Perimenopausal depression （PMD） is an affective disorder that occurs in women during the transition from sexual maturity to old age. It can induce various complications， such as insomnia and cognitive decline. The etiology of PMD is complex. Although multiple hypotheses have been proposed， there is still no unified theory that fully explains its pathogenesis. Research into its mechanisms relies heavily on animal experiments， and establishing reliable animal models is crucial for experimental studies. Appropriate animal models can better simulate human pathophysiological states， rapidly evaluate the efficacy and safety of drugs and intervention methods， grasp the essence of the disease， and uncover its intrinsic connections， thereby exploring more advanced intervention strategies. However， there is a lack of systematic review and summarization of literature related to model construction. Additionally， traditional Chinese medicine （TCM）， adhering to the principles of ''syndrome differentiation and treatment'' and ''holistic concept''， has shown significant efficacy in treating PMD. In recent years， research exploring and analyzing its therapeutic mechanisms has been increasing. Therefore， to gain a clearer and more comprehensive understanding of PMD animal modeling methods and the mechanisms of TCM， this paper reviewed Chinese and English literature on PMD animal models and mechanisms of TCM in PMD treatment. It summarized the construction methods of single-factor and multi-factor PMD models， and discussed the advantages and disadvantages of each modeling approach. Furthermore， it delved into the mechanisms of TCM intervention in PMD， revealing that TCM formulas primarily exert their effects by regulating the hypothalamic-pituitary-adrenal axis， hypothalamic-pituitary-ovarian axis， gut-brain axis， cell signaling pathways， neural circuits， hormone levels， and neurotransmitter levels. This review aims to provide a reference for future research in this field. In summary， by summarizing the progress in the methods for PMD animal model construction and the mechanisms of TCM， the paper seeks to offer new insights into the mechanistic research of TCM intervention in PMD.

Cholangiocarcinoma (CCA) is a malignancy characterized by tumor cells originating in the liver or bile ducts, exhibiting features of cholangiocyte differentiation. It poses a significant clinical challenge due to the limited diagnostic and therapeutic options available. Robust animal models are essential for advancing our understanding of CCA pathogenesis and developing effective treatments. This review provides a comprehensive overview of CCA mouse models, highlighting various approaches, including chemical induction, genetically engineered models, and tumor xenografts. Each model is discussed in terms of its establishment techniques, pathological characteristics, and research significance, with a focus on intrahepatic CCA. Chemical induction models, such as diethylnitrosamine- and azoxymethane-induced models, offer insights into tumorigenesis processes, whereas genetically modified models involving alterations in key genes such as Kirsten rat sarcoma viral oncogene homolog, tumor protein 53, and isocitrate dehydrogenase serve as important tools for studying the molecular mechanisms underlying CCA. Xenograft models, including patient-derived xenografts, bridge the gap between experimental research and clinical applications, allowing for precise therapeutic evaluations. By comparing these models, this review underscores their respective advantages and limitations, paving the way for future studies aiming to optimize and innovate CCA modeling strategies.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Objective: To investigate the role of butyric acid-producing bacteria in long bone homeostasis in mice with periodontitis under a high-fat/high-sugar diet and to provide new insights for the prevention and treatment of periodontitis and related bone metabolic diseases. Methods: This study has been approved by the Animal Welfare and Ethics Committee of the Experimental Animal Center. Initially, 14 mice were randomly divided into the CON group (the control group) and the LIG group (the periodontitis group). Mice in the LIG group had experimental periodontitis induced by ligating the second maxillary molars bilaterally and were fed a high-fat and high-sugar diet. After 8 weeks, samples were collected. Micro-computed tomography (Micro-CT) was used to analyze alveolar bone resorption and various parameters of the proximal tibia trabecular bone, including bone mineral density (BMD), bone volume per tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). After decalcification, hematoxylin and eosin (HE) staining was performed on maxillary bone sections to assess periodontal tissue inflammation and connective tissue destruction. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect related genes in the distal femur and proximal tibia bone tissues, including osteocalcin (OCN), osteogenic transcription factor (Osterix), osteoprotegerin (OPG), tartrate resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), receptor activator of nuclear factor kappa-B (RANK), and receptor activator of nuclear factor kappa-B ligand (RANK-L). Subsequently, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + butyric acid-producing bacteria (BP) group, and LIG + BP group. The breeding, sampling, and sample detection methods remained the same. Finally, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + sodium butyrate (SB) group, and LIG + SB group. The breeding, sampling, and sample detection methods remained the same. Results: ①Periodontitis modeling was successful. Compared with the CON group, the LIG group exhibited significant alveolar bone resorption of the maxillary second molar, aggravated periodontal tissue inflammation, and connective tissue destruction. ②Periodontitis exacerbated long bone resorption in mice fed a high-fat high-sugar diet. Compared with the CON group, the LIG group had significantly lower BMD, BV/TV, Tb.N, and Tb.Th (P<0.05), and significantly higher Tb.Sp (P<0.05). HE staining of the proximal tibia showed that the trabeculae in the LIG group were sparse and disordered, with some areas showing fractures or dissolution. The expression of osteoblast markers (OCN, Osterix, OPG) was significantly lower in the LIG group (P<0.05), while the expression of the osteoclast marker TRAP showed an increasing trend (P>0.05). The ratio of RANK-L/OPG was significantly higher in the LIG group compared with the CON group (P<0.05). ③ Supplementation with butyric acid-producing bacteria alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BMD and Tb.Th were significantly higher in the LIG + BP group. HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + BP group compared with the LIG group. The expression of OCN and Osterix was significantly higher in the LIG + BP group, while the expression of osteoclast-specific genes (OSCAR, RANK, RANK-L) was significantly lower (P<0.05). ④ Supplementation with butyrate alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BV/TV and Tb.N were significantly higher in the LIG + SB group, and Tb.Sp was significantly lower (P<0.05). HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + SB group compared with the LIG group. The expression of Osterix, OPG, OSCAR, TRAP, and RANK was significantly lower in the LIG + SB group compared with the LIG group (P<0.05). Conclusion Periodontitis disrupts the long bone homeostasis of mice fed a high-fat high-sugar diet, aggravating long bone resorption. Supplementation with butyric acid-producing bacteria or butyrate can effectively alleviate the disruption of long bone homeostasis caused by periodontitis.

