-type （WT） mice following inhalational infection with USA300-R. Results12 hours after USA300-R infection， compared to pre-infection， the expression level of Il17a mRNA in lung tissue and the level of IL-17A protein in bronchoalveolar lavage fluid （BALF） increased by approximately 50-fold （P<0.01） and 6-fold （P<0.001）， respectively. Compared to WT mice， Il17a^-/- mice exhibited approximately 10-fold higher bacterial loads in lung tissue at both 12 and 24 hours post-infection （P<0.001， P<0.05）. However， they showed significantly attenuated lung histopathological injury， reduced alveolar wall thickening， markedly decreased neutrophil infiltration， and an approximately 50% improvement in survival rate （P<0.05）. ConclusionIn acute Staphylococcus aureus USA300-R inhalational pneumonia， IL-17A contributes to bacterial clearance by recruiting neutrophils； however， excessive neutrophil infiltration exacerbates pulmonary inflammation and injury， reduces survival rates， and represents a potential therapeutic target.

This paper summarized professor ZHANG Zhen's clinical experience in treating rheumatoid arthritis （RA） complicated with anemia using self-formulated Yisui Shengxue Decoction （益髓生血汤） with modifications. It is proposed that the core pathogenesis of this condition is rooted in spleen and kidney depletion with insufficiency of essence and blood， while pathogenic dampness obstruction and internal blood stasis accumulation are the branches. The treatment principle focuses on tonifying the spleen and kidney， replenishing essence and nourishing the marrow， and enriching and generating blood， while simultaneously removing dampness and unblocking collaterals， activating blood and dissolving stasis. Based on this approach， Yisui Shengxue Decoction is used as the basic prescription， with flexible modifications according to syndrome patterns and clinical manifestations. For deficiency of both qi and blood combined with damp turbidity syndrome， medicinals that tonify qi and nourish blood， fortify the spleen and eliminate dampness， and mildly disperse obstruction are added. For wind-cold-dampness bi （痹） syndrome， medicinals that dispel wind and disperse cold， remove dampness and unblock the collaterals are incorporated. For wind-dampness-heat bi syndrome， medicinals that clear heat and eliminate dampness， unblock the collaterals and relieve bi are selected. For blood stasis obstructing the collaterals syndrome， medicinals that activate blood and resolve stasis， unblock the collaterals and relieve pain are combined. For yin deficiency with internal heat syndrome， medicinals that nourish yin and clear heat， cool blood and unblock the collaterals are prescribed.

This paper summarized professor ZHANG Zhen's clinical experience in treating rheumatoid arthritis （RA） complicated with anemia using self-formulated Yisui Shengxue Decoction （益髓生血汤） with modifications. It is proposed that the core pathogenesis of this condition is rooted in spleen and kidney depletion with insufficiency of essence and blood， while pathogenic dampness obstruction and internal blood stasis accumulation are the branches. The treatment principle focuses on tonifying the spleen and kidney， replenishing essence and nourishing the marrow， and enriching and generating blood， while simultaneously removing dampness and unblocking collaterals， activating blood and dissolving stasis. Based on this approach， Yisui Shengxue Decoction is used as the basic prescription， with flexible modifications according to syndrome patterns and clinical manifestations. For deficiency of both qi and blood combined with damp turbidity syndrome， medicinals that tonify qi and nourish blood， fortify the spleen and eliminate dampness， and mildly disperse obstruction are added. For wind-cold-dampness bi （痹） syndrome， medicinals that dispel wind and disperse cold， remove dampness and unblock the collaterals are incorporated. For wind-dampness-heat bi syndrome， medicinals that clear heat and eliminate dampness， unblock the collaterals and relieve bi are selected. For blood stasis obstructing the collaterals syndrome， medicinals that activate blood and resolve stasis， unblock the collaterals and relieve pain are combined. For yin deficiency with internal heat syndrome， medicinals that nourish yin and clear heat， cool blood and unblock the collaterals are prescribed.

