ObjectiveTaking Aurantii Fructus Immaturus juice（AFI）-processed Atractylodis Macrocephalae Rhizoma（AMR） as an example， this study aims to systematically compare the volatile and non-volatile components of AMR and its processed products， investigate the key differential components， evaluate their anti-inflammatory activities， and elucidate the synergistic mechanism of processing. MethodsThe chemical compositions of volatile and non-volatile components in AMR and AFI-processed AMR were systematically characterized using gas chromatography-mass spectrometry（GC-MS） and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， with relative mass fractions and response values determined separately. Volatile components were identified through searches in the National Institute of Standards and Technology（NIST）17 database， comparison with retention index（RI） and fragmentation pattern matching. Non-volatile components were identified by searching Waters Traditional Chinese Medicine （TCM） spectral library， in conjunction with PubChem and MassBank， characteristic fragmentation patterns and response values were also used to support identification. Differential components were screened using principal component analysis（PCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， with variable importance in the projection（VIP） value >1. Components with high log₂fold change（FC） among major differential groups were selected as those exhibiting significant changes before and after processing. The anti-inflammatory activity of the differential compounds was evaluated by assessing their effects on nitric oxide（NO） production in a lipopolysaccharide（LPS）-induced RAW264.7 macrophage model. Enzyme-linked immunosorbent assay（ELISA） was used to detect the effects of the differential components on tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6， and monocyte chemotactic protein（MCP）-1 levels， and immunofluorescence（IF） was employed to assess their effects on nuclear transcription factor（NF）-κB p65 translocation， thereby elucidating the underlying molecular mechanisms. ResultsA total of 36 compounds were identified in the volatile components of AMR and AFI-processed AMR， among which， sesquiterpenes and monoterpenes were significantly increased after processing. In the non-volatile components， 36 compounds were identified， and the main differential components were flavonoids， sesquiterpenoids， and triterpenoids. Flavonoids were the primary differential components distinguishing AMR from its processed products， representing compounds directly introduced during processing. Five compounds， including atractylenolide Ⅲ， tangeritin， nobiletin， hesperidin and narirutin， were selected as representatives of three classes based on their most prominent differential expression among different compound types for subsequent anti-inflammatory activity studies. The results showed that 100 μmol·L^-1 tangerine and narirutin could significantly inhibit LPS-induced NO production（P<0.01） in a concentration-dependent manner. Tangeritin was able to significantly inhibit the levels of TNF-α and MCP-1 secreted by RAW264.7（P<0.05）， while narirutin significantly inhibited the levels of TNF-α， IL-1β， MCP-1 and IL-6（P<0.01）. IF revealed that both tangeritin and narirutin significantly blocked the translocation of NF-κB p65 from the cytoplasm to the nucleus. ConclusionAFI-processed AMR significantly alters the chemical composition profile of AMR， and the newly introduced flavonoid components during processing may be key to its enhanced anti-inflammatory effects.

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

This study aims to evaluate the effects of sodium butyrate(NaBu)on preliminary follicle development of mice,using an in vitro 3D culture system.Preantral follicles were isolated from mouse ovaries(12.5 days post-birth)and cultured in vitro,NaBu was added for treatment during the culture process.Follicle morphology was observed and follicular diameter,survival rate,antral formation rate,oocyte maturation rate and early embryonic development were evaluated.The re-sults showed that an in vitro 3D culture system for preantral follicles of mice was successfully es-tablished.Matured follicles were cultured following an initial induction period of 8 days,after which M Ⅱ-stage oocytes were effectively expelled.During the process of follicle culture,the addition of varying doses(0.05-1.00 mmol/L)of NaBu from 0th day to 8 days had not showed any significant promotion in follicle development at any of the tested concentrations.NaBu at a dose of 0.10 mmol/L significantly increased antral formation rate(treated on 4th day for 2 days).In conclusion,short-term administration of appropriate doses of NaBu could significantly facilitate in vitro preantral follicle development and oocyte maturation by ensuring sustained developmental potential within follicles.This study may provide a theoretical basis for sodium butyrate to improve the reproduc-tive capacity of livestock and poultry in the breeding process.