Objective To investigate the relationship between tooth loss and the occurrence of esophageal cancer in a natural village in Wenfeng District, Anyang City, Henan Province. Methods A prospective cohort study was conducted to observe the occurrence of tooth loss and esophageal cancer among the asymptomatic residents of the natural village for 16 years from January 2008 to July 2024. Data were analyzed by chi-square test, binary logistic regression, and restricted cubic spline. Results Among the total population of 711 cases, 136 cases were lost to follow-up and 575 cases were included in the final statistics, including 45 cases with esophageal cancer. Significant statistical difference was found between esophageal cancer patients with and without tooth loss (P<0.05). Logistic regression analysis showed that tooth loss was associated with the occurrence of esophageal cancer (OR=3.977, 95%CI: 1.543-10.255). After the adjustment for confounders, tooth loss remained significantly associated with the occurrence of esophageal cancer (OR=3.038, 95%CI: 1.035-8.914). A nonlinear dose-response relationship was observed between the number of teeth lost and the incidence of esophageal cancer. When the number of teeth lost was less than 12, the risk of esophageal cancer increased with the number of teeth lost. When more than 12 teeth were lost, the risk of esophageal cancer decreased as the number of teeth lost increased. Conclusion Tooth loss is a risk factor for the occurrence of esophageal cancer in this natural village. When the number of teeth lost is less than 12, the risk of esophageal cancer increases with the number of teeth lost.

Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the genus Aster (Asteraceae), has been reported to regulate the inflammatory response of macrophages in sepsis-induced acute lung injury. However, its function in post-stroke neuroinflammation, particularly microglia-mediated neuroinflammation, remains uninvestigated. This study found that SH significantly inhibited lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), in microglia in vitro. Furthermore, the results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which may be attributed to the inhibition of the microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited the phosphorylation of serine-threonine protein kinase B (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). These findings suggest that SH may be a potential therapeutic agent for relieving ischemic stroke (IS) by alleviating microglia-associated neuroinflammation.
Animals ; Microglia/immunology* ; Mice ; Male ; Mice, Inbred C57BL ; Brain Ischemia/immunology* ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotective Agents/administration & dosage* ; Interleukin-1beta/genetics* ; STAT3 Transcription Factor/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Proto-Oncogene Proteins c-akt/immunology* ; Nitric Oxide Synthase Type II/genetics* ; Lipopolysaccharides

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

Objective To propose a novel identification algorithm based on ensemble learning for assessing the severity of acute respiratory distress syndrome(ARDS)to achieve continuous monitoring of the disease severity.Methods Firstly,leve-raging the open-source MIMIC-Ⅳ database,a variety of non-invasive physiological parameters of patients were extracted and subjected to preliminary preprocessing.A multivariate feature selection algorithm was employed to rank these parameters and calculate feature importance scores through weighted computation.Secondly,based on the feature importance scores,a subset search algorithm was utilized to identify the subset of features that could yield optimal performance across four machine learning algorithms:neural networks,logistic regression,AdaBoost and XGBoost.Finally,a soft voting ensemble method was designed using a generalized linear regression model to integrate the results of each single machine learning algorithm,and a multivariate ensemble learning algorithm was proposed by combining the optimal feature subsets.The algorithm proposed when used to identify the severity of ADRS was evaluated with MIMIC-Ⅳ database,and compared with the traditional algorithms.Results The sensitivity,specificity,accuracy and AUC of the algorithm were 87.15％,89.23％,88.34％and 0.923 4,respectively,all of which outperformed those of the traditional algorithms.Conclusion The ARDS severity identification algorithm based on ensemble learning is capable of achieving continuous and real-time monitoring of the severity of ARDS,thereby offering robust support for the early identification and warning of ARDS in patients.[Chinese Medical Equipment Journal,2025,46(2):1-9]

