OBJECTIVES: To explore the therapeutic mechanism of Guizhi Fuling (GZFL) Pellets against cervical cancer. METHODS: Publicly available databases were used to identify the targets of GZFL Pellets and cervical cancer to construct the protein-protein interaction (PPI) network, followed by GO biological process and KEGG pathway enrichment analysis of the hub genes. The "Traditional Chinese Medicine-Active Ingredients-Targets-Pathways" network for GZFL Pellets in cervical cancer treatment was generated using Cytoscape v10.0.0, and molecular docking of the drug and potential targets was performed to predict the specific targets of active components in Guizhi Fuling Pellets. The inhibitory effects of hederagenin, an active ingredient in GZFL Pellets, was tested in cultured cervical cancer cells and in nude mice bearing cervical cancer xenografts. RESULTS: GZFL Pellets contain 338 active components targeting 247 action sites. A total of 10127 cervical cancer-related targets were obtained, and among them 195 were identified as potential therapeutic targets of GZFL Pellets for cervical cancer treatment, including the key targets of GABRA1, PTK2, JAK2, HTR3A, GSR, and IL-17. Molecular docking study showed low binding energies of the active components such as hederagenin, campesterol, and stigmasterol for protein-molecule interaction. GO enrichment analysis suggested that GZFL Pellets inhibited cervical cancer primarily by regulating responses to steroid hormones, oxidative stress, and lipopolysaccharides. Among the active components of GZFL Pellets, hederagenin was found to inhibit cervical cancer cells in vitro and significantly reduced STAT3 phosphorylation level in the cancer cells. In nude mice bearing cervical cancer xenografts, hederagenin effectively inhibited tumor growth rate without causing obvious adverse effects. CONCLUSIONS GZFL Pellets inhibit cervical cancer cell growth through its multiple active components that target different pathways. Among these components, hederagenin inhibits tumor cell growth possibly by directly binding to JAK2 protein to inhibit STAT3 phosphorylation.
Female ; Animals ; Uterine Cervical Neoplasms/pathology* ; Mice, Nude ; Humans ; Mice ; Oleanolic Acid/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Molecular Docking Simulation ; Xenograft Model Antitumor Assays ; Cell Line, Tumor ; STAT3 Transcription Factor/metabolism* ; Protein Interaction Maps ; Janus Kinase 2/metabolism*

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objective:To explore the core competence that Neurology nurses should possess through qualitative research.Methods:In July 2023, a semi-structured interview was conducted by purposive sampling to select 15 clinical nurses and 7 head nurses in Department of Neurology of Xuanwu Hospital, Capital Medical University. Colaizzi 7-step analysis method in phenomenological research was used to analyze data.Results:The core competence model of neurology nurses were summarized into 7 themes, including clinical competence (symptom assessment ability of neurological diseases, critical rescue ability of neurological diseases, specialized skills related to neurological disease treatment), research ability, teaching ability, management ability, personal quality (communication ability, learning ability, teamwork ability), professional quality (patience, responsibility, love, empathy), and the supervision ability of neurology head nurses over nurses (development of continuing education on neurological diseases, promotion of career planning for neurology nurses) .Conclusions:The analysis of the core competence of Neurology nurses provides a basis for improving nursing quality, promoting disease prognosis for patients with neurological disorders, and enhancing their quality of life.

BACKGROUND/OBJECTIVES: The study examined the association between homocysteine and diabetes mellitus in patients with H-type hypertension and assessed the possible effect modifiers. SUBJECTS/METHODS: This cross-sectional study included 1,255 eligible participants in the ‘H-type Hypertension Management and Stroke Prevention Strategic International Science and Technology Innovation Cooperation Project’ among rural Chinese people with H-type hypertension. A multivariate logistic regression model was used to evaluate the relationship between homocysteine and diabetes mellitus. RESULTS: The mean level of total homocysteine (tHcy) in the diabetes mellitus population was 19.37 μmol/L, which was significantly higher than the non-diabetic patients (18.18 μmol/L). When tHcy was analyzed as a continuous variable, the odds ratio (OR) of diabetes was 1.17 (95% confidence interval [CI], 1.01–1.35; per interquartile range). When tHcy was stratified according to the quintile, the ORs for diabetes were 2.86 (95% CI, 1.22–6.69) in the highest quintile (tHcy ≥ 20.60 μmol/L) compared to the reference group (tHcy < 12.04 μmol/L). When tHcy was grouped by 15 μmol/L and 20 μmol/L, patients with tHcy ≥ 20 μmol/L had a significantly (P = 0.037) higher risk of diabetes (OR, 2.03; 95% CI, 1.04–3.96) than in those with tHcy < 15 μmol/L. Subgroup analysis showed that the tHcy-diabetes association was unaffected by other variables. CONCLUSION In this study of rural Chinese people with H-type hypertension, the tHcy levels showed a positive association with diabetes mellitus. This independent association is unaffected by other potential risk factors.

