Hepatitis B virus （HBV） exclusively infects liver parenchymal cells and forms covalently closed circular DNA （cccDNA） within their nuclei. HBV cccDNA serves as the essential template for viral gene transcription， the sole source of progeny virus production， and the key driver of viral antigen expression， and it is the molecular basis for the persistence of HBV infection. Therefore， elimination and/or functional silencing of cccDNA is the key to eradicate chronic HBV infection. This article discusses the critical scientific issues that need to be solved during elimination of the harm of HBV infection from the perspectives of the synthesis， transcription， and clearance of cccDNA， as well as the impact of nonparenchymal cells on cccDNA， in order to provide a reference for eradicating HBV infection in the future.

One of its primary surgical treatments of tricuspid regurgitation is tricuspid valve biological valve replacement. Catheter tricuspid valve-in-valve implantation is a novel interventional alternative for biological valve failure. The non-invasive lung fluid measuring device remote dielectric sensing (ReDSTM) has been increasingly incorporated into clinical practice as a means of monitoring chronic heart failure in recent years. This report describes the process and outcomes of the first instance of perioperative lung fluid volume evaluation following transcatheter tricuspid valve implantation utilizing ReDSTM technology. The patient has a short-term, substantial increase in postoperative lung fluid volume as compared to baseline.

Mitochondria, functioning not only as the central hub of cellular energy metabolism but also as semi-autonomous organelles, orchestrate cellular fate decisions through their endogenous mitochondrial DNA (mtDNA), which encodes core components of the electron transport chain. Emerging research has identified microRNAs localized within mitochondria, termed mitochondria-located microRNAs (mitomiRs). Recent studies have revealed that mitomiRs are transcribed from nuclear DNA (nDNA), processed and matured in the cytoplasm, and subsequently transported into mitochondria. mitomiRs regulate mtDNA through diverse mechanisms, including modulation of mtDNA expression at the translational level and direct binding to mtDNA to influence transcription. Aberrant expression of mitomiRs leads to mitochondrial dysfunction and contributes to the pathogenesis of metabolic diseases. Restoring mitomiR expression to physiological levels using mitomiRs mimics or inhibitors has been shown to improve mitochondrial function and alleviate related diseases. Consequently, the regulatory mechanisms of mitomiRs have become a major focus in mitochondrial research. Given that mitomiRs are located in mitochondria, targeted delivery strategies designed for mtDNA can be adapted for the delivery of mitomiRs mimics or inhibitors. However, numerous intracellular and extracellular barriers remain, highlighting the need for more precise and efficient delivery systems in the future. The regulation of mtDNA expression mediated by mitomiRs not only expands our understanding of miRNA functions in post-transcriptional gene regulation but also provides promising molecular targets for the treatment of mitochondrial-related diseases. This review systematically summarizes recent research progress on mitomiRs in regulating mtDNA expression and discusses the underlying mechanisms of mitomiRs-mtDNA interactions. Additionally, it provides new perspectives on precision therapeutic strategies, with a particular emphasis on mitomiRs-based regulation of mitochondrial function in mitochondrial-related diseases.

Mitochondria play a pivotal role in spermatogenesis and sperm activation in Caenorhabditis elegans, serving as the primary ATP supplier for cell division and differentiation while also acting as a key regulator of zinc ion homeostasis, membrane dynamics, and apoptotic signaling. This review systematically summarizes the essential mitochondrial mechanisms at different stages of sperm development, highlighting their multifaceted contributions beyond energy metabolism. Mitochondria are crucial for maintaining the health and stability of the gonads by regulating key apoptotic execution proteins that facilitate the proper elimination of damaged or unnecessary germ cells. Additionally, mitochondria dynamically adjust their energy supply to meet the metabolic demands of different stages of germline development. During early spermatogenesis, mitochondria provide ATP to fuel mitotic and meiotic divisions, support cellular differentiation, and regulate H⁺ and Zn²⁺ exchange to maintain cytoplasmic homeostasis, thereby ensuring the proper maturation and functionality of sperm cells. As spermatogenesis progresses, mitochondria participate in processing and sorting essential sperm proteins, such as major sperm protein (MSP), and contribute to the formation of membranous organelles (MOs), which are critical for subsequent activation events. During sperm activation, mitochondria play a dual role in ensuring a successful transition from immotile spermatids to fully functional spermatozoa. First, they provide ATP to facilitate pseudopod formation, MO fusion, and ion channel regulation, all of which are essential for sperm motility and fertilization potential. Second, mitochondria regulate the quality and quantity of functional mitochondria within sperm cells through mitopherogenesis—a recently discovered process in which mitochondrial vesicles are selectively released, ensuring that only healthy mitochondria are retained. This quality-control mechanism optimizes mitochondrial function, which is crucial for sustaining sperm motility and longevity. Beyond their traditional role in energy metabolism, mitochondria may also contribute to protein synthesis during spermatogenesis and activation. Recent evidence suggests that mitochondrial ribosomes actively translate specific proteins required for sperm function, challenging the long-standing belief that spermatozoa do not engage in de novo protein synthesis after differentiation. This emerging perspective raises important questions about the role of mitochondria in regulating sperm activation at the molecular level, particularly in modulating oxidative phosphorylation (OXPHOS) protein composition to optimize ATP production. In summary, mitochondria serve as both the central energy hub and a crucial regulatory factor in sperm activation, metabolic homeostasis, and reproductive success. Their involvement extends beyond ATP generation to include apoptotic regulation, ion homeostasis, vesicle-mediated mitochondrial quality control, and potential contributions to protein synthesis. Understanding these mitochondrial functions in C. elegans not only deepens our knowledge of nematode reproductive biology, but also provides valuable insights into broader mechanisms governing mitochondrial regulation in germline cells across species. These findings open new avenues for future research into the interplay between mitochondria, energy metabolism, and sperm function, with potential implications for reproductive health and fertility studies.

BACKGROUND: Death burden of stroke is severe with over one-third rural residents in China, but there is still a lack of specific national and high-quality reports on the urban-rural differences in stroke burden, especially for subtypes. We aimed to update the understanding of urban-rural differences in stroke deaths. METHODS: This is a descriptive observational study. Data from the national mortality surveillance system, which covers 323.8 million with 605 disease surveillance points (DSPs) across all 31 provinces, municipalities, and autonomous regions in China. All deaths from stroke as the underlying cause from 2015 to 2020 according to DSPs. Crude mortality rate and age-standardized mortality rate (ASMR) were estimated through DSPs. Average annual percentage change was used to explain the change in mortality rate. RESULTS: From 2015 to 2020, the majority of deaths from all stroke subtypes occurred in rural areas. There were significant differences between the changes of urban and rural ASMRs. On the whole, the changes in urban areas were evidently better, and the ASMR differences were basically expanding. Stroke ASMR in urban China decreased by 15.5%. The rural ASMR of ischemic stroke increased by 12.9%. The rural and urban ASMRs of intracerebral hemorrhage decreased by 24.9% and 27.4%, and those of subarachnoid hemorrhage decreased by 29.5% and 40.4%, respectively. The highest ASMRs of all stroke subtypes and the increasing trend of ischemic stroke ASMR make rural males the focus of stroke management. CONCLUSIONS The death burden of stroke varies greatly between urban and rural China. Rural residents face unique challenges.
Humans ; China/epidemiology* ; Stroke/mortality* ; Rural Population/statistics & numerical data* ; Male ; Female ; Urban Population/statistics & numerical data* ; Middle Aged ; Aged ; Aged, 80 and over ; Adult

With Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum drug pair as the research object, supramolecular chemistry of traditional Chinese medicine(TCM) was used to study differences between the compatibility of herbal medicine Glycyrrhizae Radix et Rhizoma with mineral medicine Gypsum Fibrosum and its main component CaSO_4·2H_2O, so as to preliminarily discuss the scientific connotation of compatibility of Gypsum Fibrosum in clinical application. A Malvern particle sizer, a scanning electron microscope(SEM), and a conductivity meter were used to observe and determine the physical properties such as microscopic morphology, particle size, and conductivity of Gypsum Fibrosum, CaSO_4·2H_2O, and water decoctions of them with Glycyrrhizae Radix et Rhizoma. An inductively coupled plasma optical emission spectrometer(ICP-OES) was employed to detect the inorganic metal elements in Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Isothermal titration calorimetry(ITC) was conducted to quantify the interactions of Gypsum Fibrosum and CaSO_4·2H_2O with Glycyrrhizae Radix et Rhizoma. A Fourier transform infrared spectrometer(FTIR) was used to analyze the characteristic absorption peak change of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. X-ray diffraction(XRD) was performed to determine the crystal structure and phase composition of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Further, glycyrrhizic acid(GA) was substituted for Glycyrrhizae Radix et Rhizoma to co-decoct with Gypsum Fibrosum, CaSO_4·2H_2O, and freeze-dried powder of their respective water decoctions. The results of XRD were used for verification analysis. The results showed that although CaSO_4·2H_2O is the main component of Gypsum Fibrosum, there were significant differences between their decoctions and between the decoctions of them with Glycyrrhizae Radix et Rhizoma. Specifically,(1) Both CaSO_4·2H_2O and Gypsum Fibrosum were amorphous fibrous. However, the particle size and conductivity were significantly different between the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(2) Under SEM, Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O was a hybrid system with various morphologies, while Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum presented uniform nanoparticles.(3) The particle sizes and conductivities of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum were significantly different and did not follow the same tendency as those of the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(4) Compared with Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O, Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum had stronger molecular binding ability and functional group structure change.(5) The crystal form was largely different between the freeze-dried powder of CaSO_4·2H_2O decoction and Gypsum Fibrosum decoction, and their crystal forms were also significantly different from those of the freeze-dried powder of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum decoctions. The reason for the series of differences is that Gypsum Fibrosum is richer in trace elements than CaSO_4·2H_2O. The XRD results of GA-Gypsum Fibrosum and GA-CaSO_4·2H_2O decoctions further prove the importance of trace elements in Gypsum Fibrosum for supramolecule formation. This research preliminarily reveals the influence of compatibility of Gypsum Fibrosum or CaSO_4·2H_2O on decoction phase state, material form, and crystal form, providing a basis for the rational clinical application of Gypsum Fibrosum.
Drugs, Chinese Herbal/chemistry* ; Calcium Sulfate/chemistry* ; Glycyrrhiza/chemistry* ; Crystallization ; Particle Size ; Medicine, Chinese Traditional ; Rhizome/chemistry*

Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

OBJECTIVE: To explore the mechanism by which the extract of Semen Ziziphi Spinosae extract promotes bone growth in mice by modulation of the expression of miR-34a-5p in brain tissue. METHODS: Mice were assigned to four experimental groups:a normal control group, a drug administration group (receiving 0.320 mg·g^-1 body weight of Semen Ziziphi Spinosae extract via intragastric administration), a positive control group (receiving 0.013 mg·g^-1 body weight of jujube seed saponin via intragastric administration), and a combination group administration with Semen Ziziphi Spinosae extract plus a 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist (intragastric administration of Semen Ziziphi Spinosae extract combined with intracerebroventricular injection of 8 μg P-MPPF per mice for the final three days of the experiment). Following a 20-day administration period, the effects of the interventions on bone growth, serum growth hormone (GH) levels, and 5-HT2AR expression in brain tissue were evaluated. MicroRNAs (miRNAs) that were differentially expressed in the brain tissues of mice exhibiting bone growth induced by Semen Ziziphi Spinosae extract, as compared to those in normal mice, were identified using a gene chip approach. The interaction between miR-34a-5p and 5-HT2AR was subsequently validated through quantitative reverse transcription polymerase chainreaction (RT-qPCR) and dual-luciferase reporter gene assays. Subsequently, by utilizing the miR-34a-5p inhibitor group and mimics group, along with the normal control group, the drug administration group, the positive control group, and the drug administration combined with miR-34a-5p inhibitor group, the variations in 5-HT2AR expression in mouse brain tissue across all groups were examined, and the binding activity of 5-hydroxytryptamine (5-HT) to the 5-hydroxytryptamine 1A receptor (5-HT1AR) in mice was assessed. RESULTS: The body lengths of the normal control group and the drug administration group were(8.9±0.3) and(10.4±0.4) cm;femur lengths were (8.5±0.3) and (9.1±0.5) mm;tibia lengths were (10.7±0.3) and (11.2±0.4) mm, respectively. The contents of GH levels were (58.6±8.2) and (72.9±6.1) ng·ml-1;and the contents of 5-HT2AR were (32.0±5.0) and (21.9± 5.5) ng·ml-1, respectively. Compared with the normal control group, the drug administration group promoted the growth of body length, femur, and tibia in mice, and increased GH secretion, showing statistically significant differences (P<0.05). Additionally, it significantly reduced the content of 5-HT2AR in brain tissue, with statistical significance (P<0.01). The gene chip analysis identified a total of 16 differentially expressed miRNAs, of which 13 were up-regulated and 3 were down-regulated. Bioinformatics analysis predicted that the up-regulated miR-34a-5p could regulate the expression of 5-HT2AR, a prediction that was confirmed through a dual-luciferase reporter gene assay, demonstrating a direct regulatory interaction between the two. Furthermore, in vivo experiments in mice revealed that overexpression and silencing of miR-34a-5p resulted in corresponding changes in the expression levels of 5-HT2AR in brain tissues/cells, as well as in the binding activity between 5-HT and 5-HT1AR. CONCLUSION The Semen Ziziphi Spinosae extract promotes animal bone growth by enhancing miR-34a-5p expression in brain tissue, downregulating the expression level of 5-HT2AR, improving the binding activity between 5-HT and 5-HT1AR, and extending slow-wave sleep duration, thereby stimulating GH secretion.
Animals ; MicroRNAs/metabolism* ; Mice ; Male ; Brain/metabolism* ; Ziziphus/chemistry* ; Bone Development/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Plant Extracts/pharmacology*

OBJECTIVE: To investigate the clinical efficacy and safety of single Kirschner wire assisted poking and closed reduction in the treatment of Gartland type Ⅲ supracondylar humeral fractures in children. METHODS: A retrospective analysis was performed on patients diagnosed with Gravland type Ⅲ supracondylar humeral fractures between January 2022 and June 2023. A total of 46 patients were treated with closed reduction assisted by Kirschner wires and percutaneous Kirschner wire internal fixation.There were 25 males and 21 females. The age ranged from 5 to 10 years old, with an average of (5.8±1.8) years old. The left side was involved in 28 patients and the right side in 18 patients. Record the operative duration for patients, the number of fluoroscopic exposures, fracture healing time, postoperative carrying angle, Baumann angle, elbow joint function score at three months post-operation, and any associated complications. RESULTS: All 46 patients were followed up for a period of 12 to 16 weeks, with an average of (13.74±1.44 )weeks. The operation duration was (30.7±5.1) minutes, the fluoroscopy count was (10.2±2.7) times, the postoperative carrying angle of the elbow joint was (8.7±2.2) degrees, and the Baumann angle was (71.5±2.9) degrees. All fractures achieved successful union in all patients, with a mean healing time of (25.5±1.7) days.At the final follow-up, elbow joint function was assessed using the Flynn criteria, with 43 patients rated as excellent and 3 patients rated as good. No complications were observed, including cubitus varus, nerve injury, or local infection. CONCLUSION The use of a single Kirschner wire assisted prying reduction for treating Gartland type Ⅲ supracondylar humeral fractures in children demonstrates excellent clinical efficacy and safety.
Humans ; Male ; Female ; Child ; Bone Wires ; Child, Preschool ; Humeral Fractures/physiopathology* ; Retrospective Studies ; Fracture Fixation, Internal/instrumentation* ; Treatment Outcome ; Fracture Healing