BACKGROUND:Iron overload refers to excessive accumulation of iron in the body,which can cause pathological changes in various tissues.At present,the molecular mechanism and potential gene targets related to iron overload in osteoarthritis still need to be further studied and explored. OBJECTIVE:To analyze the key genes of iron overload in osteoarthritis by means of bioinformatics and verify them in animal experiments,so as to provide a new idea for preventing and treating osteoarthritis from the perspective of iron overload. METHODS:GEO database and GeneCards database were used to screen out genes associated with osteoarthritis and genes associated with iron overload.Then,the intersection of the two was taken to obtain a collection of genes commonly associated with osteoarthritis and iron overload.GO and KEGG enrichment analyses were used to screen the functions and pathways of these genes.To further investigate the interactions between these genes,a protein-protein interaction network was constructed and five computational methods of Cytoscape software were utilized to identify the Hub genes for iron overload in osteoarthritis.Finally,12 male Sprague-Dawley rats were divided into osteoarthritis group and normal group,with 6 rats in each group.A knee osteoarthritis model was established by the modified Hulth method in the osteoarthritis group.The expression of Hub genes in the knee joint of rats in each group was detected by PCR. RESULTS AND CONCLUSION:(1)A total of 51 genes associated with iron overload were identified in osteoarthritis.GO enrichment analysis showed that these genes were mainly involved in cytokine receptor binding,chemokine receptor binding,cytokine activity,growth factor receptor binding and oligosaccharide binding.(2)KEGG enrichment analysis showed that genes associated with iron overload in osteoarthritis was mainly involved in tumor necrosis factor signaling pathway and lipid and atherosclerosis signaling pathway.(3)The protein-protein interaction network was constructed,and five Hub genes of iron overload,intercellular cell adhesion molecule-1,tumor necrosis factor superfamily member 11,myelocytomatosis oncogene,janus kinase 2,and interleukin 6,were obtained by further analysis.Animal experiments verified that there were significant differences in the expression of the above Hub genes in the rat knee joint between the control group and the experimental group(P<0.05).(4)All these findings show that intercellular cell adhesion molecule-1,tumor necrosis factor superfamily member 11,myelocytomatosis oncogene,janus kinase 2,and interleukin 6 can be used as the Hub genes of iron overload in osteoarthritis,which are expected to become new targets for the prevention and treatment of osteoarthritis.

Objective To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy. Methods The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed. Results Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%). Conclusion HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.

Objective: To investigate the therapeutic effect of patchouli alcohol on mice with lung-heat syndrome based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/nuclear factor-kappa B(NF-κB) signaling pathway. Methods: First, network pharmacology was used to predict the potential targets of patchouli alcohol in the treatment of lung-heat syndrome, and a "component-disease-key target" network was constructed for pathway analysis. Then, 40 BALB/c mice were assigned to the normal, lung-heat model, honeysuckle, and low-dose and high-dose patchouli alcohol groups. All groups, except the blank group, were intranasally infected with 50 μL (103 TCID50) of influenza virus solution. After two hours of infection, mice were treated once a day for seven consecutive days. The therapeutic mechanism of patchouli alcohol was explored by measuring pulmonary inflammatory factors, the PI3K/Akt/NF-κB pathway, hypothalamic fever markers (PGE2, cAMP, cGMP levels), rectal temperature, and tissue energy metabolism. Results: Network pharmacology identified 135 target genes related to patchouli alcohol and lung-heat syndrome, with the key targets being STAT3, H1F1A, and NF-κB1. In animal experiments, patchouli alcohol significantly alleviated influenza virus-induced lung inflammatory damage in mice with lung-heat syndrome, inhibited the expression of TNF-α and IL-6 in lung tissues(P<0.01), and suppressed the activation of the PI3K/Akt/NF-κB pathway. It also reduced hypothalamic levels of PGE2 and cAMP(P<0.01), suppressed the increase in rectal temperature, significantly decreased liver glycogen and pyruvate levels(P<0.01), and increased the activities of SDH, LDH, and Na+ -K+ -ATPase in the liver(P<0.01) Conclusion Patchouli alcohol improves the symptoms of lung-heat syndrome in mice by inhibiting the activation of the PI3K/Akt/NF-κB pathway, reducing proinflammatory cytokines and inflammatory damage, and regulating hypothalamic fever markers and energy metabolism.

