Objective:To explore the efficacy and safety of brain radiotherapy combined with pyrotinib and capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with brain metastases.Methods:Clinical data of 30 HER2-positive breast cancer patients with brain metastases treated at the Fourth Hospital of Hebei Medical University between January 2018 and January 2024 were retrospectively analyzed. According to the timing of drug administration, patients were divided into the concurrent radiotherapy and medication group ( n=20) and the sequential group receiving pyrotinib plus capecitabine within 1 month before or after radiotherapy ( n=10). Intracranial progression-free survival (iPFS), intracranial and extracranial objective response rates (ORR), overall survival (OS), and treatment safety were analyzed. Survival curves were plotted using the Kaplan-Meier method, and survival differences were compared by log-rank test. Results:The median follow-up time was 23.5 months (range, 5.2-37.8), with a median iPFS of 13.0 months (range, 1.7-27.3) and a median OS of 28.2 months (range, 7.3-46.2). The 1-year iPFS and OS in the concurrent radiotherapy with pyrotinib and capecitabine group were numerically higher than those in the sequential group treated within 1 month before or after radiotherapy, but the differences were not statistically significant ( P=0.825, 0.724, respectively). The intracranial and extracranial ORRs were 83.3% and 64.3%, respectively. The most common grade ≥3 treatment-related adverse reactions were diarrhea (27%) and neutropenia (23%). Conclusions:Radiotherapy combined with pyrotinib and capecitabine provides prolonged survival benefits with acceptable safety in patients with HER2-positive breast cancer brain metastases. Compared to concurrent administration, pyrotinib plus capecitabine given within 1 month before or after radiotherapy does not appear to affect prognosis.

Objective:To explore the efficacy and safety of brain radiotherapy combined with pyrotinib and capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with brain metastases.Methods:Clinical data of 30 HER2-positive breast cancer patients with brain metastases treated at the Fourth Hospital of Hebei Medical University between January 2018 and January 2024 were retrospectively analyzed. According to the timing of drug administration, patients were divided into the concurrent radiotherapy and medication group ( n=20) and the sequential group receiving pyrotinib plus capecitabine within 1 month before or after radiotherapy ( n=10). Intracranial progression-free survival (iPFS), intracranial and extracranial objective response rates (ORR), overall survival (OS), and treatment safety were analyzed. Survival curves were plotted using the Kaplan-Meier method, and survival differences were compared by log-rank test. Results:The median follow-up time was 23.5 months (range, 5.2-37.8), with a median iPFS of 13.0 months (range, 1.7-27.3) and a median OS of 28.2 months (range, 7.3-46.2). The 1-year iPFS and OS in the concurrent radiotherapy with pyrotinib and capecitabine group were numerically higher than those in the sequential group treated within 1 month before or after radiotherapy, but the differences were not statistically significant ( P=0.825, 0.724, respectively). The intracranial and extracranial ORRs were 83.3% and 64.3%, respectively. The most common grade ≥3 treatment-related adverse reactions were diarrhea (27%) and neutropenia (23%). Conclusions:Radiotherapy combined with pyrotinib and capecitabine provides prolonged survival benefits with acceptable safety in patients with HER2-positive breast cancer brain metastases. Compared to concurrent administration, pyrotinib plus capecitabine given within 1 month before or after radiotherapy does not appear to affect prognosis.

