OBJECTIVES: To explore the mechanism through which moxibustion promotes endometrial repair in rats with in thin endometrium (TE). METHODS: Female SD rats were randomized into control group, 95% anhydrous ethanol-induced TE model group and moxibustion (at "Guan Yuan") group. High-throughput sequencing was used to identify the target genes of TE, and the targeting relationship between miR-223-3p and NLRP3 was verified using a dual luciferase assay. Histopathological of rat uterus was observed with HE staining, and expressions of miR-223-3p and NLRP3 were detected using RT-qPCR; serum levels of IL-1β and IL-18 of the rats were detected using ELISA, and protein expressions of NLRP3, ASC, caspase-1 and GSDMD in the uterus were detected with Western blotting. The pregnancies of the rats after treatment were counted. RESULTS: Enrichment analysis of the differential genes suggested up-regulated inflammatory response in TE, and dual luciferase assay verified targeted inhibition of NLRP3 expression by miR-223-3p. The rat models of TE had significantly decreased endometrial thickness and reduced endometrial glands and blood vessels with enhanced mRNA expression of NLRP3, increased serum levels of IL-1β and IL-18, up-regulated protein expressions of NLRP3, ASC, caspase-1 and GSDMD, lowered pregnancy rates on both the affected and unaffected sides and the overall number of pregnancies. Treatment of the rat models with mo-xibustion obviously increased the endometrial thickness and the density of glands and blood vessels, up-regulated miR-223-3p expression, lowered serum IL-1β and IL-18 levels and the protein expressions of NLRP3, ASC, caspase-1 and GSDMD, and significantly increased the number of pregnancies. CONCLUSIONS Moxibustion at "Guan Yuan" acupoint up-regulates the expression of miR-223-3p, which results in targeted inhibition of NLRP3 to suppress pyroptosis and promote endometrial repair in rat models of TE.
Animals ; Female ; MicroRNAs/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Endometrium/pathology* ; Rats, Sprague-Dawley ; Rats ; Moxibustion ; Pyroptosis ; Up-Regulation ; Interleukin-1beta/metabolism* ; Interleukin-18 ; Caspase 1/metabolism*

BACKGROUND: The main cause of restenosis after percutaneous transluminal angioplasty (PTA) is the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Lin28a has been reported to play critical regulatory roles in this process. However, whether CCAAT/enhancer-binding proteins β (C/EBPβ) binds to the Lin28a promoter and drives the progression of restenosis has not been clarified. Therefore, in the present study, we aim to clarify the role of C/EBPβ-Lin28a axis in restenosis. METHODS: Restenosis and atherosclerosis rat models of type 2 diabetes ( n   =  20, for each group) were established by subjecting to PTA. Subsequently, the difference in DNA methylation status and expression of C/EBPβ between the two groups were assessed. EdU, Transwell, and rescue assays were performed to assess the effect of C/EBPβ on the proliferation and migration of VSMCs. DNA methylation status was further assessed using Methyltarget sequencing. The interaction between Lin28a and ten-eleven translocation 1 (TET1) was analysed using co-immunoprecipitation (Co-IP) assay. Student's t -test and one-way analysis of variance were used for statistical analysis. RESULTS: C/EBPβ expression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis. In vitroC/EBPβ overexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression. Conversely, C/EBPβ knockdown resulted in the opposite effects. Chromatin immunoprecipitation assays further demonstrated that C/EBPβ could directly bind to Lin28a promoter. Increased C/EBPβ expression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment. Further, mechanical stretch promoted C/EBPβ and Lin28a expression accompanied by C/EBPβ hypomethylation. Additionally, Lin28a overexpression reduced C/EBPβ methylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs. The opposite was noted in Lin28a knockdown cells. CONCLUSION Our findings suggest that the C/EBPβ-Lin28a axis is a driver of restenosis progression, and presents a promising therapeutic target for restenosis.
Animals ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Muscle, Smooth, Vascular/metabolism* ; Rats ; DNA Methylation/physiology* ; CCAAT-Enhancer-Binding Protein-beta/genetics* ; Male ; Myocytes, Smooth Muscle/cytology* ; Rats, Sprague-Dawley ; RNA-Binding Proteins/genetics* ; Cells, Cultured ; Coronary Restenosis/metabolism*

BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

Objective:To analyze the impact of stressful life events on the social activity participation of middle-aged and elderly adults in China, providing a scientific basis for improving their quality of life.Methods:This study was conducted in January 2024.Data were derived from the China health and retirement longitudinal study (CHARLS) conducted from 2011 to 2020. SPSS 25.0 software was used for statistical analysis.Ordered Logistic regression analysis was employed to explore the association between stressful life events experienced over the past decade and the level of social activity participation, with stratified analysis by age, gender, and place of residence.Results:A total of 10 838 middle-aged and elderly adults were included in this study. The proportions of individuals with no social activity participation, low social activity participation, and high social activity participation were 52.07%(5 643/10 838), 24.21%(2 624/10 838), and 23.72%(2 571/10 838), respectively. After adjusting for sociodemographic characteristics and health-related behaviors, individuals who experienced stressful life events were 15.2% less likely to participate in social activities compared to those who did not ( RR=0.848, 95% CI=0.786-0.915).Stratified analysis revealed that the decrease in the likelihood of social activity participation following stressful life events was significantly greater in urban residents than that in rural residents ( Pinteraction=0.004). Conclusion:Experiencing stressful life events over the past decade may reduce the level of social activity participation among middle-aged and elderly adults. It is recommended to strengthen psychological counseling for this population and encourage active social engagement.

Objective:To analyze the impact of stressful life events on the social activity participation of middle-aged and elderly adults in China, providing a scientific basis for improving their quality of life.Methods:This study was conducted in January 2024.Data were derived from the China health and retirement longitudinal study (CHARLS) conducted from 2011 to 2020. SPSS 25.0 software was used for statistical analysis.Ordered Logistic regression analysis was employed to explore the association between stressful life events experienced over the past decade and the level of social activity participation, with stratified analysis by age, gender, and place of residence.Results:A total of 10 838 middle-aged and elderly adults were included in this study. The proportions of individuals with no social activity participation, low social activity participation, and high social activity participation were 52.07%(5 643/10 838), 24.21%(2 624/10 838), and 23.72%(2 571/10 838), respectively. After adjusting for sociodemographic characteristics and health-related behaviors, individuals who experienced stressful life events were 15.2% less likely to participate in social activities compared to those who did not ( RR=0.848, 95% CI=0.786-0.915).Stratified analysis revealed that the decrease in the likelihood of social activity participation following stressful life events was significantly greater in urban residents than that in rural residents ( Pinteraction=0.004). Conclusion:Experiencing stressful life events over the past decade may reduce the level of social activity participation among middle-aged and elderly adults. It is recommended to strengthen psychological counseling for this population and encourage active social engagement.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective To investigate the dietary patterns of rural residents in the high-incidence areas of esophageal cancer (EC), and to explore the clustering and influencing factors of risk factors associated with high-incidence characteristics. Methods A special structured questionnaire was applied to conduct a face-to-face survey on the dietary patterns of rural residents in Yanting county of Sichuan Province from July to August 2021. Univariate and multivariate logistic regression models were used to analyze the influencing factors of risk factor clustering for EC. Results There were 838 valid questionnaires in this study. A total of 90.8% of rural residents used clean water such as tap water. In the past one year, the people who ate fruits and vegetables, soybean products, onions and garlic in high frequency accounted for 69.5%, 32.8% and 74.5%, respectively; the people who ate kimchi, pickled vegetables, sauerkraut, barbecue, hot food and mildew food in low frequency accounted for 59.2%, 79.6%, 68.2%, 90.3%, 80.9% and 90.3%, respectively. The clustering of risk factors for EC was found in 73.3% of residents, and the aggregation of two risk factors was the most common mode (28.2%), among which tumor history and preserved food was the main clustering pattern (4.6%). The logistic regression model revealed that the gender, age, marital status and occupation were independent influencing factors for the risk factors clustering of EC (P<0.05). Conclusion A majority of rural residents in high-incidence areas of EC in Yanting county have good eating habits, but the clustering of some risk factors is still at a high level. Gender, age, marital status, and occupation are influencing factors of the risk factors clustering of EC.