Objective: To investigate the biological effects of carvacrol on rats with stomach-heat and stomach-cold and its regulation on transient receptor potential(TRP) channels in rats with stomach-heat, and to study the cold and heat properties of carvacrol and its possible mechanism. Methods: According to the random number method, 100 SD rats were divided into stomach-heat blank group, stomach-heat model group, Coptidis Rhizoma group, stomach-heat low-dose and high-dose carvacrol group, stomach-cold blank group, stomach-cold model group, Baked ginger group, stomach-cold low-dose group and high-dose carvacrol group, 10 rats in each group. The rat model of stomach-heat was established by intragastric administration of pepper aqueous solution (0.80 g/kg) and anhydrous ethanol, and the rat model of stomach-cold was established by intragastric administration of water extract of Anemarrhena asphodeloides and sodium hydroxide (10.40 g/kg). On the day of modeling, the rats in the Baked ginger group were given Baked ginger decoction (0.78 g/kg), and the rats in the Coptidis Rhizoma group were given Coptidis Rhizoma decoction (0.43 g/kg).The stomach-cold and stomach-heat low-dose group of carvacrol was given carvacrol emulsion (40 mg/kg), high-dose group was given carvacrol emulsion (80 mg/kg).All rats of the blank and model groups were given the equal volume of emulsion prepared by 5% dimethyl sulfoxide, 1% Tween 80, 1% polyethylene glycol 400, and 93% normal saline, once a day, for 7 days. The general condition of rats was observed and the body mass was recorded. The pathological morphology of gastric tissue was observed by hematoxylin-eosin staining. The changes of material and energy metabolism, cyclic nucleotide (cAMP), thyroid hormone and gastrointestinal hormone in each group were determined by enzyme-linked immunosorbent assay. The expression levels of transient receptor potential vanilloid subtype 1 (TRPV1), transient receptor potential channel M8 (TRPM8) and uncoupling protein-1 (UCP1) in rats with gastric fever were detected by Western blotting. Results: Compared with the stomach-heat blank group, the body mass of rats in the stomach-heat model group decreased at the fifth and seventh day (P<0.05). The contents (or ratio) of hepatic glycogen (HGlyc), total cholesterol (TC), triglyceride (TG), and vasoactive intestinal peptide (VIP) were decreased (P<0.05), and Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, cytochrome C oxidase (COX), NADH dehydrogenase (ND), cyclic adenosine phosphate (cAMP), cAMP/cyclic guanosine phosphate (cGMP), triiodothyronine (T3), thyroxine (T4), gastrin (GAS), motilin (MTL), and α-amylase (α-AMS) all increased (P<0.05). Compared with the stomach-heat model group, the body mass of rats in the Coptidis Rhizoma group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, VIP and α-AMS were increased, and Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and GAS all decreased (P<0.05). The body mass of rats in the stomach-heat low-dose carvacrol group decreased at the seventh day. The contents (or ratio) of HGlyc, TC, and VIP were increased, Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and MTL all decreased, the expression of TRPV1 and UCP1 in gastric tissue decreased, while TRPM8 increased (P<0.05) in rats of the stomach-heat low-dose and high-dose carvacrol groups. Compared with the stomach-cold blank group, the body mass of rats in the stomach-cold model group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, α-AMS, and VIP all increased, while Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, GAS, and MTL all decreased (P<0.05). Compared with the stomach-cold model group, the body mass of rats in the Baked ginger group was increased at the seventh day, and the contents (or ratio) of HGlyc, VIP, and α-AMS all decreased, while Na+ -K+ -ATPase, COX, ND, cAMP/cGMP, T3, T4, GAS, and MTL all increased (P<0.05). The contents of HGlyc, cAMP, α-AMS, and VIP of rats in the stomach-cold low and high-dose carvacrol group all decreased (P<0.05). TG in the stomach-cold low-dose carvacrol group was increased. TC, Ca2+ -Mg2+ -ATPase, and cGMP all increased, while cAMP/cGMP decreased (P<0.05) in the high-dose carvacrol group. Conclusion In this study, the rat model of stomach-cold and stomach-heat were successfully established by using cold and heat factors. The result showed that carvacrol had a certain inhibitory effect on body mass, material energy metabolism, cyclic nucleotide level, thyroid hormone and gastrointestinal function in rats with stomach-heat, indicating that the drug was cold. Carvacrol′s cold medicinal property could be biologically explained by TRPV1 activation, UCP1 induction, and TRPM8 suppression.

