Triclosan (TCS) and triclocarban (TCC) are widely used synthetic broad-spectrum antibacterial agents that can enter the human body through the skin, gastrointestinal tract, and other pathways. More and more studies have found that exposure to TCS and TCC can affect human health, but currently, review reports on the health effects of human exposure to TCS and TCC are limited. Therefore, this study reviewed population studies on the relationship between TCS and TCC exposure and health effects by searching the PubMed database, summarized the associated health outcomes, and elucidated the biological mechanisms. A total of 56 studies were retrieved, among which cross-sectional studies (25 studies, 44.64%) and cohort studies (25 studies, 44.64%) accounted for a relatively large proportion, while case-control studies (6 studies, 10.72%) were relatively few. Studies on TCS exposure (48 studies, 85.71%) were far more prevalent than those on TCC exposure (2 studies, 3.57%). The remaining 6 studies involved both TCS and TCC exposure. The research results revealed that TCS exposure was associated with male and female abnormal reproductive functions, fetal growth restriction, abnormal behavior development in children, obesity, gestational diabetes mellitus (GDM), and immune-related diseases. Although the results of different studies show significant differences, they have indicated that exposure to TCS is a potential risk factor for these health problems. Due to the limited number of studies, the evidence for the relationship between TCC exposure and most of the aforementioned health effects is insufficient. Population studies and in vitro and in vivo studies have shown that exposure to TCS and TCC can interfere with the microbial homeostasis, the endocrine system, oxidative stress and immune function of the body, which are potential mechanisms causing adverse health effects. In the future, large-scale prospective cohort studies, as well as in vivo and in vitro studies, are still needed to further clarify the associations between TCS and TCC exposure and health effects, and to deeply explore its mechanism of action. These efforts will provide references for clarifying the human health hazards of TCS and TCC exposure and formulating targeted prevention and control strategies.

Objective In order to understand the current resistance status of Aedes albopictus(Ae. albopictus) adult population to commonly used insecticides and the resistance dynamics development in Zhejiang Province and provide a theoretical basis for the scientific and rational use of hygienic insecticides. Methods Resistance determination was carried out using the diagnostic dose method(GB/T 26347-2010)recommended by WHO in the adult mosquito contact cylinder method to monitor the resistance of Ae. albopictus field populations in 11 cities and districts in Zhejiang Province in 2024. Results The monitoring result showed that adult Ae. albopictus in 11 areas were resistant or suspected resistant populations to both cis-cypermethrin and permethrin; suspected and resistant populations to the organophosphate insecticide malathion were as high as 81.82%; while suspected resistance to the carbamate insecticide residual carbofuran accounted for 45.45%, and the rest of the monitoring sites were sensitive to it. Conclusions The result suggest that the generalized resistance of Ae. albopictus populations to pyrethroids and organophosphorus insecticides in the field in Zhejiang Province needs to be highly emphasized. In future mosquito vector and mosquito-borne disease control, insecticides should be selected based on the resistance monitoring information, while following scientific guidelines for insecticide use.

AIM: To investigate the current incidence of retinopathy of prematurity(ROP)in Sichuan Province and analyze its risk factors, providing a scientific basis for establishing and improving the regional ROP screening and prevention system.METHODS: A retrospective study was conducted on premature infants who underwent fundus screening at the Departments of Ophthalmology and Neonatology of Sichuan Provincial Maternity and Child Health Care Hospital from January 20, 2017 to February 10, 2025. The incidence of ROP was calculated. The patients were divided into ROP group and non-ROP group according to whether ROP occurred, and the clinical characteristics of the two groups were compared. Multivariate Logistic regression was used to analyze risk factors for ROP.RESULTS:This study included a total of 861 premature infants, with 445 males(51.7%)and 416 females(48.3%).ROP occurred in 166 cases, with an incidence rate of 19.3%, and the non-ROP group consisted of 695 cases. The mean gestational age of the ROP and non-ROP groups was 30.24±2.20 and 33.06±1.90 wk(P<0.01), while the mean birth weight was 1438.94±389.66 and 1977.32±438.68 g(P<0.01). By comparing the clinical data of the two groups of preterm infants, the following factors were found to be associated with the occurrence of ROP: younger gestational age, low birth weight, history of oxygen therapy, respiratory distress syndrome, intracranial hemorrhage, neonatal anemia, bronchopulmonary dysplasia, patent ductus arteriosus, and sepsis(all P<0.01). Multivariate Logistic regression analysis revealed that gestational age(OR=0.685,95%CI:0.592-0.792,P<0.01), birth weight(OR=0.999,95%CI:0.998-0.999,P<0.01), and respiratory distress syndrome(OR=2.312,95%CI:1.313-4.070,P<0.01)were risk factors for ROP. Gestational age had the greatest impact.The younger the gestational age at birth, the higher the risk of ROP.CONCLUSION:The incidence of ROP in Sichuan Province is relatively high compared to multicenter results from China. Significant risk factors include younger gestational age, low birth weight, and respiratory distress syndrome. Screening criteria should be formulated based on the local incidence of ROP, and a screening, prevention, and treatment system for ROP should be established and improved.