Objective To explore the medication rules and mechanism of action of traditional Chinese medicine compound patent formulas for vitiligo,and provide ideas for the development and the patent declaration work of new Chinese medicines for vitiligo.Methods China Patent Publication Bulletin website,National Knowledge Infrastructure Database,Patent Information Service Platform of China Intellectual Property Right Net(CNIPR),and Baiten Patent Platform were used to search for the patents of traditional Chinese medicine compound formulas for vitiligo from the establishment of the databases to 30th September,2023.Excel software and Traditional Chinese Medicine Inheritance Computing Platform(TCMICS V3.0)were used to establish a database of compound formulas,and carry out the statistics of frequency,association rules and clustering analysis of the formulas for internal and external prescriptions.The target and mechanism of action of the internal prescriptions of core high-frequency Traditional Chinese Medicine group for the treatment of vitiligo were further explored by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Symptom Mapping(Symmap),The Human Gene Database(Genecards),UniversalProtein(UniProt),STRING,Pharmaceutical DataBase(PDB)and other databases as well as software such as R Studio 4.2.2 and Cytoscape 3.9.1,and AutoDock Vina was used for molecular docking validation.Results The internal formulas included 335 patents and the external formulas included 189 patents.The rules of internal and external use are similar.The high-frequency traditional Chinese medicines are Tribuli Fructus,Psoraleae Fructus,Angelicae sinensis,Radix Polygoni Multiflori,Carthami Flos,Angelica dahurica,etc.;the key efficacies of the medicines are based on tonifying the deficiency,activating blood circulation and removing blood stasis;and the properties of the Chinese medicines are the nature of warmth,coldness and flatness,sweetness,bitterness,pungency and attribution to the liver,the spleen,the heart and the kidneys.Commonly used oral medicine pairs are Chuanxiong rhizome-Angelica,Astragalus-Angelica,etc.,high-frequency pairs of external medicines are Fructus mume-Psoraleae fructus,cuscuta-Psoraleae fructus,etc.;internal and external clustering of the core drugs are Psoraleae fructus,Tribuli Fructus,Angelica,Polygonum multiflorum,Angelica dahurica,Safflower,and other high-frequency medicines.The key targets of internal patents for the treatment of vitiligo are genes such as albumin,protein kinase B1,cystatinase 3,etc.The main active ingredients of the internal grouping for the treatment of vitiligo may be quercetin,kaempferol,luteolin,etc.,and the therapeutic mechanism may be related to the end products of glycosylation/receptor for glycosylation end products,tumour necrosis factor signalling pathway,phosphatidylinositol 3-kinase/protein kinase B and other signalling pathways,and involved in the process of blood lipids and atherosclerosis,human cytomegalovirus infection.The molecular docking results confirmed the docking activity of the herbal components with key receptor proteins.Conclusion This study reveals the similarity between the internal and external patented formulas of vitiligo in terms of medication,flavour,and meridian,suggesting that the pathways and indexes such as albumin,interleukin,and tumour necrosis factor of vitiligo patients can be improved by tonifying the liver and kidney,activating blood circulation and removing blood stasis,which also provides a reference for the research and development of new medicines for vitiligo,patent protection,and the use of clinical prescriptions.

[Objective]To explore the etiology,pathogenesis and treatment methods of ulcerative colitis(UC),in order to provide theoretical basis for expanding the differentiation and treatment of UC.[Methods]Based on a review of the theoretical connotation of"spleen acting as the guard for five Zang-organs and six Fu-organs",and the understanding of the pathogenesis of UC in modern medicine,the correlation between spleen dysfunction and UC was explored from the perspective of"spleen losing of guard".Combined with the changes in the pathogenesis of UC during its progression,the principles of differentiation and treatment in each substage were specifically discussed.[Results]The key pathogenesis of UC is"spleen losing of guard",which runs through all stages of the disease.Therefore,it is proposed to use"assisting spleen to restore the function of guard"as the treatment principle.In the active phase,the method of treatment is to eliminate accumulation and transform stagnation,regulate the spleen and defensive Qi.In the remission phase,the method of treatment is to regulate Qi and relieve depression,and strengthen the spleen and promote defensive Qi.In the recovery phase,the method of treatment is to nourish the muscles,and strengthen the spleen and defensive Qi.[Conclusion]The application of the theory of"spleen acting as the guard for five Zang-organs and six Fu-organs"helps to understand the close relationship between the pathogenesis of UC and the spleen,refine the treatment rules and specific prescriptions of UC related to the spleen in each stage.

Objective:To analyze the prognosis and influencing factors of different radiotherapy modes in patients with brain metastases from non-small cell lung cancer (NSCLC), and to explore the best benefit population with radiotherapy boost under different prognostic scores.Methods:634 patients with brain metastasis from NSCLC admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different radiotherapy modes, they were divided into three groups: no radiotherapy group ( n=330), whole-brain radiotherapy group (WBRT)( n=127) and whole-brain radiotherapy combined with boost group (WBRT+ boost)( n=177). The intracranial progression-free survival (iPFS) and overall survival (OS) were calculated by Kaplan-Meier method. The multivariate prognostic factors were analyzed by the Cox models. Results:The median iPFS and OS of all patients were 6.9 months and 9.0 months, respectively. In the no radiotherapy, WBRT and WBRT+ boost groups, the 1-year iPFS was 15.1%, 16.3% and 40.2%( P=0.002), and the 1-year OS was 33.7%, 38.2% and 48.1%( P<0.001), respectively. Multivariate survival analysis demonstrated that different radiotherapy modes were the independent factors affecting iPFS and OS. Subgroup analysis revealed that for patients with 1-3 brain metastases, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone ( P=0.026, P=0.044) when GPA score was 2.5-4.0; the 1-year OS and iPFSin the WBRT+ boost group were better than those of WBRT alone ( P=0.036, P=0.049) when there was no targeted therapy; for patients with ≥4 brain metastases, the 1-year iPFS in the WBRT+ boost group was better than that of WBRT alone ( P=0.019, P=0.012) when GPA score was 2.5-4.0 and there was no targeted therapy. When the GPA score was 0-2 or there was targeted therapy, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone, but the difference was not statistically significant (all P>0.05). Conclusions:Radiotherapy can significantly improve the iPFS and OS of NSCLC patients with brain metastases. When the number of brain metastases is 1-3, GPA score is 2.5-4.0 or no targeted therapy, boost may improve the iPFS and OS; when the number of brain metastases is more than 4, GPA score is 2.5-4.0 or no targeted therapy, boost may only bring iPFS benefit; when GPA score is 0-2 or targeted therapy, boost may not benefit significantly.

