Licochalcone E is a chalcone isolated from Glycyrrhiza uralensis and G. inflata Batal. This study explored the effect of licochalcone E on improving hepatic steatosis in obese mice and evaluated the role of licochalcone E in regulating lipid accumulation in hepatocytes. In vitro, oleic acid–induced hepatocytes were treated with licochalcone E to investigate its effect on lipid metabolic pathways. In animal experiments, male C57BL/6 mice were fed with a high-fat diet (HFD) and treated with licochalcone E by intraperitoneal injection for 12 weeks to assess its effects on biochemical indexes and hepatic steatosis. Furthermore, mice were fed a methionine/choline-deficient (MCD) diet and administered licochalcone E, followed by evaluation of liver fibrosis. Licochalcone E effectively reduced body weight, epididymal and inguinal fat weight, and adipocyte size in HFD-induced obese mice. Licochalcone E treatment of obese mice also reduced hepatic lipid accumulation and improved hepatocyte steatosis. Licochalcone E regulated the expression of lipogenesis- and lipolysis-related genes in the livers of obese mice and increased AMPK phosphorylation and Sirt1 expression in the liver. Licochalcone E also attenuated hepatic inflammation and oxidative stress in obese mice. Furthermore, treatment of MCD-induced mice with licochalcone E reduced the number of lipid vacuoles and the extent of fibrosis and inhibited liver inflammation. In FL83B hepatocytes, licochalcone E could regulate lipogenesis and lipolysis, and increase the phosphorylation of AMPK and ACC. These findings provide new insights into the role of licochalcone E in regulating lipid metabolism and preventing hepatic steatosis.

ObjectiveTo investigate the preventive and therapeutic effects of Qingfei Paidu decoction (QFPDD) on acute lung injury (ALI) in mice and its underlying molecular mechanisms based on miRNA sequencing technology. MethodsTwenty-four 4-week-old male KM mice were randomly divided into a control group, a model group, and a QFPDD group (n = 8 per group). After one week of acclimatization, mice in the control and model groups were intragastrically administered ultrapure water (0.2 mL per dose), whereas mice in the QFPDD group were intragastrically administered QFPDD (1.6 g crude drug/mL, 0.2 mL per dose), twice daily for 8 consecutive days. On days 2–8, mice in the model and QFPDD groups were exposed to aerosolized lipopolysaccharide (LPS) solution (2.5 g/L, 4 mL per exposure) for 7 consecutive days. On day 9, blood was collected via the retro-orbital venous plexus under deep anesthesia, and lung tissues were harvested. Body weight and lung weight were measured, and the lung coefficient was calculated. Serum levels of inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were detected by ELISA. Lung histopathological changes were observed by HE staining of paraffin-embedded sections. miRNA expression profiles in lung tissues were analyzed using the Illumina HiSeq 2500 sequencing platform. Target genes of differentially expressed miRNAs were predicted using bioinformatics databases, and functional enrichment analysis of these target genes was performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Differentially expressed miRNAs were validated by reverse transcription quantitative real-time PCR (RT-qPCR). ResultsCompared with the control group, the model group showed a consistent body weight growth trend but a significantly increased lung coefficient (P < 0.01). ELISA results showed that serum levels of TNF-α and IL-6 were significantly elevated in the model group compared with the control group (P < 0.01), whereas QFPDD treatment significantly reduced serum TNF-α and IL-6 levels compared with the model group (P < 0.05). HE staining showed that, compared with the control group, the model group exhibited widened alveolar septa, massive inflammatory cell infiltration, partial alveolar expansion, and mild capillary dilation with congestion. In contrast, the QFPDD group showed only slightly widened alveolar septa and mild inflammatory cell infiltration compared with the model group. Intersection analysis of miRNA sequencing data identified 13 differentially expressed miRNAs common to both the model vs. control and QFPDD vs. model comparisons. Among them, 6 miRNAs (mmu-miR-203-3p, mmu-miR-181b-5p_R-1, hsa-miR-4286_R+1, mmu-miR-1843b-5p_L+1R-1_2, mmu-miR-22-3p, and mmu-miR-1964-3p) were significantly up-regulated in the model group (P < 0.05) and significantly down-regulated after QFPDD treatment (P < 0.05), showing a therapeutic reversal trend. GO analysis revealed that the target genes of the differentially expressed miRNAs were mainly enriched in biological processes such as RNA polymerase Ⅱ transcriptional regulation. KEGG analysis indicated that target genes were mainly enriched in signaling pathways including the mitogen-activated protein kinase (MAPK) pathway. RT-qPCR validation result for mmu-miR-203-3p was consistent with the sequencing analysis results. ConclusionQFPDD may exert preventive and therapeutic effects against ALI by regulating the expression of mmu-miR-203-3p and other miRNAs, thereby modulating inflammatory responses and the MAPK signaling pathway and participating in the pathological process of lung injury.

