ObjectiveTo explore the possible mechanisms of Wenyang Huazhuo Formula （温阳化浊方， WHF） in improving reproductive aging from the perspective of the ovarian mechanical microenvironment. MethodsThe experiment included five groups， 3-month group （20 female mice at 3 months of age）， 6-month group （20 female mice at 6 months of age）， 6-month + WHF group （20 female mice at 5 months of age treated with WHF）， 9-month group （20 female mice at 9 months of age）， and 9-month + WHF group （20 female mice at 8 months of age treated with WHF）. The 6-month + WHF group and 9-month + WHF group were orally administered WHF 41.2 g/（kg·d） once daily for 4 consecutive weeks. The other three groups received no intervention. Reproductive hormone levels were measured by ELISA. HE staining was used to count the numbers of various stages of follicles. Ovarian hyaluronic acid （HA） content and collagen fiber content were measured to evaluate the ovarian mechanical microenvironment. Superovulation was performed to observe the number of eggs obtained， as well as the number of offspring and birth weight to assess fertility. The in vitro fertilization and blastocyst culture of oocytes from female offspring in each group were observed to evaluate the effect of WHF on offspring reproductive potential. ResultsCompared with the 3-month group， the 6-month group and 9-month group showed significantly decreased serum levels of gonadotropin-releasing hormone （GnRH）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH）， decreased ovarian collagen content， and reduced numbers of primordial and secondary follicles. In contrast， the numbers of primary follicles， antral follicles， and atretic follicles increased. The levels of anti-Müllerian hormone （AMH）， ovarian HA content， and the fertilization rate， cleavage rate， and blastocyst formation rate of oocytes from offspring were significantly lower （P＜0.05）. Compared with the 6-month group， the 6-month + WHF group showed significantly reduced serum levels of GnRH， FSH， and LH， with a significant decrease in primary follicles， antral follicles， and atretic follicles as well as increase of AMH levels， ovarian HA content， number of primordial and secondary follicle， egg count， and offspring birth weight （P＜0.05）. Compared with the 9-month group， the 9-month + WHF group exhibited reduced GnRH， FSH， and collagen fiber content， as well as reduced number of primary follicles， antral follicles， and atretic follicles. However， AMH levels， ovarian HA content， number of primordial and secondary follicle， egg count， offspring numbers， birth weight， fertilization rate， cleavage rate， and blastocyst formation rate of oocytes from offspring all significantly increased （P＜0.05）. ConclusionWHF can significantly improve the ovarian reserve， fertility， and reproductive potential in offspring during reproductive mid-life and late-life stages. Its effect may be related to the remodeling of the mechanical microenvironment of aging ovaries. Moreover， the effect on the mechanical microenvironment remodeling of late-stage ovaries and the improvement of the offspring reproductive potential is more significant.

BACKGROUND:Multiple studies have confirmed that mitogen-activated protein kinase(MAPK)signaling pathway is involved in cell proliferation,and microRNA(miR)is involved in the occurrence and development of hypertrophic scars.Therefore,the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE:To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS:The primary fibroblasts were isolated and collected from the skin samples.The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence.The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR.The target genes of hsa-miR-27a-3p were predicted using the database,and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes.There were seven groups:blank control,negative control,miR-27a-3p mimic,miR-27a-3p inhibitor,miR-27a-3p mimic+p38 MAPK inhibitor,miR-27a-3p mimic+extracellular regulated protein kinase inhibitor,miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor.Western blot was used to detect the levels of extracellular regulated protein kinase,c-Jun N-terminal kinase inhibitor.and p38 kinase and their phosphorylation levels.Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION:Compared with normal skin fibroblasts,hypertrophic scar fibroblasts had stronger proliferative activity(P<0.05)and faster proliferation level(P<0.001).Compared with normal skin,miR-27a-3p was highly expressed in hypertrophic scars(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p could promote cell proliferation activity(P<0.001)and proliferation levels(P<0.001).Compared with the negative control group,knockdown of miR-27a-3p could inhibit the proliferation activity(P<0.05)and proliferation levels(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase(P<0.05).Compared with the negative control group,knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK(P<0.05).Compared with the miR-27a-3p mimic group,specific inhibitors of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity(P<0.01)and proliferation level(P<0.001)of fibroblasts.To conclude,these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway.

Transjugular intrahepatic portosystemic shunt （TIPS） is currently an effective procedure for the complications of portal hypertension. In recent years， rapid progress has been made in the field of TIPS in terms of technical approaches， prognostic models， and an expanding range of indications. The EASL recently issued the clinical practice guidelines on TIPS to comprehensively address all aspects of TIPS in patients with liver cirrhosis. This article makes an excerpt of the key recommendations in the guidelines.