Objective:To analyze the current status of internet-based patient education materials related to labor analgesia in China.Methods:Labor analgesia-related materials were retrieved and screened according to the search habits of Chinese search engine users. The coverage and accuracy of the content were evaluated by 3 anesthesiologists. The Chinese version of the Patient Education Materials Assessment Tool for Print Materials was used to subjectively assess comprehensibility and operability from a medical text perspective. The consistency of the evaluation results of the three anesthesiologists was analyzed using the intraclass correlation coefficient method. A machine learning method combined with ChatGPT-4.0 was employed to establish a Chinese readability classification model to objectively evaluate the readability difficulty of the included materials from a Chinese text perspective.Results:A total of 97 web pages were retrieved, with 21 valid materials included in the study. The coverage rate of contraindications for labor analgesia was only 62% (13/21), and the accuracy rate of materials exceeding 90% was 71% (15/21). Internet-based materials that were easy to understand accounted for 81% (17/21), while the constituent ratio of internet-based materials with instructional significance were only 5% (1/21). The intraclass correlation coefficient values of consistency evaluation for coverage rate, accuracy rate, and comprehensibility and operability were 0.975, 0.833, 0.758, and 0.773, respectively ( P<0.001). Internet-based materials suitable for compulsory education level were only 5% (1/21), while those suitable for high school and above education level accounted for 43% (9/21). Conclusions:There are numerous internet-based patient education materials related to labor analgesia in China, but the quality needs improvement. In the future, a collaborative model of " anesthesiology+ linguistics" should be developed to provide patients with more comprehensive, accurate, and pregnant-friendly patient education materials.

Objective To compare the reparative effects of moxibustion at"Guanyuan"and"Shenshu"points in rats with a thin endometrium.Methods Thirty-two female Sprague-Dawley rats were divided randomly into control(CON),model(MOD),Guanyuan(GY),and Shenshu(SS)groups.A thin endometrium model was established using 95％anhydrous alcohol.The Guanyuan and Shenshu groups underwent moxibustion at the Guanyuan and Shenshu points,respectively,and the other two groups of rats were fixed in the same way.Temperature changes at the acupoint area were measured at different time points.The pathological morphology of the uterus was observed by hematoxylin and eosin(HE)staining,and serum levels of inflammatory factors and hormone levels were detected by enzyme-linked immunosorbent assay(ELISA).Expression levels of proliferation and endometrial receptivity factors were detected by immunohistochemistry(IHC),and angiogenesis factors were detected by Western blot.Results The temperatures immediately after moxibustion and after 5 min were higher at the Shenshu compared with the Guanyuan acupoint(P＜0.01).Endometrial thickness and numbers of glands and blood vessels were decreased in the MOD group compared with the CON group(P＜0.01),serum interleukin 1 β(IL-1 β)was increased(P＜0.01)and PROG was decreased(P＜0.01),and Ki67,proliferating cell nuclear antigen(PCNA),leukemia inhibitory factor(LIF),integrin β3(ITG-β3),angiopoietin-1(ANG-1),and CD34 protein in uterine tissue were all decreased(P＜0.01).Endometrial thickness and numbers of glands and blood vessels were increased in the GY and SS groups compared with the MOD group(P＜0.01),while serum IL-1 β was decreased(P＜0.05),E2 and PROG were increased(P＜0.05),and serum interleukin 10(IL-10)was increased in the SS group(P＜0.05).Ki67,PCNA,LIF,and ITG-β3 were all increased in both treatment groups compared with the MOD group(P＜0.01).PCNA was higher in the GY group compared with the SS group(P＜0.05),while LIF and ITG-β3 were higher in the SS group compared with the GY group(P＜0.01,P＜0.05,respectively).CD34 and VEGFA levels were increased in the two treatment groups compared with the model group(P＜0.01).ANG-1 was higher in the GY group than that in the SS group(P＜0.01),while CD34 was higher in the SS group than that in the GY group(P＜0.05).Conclusions Moxibustion at the Guanyuan and Shenshu points could help to repair the pathological thin endometrium in rats.The GY group may be superior to the SS group for reducing the levels of serum IL-1 β,increasing E2,and promoting the expression of proliferation factors,while the SS group may be superior to the GY group for increasing the levels of PROG and promoting the expression of endometrium receptor-related factors.Both acupoints can promote the expression of angiogenesis factors,potentially acting via different pathways.