Objective:To investigate the mechanism by which lycopene prevents and alleviates ionizing radiation-induced intestinal injury.Methods:Forty specific pathogen-free male C57BL/6 mice were randomly divided into 4 groups: control group (gavage with an equal volume of corn oil), radiation group (gavage with an equal volume of corn oil and exposed to a single dose of 12 Gy X-ray irradiation on day 3), lycopene group (gavage with lycopene), and lycopene + radiation group (gavage with lycopene and irradiated with 12 Gy X-ray on day 3). All gavage treatments continued for 7 days after irradiation. On day 7 post-irradiation, intestinal tissues were collected. Hematoxylin and eosin (HE), Masson's trichrome, and Sirius red staining were used to assess intestinal injury and fibrosis. Immunohistochemistry was used to detect the expression of α-smooth muscle actin (α-SMA). Immunofluorescence staining was performed to assess the expression of transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) in intestinal tissues. Serum levels of malondialdehyde (MDA), total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-PX) were measured to evaluate oxidative stress. mRNA expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, and CD68 in intestinal tissue was quantified using real-time quantitative PCR (RT-qPCR). Western blot was used to detect the expression of apoptosis-related proteins. One-way ANOVA was used to compare differences among groups.Results:Compared with the radiation group, the lycopene + radiation group showed significantly reduced radiation-induced intestinal injury index, fibrosis, and expression of α-SMA, TGF-β, and CTGF (all P<0.05). Oxidative stress assays showed that serum MDA levels were decreased, while T-SOD, T-AOC, and GSH-PX activities were significantly increased in the lycopene + radiation group (all P<0.05). The mRNA expression of inflammatory cytokines such as TNF-α and IL-6 was significantly downregulated (all P<0.05), while pro-apoptotic protein expression was reduced and anti-apoptotic protein expression was upregulated (all P < 0.05) in the lycopene + radiation group. Conclusions:Lycopene significantly alleviates ionizing radiation-induced intestinal injury through its antioxidant, anti-inflammatory, and anti-apoptotic effects, making it a promising agent for the prevention and treatment of radiation-induced intestinal injury.

Objective To investigate the protective effects and potential mechanisms of the preparation of Abelmoschus manihot(L.)Medik(Jiahua Tablet)against acute radiation-induced myocardial injury,based on myo-cardial injury markers(sST2,cTnI)and oxidative stress damage-related indicators(SOD,MDA),and to provide new avenues for the prevention and treatment of radiation-induced heart disease(RIHD).Methods Sixty-nine patients with thoracic malignant tumor who received radiotherapy at the department of radiation oncology in Hospital Affiliated to Nanjing University of Chinese Medicine from December 2023 to November 2024 were enrolled in the study.Participants were randomly divided into control group(n=38)and observation group(n=31).The control group received standard radiotherapy in conjunction with conventional medications for RIHD,while the observation group was additionally administered Jiahua Tablet alongside the same regimen.Both groups took medications continuously for 1 month.Changes in serum levels of sST2,cTnI,SOD,and MDA were compared between the two groups 3 days prior to radiotherapy and 7 days after radiological therapy.Results On day 7 post-radiotherapy,the levels of sST2 and cTnI in the control group were highly elevated,showing statistically significant difference(P<0.01).In contrast,the levels of sST2 and cTnI in the observation group showed only mild elevation,and no statistically significant difference was observed(P>0.05).Between-group analysis demonstrated that post-treatment sST2 and cTnI levels in the observation group were substantially lower compared to those in the control group,indicating statistically significant difference(P<0.05).After treatment,SOD level in the control group was considerably lower compared to its pre-treatment level,and marked statistical significance was observed(P<0.01).SOD level in the observation group demonstrated a downward trend compared to baseline value,indicating no statistical significance(P>0.05).Between-group analysis demonstrated that post-treatment SOD level in the observation group was substantially elevated compared to that in the control group,indicating a highly significant disparity(P<0.05).After treatment,MDA level in the control group was considerably higher compared to its pre-treatment level,and a marked statistical significance was observed(P<0.05),whereas MDA level in the observation group showed only a mild increase compared to baseline value,with no statistically significant difference(P>0.05).Between-group analysis demonstrated that post-treatment MDA level in the observation group was substantially lower compared to that in the control group,demonstrating a remarkably statistically significant difference(P<0.01).Conclusion The preparation of Abelmoschus manihot(L.)Medik(Jiahua Tablet)effectively inhibits acute radiation-induced myocardial injury,with its potential mechanism closely linked to the suppression of oxidative stress responses.