Objective:To analyze the prognosis and influencing factors of patients with brain metastases from non-small cell lung cancer (NSCLC) treated with different doses of whole brain radiotherapy (WBRT).Methods:A total of 244 NSCLC patients with brain metastases who underwent WBRT in the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different doses of WBRT (EQD 2Gy), they were divided into the 30-39 Gy group ( n= 104) and ≥40 Gy group ( n= 140). The intracranial progression-free survival (iPFS) and overall survival (OS) were compared betweentwo groups. According to the number of brain metastases, GPA score, KPS score, chemotherapy and targeted therapy, the prognosis of different doses of WBRT was further analyzed. Results:The median iPFS and OS of all patients were 6.9 months and 11.8 months, respectively. Univariate survival analysis: the 1-year iPFS and 1-year OS between two groups were 22.5% and 25.4%( P=0.430) and 41.1% and 46.4%( P=0.068), respectively. Multivariate survival analysis: different doses of WBRT were not associated with the improvement of iPFS and OS; independent factors influencing iPFS included local boost, gender, number of brain metastases, chemotherapy and targeted therapy; independent factors influencing OS included gender, number of brain metastases, chemotherapy and targeted therapy. Subgroup analysis: in patients with KPS≥90, the 1-year iPFS and OS of patients with WBRT ≥ 40 Gy were seemingly better than those of their counterparts with 30-39 Gy, but the difference was statistically significant only in OS ( P=0.047), the difference was not statistically significant in iPFS ( P=0.068); in patients with chemotherapy, the 1-year iPFS and OS of patients with WBRT≥40 Gy were better than those of their counterparts with 30-39 Gy ( P=0.017, P=0.012); in patients with targeted therapy, the 1-year iPFS and OS in the WBRT≥40 Gy group were better than those in the 30-39 Gy group ( P=0.012, P=0.045). Conclusions:The 30-39 Gy may be the appropriate dose of WBRT for NSCLC patients with brain metastases. WBRT≥40 Gy does not bring more benefits. WBRT≥40 Gy may benefit NSCLC patients with brain metastases with high KPS score or active systemic therapy.

PURPOSE: Although the effect of lysosome-associated protein transmembrane 4 beta (LAPTM4B) on the proliferation, migration, and invasion of breast cancer (BC) cells has already been studied, its specific role in BC progression is still elusive. Here, we evaluated the effect of different levels of LAPTM4B expression on the proliferation, invasion, adhesion, and tumor formation abilities of BC cells in vitro, as well as on breast tumor progression in vivo. METHODS: We investigated the influence of LAPTM4B expression on MCF-7 cell proliferation, invasion, adhesion, and tube formation abilities in vitro through its overexpression or knockdown and on breast tumor progression in vivo. RESULTS: Cell growth curves and colony formation assays showed that LAPTM4B promoted the proliferation of breast tumor cells. Cell cycle analysis results revealed that LAPTM4B promoted the entry of cells from the G1 into the S phase. Transwell invasion and cell extracellular matrix adhesion assays showed that LAPTM4B overexpression increased the invasion and adhesion capabilities of MCF-7 cells. More branches were observed in MCF-7 cells overexpressing LAPTM4B under an electron microscope. In comparison with LAPTM4B overexpression, LAPTM4B knockdown decreased the expression of vascular endothelial growth factor-A and significantly inhibited the vasculogenic tube formation ability of tumors. These results were also verified with western blot analysis. CONCLUSION: LAPTM4B promoted the proliferation of MCF-7 cells through the downregulation of p21 (WAF1/CIP1) and caspase-3, and induced cell invasion, adhesion, and angiogenesis through the upregulation of hypoxia-inducible factor 1 alpha, matrix metalloproteinase 2 (MMP2), and MMP9 expression. This specific role deems LAPTM4B as a potential therapeutic target for BC treatment.
Blotting, Western ; Breast Neoplasms ; Breast ; Caspase 3 ; Cell Cycle ; Disease Progression ; Down-Regulation ; Extracellular Matrix ; Hypoxia-Inducible Factor 1 ; In Vitro Techniques ; Matrix Metalloproteinase 2 ; MCF-7 Cells ; S Phase ; Up-Regulation ; Vascular Endothelial Growth Factor A

