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.

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.

ObjectiveTo investigate the effect and possible mechanism of Shenfu Injection （参附注射液） on rat cardiomyocyte injury induced by isoproterenol from the perspective of regulating the high mobility group protein B1 （HMGB1）/ Toll-like receptor 4 （TLR4）/nuclear factor κB （NF-κB） pathway through the deacetylation modification of silent information regulator 1 （SIRT1）. MethodsThe optimal concentration and intervention duration of isoproterenol hydrochloride and the optimal intervention concentration of Shenfu Injection were screened out by CCK-8 method. Logarithmically growing H9c2 rat cardiomyocytes were taken at 5×10⁴ cells/well and divided into normal group， model group， Shenfu Injection group， and SIRT1 inhibitor group， with 3 replicates in each group.Except for the normal group， the cells in the other groups were induced by isoproterenol hydrochloride to establish a chronic heart failure cell model. After modeling， the Shenfu Injection group was given Shenfu Injection at the optimal intervention concentration， and the SIRT1 inhibitor group was given 1 μmol/L of SIRT1 inhibitor EX-527， for optimal intervention duration.CCK-8 assay was used to detect the cell activity and calculate the inhibitory rate. ELISA assay was used to detect the nicotinamide adenine dinucleotide oxidation state/ nicotinamide adenine dinucleotide reduction state （NAD+/NADH） in cardiomyocytes. Immunofluorescence was used to detect the immunofluorescence localization of HMGB1 and SIRT1 in cardiomyocytes. Western blotting was used to detect the protein expression of acetylated HMGB1 in cardiomyocytes， HMGB1 in the nucleus and cytoplasm， and SIRT1， TLR4， myeloid differentiation factor 88 （MYD88） and NF-κB p65 in cardiomyocytes. RT-qPCR was used to detect the mRNA expression of SIRT1， HMGB1， TLR4， MYD88 and NF-κB p65 in cardiomyocytes. ResultsThe optimal intervention concentration of isoproterenol hydrochloride was 300 μmol/L， and the intervention duration was 48 hours； 8% was the optimal intervention concentration of Shenfu Injection. Compared to those in the normal group， the cell activity， NAD+/NADH value， nuclear HMGB1 protein expression， cardiomyocyte SIRT1 protein and mRNA expression in the model group decreased， while the cell inhibition rate， cardiomyocyte acetylated HMGB1 and cytoplasmic HMGB1 protein expression， cardiomyocyte TLR4， MYD88， NF-κB p65 protein and mRNA expression all increased （P＜0.05）； fluorescence localization showed that the content of HMGB1 in cardiomyocytes in the model group increased and was localized in both the nucleus and cytoplasm.Compared to the model group and the SIRT1 inhibitor group， the Shenfu Injection group showed significant improvements in all the above indicators （P＜0.05）； fluorescence localization showed that the SIRT1 content increased in the Shenfu injection group， while the HMGB1 content decreased， and was mainly located in the nucleus. ConclusionShenfu Injection can improve myocardial cell damage by increasing SIRT1 expression to reduce the acetylation level of HMGB1， regulating the HMGB1/TLR4/NF-κB pathway and inhibiting the nuclear translocation of HMGB1.

ObjectiveTo study the modeling characteristics of primary dysmenorrhea models in animals and to provide references for the standardization of the primary dysmenorrhea animal models. MethodThe research articles on animal models of primary dysmenorrhea were retrieved to establish a database. The types of experimental animals， modeling methods， modeling cycle， drug dosage， drug injection methods， high-frequency detection indicators， positive drug types， etc.， were summarized and analyzed. ResultA total of 171 research articles that met the criteria were included. The animals for primary dysmenorrhea model induction were mainly SD rats， Wistar rats， and Kunming mice. Most of them were prepared by combining estradiol and oxytocin with the modeling cycle of 9 d≤t≤12 d. In terms of drug dosage for rats， estradiol benzoate was 0.5 mg·d^-1 on the 1st and 10th days and 0.2 mg·d^-1 on the 2^nd to 9^th days， while oxytocin at 2 U·d^-1 was the most common. In terms of drug dosage for mice， diethylstilbestrol at 2 mg·kg^-1·d^-1 and oxytocin at 20 U·kg^-1·d^-1 were the most common. In terms of injection methods， oxytocin was mainly administered by intraperitoneal injection and estradiol （estradiol benzoate and diethylstilbestrol） by subcutaneous injection. The detection indicators were mainly behavioral indicators of the writhing assay or the related biochemical indicators in the uterus or serum by enzyme-linked immunosorbent assay. The positive western medicines were dominated by ibuprofen and Chinese medicines by Tongjingbao. ConclusionAlthough primary dysmenorrhea animal models have become a hot topic， the existing reviews are not comprehensive， and the modeling standards and traditional Chinese medicine （TCM） syndrome evaluation are inadequate. By summarizing and analyzing the big data of the animal models， this study proposed some specific views to provide guidance and references for establishing the standard and ideal animal models of primary dysmenorrhea， so as to carry out research on this disease.

In order to explore a suitable pathway for the scientific and technological achievement transformation at prefecture-level public hospitals, in October 2020, a prefecture-level tertiary hospital carried out the " 3+ 3+ 3" mode for scientific and technological innovation and achievement transformation. A three-level management structure was established, consisting of the ministry of science and education, the working group on the transformation of scientific and technological achievements, and the leading group. Three management systems were improved and formulated, including the " measures for reimbursement and rewards of scientific and technological achievements ", the " measures for intellectual property management", and the " implementation plan for promoting the transfer and transformation of scientific and technological achievements". The management measures for the three stages of intellectual property protection, incubation of scientific and technological achievements, and transfer and transformation of achievements were improved. These measures provided organizational support, institutional support, and feasible paths for this practice. After nearly three years of practice, hospitals had reduced the number of low-quality patent applications, and the number and amount of scientific and technological achievements transformed increased from 1 achievement and 10 000 yuan in 2020 to 9 achievements and 320 000 yuan in 2022. This exploration could provide a reference for the transfer and transformation of professional scientific and technological achievements in prefecture-level public hospitals in China.