Objective To evaluate the efficacy and safety of different surgical approaches for extracting high-positioned supernumerary teeth in the maxillary anterior midline region.Three surgical methods,the labial approach,the palatal approach,and a longitudinal incision beside the upper lip frenum were compared.Methods A total of 102 patients were recruited from the Department of Oral and Maxillofacial Surgery at the Affiliated Stomatological Hospital of Anhui Medical University between January and September 2024.They were randomly assigned via a random-digit table to three groups:the labial approach group(n=32),the palatal approach group(n=34),and the longitudinal incision beside the upper lip frenum group(n=36).Operation time,bone removal volume,post-operative midfacial swelling,degree of pain,and patient satisfaction across the three groups were recorded and compared.Results The average operation time in the labial approach group((20.50±3.02)min)and the longitudinal incision group((21.66±2.31)min)were both significantly shorter than that in the palatal approach group((29.19±3.40)min).In contrast,the palatal approach group demonstrated markedly lower postoperative swelling and pain scores(P＜0.05),along with the highest patient satisfaction,as reflected in the OHIP-14 scale.However,the palatal approach required the greatest bone removal volume,measuring(91.19±9.86)mm3.Conclusion Despite the palatal approach yielding superior outcomes in terms of postoperative pain control,swelling reduction,and patient satisfaction,it necessitated longer operation time and involved greater bone removal.Meanwhile,the labial approach and the longitudinal incision beside the upper lip frenum were comparable in all measured parameters,showing no statistically significant differences.Therefore,when extracting high midline impacted teeth in the maxillary anterior region,the choice of surgical approach should balance safety,minimal invasiveness,and patient satisfaction.

This study aims to evaluate the effects of sodium butyrate(NaBu)on preliminary follicle development of mice,using an in vitro 3D culture system.Preantral follicles were isolated from mouse ovaries(12.5 days post-birth)and cultured in vitro,NaBu was added for treatment during the culture process.Follicle morphology was observed and follicular diameter,survival rate,antral formation rate,oocyte maturation rate and early embryonic development were evaluated.The re-sults showed that an in vitro 3D culture system for preantral follicles of mice was successfully es-tablished.Matured follicles were cultured following an initial induction period of 8 days,after which M Ⅱ-stage oocytes were effectively expelled.During the process of follicle culture,the addition of varying doses(0.05-1.00 mmol/L)of NaBu from 0th day to 8 days had not showed any significant promotion in follicle development at any of the tested concentrations.NaBu at a dose of 0.10 mmol/L significantly increased antral formation rate(treated on 4th day for 2 days).In conclusion,short-term administration of appropriate doses of NaBu could significantly facilitate in vitro preantral follicle development and oocyte maturation by ensuring sustained developmental potential within follicles.This study may provide a theoretical basis for sodium butyrate to improve the reproduc-tive capacity of livestock and poultry in the breeding process.

Objective To evaluate the efficacy and safety of different surgical approaches for extracting high-positioned supernumerary teeth in the maxillary anterior midline region.Three surgical methods,the labial approach,the palatal approach,and a longitudinal incision beside the upper lip frenum were compared.Methods A total of 102 patients were recruited from the Department of Oral and Maxillofacial Surgery at the Affiliated Stomatological Hospital of Anhui Medical University between January and September 2024.They were randomly assigned via a random-digit table to three groups:the labial approach group(n=32),the palatal approach group(n=34),and the longitudinal incision beside the upper lip frenum group(n=36).Operation time,bone removal volume,post-operative midfacial swelling,degree of pain,and patient satisfaction across the three groups were recorded and compared.Results The average operation time in the labial approach group((20.50±3.02)min)and the longitudinal incision group((21.66±2.31)min)were both significantly shorter than that in the palatal approach group((29.19±3.40)min).In contrast,the palatal approach group demonstrated markedly lower postoperative swelling and pain scores(P＜0.05),along with the highest patient satisfaction,as reflected in the OHIP-14 scale.However,the palatal approach required the greatest bone removal volume,measuring(91.19±9.86)mm3.Conclusion Despite the palatal approach yielding superior outcomes in terms of postoperative pain control,swelling reduction,and patient satisfaction,it necessitated longer operation time and involved greater bone removal.Meanwhile,the labial approach and the longitudinal incision beside the upper lip frenum were comparable in all measured parameters,showing no statistically significant differences.Therefore,when extracting high midline impacted teeth in the maxillary anterior region,the choice of surgical approach should balance safety,minimal invasiveness,and patient satisfaction.

Objective To understand the implementation of the nursing group standards for oxygen inhalation therapy in clinical practice,and to provide a reference for improving the nursing practice of oxygen therapy.Methods A convenience sampling method was used to investigate nurses from 902 hospitals in 24 provinces and municipalities directly under the central government using a self-designed questionnaire from December 15th,2022,to January 14th,2023.The content of questionnaire included whether they had implemented the recommendations of the oxygen therapy standards,the knowledge of safety related to oxygen therapy,and the components of oxygen therapy prescriptions,the indications used for patients receiving oxygen therapy and practice status of oxygen therapy.Results A total of 10481 questionnaires were returned,of which 10447 were valid,with a valid questionnaire recovery rate of 99.68%.63.14%of the nurses indicated that the hospital had organized training on oxygen therapy standards.Only 47.82%of nurses know the correct use of the Venturi mask.41.90%of nurses could indicate the correct indicator of flow adjustment.31.88%of the nurses stated that they will adjust the oxygen flow rate based on the oxygenation status of carbon dioxide storage patients.Only 19.56%of nurses indicated that humidification is applied in oxygen therapy based on the oxygen flow and duration.Conclusion Even though nurses had received training related to oxygen therapy standards,the level of knowledge of oxygen therapy standards was still low;therefore continuous systematic training was needed,and the implementation of the content of oxygen therapy standards needed to be further standardized.Healthcare institutions would focus on organizing systematic training and maintaining the training effect,enhancing infrastructure and providing support for implementation.Recommendation to the nursing administration is to explore how to comprehensively and continuously implementing the oxygen therapy nursing standards with the ultimate goal of providing patients safer and more accurate oxygen therapy.

