The multimorbidity of rheumatoid arthritis （RA） and periodontitis （PD） has drawn increasing attention， as both conditions are characterized by chronic inflammation， immune dysregulation， and progressive bone destruction. Modern research confirms that PD is a significant risk factor for RA development， and their coexistence mutually exacerbates disease progression. However， traditional Chinese medicine （TCM） currently lacks a systematic theoretical explanation for this complex multimorbid relationship. This study， based on the TCM theory of abnormal collateral， thoroughly examines the intrinsic connection between RA and PD multimorbidity， proposing "abnormal collateral as the pivot， with accumulated toxins eroding bone" as the core TCM pathogenesis. The research elucidates PD as the "origin of abnormal collateral"， where its pathogens act as toxic factors that invade the joints through collaterals， triggering RA via mechanisms such as molecular mimicry. The dynamic pathological progression of RA-PD multimorbidity can be described as follows： the displacement of Ying and Wei at the microscopic level manifests as immune hyperactivation， leading to collateral malnutrition； heat-toxins traversing collaterals induce collateral hyperactivity， resulting in pathological angiogenesis； ultimately， toxin accumulation at the pivotal abnormal collateral site erodes bone， activating the receptor activator of nuclear factor kappa-B ligand （RANKL）-receptor activator of nuclear factor kappa-B （RANK） signaling pathway-driven osteoclast differentiation. This theoretical framework innovatively integrates modern findings in oral microbiology， immune-inflammation， and bone metabolism， offering a holistic and dynamic perspective to understand the complexity of multimorbidity. Given the limited efficacy of current periodontal treatments for RA and the scarcity of reported TCM compound interventions for multimorbidity， the abnormal collateral theory proposes a systematic intervention strategy centered on "governing diseases through collaterals and regulating collaterals with herbs"， along with TCM therapeutic principles such as "unblocking， clearing， and nourishing collaterals". Potential herbal treatments for multimorbidity are also highlighted. Future research should focus on refining TCM syndrome patterns in multimorbid patients and leveraging omics technologies for deeper exploration， thereby providing a theoretical foundation and research direction for TCM in addressing complex multimorbid conditions.

The multimorbidity of rheumatoid arthritis （RA） and periodontitis （PD） has drawn increasing attention， as both conditions are characterized by chronic inflammation， immune dysregulation， and progressive bone destruction. Modern research confirms that PD is a significant risk factor for RA development， and their coexistence mutually exacerbates disease progression. However， traditional Chinese medicine （TCM） currently lacks a systematic theoretical explanation for this complex multimorbid relationship. This study， based on the TCM theory of abnormal collateral， thoroughly examines the intrinsic connection between RA and PD multimorbidity， proposing "abnormal collateral as the pivot， with accumulated toxins eroding bone" as the core TCM pathogenesis. The research elucidates PD as the "origin of abnormal collateral"， where its pathogens act as toxic factors that invade the joints through collaterals， triggering RA via mechanisms such as molecular mimicry. The dynamic pathological progression of RA-PD multimorbidity can be described as follows： the displacement of Ying and Wei at the microscopic level manifests as immune hyperactivation， leading to collateral malnutrition； heat-toxins traversing collaterals induce collateral hyperactivity， resulting in pathological angiogenesis； ultimately， toxin accumulation at the pivotal abnormal collateral site erodes bone， activating the receptor activator of nuclear factor kappa-B ligand （RANKL）-receptor activator of nuclear factor kappa-B （RANK） signaling pathway-driven osteoclast differentiation. This theoretical framework innovatively integrates modern findings in oral microbiology， immune-inflammation， and bone metabolism， offering a holistic and dynamic perspective to understand the complexity of multimorbidity. Given the limited efficacy of current periodontal treatments for RA and the scarcity of reported TCM compound interventions for multimorbidity， the abnormal collateral theory proposes a systematic intervention strategy centered on "governing diseases through collaterals and regulating collaterals with herbs"， along with TCM therapeutic principles such as "unblocking， clearing， and nourishing collaterals". Potential herbal treatments for multimorbidity are also highlighted. Future research should focus on refining TCM syndrome patterns in multimorbid patients and leveraging omics technologies for deeper exploration， thereby providing a theoretical foundation and research direction for TCM in addressing complex multimorbid conditions.