Objective To explore the clinical effect of corticosteroids combined with Chinese medicine sequential therapy of Guishao Dihuang pill and Yupingfeng granules on children nephrotic syndrome (NS) with yin deficiency of liver and kidney.Methods Fifty patients (the loss of children during the course of treatment were not included in the statistical analysis) with definitely diagnosed NS accompanied by yin deficiency of the liver and kidney admitted to the First Affiliated Hospital of Gannan Medical University from January 2012 to June 2016 were enrolled,and they were divided into control group and observation group by random number table,25 cases in each group.Conventional treatment of western medicine and long-term treatment of corticosteroids were given to the two groups.In addition,sequential therapy of Guishao Dihuang pills and Yupingfeng granules was given to the observation group on the bases of conventional treatment.The changes of platelet aggregation rate (PAT),cholesterol,cortisol,T cell subsets CD3,CD4,CD4/CD8 were observed before and after treatment for 8 weeks and 6 months,then the clinical efficacy and infection,etc.complications were compared between the two groups.Results There were no statistical significant differences in cholesterol,cortisol and curative effect compared between the two groups before treatment and after treatment for 8 weeks and 6 months (all P ＞ 0.05).Mter treatment for 8 weeks and 6 months,the PAT,cholesterol,cortisol of two groups were significantly decreased compared with those before treatment,while CD3,CD4 were obviously higher than those before treatment,and the degrees of changes of PAT,CD3,CD4 in the observation group were more remarkable than those of the control group [PAT:treatment after 8 weeks was (63.01 ± 6.99)％ vs.(66.62 ± 4.65)％,treatment after 6 months was (51.42 ± 7.74)％ vs.(57.01 ± 6.77)％,CD3:treatment after 8 weeks was 0.56 ± 0.06 vs.0.52± 0.06,treatment after 6 months was 0.61 ± 0.05 vs.0.58 ± 0.03,CD4:treatment after 8 weeks was 0.33 ± 0.06 vs.0.30 ± 0.05,treatment after 6 months was 0.39 ± 0.05 vs.0.33 ± 0.06,all P ＜ 0.05].CD4/CD8 ratio was significantly higher in observation group after treatment for 8 weeks and 6 months than those before therapy (1.68 ± 0.76,1.82 ± 0.95 vs.1.16 ± 0.67,both P ＜ 0.05);the number of patients with infection in observation group was obviously lower than that of the control group (86 cases vs.175 cases,P ＜ 0.05).Conclusions The therapeutic effect of corticosteroids combined with Chinese medicine sequential therapy of Guishao Dihuang pills and Yupingfeng granules for treatment of children NS with yin deficiency of the liver and kidney is better than that of using western medicine therapy alone,as the combined sequential therapy has good effects on reduction of infection,anti-thrombosis and elevation of immunity.

Objective The aim of this study was to investi-gate the changes of brain function in patients with drug-naive idiopath-ic epilepsy ( DNIE ) using resting-state functional MRI ( rs-fMRI ) amplitude of low-frequency fluctuation ( ALFF) , analyze the correlation of abnormal brain regions with the clinical variable ( disease course) , and gain a deeper insight into the pathophysiological mechanisms of idiopathic epilepsy. Methods This study included 25 cases of DNIE (15 males and 10 females) and 34 cases of drug idiopathic epilepsy (DIE, 22 males and 12 females).Another 25 healthy volunteers matched with the DNIE patients in sex, age, education and handedness were recruited as normal controls.The rs-fMRI data obtained from all the subjects were processed, subjected to ALFF analysis, and compared among the DNIE, DIE, and nor-mal control groups.The correlation was evaluated between the ALFF statistical brain mapping and the course of disease. Results Obvious differences were found in ALFF among the DNIE, DIE and control subjects.Compared with the normal controls, the DNIE pa-tients showed increased ALFF in the right inferior temporal gyrus, right lingual gyrus and right cuneus, but decreased ALFF in the right insula, left hippocampus, right midbrain, right middle frontal gyrus, left anterior cingulated gyrus, left middle cingulate gyrus and right inferior parietal lobule.In comparison with the DIE patients, those of the DNIE group exhibited increased ALFF in the left inferior occipital gyrus, right middle occipital gyrus and left middle occipital gyrus, but decreased ALFF in the right inferior frontal gyrus, left insula, right superior temporal gyrus and right middle frontal gyrus.In the DNIE patients, the disease course was found to be correlated positively with ALFF in the right cerebellum posterior lobe, left cerebellar tonsil, right lingual gyrus, left orbital gyrus, left middle oc-cipital gyrus, left corpus callosum, left caudate nuclear, left superior frontal gyrus, left medial frontal gyrus, right precuneus and left middle frontal gyrus, but negatively with ALFF in the right parahippocampal, right superior temporal gyrus, left superior temporal gyrus and right post-central gyrus. Conclusion The ALFF of resting-state cerebral function is abnormal in DNIE patients.The correlation between ALFF and the clinical variable ( disease course) provides a new insight into the pathophysiological mechanisms of epilepsy.