OBJECTIVE: High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear. METHODS: In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models. RESULTS: Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure. CONCLUSION: Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure. GRAPHICAL ABSTRACT available in www.besjournal.com.
Animals ; Oxidative Stress ; Hippocampus/metabolism* ; Rats ; Nogo Proteins/genetics* ; Male ; Rats, Sprague-Dawley ; Hypoxia/metabolism* ; Altitude ; Synapses ; Humans ; Altitude Sickness/metabolism*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To investigate the dose characteristics of the Zeiss INTRABEAM system in air and water, providing dose reference for electronic brachytherapy.Methods:A Monte Carlo program was used to establish a three-dimensional model of a miniature X-ray source vacuum drift tube and a 4 cm spherical applicator. The process of electron beam bombardment on a gold target to generate X-rays was simulated, and parameters such as photon fluence spectrum, percentage depth dose, and half-value layer were calculated. Additionally, the radial dose uniformity in water was measured.Results:The average energy of X-rays at 3 cm in air was 20.8 keV, with a half-value layer of 0.08 mm Al. Under the influence of the applicator, the spectrum becomes hardened, with axial and radial average energies of 28.7 and 29.0 keV, respectively. In water, the percentage depth dose (PDD) curve follows an inverse cubic decay with depth, indicating strong dose concentration and rapid fall-off in near-field irradiation. The radial dose uniformity in water exceeded 99.5%.Conclusions:The INTRABEAM device emits low-energy X-rays characterized by shallow penetration depth, and concentrated dose delivery. Its highly uniform dose distribution ensures comprehensive coverage of the target area, making it particularly suitable for treating superficial tumors and for intraoperative radiotherapy at close range.

Objective:To investigate the clinical application value of a novel filter's retraction hook capture technique of pull-assisted method for the endovascular retrieval of conical inferior vena cava (IVC) filters whose hook attached to the wall.Methods:From January 2020 to December 2024, patients with conical filters whose hook attached to the wall admitted at Beijing Jishuitan Hospital were enrolled consecutively.Results:A total of 46 patients underwent filter retrieval using filter's retraction hook capture technique of pull-assisted method. Among these patients, 39 cases (84.8%) were successful in filter retrieval, with the penetration distance of cranial anchor vertex of 3.3(2.5, 4.4) mm, and 13 (33.3%) filters were deformed. The other 7 cases were unsuccessful, with a penetration distance of cranial anchor vertex of 5.0 (4.3, 5.0) mm, and 6 (85.7%) filters were deformed. There was a statistically significant difference between the two groups ( P<0.05). One case (2.2%) had IVC injury, one case (2.2%) experienced filter fracture, and no symptomatic pulmonary embolism occurred. Logistic regression analysis showed that filter deformation was an independent dangerous factor for filter's retraction. Conclusions:Filter's retraction hook capture technique of pull-assisted method is effective in removing conical filters whose hook attached to the wall, with no symptomatic PE occurring. This method can be considered as a new adjuvant technique for filter retrieval.

Objective The experimental method of cervical vestibular evoked myogenic potential(cVEMP)with high retest reliability was designed to verify the accuracy of locating sternocleidomastoid muscle in mice.Methods Three 2-month-old ICR male mice were selected,one of which was dissected to locate the sternocleidomastoid muscle,while the other two were used to design the experimental plan to verify the accuracy of localization.Results The recording electrode positioned on the sternocleidomastoid muscle of mice can repeatedly elicit clear cVEMP waveform.Conclusion The cVEMP waveform with high retest reliability can be measured in both experimental mice,suggesting that the localization of sternocleidomastoid muscle in this research is accurate.

Objective To observe the effect of mild moxibustion at"Qihai","Guanyuan"and"Zhongji"on GnRH and its receptor in rats with gynecological cold coagulation and blood stasis syndrome(CCBS);To explore the mechanism of moxibustion on reproductive function of gynecological CCBS.Methods Totally 48 female SD rats were randomly divided into blank group,model group,moxibustion group,inhibitor group,inhibitor+moxibustion group and angonist group,with 8 rats in each group.The gynecological CCBS model was prepared by ice bath and adrenalin injection.GnRHant or GnRHa injection and mild moxibustion intervention were given to each treatment group.The score of CCBS symptoms and the amount of microcirculation blood perfusion in uterus were detected,the morphology of ovarian tissue and uterine tissue were observed by HE staining,serum reproductive hormones(GnRH,FSH,LH)and neurotransmitters(DA,GABA)contents were detected by ELISA,the expressions of GnRHR,FSHR and LHR mRNA and protein in ovarian and uterine tissue were detected by immunohistochemistry,RT-qPCR and Western blot.Results Compared with the blank group,the symptom score of CCBS in model group was significantly increased,the amount of microcirculation blood perfusion in uterus was decreased,the ovarian follicles were decreased,and the endometrial epithelium was thinner and the structure was chaotic,the contents of serum GnRH,FSH,LH,GABA decreased,DA content increased;the mRNA and protein expressions of GnRHR,FSHR and LHR in ovarian tissue decreased(P<0.01).Compared with the model group,the symptom score of CCBS in each intervention group were significantly decreased,the amount of microcirculation blood perfusion in uterus increased,ovarian follicles increased,endometrium thickened and glands increased,the contents of serum GnRH,FSH,LH,GABA increased,DA content decreased;the mRNA and protein expressions of GnRHR,FSHR and LHR were increased(P<0.05,P<0.01).Conclusion Moxibustion can regulate GnRH and its receptor and improve HPO axis function by regulating neurotransmitters,so as to improve the general state and reproductive function of gynecological CCBS model rats.