OBJECTIVES: To explore the mechanism of Chinese medicine Jiangzhuo mixture regulating glucose and lipid metabolism in obese rats. METHODS: Thirty healthy male SD rats were randomly divided into normal control group, model control group, and Jiangzhuo mixture treatment group, with 10 rats in each group. The rats in the normal control group were fed with normal diet, the obesity model was induced by feeding high-fat diet in the model control group and the Jiangzhuo mixture treatment group, the rats in the treatment group were given with Jiangzhuo mixture 50 g/kg by gavage. After 8 weeks of intervention, the blood glucose (GLU), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured in the three groups. Quantitative reverse transcription PCR were used to detect the expression levels of PR domain containing 16 (PRDM16) and uncoupling protein 1 (UCP1) in white and brown adipose tissues of the rats in each group; Western blotting was used to detect the expression of PRDM16 in the white and brown adipose tissue of rats, and Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) and inhibitor of NF-κB alpha (IκBα) in the white adipose tissue; immunohistochemistry was used to detect the expression of UCP1 protein in white and brown adipose tissues. RESULTS: Compared with the normal control group, the white fat weight (P<0.01), white fat coefficient (P<0.05) and Lee's coefficient (P<0.01) were significantly increased in the model control group; the contents of GLU, TC, TG and LDL-C were all increased, and the content of TG was significantly increased (P<0.05) in the model control group. The mRNA and protein expression levels of PRDM16 and UCP1 in white fat and brown fat were significantly decreased (P<0.05) in the model control group. Compared with the model control group, the white fat weight and white fat coefficient and Lee's coefficient were significantly reduced in the Jiangzhuo mixture treatment group (all P<0.01), the levels of GLU, TC, TG, and LDL-C in the the treatment group were all reduced, and the content of TG was reduced more obviously (P<0.01); expression levels of PRDM16 and UCP1 mRNA and protein were increased in brown and white adipose tissue. Compared with the normal control group, the expression levels of TLR4, phospho-IκBα and NF-κB-p65 proteins in white adipose tissue of the model control group were significantly increased (all P<0.01), while the expression levels of these proteins in the treatment group were significantly lower than those in the model control group (all P<0.05). CONCLUSIONS Jiangzhuo mixture can alleviate high-fat diet-induced increase in body fat, abnormal expression of biochemical indexes and promote the expression of key proteins including UCP1 and PRDM16 in white and brown adipose tissues by regulating TLR4/IκBα/NF-κB signaling pathway.
Rats ; Male ; Animals ; NF-kappa B/metabolism* ; Rats, Sprague-Dawley ; Glucose ; Lipid Metabolism ; Toll-Like Receptor 4 ; Cholesterol, LDL/metabolism* ; NF-KappaB Inhibitor alpha/metabolism* ; Medicine, Chinese Traditional ; Signal Transduction ; Triglycerides ; Transcription Factors/metabolism* ; Obesity ; RNA, Messenger

Osteonecrosis of the femoral head （ONFH） is a painful and debilitating disease caused by impaired blood supply to the femoral head and cellular and tissue degeneration， leading to gradual destruction of the bone structure and progressive collapse of the femoral head. The main pathological mechanism of ONFH is the disruption of the balance between bone absorption and the reconstruction of new bone， resulting from microcirculation damage and decreased cellular tissue ability. This imbalance leads to biomechanical changes and accelerates the pathological progression of ONFH. In the early stages， clinical manifestations may not be obvious， mainly presenting as pain or discomfort in the hip or groin area， which can be relieved after rest. In the later stage of the disease， pain intensifies， and limb shortening， lower limb weakness， difficulty walking， or limping may occur. Currently， western medicine commonly uses osteogenic agents， anticoagulants， and artificial joint replacement for treatment， but there are also many issues such as prosthesis loosening and infection. Research has shown that traditional Chinese medicine （TCM） treatment of ONFH takes a holistic approach and employs multi-functional， multi-target， and multi-system Chinese medicine therapies， ensuring the safety and effectiveness of the treatment. The osteoprotegerin （OPG）/receptor activator of nuclear factor-κB （RANK）/RANK ligand （RANKL） signaling pathway plays a crucial role in maintaining the dynamic balance of bone remodeling. TCM treatments utilize this pathway to promote apoptosis of osteoclasts， reduce bone resorption， and accelerate bone formation， thereby playing an important role in the prevention and treatment of ONFH. This paper reviewed the role of OPG/RANK/RANKL signaling pathway and related cytokine expression in ONFH by reviewing relevant literature in China and abroad and research status of Chinese medicinal monomers， Chinese medicinal formulations， and combinations with physical therapy in increasing osteoblast secretion， promoting OPG expression， enhancing cytokine expression levels， and inhibiting osteoclast activity for the prevention and treatment of ONFH. This paper is expected to provide new ideas and directions for TCM in the prevention and treatment of ONFH.

