Small intestinal bacterial overgrowth （SIBO） is significantly more prevalent in patients with liver cirrhosis. Recent studies indicate that SIBO is not merely a concomitant phenomenon but a key driver of cirrhosis progression via the “gut-liver axis” mechanism. This review innovatively proposes a “microbiota-immunity-fibrosis” pathological positive feedback loop model， systematically elucidating the sequential pathological process through which SIBO drives disease progression via multiple mechanisms—including disruption of intestinal barrier function， facilitation of bacterial and endotoxin translocation， induction of systemic inflammatory responses， and acceleration of hepatic fibrosis. Furthermore， it provides a systematic evaluation of the clinical application value and limitations of current SIBO-targeted therapeutic strategies， such as antibiotic therapy， microbial modulation， herbal medicine interventions， and dietary therapies. This work aims to establish a theoretical foundation and identify future research directions for the development of multi-targeted and personalized comprehensive treatment strategies.

Guided by the theory of latent pathogens， it is believed that the basic pathogenesis of adult-onset Still's disease is the latent pathogens in the deep yin level. The onset of the disease is fundamentally characterized by the deficiency of both qi and yin as the root， with dampness， heat， phlegm， and blood stasis as the branch， which triggered by intruding pathogens activate the latent pathogens in yin level. The treatment focuses on nourishing yin and dispersing heat as the key therapeutic method. It is proposed that clearing and resolving dampness-heat， expelling pathogens outward， dispersing the latent pathogens， reinforcing healthy qi and consolidating the root， boosting qi and nourishing yin as treatment idea. In clinic， Qinghao Biejia Decoction （青蒿鳖甲汤） could be used as the basic formula， and modified with characteristic herb pairs such as Qinghao （Artemisia annua） - Digupi （Lycium chinense） to enrich yin and clear heat， and enforce the power of clearing deficient heat； Biejia （Lawsonia inermis） - Xuchangqing （Vincetoxicum mukdenense） to enrich yin and activate blood， unblock the collaterals and dissipate masses； Duhuo （Angelica biserrata） - Mudanpi （Paeonia × suffruticosa） to dispel wind and activate blood， resolve dampness and unblock the collaterals， so as to clear and warm simultaneously， and regulate qi and blood at the same time； and Chuanshanlong （Dioscorea nipponica） - Difuzi （Bassia scoparia） to dissolve stasis and dispel phlegm， explore and dispel latent pathogens.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

AIM:Uterine leiomyoma is the most prevalent benign tumor among women of reproductive age.This study aims to investigate the involvement of vascular endothelial growth factor A(VEGFA)in the progression of uterine leiomyoma through the cell division cycle protein 42(Cdc42)/Wnt/β-catenin signaling pathway.METHODS:Clinical data and tissue samples were collected from 36 patients who underwent either laparoscopic or open hysteromyomectomy at the Gynecology Department of Chizhou People's Hospital between January 2022 and December 2023.Immunohistochemi-cal staining was utilized to assess the expression of VEGFA and Cdc42.Cell viability was evaluated using the CCK-8 as-say,while cell proliferation was measured by EdU staining and flow cytometry.The expression levels of VEGFA,Cdc42,β-catenin,and their downstream targets,cyclin D1 and c-Myc,were analyzed via Western blot.RESULTS:Immunohis-tochemical and Western blot analyses revealed significantly higher levels of VEGFA and Cdc42 in leiomyoma tissues com-pared with normal uterine smooth muscle tissues.Further subgroup analysis via Western blot indicated that the expression levels of VEGFA and Cdc42 were elevated in intermuscular fibroids compared with submucosal and subserous fibroids.The CCK-8 assay demonstrated that VEGF receptor inhibitor axitinib effectively reduced the viability of uterine leiomyoma cells.Moreover,the proliferation capacity of uterine leiomyoma cells was significantly greater than that of normal uterine smooth muscle cells,and axitinib substantially inhibited this proliferation.Western blot results further confirmed signifi-cant increases in the expression of VEGFA,Cdc42,β-catenin,and their downstream proteins,cyclin D1 and c-Myc,in uterine leiomyoma cells.Axitinib was shown to inhibit the expression levels of Cdc42,β-catenin,and their downstream targets,cyclin D1 and c-Myc.The Cdc42 inhibitor ML141 did not affect VEGFA expression,but effectively inhibited the expression of β-catenin and its downstream target proteins,cyclin D1 and c-Myc.CONCLUSION:The VEGFA may play a significant role in the progression of uterine leiomyoma via the Cdc42/Wnt/β-catenin signaling pathway,suggesting that VEGFA could serve as a potential therapeutic target for the treatment of uterine leiomyoma.

Objective:To explore the relationship between obesity indicators and DNA methylation clocks acceleration,and to analyze their temporal sequence.Methods:Data were obtained from two sur-veys conducted in 2013 and 2017-2018 by the Chinese National Twin Registry.Peripheral blood DNA methylation data were measured using the Illumina Infinium Human Methylation 450K BeadChip and EPIC BeadChip.DNA methylation clocks/acceleration metrics(GrimAA,PCGrimAA and Dunedin-PACE)were calculated using the DNA methylation online tool(https://dnamage.genetics.ucla.edu/)or R code provided by researchers.Obesity indicators included weight,body mass index(BMI),waist circumference,waist-hip ratio,and waist-height ratio.A total of 1 070 twin individuals were included in the cross-sectional analysis,comprising 378 monozygotic(MZ)twin pairs and 155 dizygotic(DZ)twin pairs for within-pair analysis.Mixed-effects models were used to examine the associations between obesity indicators and DNA methylation clocks,as well as their acceleration measures.The longitudinal analysis included 314 twin individuals,comprising 95 MZ twin pairs and 62 DZ twin pairs for within-pair analy-sis.Cross-lagged panel models were applied to further explore the temporal relationships between obesity and DNA methylation clock indicators.All analyses were conducted both in the full twin sample and separately within MZ and DZ twin pairs.Results:In the cross-sectional analysis population,monozygotic twins accounted for 71.0％,males for 68.0％,and the mean chronological age was(49.9±12.1)years.In the longitudinal analysis population,monozygotic twins accounted for 60.5％,males for 60.8％,with a mean baseline chronological age of(50.4±10.2)years and a mean follow-up duration of(4.6±0.6)years.Except for the waist-to-hip ratio,which was significantly higher at follow-up com-pared with baseline,no statistically significant differences were observed in the means of other obesity in-dicators between baseline and follow-up.Correlation analysis revealed that weight,BMI,waist circumfe-rence,waist-hip ratio(WHR),and waist-height ratio(WHtR)were positively correlated with Dunedin-PACE in all the twins,with WHtR showing the strongest association(β=0.21,95％CI:0.11 to 0.31).Weight and BMI were negatively associated with GrimAA(β=-0.03,95％CI:-0.05 to-0.01;β=-0.07,95％CI:-0.12 to-0.02),while weight was negatively associated with PCGrim-AA(β=-0.02,95％CI:-0.03 to 0.00).However,within-twin-pair analyses showed no statistically significant correlations.Cross-lagged panel model analysis indicated that higher baseline weight might lead to increased GrimAA at follow-up,while elevated baseline weight,BMI,and waist circumference might increase PCGrimAA.Higher baseline WHR was associated with increased DunedinPACE at follow-up.Conclusion:Obesity indicators correlate with DNA methylation clock acceleration metrics.Baseline obesity may influence changes in certain DNA methylation clock indicators over time,suggesting that obesity could exert long-term health effects by accelerating DNA methylation aging.However,these associations may be confounded by shared genetic or environmental factors among the twins.