Histone deacetylase has proved to be a promising new antimalarial target in the development of novel antimalarial drugs. This article introduces the mechanism of action of histone deacetylase inhibitors and their antimalarial activity, with a focus on the discovery process of Plasmodium histone deacetylase inhibitors and their recent research progress both domestically and internationally. Recent research findings on hydroxamic acid-based and cyclic peptide inhibitors are reviewed and analyzed in detail according to their different structural types. Key challenges hindering drug development and approval, such as drug toxicity issues and the lag in related biological studies, are highlighted. Furthermore, future directions for drug research and development are proposed, offering insights for the further development of new antimalarial drugs.

Objective: To investigate the prevalence of overweight and obesity among children and adolescents in Yangzhou City, and its association with screen behaviors, so as to provide scientific evidence for weight management among students. Methods: In May 2025, an electronic questionnaire survey was conducted among children and adolescents in Yangzhou City. A total of 3 722 participants were selected from grades 4 to 12 in 18 primary and secondary schools (108 classes) by using stratified cluster random sampling. The Chi square test was used to compare the differences in the detection rates of overweight and obesity among children and adolescents with 5 types of screen behaviors (watching TV, playing electronic games, scrolling short videos, screen based learning, electronic socializing) in different time groups each day (never, >0~<2 h, ≥2 h). Multivariate Logistic regression analysis was performed to examine the associations of five types of screen behaviors, presence of electronic devices in the bedroom, and screen use during meals on the weight status of children and adolescents. Results: The prevalence of overweight and obesity among children and adolescents was 37.3%. For all five types of screen behaviors, the differences in the distribution of overweight and obesity detection rates among children and adolescents across the three time spent categories were statistically significant ( χ 2=30.76- 70.78 , all P <0.01). After adjusting for confounding factors, multivariate Logistic regression analysis revealed that frequent or always using screens during meals( OR =1.63, 95％ CI =1.14~2.31), playing video games ( OR =1.28, 95% CI =1.11-1.48), browsing short videos ( OR =1.29, 95％ CI=1.09-1.54), and screen based learning ( OR =1.26, 95％ CI =1.10-1.44) were significantly associated with overweight and obesity among children and adolescents (all P <0.05). Conclusions Excessive screen use is positively correlated with the incidence of overweight and obesity in children and adolescents. Targeted interventions on screen behaviors among children and adolescents are therefore warranted.

Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

OBJECTIVE To investigate the ameliorative effect and mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles（Eh-ENVs） on acetaminophen （APAP）-induced liver injury based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H：quinone oxidoreductase 1 （NQO1） pathway. METHODS The safety of Eh-ENVs was evaluated by examining their effects on the viability of RAW264.7 and AML12 cells， as well as serum liver and kidney function indicators and histopathology of liver， lung， and other tissues in normal mice. A lipopolysaccharide （1 μg/mL）-induced RAW264.7 cell inflammation model was constructed to investigate the effects of 10 and 20 μg/mL Eh-ENVs on the mRNA expression of inflammatory factors and reactive oxygen species （ROS） level in model cells， and the uptake efficiency of Eh-ENVs by RAW264.7 cells was also examined. An APAP-induced liver injury mouse model was established to investigate the effects of 4 mg/kg Eh-ENVs on serum liver function indicators， liver histopathology， mRNA expression of inflammatory factors， malondialdehyde （MDA） level， superoxide dismutase （SOD） level， and mRNA and protein expressions related to the Nrf2/HO-1/NQO1 pathway in liver tissue of model mice. RESULTS In vitro results showed that Eh-ENVs had no inhibitory effect on the proliferation of RAW264.7 and AML12 cells；Eh-ENVs could be efficiently taken up by RAW264.7 cells and significantly reduced the mRNA expression of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and ROS level in cells （ P ＜0.05）. In vivo results showed that 4 mg/kg Eh-ENVs had no obvious toxic side effects on normal mice，could significantly decrease the serum alanine transaminase （ALT） and aspartate transaminase （AST） levels in model mice （ P ＜0.05），upregulated/increased the mRNA expressions of IL-10， as well as the mRNA and protein expressions of Nrf2， HO-1， and NQO1， and SOD level in liver tissue （ P ＜0.05）， and down-regulated/decreased the mRNA expression of TNF-α， IL-1β and MDA level in liver tissue （ P ＜0.05）. CONCLUSIONS Eh-ENVs may activate the Nrf2/HO-1/NQO1 pathway to inhibit inflammatory response and alleviate oxidative stress， thereby improving APAP-induced liver injury.

ObjectiveTo explore the effects of Jingui Shenqiwan （JSW） and Liuwei Dihuangwan （LDW） on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group， the other six groups were as follows： a group of both males and females receiving JSW （3.0 g·kg^-1）， a group of both males and females receiving LDW （4.5 g·kg^-1）， a group of males receiving water and females receiving JSW， a group of males receiving water while females receiving LDW， a group of females receiving water while males receiving JSW， and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 （female∶male） ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth， which was followed by the observation of newborn mice， calculation of their average number， and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment， the weights of the thymus and spleen were measured to calculate the organ coefficients， and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems， while novel object recognition test （NOR） was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction （Real-time PCR） assay， and protein expression was analyzed with Western blot. ResultsCompared with the control group， oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together （P<0.05）， while LDW showed a trend but no statistical significance. Additionally， compared with the control group， JSW could upregulate the gene expression of gonadotropin-releasing hormone （GnRH） in the thalamus， as well as reproductive stem cell factor （SCF） and tyrosine kinase receptor （c-Kit） in the testes and reproductive stem cell marker mouse vasa homologue （MVH） in the ovaries， upregulate the expression of proteins influencing neuronal functional activity， such as brain-derived neurotrophic factor （BDNF）， in hippocampal neurons （P<0.05）， and enhance sucrose preference in male mice （P<0.05）. Compared with the control group， JSW significantly increased sucrose preference and novel object recognition index in offspring mice （P<0.05）， which was related to the upregulation of hippocampal dopamine D1 receptor （D1R） and N-methyl-D-aspartate receptor （Nmdar） gene expression. Compared with the control group， both JSW and LDW could upregulate the protein expression of glucocorticoid receptor （GR）， BDNF， and tyrosine kinase receptor B （TrkB） in the hippocampus of offspring mice （P<0.05）. ConclusionJSW significantly enhances the reproductive ability of normal mice， which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally， JSW has a certain regulatory effect on the brain function of the offspring mice.

Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

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.

ObjectiveTo explore the effect of Shenge Bushen Capsules （SBC） on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part， mice were divided into four groups： The control group and the low， medium， and high-dose SBC groups （234.7， 469.4， 938.7 mg·kg^-1， respectively）. In the second part， mice were divided into four groups： Control group， Pseudostellariae Radix polysaccharide （PRP） group， total flavonoids group， and SBC group， all receiving a dose of 469.4 mg·kg^-1. After 7 days of administration， the vaginal opening of female mice and the descent of testes and scrotum in male mice， as well as the ovarian and testicular organ indices， were observed. After 4 weeks of administration， female and male mice were housed together for 2 days， and the pregnancy rate of females was monitored. After delivery， the pregnant female mice continued receiving the treatment for 4 weeks， and the sexual development of their offspring， including vaginal opening， testicular descent， and organ indices of ovaries and testes， was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of gonadotropin-releasing hormone （GnRH） and growth hormone （GH） proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group， there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration， the pregnancy rate in the low-dose group was significantly reduced （P<0.05）， but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices， and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC， Pseudostellariae Radix polysaccharide， significantly reduced the vaginal opening in female mice after 7 days of administration （P<0.05）. After 4 weeks， the serum estradiol levels of non-pregnant female mice were decreased （P<0.05）， but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally， there were no significant effects on precocious puberty indicators， such as vaginal opening and testicular descent， in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice， and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.