AIM:This study aims to investigate the effects and mechanisms of silent information regulator 6(SIRT6)on carbon tetrachloride(CCl4)-induced liver fibrosis in mice,as well as the expression changes in the down-stream pathways of hepatic stellate cells after SIRT6 silencing.METHODS:Thirty male C57BL/6J mice were randomly divided into a normal control group(n=6)and a model group(modeling at 2,4,8,12 weeks,n=24).A liver fibrosis model in mice was prepared by intraperitoneal injection of CCl4 twice a week for 12 weeks.Serum alanine aminotransfer-ase(ALT)and aspartate aminotransferase(AST)levels were measured to assess liver injury.Hematoxylin-eosin(HE)and Masson staining were used to observe the pathological changes in mouse liver tissues.Immunohistochemical staining was conducted to detect the expression of α-smooth muscle actin(α-SMA)in the liver,Western blot analysis was used to measure the expression of liver α-SMA,SIRT6,acetyl histone H3 at Lys9(H3K9ac),acetyl histone H3 at Lys56(H3K56ac),interleukin-1β(IL-1β),and IL-18 proteins.Hepatic stellate cells-T6(HSC-T6)underwent SIRT6 gene si-lencing,divided into NC siRNA group and SIRT6 siRNA group,with Western blot performed to detect the expression of SIRT6,H3K9ac,and H3K56ac proteins.RESULTS:Compared with the normal control group,the serum ALT and AST levels in the model group were significantly increased(P<0.05);HE and Masson staining results showed that the patho-logical changes in the liver of the model group worsened over time,with an increase in collagen fiber deposition.Both im-munohistochemistry and Western blot showed that the expression of liver α-SMA significantly increased at 8 and 12 weeks in the model group(P<0.05).Western blot results showed that the expression of SIRT6 protein in the liver of all model group mice was lower than that in the normal control group(P<0.05),and decreased gradually with the progression of liv-er fibrosis;also,the expression levels of H3K9ac,H3K56ac,IL-1β,and IL-18 in the liver of the model group mice were significantly elevated at 8 and 12 weeks(P<0.05);after SIRT6 silencing,compared with the NC siRNA group,the levels of H3K9ac and H3K56ac in the SIRT6 siRNA group significantly increased(P<0.05).CONCLUSION:The deficiency of SIRT6,by abnormally increasing H3K9ac and H3K56ac,raises the expression of IL-1β and IL-18,intensifying the in-flammatory response and promoting the progression of liver fibrosis,indicating that the aberrant expression of SIRT6 is in-volved in the development of liver fibrosis.

Hepatocellular carcinoma （HCC） is the sixth most common cancer in the world. In recent years， the clinical early diagnosis and treatment protocols of HCC have been improved， whereas the prognosis of patients is still not satisfactory， which is due to the fact that the mechanism of HCC development has not been fully elucidated. Therefore， it is of great significance to explore the molecular mechanisms and key regulatory links of hepatocellular carcinoma development to further improve the diagnosis and treatment of HCC in China. Epigenetics has become a research hotspot because of its reversibility and easy regulation. According to relevant studies， HCC involves the accumulation of multiple genetic and epigenetic changes during the initiation， promotion， and progression stages. HCC is categorized as infantile malnutrition with accumulation， hypochondriac pain， tympan ites， and abdominal mass in traditional Chinese medicine （TCM）. In the treatment of HCC， TCM with low toxicity， multi-targets， and multi-mechanisms can inhibit tumor growth， alleviate the clinical symptoms， and enhance the quality of life of the patients. Chinese medicines and their active ingredients exert anti-HCC effects through epigenetic regulation of DNA methylation， histone modification， and non-coding RNA. Abnormal gene expression due to epigenetic regulation disorders is involved in all stages of HCC development. There are few studies on epigenetic regulation in TCM treatment of HCC， and there is still much room for development in basic and clinical trials. This paper reviews the mechanism of epigenetic regulation in HCC and summarizes the experimental results of TCM research on the related mechanism， with a view to providing a theoretical basis for future research on the mechanism of HCC development and clinical diagnosis and treatment of hepatocellular carcinoma with TCM.

