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*

Objective:To investigate the targets and mechanisms of cycloastragenol in ameliorating azithromycin-induced drug-induced liver injury(DILI)based on network pharmacology and in vitro experiment validation.Methods:Potential targets of cycloastragenol and DILI were predicted using databases.The common and key targets were screened and subjected to GO and KEGG enrichment analyses,as well as molecular docking validation.Primary hepatocytes from C57BL/6 mice were isolated.The optimal concentration and time for azithromycin-induced DILI in mouse primary hepatocytes were determined using CCK8 and ROS assays.The expression of genes and proteins such as NF-κB p65,p-NF-κB p65,AMPKα,and p-AMPKα was assessed using RT-qPCR and Western blot to evaluate the intervention effect of cycloastragenol(10-50 μmol/L).Results:Network pharmacology analysis identified 10 key genes related to cycloastragenol's improvement of DILI,including heat shock protein 90AA1(HSP90AA1),matrix metalloproteinase 2(MMP2),etc.GO enrichment analysis suggested that cycloastragenol primarily regulates biological processes such as membrane potential and chemical synaptic transmission,and affects cellular components such as neuronal cell bodies and distal axons,and related kinase activities.KEGG enrichment analysis showed that it mainly exerts intervention effects through neuro-signaling pathways and IL-17 signaling pathways.Molecular docking demonstrated strong binding of cycloastragenol to HSP90AA1,MMP2,NF-κB p65,AMPKα,nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1),with a binding energy≤-5.0 kcal/mol for Nrf2.In vitro experiments showed that azithromycin(50 μmol/L,12 h)significantly reduced hepatocyte viability and increased ROS levels(P＜0.01).Different concentrations of cycloastragenol significantly improved the activity of mouse primary hepatocytes,reduced the generation of intracellular ROS,downregulated the phosphorylation level of NF-κB p65,and upregulated the mRNA and protein levels of AMPKα,Nrf2,HO-1,NQO1(P＜0.05).Conclusions:Cycloastragenol may alleviate azithromycin-induced hepatocyte oxidative stress and inflammation by inhibiting NF-κB phosphorylation and activating the AMPK/Nrf2/HO-1/NQO1 pathway,with its mechanism likely closely linked to targeting Nrf2.However,the complex mechanisms of DILI may involve additional unverified pathways.Therefore,further studies are necessary to validate the efficacy and safety of cycloastragenol in animal models.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective:To investigate the targets and mechanisms of cycloastragenol in ameliorating azithromycin-induced drug-induced liver injury(DILI)based on network pharmacology and in vitro experiment validation.Methods:Potential targets of cycloastragenol and DILI were predicted using databases.The common and key targets were screened and subjected to GO and KEGG enrichment analyses,as well as molecular docking validation.Primary hepatocytes from C57BL/6 mice were isolated.The optimal concentration and time for azithromycin-induced DILI in mouse primary hepatocytes were determined using CCK8 and ROS assays.The expression of genes and proteins such as NF-κB p65,p-NF-κB p65,AMPKα,and p-AMPKα was assessed using RT-qPCR and Western blot to evaluate the intervention effect of cycloastragenol(10-50 μmol/L).Results:Network pharmacology analysis identified 10 key genes related to cycloastragenol's improvement of DILI,including heat shock protein 90AA1(HSP90AA1),matrix metalloproteinase 2(MMP2),etc.GO enrichment analysis suggested that cycloastragenol primarily regulates biological processes such as membrane potential and chemical synaptic transmission,and affects cellular components such as neuronal cell bodies and distal axons,and related kinase activities.KEGG enrichment analysis showed that it mainly exerts intervention effects through neuro-signaling pathways and IL-17 signaling pathways.Molecular docking demonstrated strong binding of cycloastragenol to HSP90AA1,MMP2,NF-κB p65,AMPKα,nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1),with a binding energy≤-5.0 kcal/mol for Nrf2.In vitro experiments showed that azithromycin(50 μmol/L,12 h)significantly reduced hepatocyte viability and increased ROS levels(P＜0.01).Different concentrations of cycloastragenol significantly improved the activity of mouse primary hepatocytes,reduced the generation of intracellular ROS,downregulated the phosphorylation level of NF-κB p65,and upregulated the mRNA and protein levels of AMPKα,Nrf2,HO-1,NQO1(P＜0.05).Conclusions:Cycloastragenol may alleviate azithromycin-induced hepatocyte oxidative stress and inflammation by inhibiting NF-κB phosphorylation and activating the AMPK/Nrf2/HO-1/NQO1 pathway,with its mechanism likely closely linked to targeting Nrf2.However,the complex mechanisms of DILI may involve additional unverified pathways.Therefore,further studies are necessary to validate the efficacy and safety of cycloastragenol in animal models.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective To retrospectively analyze of factors influencing early preterm birth(EPB)and late preterm birth(LPB)in pregnancy women with placenta previa complicated by placenta accreta spectrum disorders(PAS),and assess maternal and infant outcomes.Methods We included 590 cases of pregnancy women with placenta previa complicated by PAS who underwent cesarean sections at five hospitals in Wuhan and Xianning cities between January 2018 and June 2021.These patients were divided into three groups based on delivery gesta-tional age:EPB,LPB,and term birth(TB).A multiple logistic regression model was employed to analyze the risk factors associated with EPB and LPB.Additionally,differences in early maternal and infant outcomes among these groups were examined.Results Among 590 pregnancy women with placenta previa complicated by PAS,the proportions of EPB and LPB were 9.7%and 54.4%.The use of uterine contraction inhibitors prior to cesarean section,vaginal bleeding,and previous cesarean sections history were identified as risk factors for both EPB and LPB.The proportion of severe postpartum hemorrhage was comparable between the EPB group and the LPB group;however,the incidence of neonatal asphyxia,low birth weight infants,and the rate of newborns transferred to the Neonatal Intensive Care Unit(NICU)within 24 hours after cesarean delivery were significantly higher in the EPB group compared to the LPB group.Conclusions Placenta previa complicated by PAS predominantly leads to LPB.The history of prior cesarean sections,uterine contractions,and vaginal bleeding prior to cesarean section,are sig-nificantly associated with both EPB and LPB.During the perinatal period,efforts should be made to extend gesta-tional weeks under close monitoring to minimize the incidence of premature births and thereby improve early mater-nal and infant outcomes.