Objective: To understand classroom environmental conditions and their association with spinal curvature abnormalities among students of primary and secondary schools in Guizhou Province, so as to provide a basis for formulating school health policies and scientific prevention and control measures for abnormal spinal curvature in students. Methods: Using a stratified random sampling method, 471 schools (2 811 classrooms) were selected annually across the province from 2022 to 2024 in order to monitor and evaluate classroom environment according to national standards. Spinal examinations were conducted for 196 606 (2022), 194 876 (2023), and 195 048 (2024) students, and χ 2 test was used to analyze the correlation of desk and chair compliance with student spinal curvature abnormalities. Results: The qualified rates of classroom blackboard illuminance uniformity ( 85.41 %) and the blackboard size (82.24%) were the highest in primary and secondary schools in Guizhou Province, while the average blackboard surface illumination qualified rate (20.10%) was the lowest. The average desk illumination (50.11%-58.63%), desk illumination uniformity (61.92%-72.27%) and qualified noise rate (50.04%-51.94%) increased significantly in 3 years; in addition, the compliance rate of desks and chairs decreased from 25.00% to 13.52%, and the differences were all statistically significant ( χ 2=42.48, 80.93, 46.09, 129.72, all P <0.05). Middle school classrooms outperformed primary schools in terms of per capita area, average blackboard illuminance, blackboard illuminance uniformity, average desktop illuminance, desktop illuminance uniformity, and noise compliance ( χ 2=311.55, 12.41, 20.64, 40.76, 10.25, 52.47), but had lower compliance for blackboard size and reflectance ( χ 2=537.29, 7.59) (all P <0.01). Urban schools had higher compliance than suburban schools for per capita area, average blackboard illuminance, average desktop illuminance, and desktop illuminance uniformity ( χ 2=73.71, 17.68, 29.30 , 36.03), but lower compliance for desk-chair suitability, blackboard size, and blackboard reflectance ( χ 2=4.72, 26.02, 5.43 ) (all P <0.05). The spinal curvature abnormality detection rate was 0.83%. A significant association was found between abnormality detection and desk-chair non compliance ( χ 2=223.85, P <0.01). Conclusions Classroom environment hygiene in Guizhou schools is suboptimal. Strengthening school environmental hygiene infrastructure and greater attention to its impact on student s health are essential.

Objective: To understand the epidemiological characteristics of abnormalities spinal curvature among children and adolescents in Karst landform in Guizhou Province, so as to provide a scientific basis for targeted comprehensive intervention. Methods: From September to December 2023, 194 875 children and adolescents aged 6-18 were selected from all countieldistricts of 9 cities (prefectures) in Guizhou Province by stratified random cluster sampling method according to the proportion of Karst landform area in Guizhou Province for carrying out spinal curvature abnormality screening, and a questionnaire survey was conducted on 139 449 students in the fourth grade and above of primary school. Binary Logistic regression was used for multivariate analysis. Results: The detection rate of abnormal spinal curvature among children and adolescents aged 6-18 in Guizhou Province was 1.13%. The detection rates of abnormal spinal curvature in areas with a high proportion of Karst landform, areas with a low proportion of Karst landform, intercalation areas, and nonKarst landform areas were 1.10%, 2.00%, 0.90%, and 0.60%, respectively. Among them, the detection rates of abnormal spinal curvature in female students (2.40%, 1.60%, 0.90%) in areas with a low proportion of Karst landform, intercalation areas and nonKarst landform were higher than those in male students (1.60%, 0.10%, 0.30) (χ2=12.66, 112.69, 30.22, all P<0.05). The detection rates of abnormal spinal curvature among senior high school students (2.00%, 4.30%, 1.40%, 1.30%) in different Karst landform distributions were successively higher than those among junior high school students (1.40%, 3.20%, 1.00%, 0.60%) and primary school students (0.70%, 0.80%, 0.60%, 0.30%) (χ2=306.11, 175.80, 14.24, 39.57, all P<0.05). The results of multivariate Logistic regression analysis showed that the detection rates of abnormal spinal curvature in both highproportion and lowproportion Karst landform areas were higher than those in nonKarst landform areas [OR(95%CI)=1.84(1.05-2.25), 1.60(1.23-2.09), both P<0.05]. Conclusion The detection rate of abnormal spinal curvature in children and adolescents aged 6-18 in Guizhou Province is related to the distribution of Karst landform, so it is necessary to strengthen screening and appropriate comprehensive interventions.

ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen （TFCC） in the mouse model of chronic unpredictable mild stress （CUMS）. MethodsFifty male 4-week-old ICR mice were randomized into five groups （n=10 per group）： blank control， model， Cuscutae Semen decoction （10.2 g·kg^-1·d^-1）， paroxetine （2.6 mg·kg^-1·d^-1）， and TFCC （173.2 mg·kg^-1·d^-1）. The other groups except the blank control group underwent chronic unpredictable mild stress （CUMS） for 4 weeks. Behavioral assessments were conducted post-modeling. Then， the model group received distilled water （10 mL·kg^-1·d^-1）， while treatment groups were administrated with respective agents via oral gavage （10 mL·kg^-1） for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test （SPT）， forced swimming test （FST）， and tail suspension test （TST）. Hippocampal neuronal morphology was observed via hematoxylin-eosin staining， and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the hippocampal levels of inflammatory cytokines ［interleukin （IL）-1β， IL-6， and TNF-α）］ and neurotransmitters ［5-hydroxytryptamine （5-HT）， dopamine （DA）， and brain-derived neurotrophic factor （BDNF）］， while the reactive oxygen species （ROS） levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated Speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， IL-1β， and inducible nitric oxide synthase （iNOS）. Western blot was employed to evaluate the protein levels of NLRP3， ASC， Caspase-1， uncoupling protein 2 （UCP2）， and thioredoxin-interacting protein （TXNIP）. ResultsCompared with the blank control group， the model group exhibited weight loss （P<0.01）， reduced sucrose preference （P<0.01）， prolonged immobility time in FST and TST （P<0.01）， neuron disarrangement with nuclear pyknosis in hippocampal CA3 region， increased apoptosis in the brain tissue， elevated levels of IL-1β， IL-6， and TNF-α （P<0.01）， declined levels of 5-HT， DA， and BDNF （P<0.01）， increased ROS accumulation （P<0.01）， upregulated mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， down-regulated protein level of UCP2 （P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Compared with the model group， the interventions restored sucrose preference （P<0.01）， shortened immobility time （P<0.01）， repaired hippocampal neuronal structure， reduced apoptosis， lowered the levels of inflammatory cytokines （P<0.01）， restored the levels of neurotransmitters （P<0.01）， alleviated ROS accumulation （P<0.01）， downregulated the mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， upregulated the protein level of UCP2 （P<0.01）， and reduced the protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Moreover， TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair， neurotransmitter regulation， anti-inflammatory effects， and modulation of the UCP2/TXNIP/NLRP3 pathway （P<0.05）. ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation， reduce oxidative stress， restore neurotransmitters， thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.

Objective To explore the rehabilitation effect of abdominal breathing training and the improvement status of cardiopulmonary function in elderly patients with chronic obstructive pulmonary disease (COPD) over 60 years old. Methods A total of 520 COPD patients over 60 years old admitted to the hospital were selected from June 2021 to March 2024 as the research subjects. The patients were divided into reference group (routine intervention, n=260) and abdominal rehabilitation group (abdominal breathing training on the basis of routine intervention, n=260) by adopting computer random function. Cardiopulmonary tolerance, respiratory muscle condition and pulmonary function markers were compared between the two groups before and after intervention. Results Compared with the reference group after intervention, the abdominal rehabilitation group had higher maximum oxygen uptake and minute ventilation volume, lower anaerobic threshold, and higher maximal expiratory pressure (MEP). The maximal inspiratory pressure (MIP), forced expiratory volume in one second (FEV1), forced expiratory volume (FVC), ratio of forced expiratory volume to forced vital capacity in one second (FEV1/FVC), the percentage of FEV1 to the predicted value (FEV1%pred) and 1 min maximum ventilation volume (MVV) (P<0.05) were all higher in the abdominal rehabilitation group than the reference group after intervention. Conclusion Abdominal breathing training for patients with COPD over 60 years old can effectively enhance cardiopulmonary tolerance, and improve respiratory muscle physiology and pulmonary function.

ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen （TFCC） in the mouse model of chronic unpredictable mild stress （CUMS）. MethodsFifty male 4-week-old ICR mice were randomized into five groups （n=10 per group）： blank control， model， Cuscutae Semen decoction （10.2 g·kg^-1·d^-1）， paroxetine （2.6 mg·kg^-1·d^-1）， and TFCC （173.2 mg·kg^-1·d^-1）. The other groups except the blank control group underwent chronic unpredictable mild stress （CUMS） for 4 weeks. Behavioral assessments were conducted post-modeling. Then， the model group received distilled water （10 mL·kg^-1·d^-1）， while treatment groups were administrated with respective agents via oral gavage （10 mL·kg^-1） for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test （SPT）， forced swimming test （FST）， and tail suspension test （TST）. Hippocampal neuronal morphology was observed via hematoxylin-eosin staining， and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the hippocampal levels of inflammatory cytokines ［interleukin （IL）-1β， IL-6， and TNF-α）］ and neurotransmitters ［5-hydroxytryptamine （5-HT）， dopamine （DA）， and brain-derived neurotrophic factor （BDNF）］， while the reactive oxygen species （ROS） levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated Speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， IL-1β， and inducible nitric oxide synthase （iNOS）. Western blot was employed to evaluate the protein levels of NLRP3， ASC， Caspase-1， uncoupling protein 2 （UCP2）， and thioredoxin-interacting protein （TXNIP）. ResultsCompared with the blank control group， the model group exhibited weight loss （P<0.01）， reduced sucrose preference （P<0.01）， prolonged immobility time in FST and TST （P<0.01）， neuron disarrangement with nuclear pyknosis in hippocampal CA3 region， increased apoptosis in the brain tissue， elevated levels of IL-1β， IL-6， and TNF-α （P<0.01）， declined levels of 5-HT， DA， and BDNF （P<0.01）， increased ROS accumulation （P<0.01）， upregulated mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， down-regulated protein level of UCP2 （P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Compared with the model group， the interventions restored sucrose preference （P<0.01）， shortened immobility time （P<0.01）， repaired hippocampal neuronal structure， reduced apoptosis， lowered the levels of inflammatory cytokines （P<0.01）， restored the levels of neurotransmitters （P<0.01）， alleviated ROS accumulation （P<0.01）， downregulated the mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， upregulated the protein level of UCP2 （P<0.01）， and reduced the protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Moreover， TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair， neurotransmitter regulation， anti-inflammatory effects， and modulation of the UCP2/TXNIP/NLRP3 pathway （P<0.05）. ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation， reduce oxidative stress， restore neurotransmitters， thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.

Objective To explore the rehabilitation effect of abdominal breathing training and the improvement status of cardiopulmonary function in elderly patients with chronic obstructive pulmonary disease (COPD) over 60 years old. Methods A total of 520 COPD patients over 60 years old admitted to the hospital were selected from June 2021 to March 2024 as the research subjects. The patients were divided into reference group (routine intervention, n=260) and abdominal rehabilitation group (abdominal breathing training on the basis of routine intervention, n=260) by adopting computer random function. Cardiopulmonary tolerance, respiratory muscle condition and pulmonary function markers were compared between the two groups before and after intervention. Results Compared with the reference group after intervention, the abdominal rehabilitation group had higher maximum oxygen uptake and minute ventilation volume, lower anaerobic threshold, and higher maximal expiratory pressure (MEP). The maximal inspiratory pressure (MIP), forced expiratory volume in one second (FEV1), forced expiratory volume (FVC), ratio of forced expiratory volume to forced vital capacity in one second (FEV1/FVC), the percentage of FEV1 to the predicted value (FEV1%pred) and 1 min maximum ventilation volume (MVV) (P<0.05) were all higher in the abdominal rehabilitation group than the reference group after intervention. Conclusion Abdominal breathing training for patients with COPD over 60 years old can effectively enhance cardiopulmonary tolerance, and improve respiratory muscle physiology and pulmonary function.

AIM: To investigate the protective effect of β-sitosterol on retinal structure and function and its underlying molecular mechanism in a sodium iodate(NaIO3)-induced mouse model of dry age-related macular degeneration(ARMD).METHODS: A dry ARMD mouse model was established by NaIO3 injection. The therapeutic effect of β-sitosterol intervention was evaluated using fundus photography, histopathology(HE staining), and electroretinography(ERG). Network pharmacology was employed to screen potential targets of β-sitosterol in ARMD, and molecular docking was used to validate the binding ability between β-sitosterol and these targets. The impact of β-sitosterol on ARPE-19 cell viability and apoptosis pathways was analyzed using CCK-8 assay, Hoechst staining, and Western blotting.RESULTS: The β-sitosterol significantly alleviated structural damage in the retinas of model mice(increased retinal and outer nuclear layer thickness, reduced yellowish-white drusen-like deposits)and functional impairment(partial restoration of a-wave and b-wave amplitudes). Network pharmacology identified PON1 as a key target of β-sitosterol; molecular docking demonstrated that β-sitosterol binds to PON1 via hydrophobic interactions and hydrogen bonds. In vitro experiments showed that β-sitosterol(10 μmol/L)significantly increased ARPE-19 cell viability(P<0.01), reduced apoptosis(P<0.01), upregulated PON1 expression(P<0.01), and concurrently suppressed cleaved-Caspase3 expression(P<0.01).CONCLUSION: The β-sitosterol likely protects against oxidative stress-induced retinal damage by modulating PON1 to suppress the Caspase3-dependent apoptotic pathway. These findings provide experimental evidence supporting the development of β-sitosterol as a novel therapeutic agent for dry ARMD.