OBJECTIVE To provide references for further improving the management level of Chinese herbal pieces covered by the healthcare security drug catalog （hereinafter referred to as “healthcare security covered Chinese herbal pieces”）. METHODS Policy documents related to healthcare security covered Chinese herbal pieces were retrieved from official websites of National Healthcare Security Administration and medical insurance bureaus of various provinces （autonomous regions， municipalities directly under the central government）. Using text analysis， the current management status of healthcare security covered Chinese herbal pieces in various provinces was analyzed from two dimensions： management regulations and catalog formats. RESULTS In terms of the management regulations for healthcare security covered Chinese herbal pieces， some provinces implemented both national and provincial standards for Chinese herbal pieces， while a small number of provinces adopted national standards alongside their own provincial standards. Regarding the payment categories of healthcare security covered Chinese herbal pieces， most were classified as category A， though some provinces managed them as category B， and others included both categories A and B or category C. In terms of applicants， there were three kinds： only medical institutions， only herbal piece enterprises， or both medical institutions and herbal piece enterprises being allowed to apply. During the application process， some provinces required preliminary evaluations by local healthcare security departments with recommended lists submitted， while some provinces omitted preliminary evaluations and relied solely on unified evaluation by provincial healthcare security departments. Regarding the methods for catalog formulation and adjustment， there was little variation among the provinces. In terms of the catalog format for healthcare security covered Chinese herbal pieces， some provinces had supplemented the catalog fields based on the national medical insurance catalog. In contrast， some provinces had relatively simple catalogs. Regarding the sorting of the herbal pieces catalog， some catalogs were arranged by the number of Chinese character strokes in the names of the herbal pieces， but most catalogs lacked clear sorting rules. CONCLUSIONS Significant resultshave been achieved in formulating management measures and the catalog of healthcare security covered Chinese herbal pieces. However， there is still a great necessity to develop targeted and adaptable management clauses based on local conditions and the characteristics of Chinese herbal pieces. The content and format of healthcare security drug catalog of Chinese herbal pieces should be improved； in addition， continuous tracking of the latest management policies is also essential to improve the accuracy and operability of formulated catalog.

Objective To explore the short-term efficacy of endoscopic submucosal dissection (ESD) in the treatment of early carcinoma in the remnant stomach. Methods A retrospective study was conducted on 45 patients with early residual gastric cancer underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2014 to April 2024, with a total of 45 lesions. The patients were divided into an anastomotic group (n=15) and a non-anastomotic group (n=30) based on the location of tumor occurrence, and their clinical data, endoscopic diagnosis and treatment, and histopathological conditions were compared between the two groups. Results All 45 patients had lesions with redness and erosion. There were 9 cases of poor lifting of submucosal injection in the anastomotic group and 2 cases in the non-anastomotic group, respectively, and the difference was statistically significant (P<0.05). ESD surgery was performed on 13 lesions in the anastomotic group and 28 lesions in the non-anastomotic group, with surgery times of 80.00 (50.00, 100.00) min and 55.00 (43.75, 80.00) min, respectively. The difference in surgery time between the two groups was statistically significant (P=0.03). Among the 45 patients, ESD surgery achieved curative resection in 35 cases, including 11 cases in the anastomotic group and 24 cases in the non-anastomotic group, with no statistically significant difference. Conclusions Careful preoperative evaluation of early carcinoma in the remnant stomach is essential to prevent oversight. Lesions at anastomotic sites and suture lines present higher technical challenges for complete resection. ESD is safe and effective, with auxiliary traction technique available when necessary.

Purpose/Significance To summarize the application progress of artificial intelligence (AI) in the field of digestive endoscopy, to analyze the key challenges and look forward to future trends, so as to provide guidance for clinical practice and research. Method/Process Domestic and international literature databases such as PubMed, Web of Science, and CNKI are retrieved. The application research of AI in the auxiliary diagnosis, process optimization and treatment precision of digestive endoscopy is sorted out. Result/Conclusion Although AI has significant clinical value in the field of digestive endoscopy, its application still faces major challenges, and its prospects and limitations need to be further discussed.

Objective: To analyze the influencing factors of aggressive behaviors in high school students, rank the importance of relevant variables with visual presentation, so as to provide new references for developing intervention strategies. Methods: In December 2024, a convenience sampling method was used to select 5 330 students from 5 high schools in Wuhan for an online questionnaire survey. The survey included the Buss-Perry Aggression Questionnaire (BPAQ), Interaction Anxiety Scale (IAS), Emotion Regulation Ability Scale, Inventory of Parent and Peer Attachment (IPPA), and a self designed general information questionnaire. Variables were screened using LASSO regression, followed by multivariate Logistic regression analysis. The Random Forest model was then employed to rank and visualize variable importance. Results: Univariate analysis and LASSO regression results indicated that gender, emotion regulation capability, paternal attachment quality, maternal attachment quality, maternal parenting style, paternal parenting style, parenting consistency, monthly household income per capita, school climate, relationship with classmates, interaction anxiety, and academic ranking were all significant variables (all P <0.01). Multivariate Logistic regression analysis identified the following as influencing factors of aggressive behaviors in high school students: emotional management ability ( OR=0.38, 95%CI =0.34-0.43), gender ( OR=0.83, 95%CI =0.75-0.93), mother attachment quality ( OR=0.89, 95%CI = 0.74 -1.07), father attachment quality ( OR=0.76, 95%CI = 0.66- 0.87), interaction anxiousness ( OR=1.58, 95%CI =1.40- 1.78 ), consistency of parenting styles of parents ( OR=1.40, 95%CI =1.21-1.62), school atmosphere ( OR=1.50, 95%CI =1.14-1.98), academic performance ranking (upper middle: OR=0.76, 95%CI =0.61-0.93; middle: OR=0.70, 95%CI =0.57-0.86) were the influencing factors of aggressive behavior in high school students (all P <0.05). The results of Random Forest showed that emotional management ability was the most important factor affecting aggressive behavior in high school students. Conclusion Emotion regulation capability is identified as the core predictor of adolescent aggressive behaviors, which can significantly reduce the incidence of aggressive behaviors through enhanced emotion management.