Objective To investigate the related factors of central regional lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC).Methods The clinical and pathological fea tures of 550 cases of PTMC with clinical lymph node negative (cN0) were retrospectively analyzed.x2 test and multivariate logistic regression analysis were used to analyze the related factors of CLNM.ROC curve was used to analyze tumor diameter and CLNM of PTMC.Results The CLNM rate was 35.6％.Univariate analysis showed that patients aging less than 45 y(x2=13.983,P＜0.001),with tumor diameter≥7 mm (x2=14.263,P＜0.001),with capsule invasion (x2=7.316,P=0.006),multifocality (x2=14.321,P＜0.05) and bilateral tumors (x2=9.265,P=0.002) were more likely to have CLNM.Multivariate Logistic regression analysis showed that age ＜45 y,tumor diameter ≥7 mm,invasion of capsule and multifocal are all independent risk factors of CLNM for patients with PTMC.The optimal cutoff value of CLNM by diameter was 8 mm.Conclusion The CLNM of PTMC is related to many factors.When the age of the patient is less than 45 y,the diameter of the tumor is more than 7 mm,the invasion of the capsule and the multifocal lesion,the central lymph node dissection should be performed.

Objective To discuss the operative strategies for cervical spine fracture combined with ankylosing spondylitis and the deformity of cervicothoracic kyphosis.Methods Retrospectively analyzed 21 cases of cervical spine fracture combined with ankylosing spondylitis and the deformity of cervicothoracic kyphosis,who underwent surgeries from January,2007 to August,2014.Twenty males and 1 female were included.Mean age was (48.6±7.5) years (range,36-65 years).The preoperative American Spine Injury Association (ASIA) classification distribution:2 cases of Grade A,6 cases of Grade B,7 cases of Grade C,5 cases of Grade D,and 1 case of of Grade E.The investigative surgical methods including posterior cervical open reduction,internal fixation and bone graft fusion;posterior cervical open reduction/decompression,internal fixation and bone graft fusion;or combined posterior and anterior cervical decompression,bone graft fusion and instrumentation.The operative time and blood loss were recorded,the clinical therapeutic effect was evaluated by visual analogue scale (VAS) score,ASIA grade improvement,cervical curvature (the angle between a line drawn parallel to the inferior endplate of C2 and a line drawn parallel to the inferior endplate of C7 in the lateral plane of an X-ray image) and radiological assessment (including bone graft fusion condition and internal fixation position).Results One case died from severe pulmonary infection and respiratory failure at the 45th day after operation.All the other 20 patients obtained complete follow-up with a mean time of (39.4±8.76) months (range,25-59 months).7 cases received posterior cervical open reduction,internal fixation and bone graft fusion,average operative time was (92.1±5.4) minutes and average blood loss was (96.1+23.7) ml.9 cases received the posterior cervical open reduction and decompression,internal fixation and bone graft fusion,mean operation time was (121.4± 14.0) minutes and blood loss was (250.0±38.9) ml.3 cases experienced combined posterior and anterior cervical decompression,bone graft fusion and fixation,average operative time was (222.4± 14.9) minutes and average blood loss was (354.3+46.7) ml.Mean of VAS scores at the 3th month postoperatively was 2.76±0.46,significantly lower than the preoperatively VAS scores (8.95±0.36).Mean of VAS scores at the 24th month postoperatively was 1.77±0.39,significantly lower than those at the 3th month postoperatively.The neurological function of spinal cord achieved significant improvement after operations and continued recovered gradually in the subsequent follow up.ASIA Classification distribution at the 24th month postoperatively was:0 case of Grade A,0 case of Grade B,3 cases of Grade C,8 cases of Grade D,9 case of Grade E.Mean of the cervical curvature after operation was-7.1°± 1.9°,significantly higher than preoperatively(-13.4°±3.3°) and did not have any loss of Cobb's angles at 24th month after operation.All the surviving cases achieved solid bone graft fusion.Mean bone graft fusion time was 5.8 months (range,4-9 months).There was no internal fixation loose,fracture and dislocation occurred during follow up.Conclusion All procedures can significantly relieve the painful symptoms,effectively restore the normal cervical alignment and stability,and remarkably improve the neural function of the patients suffering cervical spine fracture combined with ankylosing spondylitis and the deformity of cervicothoracic junction kyphosis.