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.

OBJECTIVE: To compare the performance of Clear Cell Likelihood Score (ccLS) v1.0 and v2.0 in diagnosing clear cell renal cell carcinoma (ccRCC) from small renal masses (SRM). METHODS: We retrospectively analyzed the clinical data and MR images of patients with pathologically confirmed solid SRM from the First Medical Center of the Chinese PLA General Hospital between January 1, 2018, and December 31, 2021, and from Beijing Friendship Hospital of Capital Medical University and Peking University First Hospital between January 1, 2019 and May 17, 2021. Six abdominal radiologists were trained for use of the ccLS algorithm and scored independently using ccLS v1.0 and ccLS v2.0. Random- effects logistic regression modeling was used to generate plot receiver operating characteristic curves (ROC) to evaluate the diagnostic performance of ccLS v1.0 and ccLS v2.0 for ccRCC, and the area under curve (AUC) of these two scoring systems were compared using the DeLong's test. Weighted Kappa test was used to evaluate the interobserver agreement of the ccLS score, and differences in the weighted Kappa coefficients was compared using the Gwet consistency coefficient. RESULTS: In total, 691 patients (491 males, 200 females; mean age, 54 ± 12 years) with 700 renal masses were included in this study. The pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ccLS v1.0 for diagnosing ccRCC were 77.1%, 76.8%, 77.7%, 90.2%, and 55.7%, as compared with 80.9%, 79.3%, 85.1%, 93.4%, 60.6% with ccLS v2.0, respectively. The AUC of ccLS v2.0 was significantly higher than that of ccLS v1.0 for diagnosis of ccRCC (0.897 vs 0.859; P < 0.01). The interobserver agreement did not differ significantly between ccLS v1.0 and ccLS v2.0 (0.56 vs 0.60; P > 0.05). CONCLUSION ccLS v2.0 has better performance for diagnosing ccRCC than ccLS v1.0 and can be considered for use to assist radiologists with their routine diagnostic tasks.
Female ; Male ; Humans ; Adult ; Middle Aged ; Aged ; Carcinoma, Renal Cell/diagnosis* ; Retrospective Studies ; Kidney ; Carcinoma ; Kidney Neoplasms/diagnosis*

OBJECTIVE： To establish the method for content determination of eugenol in Syzygium aromaticum oil dropping pills， and to optimize the preparation technology. METHODS： The content of eugenol in S. aromaticum oil dropping pills was determined by UV spectrophotometry. Based on single factor test， using the percentage of drugs in total amount， liquid temperature， falling distance of condensate， liquid drop distance as factors， taking the roundness， weight and hardness difference and comprehensive score as factors， L9（34） orthogonal design test was adopted to optimize the preparation process. RESULTS： The linear range of eugenol was 15.15-45.45 μg/mL（r＝0.999 6）； RSDs of precision， stability and reproducibility tests were all lower than 1％； the recoveries were 97.41％-100.59％（RSD＝1.35％， n＝6）. The optimal preparation technology included that the percentage of drugs in total amount was 5％； liquid temperature was 80 ℃； falling distance of condensate was 13 cm； liquid drop distance was 6 cm. The dropping pills had smooth appearance， good roundness and moderate hardness； the average content of engenol was 4.073％（RSD＝0.35％，n＝6）. CONCLUSIONS： The established method is simple， and can be used for the content determination of eugenol in S. aromaticum oil dropping pills. The optimal preparation technology is stable and feasible.