Ankle sprains are the most common lesion of the ankle joint which might result in chronic ankle instability (CAI). Significant strides have been taken to enhance our comprehension of the underlying mechanisms of CAI, as the exploration of novel surgical techniques and the identification of previously unrecognized anatomical components. The present review aims to provide an extensive overview of CAI, encompassing its pathophysiology, epidemiology, clinical assessment, treatment, and rehabilitation. Treatment of CAI requires a multifaceted algorithm, involving historical analysis, clinical evaluations, and diagnostic imaging. Surgical interventions for CAI primarily involve the anatomical and/or non-anatomical reconstruction and/or repair of the anterior talofibular ligament. Anatomical repair has exhibited superior functional outcomes and a reduced risk of secondary osteoarthritis compared to non-anatomical repair. Non-anatomical approaches fall short of replicating the normal biomechanics of the anterior talofibular ligament, potentially leading to postoperative stiffness. This review seeks to academically review and up-to-date literature on this issue, tailored for clinical practice, with the intent of aiding surgeons in staying abreast of this critical subject matter.
Humans ; Joint Instability/physiopathology* ; Ankle Joint/physiopathology* ; Chronic Disease ; Ankle Injuries/therapy*

The translocator protein (TSPO) positron emission tomography (PET) can noninvasively detect neuroinflammation associated with epileptogenesis and epilepsy. This study explored the role of the TSPO-targeting radioligand [¹⁸F]F-TFQC, an m-trifluoromethyl ER176 analog, in the PET neuroimaging of epileptic rats. Initially, [¹⁸F]F-TFQC was synthesized with a radiochemical yield of 8%-10% (EOS), a radiochemical purity of over 99%, and a specific activity of 38.21 ± 1.73 MBq/nmol (EOS). After determining that [¹⁸F]F-TFQC exhibited good biochemical properties, [¹⁸F]F-TFQC PET neuroimaging was performed in epileptic rats at multiple time points in various stages of disease progression. PET imaging showed specific [¹⁸F]F-TFQC uptake in the right hippocampus (KA-injected site, i.e., epileptogenic zone), which was most pronounced at 1 week (T/NT 1.63 ± 0.21) and 1 month (T/NT 1.66 ± 0.20). The PET results were further validated using autoradiography and pathological analysis. Thus, [¹⁸F]F-TFQC can reflect the TSPO levels and localize the epileptogenic zone, thereby offering the potential for monitoring neuroinflammation and guiding anti-inflammatory treatment in patients with epilepsy.

Objective:To understand the factors influencing new infections of 9-valent vaccine-type human papillomavirus (9-valent type HPV) among men who have sex with men (MSM) in Urumqi City and to construct a prediction model of individual dynamics of new infections of 9-valent type HPV among MSM.Methods:In this study, a snowball method was adopted to recruit MSM in Urumqi City to establish a dynamic cohort, and participants were followed up every 6 months from 2016 to 2023, and perianal exfoliated cells were collected for HPV genotyping; joint models were established using the number of same-sex sexual partners in the last six months and the number of anal intercourse in the last one week as longitudinal variables, respectively, and joint models were utilized to analyze the influence factors of 9-valent HPV new infections in MSM individuals were analyzed by the joint model; the predictive efficacy of the model in the follow-up period was evaluated by using the time-dependent receiver operating characteristic area under the curve (AUC) values. Based on the prediction model, two study participants were randomly selected for individual dynamic prediction of new-onset HPV infections of 9-valent type types.Results:MSM with at least two follow-up visits 579 individuals were included in the analysis. The results of the two joint models showed that being divorced/widowed [hazard ratio ( HR)=1.544, 95% CI: 1.033-2.233], having a sexual behavior style of being the inserted party ( HR=1.366, 95% CI: 1.053-1.764), and having a history of STDs ( HR=1.659, 95% CI: 1.057-2.558) increased the 9-valent types of new HPV infections risk. The results of the shared parameter of the joint model of the number of same-sex partners in the last six months showed that each 2.72 increase in the number of same-sex partners in the last six months was associated with a 28.2% increase in the risk of new 9-valent HPV infections in MSM individuals ( HR=1.282, 95% CI: 1.065-1.540). The time-dependent AUC results showed that the joint model for the number of same-sex sexual partners in the last six months (0.808 0) predicted better performance than the joint model for the number of anal intercourse in the last one week (0.750 0). The joint model based on the number of same-sex sexual partners in the last six months for the prediction of MSM individual dynamics was consistent with the real situation. Conclusion:The joint model based on the number of same-sex sexual partners in the last six months, sexual behavior, history of STDs, and other risk factors has high accuracy in predicting the risk of new MSM 9-valent HPV infections in Urumqi City, which can provide a scientific basis for the prediction of individual dynamics of new MSM 9-valent HPV infections.

ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.