Objective To investigate the expressions of extracellular matrix metalloproteinase inducer(EMMPRIN),matrix metalloproteinase-9(MMP-9),lysine demethylase 6B(KDM6B)proteins and their correlation with clinicopathologic features in invasive breast cancer,and analyze the correlation among the three proteins and their value in pathological diagnosis of invasive breast cancer.Methods The surgical biopsy specimens of 124 patients with invasive breast cancer who were admitted to the Department of Pathology,the Fifth Clinical Medical College of Henan University of Chinese Medicine/People's Hospital of Zhengzhou from January 2014 to December 2017 were selected as research subjects,and 20 low-grade intraductal carcinoma tissue specimens,27 high-grade intraductal carcinoma tissue specimens,and 22 adjacent tissue specimens＞1 cm away from the invasive breast cancer were selected as controls.The expressions of EMMPRIN,MMP-9 and KDM6B proteins in cancer-adjacent tissues,low-grade intraductal carcinoma tissues,high-grade intraductal carcinoma tissues and invasive breast cancer tissues were detected by immunohistochemistry.The relationship between the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins and clinicopathologic features of invasive breast cancer was analyzed,Spearman correlation analysis was used to evaluate the correlation of EMMPRIN,MMP-9 and KDM6B proteins in breast cancer tissues,and receiver operating characteristic(ROC)curve was adopted to evaluate the diagnostic value of EMMPRIN,MMP-9 and KDM6B for invasive breast cancer.Results The relative expressions of EMMPRIN and MMP-9 proteins in high-grade intraductal carcinoma and invasive breast cancer tissues were significantly higher those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in invasive breast cancer tissues were significantly higher those in high-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than that in high-grade intraductal carcinoma tissues(P＜0.05);there was no statistically significant difference in the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins between cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P＞0.05).The relative expressions of EMMPRIN and KDM6B proteins were not related to the age,tumor location and tumor diameter of patients with invasive breast cancer(P＞0.05),and the relative expression of MMP-9 protein was not related to the age and tumor location of patients with invasive breast cancer(P＞0.05).Relative expressions of EMMPRIN,MMP-9 and KDM6B proteins were correlated with WHO grading,lymph node metastasis,and tumor,node and metastasis(TNM)staging of invasive breast cancer(P＜0.05),and the relative expression of MMP-9 protein was correlated with the tumor diameter(P＜0.05).In the WHO grades Ⅰ,Ⅱ,and Ⅲ of invasive breast cancer,the relative expressions of EMMPRIN and MMP-9 proteins increased sequentially,while the relative expression of KDM6B protein decreased sequentially(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in the lymph node metastasis group were significantly higher than those in the non-lymph node metastasis group,and the relative expression of KDM6B protein was significantly lower than that in the non-lymph node metastasis group(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in TNM stages Ⅲ-Ⅳ were significantly higher than those in stages Ⅰ-Ⅱ(P＜0.05),while the relative expression of KDM6B protein was significantly lower than that in stages Ⅰ-Ⅱ(P＜0.05).In the group of invasive breast cancer with diameter≤2 cm,2 to 5 cm,and＞5 cm,the relative expression of MMP-9 protein increased sequentially(P＜0.05).Spearman correlation analysis showed that the expression of EMMPRIN was positively correlated with MMP-9 protein in invasive breast cancer tissues(r=0.990,P=0.000),the expression of EMMPRIN was negatively correlated with KDM6B protein(r=-0.606,P=0.000),and the expression of MMP-9 was negatively correlated with KDM6B protein(r=-0.612,P=0.000).ROC curve analysis showed that the area under the curve(AUC)of EMMPRIN protein for diagnosing invasive breast cancer was 0.875[95％confidence interval(CI):0.823-0.926,P＜0.05],with an optimal threshold of 10.043,sensitivity of 79.0％,and specificity of 76.8％;the AUC of MMP-9 protein in diagnosing invasive breast cancer was 0.863(95％CI:0.808-0.917,P＜0.05),with an optimal threshold of 10.070,sensitivity of 74.2％,and specificity of 76.8％;the AUC of KDM6B protein in diagnosing invasive breast cancer was 0.267(95％CI:0.196-0.338,P＜0.05),with an optimal threshold of 11.003,sensitivity of 71.0％,and specificity of 98.6％.Conclusion EMMPRIN,MMP-9 and KDM6B are related to the occurrence and development of invasive breast cancer.Detection of the expressions of EMMPRIN,MMP-9 and KDM6B is helpful to the pathological diagnosis of invasive breast cancer and clinical judgment of invasion and metastasis of breast cancer.