Objective To investigate changes in serum brain-derived neurotrophic factor (BDNF)levels in patients with Alzheimer's disease(AD).Methods Venous blood samples were collected from 40 AD patients,40 amnestic mild cognitive impairment(aMCI)patients and 40 normal controls.Serum BDNF levels were analyzed by enzyme-linked immunosorbent assay (ELISA).The relationships of serum BDNF levels with age,gender,educational level,mini-mental state examination (MMSE) score and Beck depression scale-Ⅱ (BD Ⅰ-Ⅱ)score in AD patients were analyzed.Results Serum BDNF levels were lower in AD patients than in patients with aMCI and normal controls(4.6± 1.9 μg/L vs.9.3 ± 4.7 μg/L,10.2 ± 1.8 μg/L,F =71.083,P ＜0.05).There were 12 mild AD patients,18 moderate AD patients and 10 severe AD patients,and serum BDNF levels decreased with increased disease severity(5.5±5.4 μg/L,4.9±4.2 μg/L vs.3.8±3.0 μg/L,F=78.214,P＜0.05).Serum BDNF levels decreased in 29 AD patients aged over 65 years compared with 11 AD patients aged 65 years and younger(3.6±2.2 μg/L vs.4.64±1.06 μg/L,P＜0.05).Serum BDNF levels had no correlation with gender,educational level or BD Ⅰ-Ⅱ score(P＞0.05).Pearson correlation analysis showed that serum BDNF levels had a positive correlation with MMSE score(r =0.428,P＜0.05).Conclusions Advanced age is associated with decreased serum levels of BDNF in AD patients.Decreased serum levels of BDNF in AD patients are related to the severity of cognitive impairment.There is no correlation between serum BDNF levels and depressive symptoms in AD patients.

Objective To investigate pathogenic bacteria distribution and its effect on the expression of apoptosis protein in patients with acute cerebral infarction (ACI) complicated with pulmonary infection. Methods A retrospective analysis was conducted. From January 2014 to October 2017, the clinical data of 178 patients suffered from ACI hospitalized in Department of Neuromedical Center of Affiliated Hospital of the Chinese People's Armed Police Force Logistics Academy were collected, including 86 cases with ACI complicated with pulmonary infection selected as the observation group, and 92 cases with ACI without pulmonary infection assigned in the control group. The identification and classification of pathogenic bacteria were carried out by using the French BioMieux microorganism fully automatic identification instrument; the contents of serum interleukins (IL-8, IL-17), soluble intercellular adhesion molecule-1 (sICAM-1) and B type lymphocyte tumor-2 related X protein (Bax), B lymphocyte tumor-2 protein (Bcl-2) in two groups were detected by enzyme-linked immunosorbent assay (ELISA). Pearson correlation analysis was used to observe the correlations between sICAM-1 and Bax, Bcl-2 protein expression. Results From the bacterial cultures of 86 patients with ACI complicated with pulmonary infection, 86 strains of pathogenic bacteria were isolated, including 41 strains of gram positive (G+) bacteria (47.67%), mainly Staphylococcus aureus (25.58%); 37 strains of gram negative (G-) bacteria (43.02%), mainly Acinetobacter baumannii (11.63%); 8 strains of fungi (9.30%). The serum levels of IL-8 (μg/L: 0.72±0.15 vs. 0.68±0.09), IL-17 (μg/L: 9.31±3.58 vs. 8.12±2.76), sICAM-1 (ng/L: 421.36±39.74 vs. 385.13±28.59) and Bax (μg/L: 4.52±0.47 vs. 3.86±0.34) in the observation group were significantly higher than those in the control group, while the level of Bcl-2 in the observation group was significantly lower than that in the control group (μg/L: 0.84±0.26 vs. 1.13±0.31), all the differences were statistically significant (all P ＜ 0.05). In the observation group, sICAM-1 was significantly positively correlated with Bax protein (r = 0.401, P ＜ 0.001), while sICAM-1 was significantly negatively correlated with Bcl-2 (r = -0.447, P ＜ 0.001). Conclusion The pathogenic bacteria of ACI patients complicated with pulmonary infection is mainly G+bacteria, the infection can induce elevation of serum pro-inflammatory factors and sICAM-1 levels in the patients, and the mechanisms may be related to the up-regulation of Bax protein expression and down-regulation of Bcl-2 protein expression.