Depression is a highly heterogeneous psychiatric disorder with complex pathogenesis influenced by the interplay of biological,psychological,and social-environmental factors.Based on the 2021 edition of the Chinese Guidelines for the Prevention and Treatment of Depressive Disorders,which explicitly identify gender as a significant risk factor for depression onset,this paper systematically reviews the gender-differentiated pathogenesis and therapeutic advances in depression from both traditional Chinese medicine(TCM)and Western medical perspectives.In Western medicine,a large number of studies have demonstrated the sex-specific mechanism of estrogen/testosterone fluctuations and monoamine transmitter system regulation.While in TCM,although the constitution theory proposes that there are significant gender differences in congenital constitution and that qi depression and qi deficiency are associated with susceptibility to depression,current evidence primarily relies on cross-sectional surveys and lacks validation through high-quality RCTs.Compared with Western medicine,the direct research on gender-differentiated antidepressant effects in TCM remains relatively underdeveloped.In future study,it may be possible to deepen and improve the research on anti-depression in TCM from the biological markers of particular constitutions in the gender dimension.This paper advocates establishing a bio-psycho-social integrated intervention model,advancing mechanistic exploration through prospective cohort studies and multi-omics technologies,and promoting precision diagnosis and treatment systems based on gender differences,and to form a three-dimensional diagnosis and treatment and research system that covers biomarkers,social role assessment,and TCM constitution identification,in order to provide a new theoretical framework and a practical pathway for the precise medical treatment of depression.

Objective:To explore the mechanism by which moxibustion improves cold-induced blood stasis pattern(CIBSP)and to uncover the biological basis underlying the correlation between the Conception Vessel(CV),Governor Vessel(GV),Thoroughfare Vessel(TV),and the uterus by investigating the effects of mild moxibustion on the hypothalamic-pituitary-ovary axis(HPOA)in CIBSP model rats.Methods:Forty-eight female Sprague-Dawley rats were divided into a blank group,a model group,a CV group,a GV group,a TV group,and a non-meridian non-point(NMNP)group according to the random number table method,with 8 rats in each group.Except for rats in the blank group,the other rats were subjected to an ice water bath plus epinephrine to prepare CIBSP models.Each intervention group was given mild moxibustion on the first day of modeling.Qihai(CV6),Guanyuan(CV4),and Zhongji(CV3)were selected in the CV group;Huangshu(KI16),Dahe(KI12),and Henggu(KI11)were selected in the TV group;Xuanshu(GV5),Mingmen(GV4),and Yaoyangguan(GV3)were selected in the GV group;three NMNP spots were selected in the NMNP group.Mild moxibustion was administered for 20 min each time,once a day,for 14 consecutive days.The symptom scores of CIBSP and uterine electromyogram were compared among groups;morphological changes in reproductive organs were observed by hematoxylin-eosin staining;enzyme-linked immunosorbent assay was used to detect serum reproductive hormones and neurotransmitters.The mRNA and protein expression levels of estrogen receptor(ER),follicle-stimulating hormone receptor(FSHR),and luteinizing hormone receptor(LHR)were detected by real-time quantitative polymerase chain reaction,immunohistochemistry,or Western blotting assays.Results:Compared to the blank group,the model group showed a significantly increased CIBSP symptom score,an amplified in vivo uterine myoelectric value;decreased ovarian follicles,thinner endometrial epithelium,and disordered structure with the pathological examination,decreased serum levels of reproductive hormones,6-keto-prostaglandin F1α(6-keto-PGF1α),and β-endorphin(β-EP),increased thromboxane B2(TXB2),5-hydroxytryptamine(5-HT),and substance P(SP),and decreased mRNA and protein expression of ovarian ER,FSHR,and LHR(P<0.05 or P<0.01).Compared to the model and NMNP groups,each point-intervention group showed a decreased CIBSP symptom score and uterine myoelectric value;increased ovarian follicles,thickened endometrium,increased glands,up-regulated serum reproductive hormones,6-keto-PGF1α,and β-EP,down-regulated serum TXB2,5-HT,and SP and increased mRNA and protein expression of ovarian ER,FSHR,and LHR(P<0.05 or P<0.01).Conclusion:Moxibustion at points from the CV,GV,and TV("three branches from one source")can improve the reproductive neuroendocrine function of CIBSP rats,and this effect may be mediated through the regulation of the HPOA.These detections suggest that the biological basis of point-uterus correlation may be based on HPOA regulation.