ObjectiveTo establish and characterize an inducible， CD4+ T cell-specific ablation mouse model （CD4-iDTR） using the Cre-loxP and diphtheria toxin receptor （DTR） systems， and to evaluate its depletion efficacy and specificity. MethodsCD4-iDTR mice were generated through cross-breeding， with genotypes confirmed via PCR-based screening. Mice were categorized into an untreated （control） group and a diphtheria toxin （DT） induction group. Flow cytometry was employed to compare the baseline distribution of CD4⁺ T cells between untreated CD4-iDTR and wild-type C57BL/6 mice.In the DT group， CD4⁺ T cell ablation was induced by subcutaneous DT administration. The depletion efficiency in skin tissues and skin-draining lymph nodes （sdLNs） was quantified at 24 h and 1 week post-injection. Furthermore， the proportions of neutrophils， macrophages， dendritic cells， and other CD11b⁺ immune cell subsets in the skin were monitored to assess the model specificity. ResultsGenomic profiling confirmed the successful generation of the CD4-iDTR line. Under steady-state conditions， no significant differences were observed in the frequency or absolute number of CD4⁺ T cells in the skin and sdLNs between CD4-iDTR and C57BL/6 mice （P>0.05）. Following DT induction， the CD4⁺ T cell population in the skin exhibited decline within 24 h and 1 week （P<0.05）， whereas the CD4⁺ T cell counts in sdLNs remained stable. The percentages of cutaneous neutrophils， macrophages， and other CD11b⁺ myeloid populations were not significantly altered following DT treatment （P>0.05）. ConclusionThe CD4-iDTR mouse model is successfully established and bred， achieving efficient， specific， and inducible ablation of cutaneous CD4⁺ T cells without significant interference with the skin immune microenvironment. This model serves as an ideal experimental tool for investigating skin-specific immunological mechanisms.

BACKGROUND:Leonurine has many biological activities such as improving microcirculation,anti-oxidation,anti-apoptosis,scavenging free radicals,anti-inflammation,and anti-fibrosis,and can promote osteogenic differentiation of bone marrow mesenchymal stem cells,which has the potential to be applied in the treatment of periodontitis. OBJECTIVE:To explore the anti-inflammatory and osteogenic effects of leonurine loading into chitosan/sodium glycerophosphate/sodium alginate hydrogel. METHODS:(1)Chitosan/sodium glycerophosphate/sodium alginate hydrogel(blank hydrogel)and chitosan/sodium glycerophosphate/sodium alginate/leonurus alkali hydrogel were prepared respectively.RAW 264.7 and MC3T3-E1 cells were inoculated with the two kinds of hydrogel.The cytotoxicity of hydrogels was detected by CCK-8 assay and live/dead cell staining.(2)RAW 264.7 cells were cultured in five groups.The blank group was cultured for 24 hours routinely.The lipopolysaccharide group was treated with lipopolysaccharide.The simple hydrogel group was treated with lipopolysaccharide and blank hydrogel.The drug-loaded hydrogel group was treated with lipopolysaccharide and drug-loaded hydrogel.The inhibitor group was treated with lippolysaccharide,drug-loaded hydrogel,and PI3K inhibitor LY294002.24 hours later,mRNA expression of inflammation-related factors was detected by qRT-PCR.Western blot assay was utilized to detect the protein expression of inflammation-related factors and PI3K/AKT signaling pathway.(3)MC3T3-E1 cells were inoculated in four groups.The blank group was cultured without any material.The simple hydrogel group was treated with blank hydrogel.The drug-loaded hydrogel group was treated with drug-loaded hydrogel.The inhibitor group was treated with drug-loaded hydrogel and PI3K inhibitor LY294002 for 7 days.Alkaline phosphatase staining was performed.mRNA expression levels of osteogenic factors were detected by qRT-PCR.The protein expression levels of the PI3K/AKT signaling pathway were detected by western blot assay. RESULTS AND CONCLUSION:(1)The results of CCK-8 assay and live/dead cell staining showed that the two kinds of hydrogels had no cytotoxic effect and had good cytocompatibility.(2)Compared with the blank group,the mRNA and protein expression levels of interleukin 6,tumor necrosis factor α,and interleukin 1β were significantly increased(P<0.05),and the protein expression levels of p-AKT,p-PI3K,p-p65,and p-IκBα were significantly increased in the lipopolysaccharide group(P<0.05).Compared with lipopolysaccharide group,mRNA and protein expression levels of the above indexes were decreased in drug-loaded hydrogel group(P<0.05).Compared with the drug-loaded hydrogel group,the mRNA and protein expression levels of the above indexes were decreased in the inhibitor group(P<0.05).(3)The activity of alkaline phosphatase in drug-loaded hydrogel group was higher than that in the blank group,simple hydrogel group,and inhibitor group(P<0.05).Compared with blank group,the mRNA expression levels of alkaline phosphatase,Runx2,osteocalcin,and type I collagen were increased(P<0.05),and the protein expression levels of p-AKT and p-PI3K were increased in the simple hydrogel group(P<0.05).Compared with the simple hydrogel group,the mRNA and protein expression levels of the above indexes were increased in the drug-loaded hydrogel group(P<0.05).Compared with the drug-loaded hydrogel group,the mRNA and protein expression levels of the above indexes were decreased in the inhibitor group(P<0.05).(4)These findings conclude that chitosan/sodium glycerophosphate/sodium alginate/leonurine hydrogel has anti-inflammatory and osteogenic effects,which may be related to the regulation of PI3K/AKT signaling pathway.

ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

BACKGROUND: The American Heart Association (AHA) introduced the concept of cardiovascular-kidney-metabolic (CKM) health and stage, reflecting the interaction among metabolism, chronic kidney disease (CKD), and the cardiovascular system. However, the association between CKM stage and the long-term risk of cardiovascular disease (CVD) has not been validated. This study aimed to evaluate the long-term CVD risk associated with CKM health metrics and CKM stage using data from a population-based cohort study. METHODS: In total, 5293 CVD-free participants were followed up to around 13 years in the Chinese Multi-provincial Cohort Study (CMCS). Considering the pathophysiologic progression of CKM health metrics abnormalities (comprising obesity, central adiposity, prediabetes, diabetes, hypertriglyceridemia, CKD, and metabolic syndrome), participants were divided into CKM stages 0, 1, and 2. The time-dependent Cox regression models were used to estimate the cardiovascular risk associated with CKM health metrics and stage. Additionally, broader CVD outcomes were examined, with a specific assessment of the impact of stage 3 in 2581 participants from the CMCS-Beijing subcohort. RESULTS: Among participants, 91.2% (4825/5293) had at least one abnormal CKM health metric, 8.8% (468/5293), 13.3% (704/5293), and 77.9% (4121/5293) were in CKM stages 0, 1, and 2, respectively; and 710 incident CVD cases occurred during a median follow-up time of 13.3 years (interquartile range: 12.1 to 13.6 years). Participants with each poor CKM health metric exhibited significantly higher CVD risk. Compared with stage 0, the hazard ratio (HR) (95% confidence interval [CI]) for CVD incidence was 1.31 (0.84-2.04) in stage 1 and 2.27 (1.57-3.28) in stage 2. Significant interactive impacts existed between CKM stage and age or sex, with higher CVD risk related to increased CKM stages in participants aged <60 years or females. CONCLUSION These findings highlight the contribution of CKM health metrics and CKM stage to the long-term risk of CVD, suggesting the importance of multi-component recognition and management of poor CKM health in CVD prevention.
Humans ; Female ; Male ; Cardiovascular Diseases/etiology* ; Middle Aged ; Adult ; Cohort Studies ; Renal Insufficiency, Chronic/metabolism* ; Aged ; Risk Factors ; Metabolic Syndrome/metabolism* ; China ; East Asian People

The triterpenoid saponins of Centella asiatica, including asiaticoside, madecassoside, asiatic acid, and madecassic acid, are pivotal bioactive compounds of the plant. These constituents exhibit a spectrum of pharmacological activities, such as antioxidant, antitumor, and antidepressant effects, promotion of wound healing, and enhancement of microcirculation. Owing to these therapeutic properties, C. asiatica is widely employed in pharmaceutical and cosmetic industries. However, the escalating global demand for its extracts has led to potential supply shortages, prompting researchers to use multiple strategies such as multi-omics, molecular biology, and synthetic biology to conduct extensive studies. These studies encompass the elucidation of the biosynthetic pathways of triterpenoid saponins in C. asiatica, metabolic regulation, the hormonal induction of secondary metabolite synthesis, and the application of biotechnological strategies for natural product production to increase the yield of secondary metabolites in C. asiatica, or to produce active components via microbial chassis, thus satisfying market demands and promoting the sustainable exploitation of wild C. asiatica resources. This article first introduced the triterpenoid saponins of C. asiatica and their biological activities, then summarized the latest research advancements in their biosynthetic pathways, metabolic regulation, and heterologous biosynthesis, and provided an outlook on future development directions, with the aim of providing reference for comprehensive resource development and biotechnological synthesis of active components from C. asiatica.
Centella/genetics* ; Triterpenes/chemistry* ; Biosynthetic Pathways ; Humans ; Drugs, Chinese Herbal/chemistry* ; Plant Extracts

This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult