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.

The retrieval and evaluation of evidence is the basis for the development of clinical practice guidelines for Chinese patent medicine. As traditional Chinese medicine has a different development trajectory and utilization characteristics from modern medicine， there is certain differences in terms of evidence composition， retrieval and integration.This paper discussed multi-source body of evidence on Chinese patent medicine based on modern evidence-based medicine and ancient medical literature， and summarized the retrieval strategy as well as the possible problems and solving methods. For different types of evidence on Chinese patent medicine， the corresponding evaluation tools have been recommended， and the order to integrate the evidence based on the quality of the evidence from high to low is suggested. Finally， a multi-source based evidence retrieval-evaluation-integration scheme for Chinese patent medicine has been formed， which will provide a methodological reference for practitioners in the development of clinical practice guidelines for Chinese patent medicine.

OBJECTIVE To provide a detailed report and interpretation of the method and results for determining the weights of the technical indicators from the “multi-dimensional and multi-criteria comprehensive evaluation index system （first edition）” stated in Guideline for Multi-dimensional and Multi-criteria Comprehensive Evaluation of Chinese Patent Medicine. METHODS Normalization calculations were performed on the comprehensive weight values calculated by the analytic hierarchy process and expert weighting method to obtain the objective weights of the indicators. RESULTS The weight results of the six primary dimensions in the current comprehensive evaluation indicator system of Chinese patent medicine showed effectiveness dimension＞ safety dimension＞standard dimension＞application dimension＞scientific dimension＞economic dimension， with weight values of 0.281 0， 0.268 5， 0.195 8， 0.107 3， 0.096 1 and 0.051 3 respectively， consistent with the results of most researches currently. CONCLUSIONS The process of weight determination in this indicator system is scientifically reasonable， with clear methods and clear interpretations， and is worthy of further optimization and widespread application.

Liver failure often has rapid progression， multiple complications， and dangerous conditions. Acute pancreatitis is a common comorbidity during the progression of liver failure， and since acute pancreatitis has extremely similar clinical symptoms and signs to liver failure complicated by spontaneous peritonitis， it is often neglected in clinical practice. This article elaborates on the mechanisms of liver failure complicated by acute pancreatitis from the five aspects of inflammatory response， duodenal papillary dysfunction， gut microbiota dysbiosis， oxidative stress， and microcirculatory disturbance and proposes corresponding preventive measures based on these mechanisms.

BACKGROUND:Bone tissue defects are one of the most common diseases in orthopedics,and the current treatments for this disease are inadequate.The development of tissue engineering brings new hope for bone defect repair:by regulating the release of bioactive substances and the process of vascularization and neurogenesis at the defect site,it can effectively improve the microenvironment of bone tissue and promote osseointegration,which is the most promising research idea for large-size bone defect repair. OBJECTIVE:To explore the research progress of regulating bone microenvironment changes in bone defect repair in recent years from the effects of bioactive substances,vascularization and neurotization on three aspects of bone microenvironment changes,and to provide new ideas and strategies for the treatment of large-size bone defects. METHODS:The search terms"bone tissue engineering,angiogenesis,neurotization,cytokines,bone morphogenetic protein,vascular endothelial growth factor,neuropeptides,bone microenvironment"in Chinese and English were used to search for articles on the influence of changes in the bone microenvironment and their application in bone tissue engineering published from January 1,2001 to December 31,2022 on CNKI,WanFang,Web of Science,Science Direct,and PubMed.Finally,109 articles were included for review. RESULTS AND CONCLUSION:(1)The bone microenvironment is essential for the induction of bone tissue stem cell growth and differentiation,and mainly consists of the extracellular matrix of the bone tissue seeds and the biochemical factors required for intercellular interactions,the local blood circulation network and the surrounding nerve tissue.(2)Bone defect repair is a continuous process divided into multiple phases that overlap and are mediated by multiple cytokines,and the same cytokine can have mutually synergistic or antagonistic effects in one or more healing phases.(3)Neovascular regeneration is key to initiating bone repair,as neovascularisation not only provides essential nutrients,osteoblasts and growth factors for bone repair,but is also a gateway for repair cells to enter the injury zone.(4)In addition to regulating the type,dose and timeliness of vascular-inducing factor release to achieve blood transport reconstruction.The study of differential release delivery systems of multiple factors and the application of gene transfer technology will be the future research direction to solve large bone defects.(5)Neuropeptides can bind to relevant receptors and act on specific signaling pathways to guide vascular growth and influence bone healing,bone regeneration and the balance between osteogenesis and osteolysis through a variety of pathways.(6)In the establishment of neuralized tissue-engineered bone,the role of changes in the bone tissue microenvironment and neuromodulation is bidirectional.Cytokines in the bone matrix can participate in neuronal signaling pathways through the blood-nerve barrier.Neuropeptides secreted by glial cells act on the bone microenvironment,affecting bone healing,bone regeneration and the balance between osteogenesis and osteolysis.(7)There are still many questions regarding the regulation of the bone microenvironment by bioactive substances and the processes of vascularization and neurogenesis,such as the rapid diffusion and degradation of cytokines in the body and their loss of activity,the temporal and spatial distribution of angiogenesis-related growth factors,and the establishment of neurogenesis through the body's feedback regulatory mechanism,which need to be improved by subsequent studies.

BACKGROUND:Due to the young age of children,the occipital condyle and foramen magnum are not fully developed,and they are prone to various diseases and injuries in the occipitocervical junction,which requires surgical treatment in severe cases.However,anatomical parameters for the development of the occipital condyle and foramen magnum in children are lacking. OBJECTIVE:To measure the morphological structure of the occipital condyle and foramen magnum by three-dimensional reconstruction technique,and to provide important anatomical parameters for occipitocervical junction lesions,related surgical procedures and forensic identification. METHODS:Imaging data of 389 cases of primitive children and adolescents involved in skull base undergoing spiral CT scanning(247 males and 142 females)aged 1-18 years were collected and divided into 1-3-year-old group,4-6-year-old group,7-9-year-old group,10-12-year-old group,13-15-year-old group,and 16-18-year-old group according to their age.Mimics 16.0 software was used to reconstruct the skull base and measure the length and width of the foramen magnum.A formula was used to calculate the area and index of the foramen magnum.We measured the length,width and height of the occipital condyle,the angle between the long axis and the sagittal axis of the occipital condyle(O-S angle),the included angle between the midpoint of the front and back edges of the foramen magnum and the connection between the back edge of occipital condyle and the intersection point of the foramen magnum(F-O angle),and the included angle between the midpoint of the front and back edges of the foramen magnum and the midpoint of the back wall of the sublingual neural tube(F-H angle).Gender,side and age differences were analyzed among the indicators. RESULTS AND CONCLUSION:(1)In foramen magnum measurement,there was no significant difference between sexes in the index of the foramen magnum(P>0.05),but there were significant differences in length,width and area of the foramen magnum(P<0.05).(2)The O-S angle,F-O angle and F-H angle of the occipitral condyle were not significantly different between genders(P>0.05),but length,width and height of the occipital condyle were significantly different between genders(P<0.05).(3)There were no significant differences in the length of the occipital condyle among different groups(P>0.05),but there were significant differences in the width and height of the occipital condyle,O-S angle,F-O angle and F-H angle among different groups(P<0.05).(4)Length,width and area of the foramen magnum,length,width and height of the occipital condyle showed a wavy increasing trend with the increase of age,while O-S,F-O and F-H angles showed a wavy decreasing trend with the increase of age,while the index of the foramen magnum showed no significant change.(5)In conclusion,there are gender and lateral differences in the morphological indexes of the foramen magnum and the occipital condyle in children.These differences can provide an important reference for clinical surgical approach selection and forensic examination.