Objective To explore the mechanism of Danggui Sini Decoction in treating knee osteoarthritis(KOA)by using network pharmacology,combined with in vitro experimental verification.Methods The active components of Danggui Sini Decoction were retrieved and screened through TCMSP,CNKI and PubMed databases,and their corresponding targets were predicted using the SwissTarget Prediction platform.KOA related targets were retrieved from GeneCards and OMIM databases.Intersection of drug targets and KOA targets was obtained,and key components,core targets,and their related biological mechanisms were identified through network topology analysis,GO and KEGG pathway enrichment analysis.Molecular docking was used to verify the degree of binding between key components and core targets.Danggui Sini Decoction containing serum was prepared,and an in vitro KOA model was constructed by inducing rat articular chondrocytes with lipopolysaccharide.The CCK-8 method was used to screen for the optimal concentration of drug containing serum intervention,fluorescent probes were used to detect intracellular ROS content,immunofluorescence was used to detect NF-κB p65 nuclear translocation,RT-qPCR was used to detect the expressions of IL-6,IL-1β and TNF-α mRNA,Western blot was used to detect the expression of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),NF-κB p65 and p-NF-κB p65 proteins.Results The results of network pharmacology analysis indicated that the treatment of KOA with Danggui Sini Decoction may involve regulating Toll like receptors,MAPK,TNF,apoptosis and other inflammatory and aging signaling pathways,compounds such as quercetin,kaempferol and glycyrrhizin may play important roles.Core targets included IL6,IL1B,TNF,TLR4,NFKB1,JUN,MAPK1,RELA.In vitro experiments showed that compared with the blank group,the ROS content in chondrocytes of the model group significantly increased(P<0.01),NF-κB p65 protein was significantly nuclear translocation(P<0.01),and mRNA expressions of IL-6,IL-1β,TNF-α mRNA and protein expressions of TLR4,MyD88 and p-NF-κB p65 significantly increased(P<0.01);compared with the model group,the intervention of Danggui Sini Decoction containing serum could significantly reduce intracellular ROS content(P<0.05),inhibit NF-κB p65 nuclear translocation(P<0.01),and reduce the expression of inflammatory factor mRNA and related proteins(P<0.05,P<0.01).Conclusion Danggui Sini Decoction can significantly reduce the inflammatory response of rat articular chondrocytes induced by lipopolysaccharide and exert therapeutic effects on KOA.Its mechanism may be related to the inhibition of TLR4/MyD88/NF-κB pathway.

Objective To explore the mechanism of Danggui Sini Decoction in treating knee osteoarthritis(KOA)by using network pharmacology,combined with in vitro experimental verification.Methods The active components of Danggui Sini Decoction were retrieved and screened through TCMSP,CNKI and PubMed databases,and their corresponding targets were predicted using the SwissTarget Prediction platform.KOA related targets were retrieved from GeneCards and OMIM databases.Intersection of drug targets and KOA targets was obtained,and key components,core targets,and their related biological mechanisms were identified through network topology analysis,GO and KEGG pathway enrichment analysis.Molecular docking was used to verify the degree of binding between key components and core targets.Danggui Sini Decoction containing serum was prepared,and an in vitro KOA model was constructed by inducing rat articular chondrocytes with lipopolysaccharide.The CCK-8 method was used to screen for the optimal concentration of drug containing serum intervention,fluorescent probes were used to detect intracellular ROS content,immunofluorescence was used to detect NF-κB p65 nuclear translocation,RT-qPCR was used to detect the expressions of IL-6,IL-1β and TNF-α mRNA,Western blot was used to detect the expression of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),NF-κB p65 and p-NF-κB p65 proteins.Results The results of network pharmacology analysis indicated that the treatment of KOA with Danggui Sini Decoction may involve regulating Toll like receptors,MAPK,TNF,apoptosis and other inflammatory and aging signaling pathways,compounds such as quercetin,kaempferol and glycyrrhizin may play important roles.Core targets included IL6,IL1B,TNF,TLR4,NFKB1,JUN,MAPK1,RELA.In vitro experiments showed that compared with the blank group,the ROS content in chondrocytes of the model group significantly increased(P<0.01),NF-κB p65 protein was significantly nuclear translocation(P<0.01),and mRNA expressions of IL-6,IL-1β,TNF-α mRNA and protein expressions of TLR4,MyD88 and p-NF-κB p65 significantly increased(P<0.01);compared with the model group,the intervention of Danggui Sini Decoction containing serum could significantly reduce intracellular ROS content(P<0.05),inhibit NF-κB p65 nuclear translocation(P<0.01),and reduce the expression of inflammatory factor mRNA and related proteins(P<0.05,P<0.01).Conclusion Danggui Sini Decoction can significantly reduce the inflammatory response of rat articular chondrocytes induced by lipopolysaccharide and exert therapeutic effects on KOA.Its mechanism may be related to the inhibition of TLR4/MyD88/NF-κB pathway.

Objective:To investigate the additional value of 99Tc m-hydrazinonicotinamide (HYNIC)-Tyr3-octreotide (TOC) SPECT/CT imaging in the diagnosis and treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods:A total of 54 patients (28 males and 26 females, age: (52.6±11.7) years) who underwent enhanced CT (MR) and 99Tc m-HYNIC-TOC SPECT/CT in People′s Hospital of Zhengzhou University between December 2017 and June 2023 were analyzed retrospectively. Surgical pathology or biopsy was the gold standard of patients′ diagnosis (primary tumors), and comprehensive evaluation based on pathology, imaging and follow-up results was used as the diagnostic criteria of lesions. McNemar χ2 test was used to compare the diagnostic efficacy of different imaging methods. Results:Pathological results showed that 43 of the 54 patients were with GEP-NETs and 11 were with non-neuroendocrine tumors (NETs). The sensitivities of enhanced CT and enhanced MR in the diagnosis of patients with GEP-NETs were 65.1%(28/43) and 60.0%(15/25) respectively, which increased to 93.0%(40/43) and 92.0%(23/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 8.64, 4.90, P values: 0.002, 0.021). There were 22 and 15 patients showing atypical enhancement on enhanced CT and enhanced MR respectively. The sensitivities of these two methods for GEP-NETs in patients with atypical enhancement were 54.5%(12/22) and 8/15 respectively, which increased to 95.5%(21/22) and 14/15 with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.82, 4.17, P values: 0.012, 0.031). Compared with enhanced CT, the detection rates of liver and bone metastatic lesions were improved significantly from 90.8%(158/174) and 55.2%(32/58) to 96.6%(168/174) and 87.9%(51/58) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.79, 9.82, P values: 0.013, 0.001). Compared with enhanced MR, the detection rate of bone metastases was improved significantly from 56.0%(14/25) to 88.0%(22/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2=4.08, P=0.039). After 99Tc m-HYNIC-TOC imaging, stages were changed in 7.0%(3/43) of patients and a greater number or extent of metastases were detected in 11.6%(5/43) of patients. 99Tc m-HYNIC-TOC imaging detected additional recurrent or metastatic lesions in 40.0%(8/20) of patients during follow-up compared to enhanced CT. Conclusion:99Tc m-HYNIC-TOC imaging can provide an added value for diagnosing GEP-NETs with atypically enhanced CT(MR), and in the detection of liver metastasis and early bone metastasis, thus helping the optimization of clinical treatment strategies.

Objective:To investigate the additional value of 99Tc m-hydrazinonicotinamide (HYNIC)-Tyr3-octreotide (TOC) SPECT/CT imaging in the diagnosis and treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods:A total of 54 patients (28 males and 26 females, age: (52.6±11.7) years) who underwent enhanced CT (MR) and 99Tc m-HYNIC-TOC SPECT/CT in People′s Hospital of Zhengzhou University between December 2017 and June 2023 were analyzed retrospectively. Surgical pathology or biopsy was the gold standard of patients′ diagnosis (primary tumors), and comprehensive evaluation based on pathology, imaging and follow-up results was used as the diagnostic criteria of lesions. McNemar χ2 test was used to compare the diagnostic efficacy of different imaging methods. Results:Pathological results showed that 43 of the 54 patients were with GEP-NETs and 11 were with non-neuroendocrine tumors (NETs). The sensitivities of enhanced CT and enhanced MR in the diagnosis of patients with GEP-NETs were 65.1%(28/43) and 60.0%(15/25) respectively, which increased to 93.0%(40/43) and 92.0%(23/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 8.64, 4.90, P values: 0.002, 0.021). There were 22 and 15 patients showing atypical enhancement on enhanced CT and enhanced MR respectively. The sensitivities of these two methods for GEP-NETs in patients with atypical enhancement were 54.5%(12/22) and 8/15 respectively, which increased to 95.5%(21/22) and 14/15 with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.82, 4.17, P values: 0.012, 0.031). Compared with enhanced CT, the detection rates of liver and bone metastatic lesions were improved significantly from 90.8%(158/174) and 55.2%(32/58) to 96.6%(168/174) and 87.9%(51/58) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.79, 9.82, P values: 0.013, 0.001). Compared with enhanced MR, the detection rate of bone metastases was improved significantly from 56.0%(14/25) to 88.0%(22/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2=4.08, P=0.039). After 99Tc m-HYNIC-TOC imaging, stages were changed in 7.0%(3/43) of patients and a greater number or extent of metastases were detected in 11.6%(5/43) of patients. 99Tc m-HYNIC-TOC imaging detected additional recurrent or metastatic lesions in 40.0%(8/20) of patients during follow-up compared to enhanced CT. Conclusion:99Tc m-HYNIC-TOC imaging can provide an added value for diagnosing GEP-NETs with atypically enhanced CT(MR), and in the detection of liver metastasis and early bone metastasis, thus helping the optimization of clinical treatment strategies.

Objective:To investigate the value of 99Tc m-hydrazinonicotinamide (HYNIC)-prostate specific membrane antigen(PSMA) SPECT/CT imaging in biochemical recurrence of prostate cancer (PCa). Methods:From January 2018 to March 2023, 112 patients with biochemical recurrence of PCa (age (72.6±6.1) years) who underwent 99Tc m-HYNIC-PSMA SPECT/CT imaging in Henan Provincial People′s Hospital were retrospectively analyzed. According to the level of prostate specific antigen (PSA), patients were divided into 0.2 μg/L2 μg/L group. According to the Gleason score, patients were divided into Gleason score≥8 group and Gleason score <8 group. The detection rate between groups was analyzed by χ2 test, and the difference of the PSA level between groups was compared by Mann-Whitney U test. Results:PSMA imaging was positive in 77 cases and negative in 35 cases, with the detection rate of 68.8%(77/112). The detection rates of local recurrence, lymph node metastasis, bone metastasis and lung metastasis were 8.9%(10/112), 43.8%(49/112), 28.6%(32/112) and 0.9%(1/112), respectively. The detection rates of 0.2 μg/L2 μg/L groups were 44.7%(21/47), 8/12 and 90.6%(48/53), respectively ( χ2=24.44, P<0.001). The detection rates of Gleason score ≥8 group and <8 group were 76.4%(55/72) and 55.0%(22/40) ( χ2=5.47, P=0.032); the PSA level between the two groups was statistically different (3.11(0.75, 5.91) and 0.84(0.44, 2.92) μg/L; z=-2.99, P=0.003). Of the patients with PSMA positive imaging, 84.4%(65/77) changed their treatment regimen and 15.6%(12/77) continued to observe or maintain the original treatment plan. Of the patients with PSMA negative imaging, 40.0%(14/35) changed the treatment plan, 51.4%(18/35) continued to observe or maintain the original treatment plan, and 8.6%(3/35) discontinued the original treatment because no tumor metastasis was found. Conclusion:99Tc m-HYNIC-PSMA SPECT/CT imaging can provide reference for the lesion detection, treatment decision-making and follow-up observation of biochemical recurrence of PCa.

Objective:To investigate the efficacy and influencing factors of initial 131I therapy in serum thyroglobulin (Tg) antibody (TgAb)-positive patients with papillary thyroid cancer (PTC). Methods:A retrospective analysis was performed on the clinical data of 1 624 patients with PTC who underwent 131I therapy in Henan Provincial People′s Hospital between January 2017 and January 2023. The patients were divided into TgAb-positive group (246 cases (36 males, 210 females), age: 43.5(31.0, 52.0) years) and TgAb-negative group (1 378 cases (439 males, 939 females), age: 44.0(34.0, 53.0) years). The efficacy was evaluated 6-12 months post 131I therapy based on serological tests (TgAb, Tg) and imaging results (ultrasonography, CT, 131I-whole body scan (WBS), SPECT/CT imaging), and the patients were divided into disease persistence/recurrence and non-persistence/recurrence groups. The χ2 test was used to analyze the difference in efficacy between the TgAb-positive group and the TgAb-negative group. Among TgAb-positive patients, the clinical characteristics of disease persistence/recurrence group were compared with those of non-persistence/recurrence ones by χ2 test or Mann-Whitney U test, and the independent risk factors affecting the efficacy of 131I therapy were analyzed by binary logistic regression. Results:The disease persistence/recurrence were found in 38 cases (15.4%, 38/246) of the TgAb-positive group and 143 cases (10.4%, 143/1 378) of the TgAb-negative group, with a statistically significant difference between the two groups ( χ2=5.42, P=0.020). Among the TgAb-positive patients, statistically significant differences were found in lymph node metastasis (35 vs 23 cases), the interval between surgery and 131I therapy (2.0(1.5, 3.0) vs 2.3(2.0, 3.0) months), stimulated Tg(sTg) level before the initial 131I therapy (0.18(0.04, 5.78) vs 0.04(0.04, 0.46) μg/L), and TgAb level before the initial 131I therapy (40.15(19.13, 156.15) vs 22.25(7.53, 76.20) kU/L) between disease persistence/recurrence group and non-persistence/recurrence group ( χ2=117.13, z values: -2.29, -2.41, -2.80, all P<0.05). Lymph node metastasis was an independent risk factor (odds ratio( OR)=89.326, 95% CI: 25.005-319.106, P<0.001) for the efficacy of 131I therapy in patients with TgAb-positive PTC. Conclusion:The overall efficacy of 131I therapy in patients with TgAb-positive PTC is relatively poor, and lymph node metastasis is an independent risk factor for the efficacy of 131I therapy, while the level of TgAb is not an independent risk factor for the efficacy of 131I therapy in these patients.

Ten-eleven translocation 1 (TET1) protein is an alpha-ketoglutaric acid (α-KG) and Fe²⁺-dependent dioxygenase. It plays a role in the active demethylation of DNA by hydroxylation of 5-methyl-cytosine (5-mC) to 5-hydroxymethyl-cytosine (5-hmC). Ten-eleven translocation 1 (TET1) protein is involved in maintaining genome methylation homeostasis and epigenetic regulation. Abnormally expressed TET1 and 5-mC oxidative derivatives have become potential markers in various biological and pathological processes and a research focus in the fields of embryonic development and malignant tumors. This paper introduces the structure and demethylation mechanism of TET1, reviews the research status of epigenetic regulation by TET1 in embryonic development, immune responses, stem cell regulation, cancer progression, and nervous system development, and briefs the upstream regulatory mechanism of TET1, hoping to provide new inspirations for further research in related fields.
Proto-Oncogene Proteins/genetics* ; Epigenesis, Genetic ; Humans ; DNA-Binding Proteins/metabolism* ; DNA Methylation ; Mixed Function Oxygenases/metabolism* ; 5-Methylcytosine/analogs & derivatives* ; Animals ; Embryonic Development/genetics* ; Neoplasms/genetics* ; Dioxygenases/metabolism*

Objective:To investigate the acceptance of advance care planning and its influencing factors in heart failure patients.Methods:A total of 208 patients with heart failure were surveyed by general data questionnaires and advance care planning acceptance questionnaires.Results:The total score of advance care planning acceptance of heart failure patients was (44.26 ± 11.73), the score of feeling dimension was (13.67 ± 5.72), the score of attitude dimension was (30.59 ± 6.33). 53.4%(111/208) of patients were willing to accept the talking about advance care planning. Regression analysis results showed that education level, New York Heart Association (NYHA) classification, communication status with medical staff and whether they had received life-sustaining treatment were important factors influencing of the acceptance of advance care planning in patients with heart failure.Conclusion:Patients with heart failure had higher acceptance of advance care planning. In clinical work, it is necessary to strengthen the scientific popularization of advance care planning in patients with low education level, low NYHA grade and no exposure to life-sustaining treatment. And strengthen the daily communication with patients to prepare for the follow-up advance care planning related communication.

Objective To explore the association between serum amyloid A (SAA) and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus(T2DM).Methods A total of 148 diabetic subjects were divided into three groups according to C1MT:normal IMT group,IMT incrassation group and arteriosclerosis group.Levels of SAA,25-hydroxyvitamin D [25 (OH) D],brachial-ankle artery pulse wave velocity (baPWV),high density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C),fasting plasma glucose (FPG),glycosylated hemoglobin (HbA1 c),triglyceride (TG),total cholesterol (TC),body mass index (BMI) and blood presure were measured in all groups.The relationship between SAA,CIMT,25 (OH)D,baPWV and other factors was also analyzed.Results Compared to the normal IMT group,levels of FPG,HbA1 c,TC,BMI,SAA and ba-PWV were significantly higher in IMT incrassation group and arteriosclerosis group,while HDL-C and 25 (OH)D were lower.In arteriosclerosis group,levels of BMI,FPG,HbA1 c,SAA and ba-PWV were higher than those in IMT incrassation group,while 25 (OH) D was lower.Pearson correlation analysis showed that the level of SAA was positively correlated with baPWV,BMI,TC,course of disease and IMT,while it was negatively correlated with HDL-C and 25 (OH)D.Logistic regression analysis of IMT showed that smoking,obesity,high levels of HbAlc,FPG,TC,SAA,low levels of HDL-C and 25 (OH)D may contribute to higher levels of IMT.Conclusions SAA was closely related to carotid atherosclerosis.Further prospective studies will be helpful to explore the influence of SAA on diabetic macroangiopathy.

Objective To investigate the relationships between mindfulness,anxiety and depression in surface warship soldiers and the mediating role of attentional control.Methods Chinese versions of State-Trait Anxiety Inventory ( STAI ) , Center for Epidemiologic Studies Depression Scale ( CES-D ) , Attentional Control Scale ( ACS) and the Five Facet Mindfulness Questionnaire ( FFMQ) were used to survey 475 sur-face warship soldiers. Single factor analysis of variance,correlation analysis and path analysis were conducted by SPSS 20.0 and Amos18.0. Results ①The scores of the state anxiety,trait anxiety and depression in the soldiers and noncommissioned officers were significantly higher than that of commissioned officers (P<0.05) . As for the state anxiety,trait anxiety,depression and attentional focusing,there were statistically significant differences among different educational levels (P<0.05) . Specifically,the lower educational level,the higher anxiety and depression,the lower control focusing. ② There were significant positive correlations among at-tentional focusing (27.12±4.43),attentional shifting (29.43±3.78) and mindfulness (120.27±11.16,r=0.49-0.51,P<0.01). State anxiety (38.65±10.07) was negatively correlated with attentional focusing,atten-tional shifting and mindfulness (r=-0.32--0.54, P<0.01). Similar results were observed for trait anxiety (41.28±8.79) and depression (9.97±10.13). ③Attentional focusing partially mediated the relationships be-tween state anxiety,trait anxiety,depression and mindfulness. Conclusion Anxiety and depression of sol-diers have obvious relationships with kinds of soldiers' rank and education level. Mindfulness and attentional control are vital protective factors for marine army's mental health. This study indicates that mindfulness may improve individuals' attentional focusing and attentional shifting,and ameliorate negative moods such as anx-iety and depression.