Objective To compare the reparative effects of moxibustion at"Guanyuan"and"Shenshu"points in rats with a thin endometrium.Methods Thirty-two female Sprague-Dawley rats were divided randomly into control(CON),model(MOD),Guanyuan(GY),and Shenshu(SS)groups.A thin endometrium model was established using 95％anhydrous alcohol.The Guanyuan and Shenshu groups underwent moxibustion at the Guanyuan and Shenshu points,respectively,and the other two groups of rats were fixed in the same way.Temperature changes at the acupoint area were measured at different time points.The pathological morphology of the uterus was observed by hematoxylin and eosin(HE)staining,and serum levels of inflammatory factors and hormone levels were detected by enzyme-linked immunosorbent assay(ELISA).Expression levels of proliferation and endometrial receptivity factors were detected by immunohistochemistry(IHC),and angiogenesis factors were detected by Western blot.Results The temperatures immediately after moxibustion and after 5 min were higher at the Shenshu compared with the Guanyuan acupoint(P＜0.01).Endometrial thickness and numbers of glands and blood vessels were decreased in the MOD group compared with the CON group(P＜0.01),serum interleukin 1 β(IL-1 β)was increased(P＜0.01)and PROG was decreased(P＜0.01),and Ki67,proliferating cell nuclear antigen(PCNA),leukemia inhibitory factor(LIF),integrin β3(ITG-β3),angiopoietin-1(ANG-1),and CD34 protein in uterine tissue were all decreased(P＜0.01).Endometrial thickness and numbers of glands and blood vessels were increased in the GY and SS groups compared with the MOD group(P＜0.01),while serum IL-1 β was decreased(P＜0.05),E2 and PROG were increased(P＜0.05),and serum interleukin 10(IL-10)was increased in the SS group(P＜0.05).Ki67,PCNA,LIF,and ITG-β3 were all increased in both treatment groups compared with the MOD group(P＜0.01).PCNA was higher in the GY group compared with the SS group(P＜0.05),while LIF and ITG-β3 were higher in the SS group compared with the GY group(P＜0.01,P＜0.05,respectively).CD34 and VEGFA levels were increased in the two treatment groups compared with the model group(P＜0.01).ANG-1 was higher in the GY group than that in the SS group(P＜0.01),while CD34 was higher in the SS group than that in the GY group(P＜0.05).Conclusions Moxibustion at the Guanyuan and Shenshu points could help to repair the pathological thin endometrium in rats.The GY group may be superior to the SS group for reducing the levels of serum IL-1 β,increasing E2,and promoting the expression of proliferation factors,while the SS group may be superior to the GY group for increasing the levels of PROG and promoting the expression of endometrium receptor-related factors.Both acupoints can promote the expression of angiogenesis factors,potentially acting via different pathways.