Objective To investigate the regulatory effects of plasma-derived exosomal microRNA-1306-5p(miR-1306-5p)on inflammation,apoptosis and oxidative stress in intestinal mucosal epithelial cells in sepsis,and to explore the potential mechanisms.Methods Sepsis plasma-derived exosomes and healthy plasma exo-somes were separated and divided into healthy plasma exosomes group and sepsis plasma-derived exosomes group.The exosomes were observed by electron microscopy,the physical parameters of the two groups of exo-somes were analyzed,and the expression of miR-1306-5p in the exosomes was detected.Intestinal mucosal epi-thelial cells were divided into control group,negative control group of miR-1306-5p mimic(mimic-NC group),miR-1306-5p mimic group(mimic group),mimic combined with overexpression of PLK1 empty vector group(mimic-PLK1-EV group),and mimic combined with overexpression of Polo-like kinase 1(PLK1)group(mimic+PLK1-OE group).Real-time fluorescent quantitative PCR was used to detect the mRNA expressions of miR-1306-5p and PLK1 in each group,and protein imprinting was used to detect the expressions of miR-1306-5p target genes PLK1,caspase 3,B lymphoblastoma-2(Bcl-2)and Bcl2-associated X protein(Bax).Dual luciferase reporter gene assay was used to detect the binding effect of miR-1306-5p and PLK1,and flow cytom-etry was used to detect apoptosis.The expressions of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6 and IL-8 in the supernatant of cultured cells were detected by enzyme-linked immunosorbent assay.The expressions of reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH)and superoxide dismutase(SOD)were detected by kit method.Results The plasma derived exosomes of sepsis and healthy plasma were ellipsoid in shape,and there was no significant difference in physical parameters(P＞0.05).Compared with the healthy plasma exosomes group,the expression of miR-1306-5p was up-regulated in the plasma derived exosomes of sepsis group(P＜0.05).PLK1 was identified as the target gene of miR-1306-5p by double luciferase reporter method.Compared with mimic-NC group,the expressions of miR-1306-5p,TNF-α,IL-6,IL-8,IL-1β,caspase3,Bax,ROS and MDA were up-regulated,the apoptosis rate was increased,and the expressions of PKL1,Bcl-2,GSH and SOD were down-regulated in mimic group(all P＜0.05).Compared with mimic+PLK1-EV group,the expressions of TNF-α,IL-6,IL-8,IL-1β,caspase3,Bax,ROS,and MDA were significantly down-regulated,the apoptosis rate was decreased,and the expressions of PKL1,Bcl-2,GSH and SOD were up-regulated in mimic+PLK1-OE group(all P＜0.05).Conclusion Plasma derived exosome miR-1306-5p in sepsis promotes inflammation,apoptosis and oxidative stress damage of intestinal mucosal epi-thelial cells by targeting PKL1 inhibition.

Objective:To provide references for the application of finite element model in the study of cervical vertebra by statistically analysing the frequency, numerical value, properties, and boundary setting of the finite element model and the corresponding material features as well as boundary settings in the literature.Methods:The literature on cervical vertebra-related finite element models was collected from CNKI, Wanfang, VIP, PubMed, Web of Science, and Embase databases from January 2013 to December 2023. The quality assessment was followed by manual screening. The data sources, application classification, material properties (Young’s modulus and Poisson’s ratio), and boundary conditions of cervical vertebra, cervical intervertebral, and cervical ligaments were statistically analyzed.Results:A total of 102 papers were included. The finite element models of the cervical vertebra were derived from medical image reconstruction modeling techniques, predominantly CT plain scan and magnetic resonance imaging. Among the 102 cervical vertebra models, the C3-C7 (lower cervical segment) model appeared with the highest frequency (19). The Young’s modulus of the cortical bone, cancellous bone, and posterior structure of cervical vertebrae were set at about 12 000 or 10 000, 440, and 3 600 MPa, respectively, and the Poisson’s ratios were mainly set at about 0.29 or 0.30, 0.29, and 0.29. The Young’s modulus of the cervical intervertebral disc endplate, nucleus pulposus, and annulus fibrosus were concentrated around 500 or 2 000, 1, and 100 MPa, respectively, and the Poisson’s ratios were set at about 0.40, 0.50, and 0.40, respectively. The Young’s modulus of the anterior longitudinal ligament, posterior longitudinal ligament, transverse ligament, ligamentum flavum, interspinous ligament, capsular ligament, and articular cartilage of the cervical spine were set around 30, 20, 20, 6-10, 4-8, 10 or 20, 10 MPa, and the Poisson’s ratios were set at aoubt 0.30, 0.30, 0.30, 0.30, 0.30, 0.40, and 0.30, respectively. The Young’s modulus of the upper cervical interdental ligament, lamina, cruciate ligament, nuchal ligament, and pterygoid ligament were set at about 10, 10, 10 or 20, 20, and 5 MPa, respectively, and the Poisson’s ratios were set at about 0.30. Head weight settings were more common at 50, 74, and 100 N.Conclusions:The finite element model of the cervical vertebra has great value in the study of cervical spondylosis, but further optimization is still needed in the assignment of material properties, mesh division, and model verification to improve the accuracy and clinical applicability of the model.