Objective: To investigate the early intervention effects of metoprolol on connexin 43(Cx43) and phosphorylated Cx43 (p-Cx43) expression in rabbits with post myocardial infarction. Methods: A total of 24 adult male New Zealand white rabbits were divided into sham group (n=6), early treatment group(n=6), routine treatment group(n=6), and myocardial infarction group(n=6) with a randomized block design blocked by weight. Myocardial infarction was induced by left anterior descending coronary artery (LAD) ligation. Rabbits in sham group received similar surgical procedure without LAD ligation. Metoprolol (12.5 mg/kg dissolved in 2 ml distilled water) was applied to rabbits in early treatment group and routine treatment group per gavage immediately after recovery from anesthesia and at 24 hours after myocardial infarction, respectively, then treated daily for 40 days. Rabbits in sham group and myocardial infarction group received 2 ml distilled water per gavage daily for 40 days. Plasma lactate dehydrogenase (LDH) and creatine kinase (CK) level were detected by automatic biochemistry analyzer after 6 hours in all rabbits. Ventricular fibrillation threshold (VFT) was measured in vivo by bipolar pacing electrodes at 40 days. Cx43 and p-Cx43 distribution in ventricular tissue was detected by immunofluorescence analyses. Cx43 and p-Cx43 protein level in ventricular tissue was determined by Western blot. Results: (1) Plasma LDH ((851.7±85.9)U/L vs. (332.3±39.6)U/L, P<0.01) and CK ((1 192.7±105.3)U/L vs. (462.3±65.6)U/L, P<0.01) were significantly higher in myocardial infarction group than in sham group (both P<0.01). (2) VFT was significantly lower in myocardial infarction group than that in sham group ((470.0±91.0) beats per minute vs. (683.3±60.9) beats per minute, P<0.05), and VFT was significantly higher in early treatment group ((633.3±43.2) beats per minute) and routine treatment group ((645.0±30.8) beats per minute) than in the myocardial infarction group (both P<0.05). (3) Immunofluorescence analyses showed that Cx43 was mainly localized in the intercalated disk, which was perpendicular to the cell long axis with linear arrangement, and less lateral distribution in sham group, early treatment group and routine treatment group, which was significantly different as the case in the myocardial infarction group. The expression of p-Cx43 in myocardial infarction group was less than in sham group, which was significantly upregulated in in early treatment group and routine treatment group when compared with myocardial infarction group, and expression of p-Cx43 was significantly higher in early treatment group than in routine treatment group. (4)The p-Cx43/Cx43 ratio of protein was significantly lower in myocardial infarction group than in sham group (0.165±0.011 vs. 0.363±0.046, P<0.05), and significantly higher in early treatment group (0.720±0.063) and routine treatment group (0.364±0.030) than in myocardial infarction group (both P<0.05), and this ratio was significantly higher in early treatment group than in routine treatment group (P<0.05). Conclusion Metoprolol treatment, especially the early metoprolol treatment (within 24 hours after LAD ligation), could significantly improve VFT by ameliorating the distribution and dephosphorylation of myocardial Cx43 in rabbits with experimental myocardial infarction.

Objective To explore the lateral neck lymph node metastasis (LNM) in patients affected by papillary thyroid carcinoma(PTC) with clinically negative neck (cN0-PTC) and to discuss the necessity of prophylactic lateral neck lymph node dissection.Methods Clinical data of 651 cN0-PTC patients who underwnt surgical procedure in Tumor Hospital of Zhengzhou University from Jan.2012 to May.2015 were retrospectively analyzed.Chi-square test was used for univariate analysis.Results Of the 651 cN0-PTC patients,62.9％ had LNM (51.3％ in central neck,41.0％ in lateral neck,and 11.7％ with "skip" metastasis).The lateral neck metastasis rate was 50.9％ in men and 37.7％ in women (P＜0.05),61.9％ in patients with tumor diameter ＞1.0 cm and 25.9％ in patients with tumor diameter ≤ 1.0 cm (P＜0.001),47.2％ with multifocal cancer and 40.3％ with unifocal tumor(P＜0.05),63.1％ with extrathyroidal extention and 34.3％ without extention (P＜0.001),64.1％ with ≥3 positive nodes in central neck and 48.3％ with ＜3 positive nodes (P＜0.05),52.4％ with upper lobe cancer and 32.9％ with other locations(P＜0.001),41.0％ in patients ≤45 years and 40.9％ in patients ＞45 years(P＞0.05).Conclusion Central neck dissection should be performed in all cN0-PTC patients.Prophylactic lateral neck dissection should beselectively performed in cN0-PTC patients with following high-risk factors:male,tumor diameter ＞1.0 cm,multifocal cancer,extrathyroidal extention,≥ 3 positive nodes in central neck and upper lobe cancer.