As the pace of society increases and lifestyles change， the incidence and mortality rates of breast cancer continue to rise. Targeted therapies are now promising in the treatment of breast cancer， and a variety of protein targets have been identified to play an important role in the development of breast cancer. Among them， signal transducer and activator of transcription （STAT） proteins constitute a crucial group that serves as important targets for transducing cellular transcriptional information， which can regulate downstream cell proliferation， apoptosis， cell migration， invasion， angiogenic factors， etc. and then affect the progression of breast cancer. The STAT family is closely associated with the inflammatory response to tumors and plays a landmark role in tumor development as well as in diagnosis and prognosis. The "inflammation-cancer" transformation refers to the process in which the inflammatory microenvironment caused by uncontrolled inflammation promotes normal cells to become cancerous. According to the theory of Chinese medicine， "heat toxicity" in "cancer toxicity" corresponds to inflammation， which is closely related to tumor development. As a major link associated with the inflammatory response， the STAT family has a promising role in the development and treatment of a variety of tumors， but its relevance to breast cancer remains inadequately explored. Chinese medicine has been shown to have good efficacy in the prevention and treatment of breast cancer， and some current studies have shown that the active ingredients and compounds of Chinese medicine have certain intervention effects on breast cancer-related STAT proteins， but there has not been a systematic review. In order to better sort out and summarize the studies on the effects of Chinese herbal medicines based on the STAT family interventions in breast cancer， this paper reviewed the studies on Chinese herbal medicines acting on the STAT family in recent years， aiming to provide new ideas for clinical applications in breast cancer and to provide thoughts for the development of STAT protein-based drugs.

Objective : To study the effect and mechanism of action of Silibinin on the differentiation of 3T3-F442A preadipocytes in murine． Methods : The effects of 0－400 μmol / L Silibinin on the proliferation of 3T3-F442A adi- pocytes at 24，48 and 72 h were detected by 3-(4，5-dimethylthiazol-2) -2，5-diphenyltetrazolium bromide ( MTT) assay，and the effects of Silibinin on the adipogenesis of 3T3-F442A adipocytes were visualized by Oil Red O stai- ning ; RT-qPCR , Western blot and ELISA assays were used to detect the effects of Silibinin on 3T3-F442A adipo- cyte differentiation-associated transcription factor CCAAT / enhancer binding protein ( C / EBP) α , C / EBP β , per- oxisome proliferator-activated receptor γ cular endothelial growth factor (VEGF) -α and VEGF receptor 2 (VEGFR-2) ，matrix metalloproteinase (MMP) -2 and MMP-9，mitogen-activated protein kinase (MEK) and phosphorylated MEK (p-MEK) ，and extracellular regu- lated protein kinase (ERK) and phosphorylated ERK (p-ERK) expression. (PPARγ) ，adipocyte protein 2 (aP2) ，adipose generation-associated vas Results : MTT assay showed that the cell proliferation rate of 3T3-F442A preadipocytes decreased after 100，200，and 400 μmol /L Silibinin treatment compared with the control group (P＜0. 001) ; Oil Red O staining assay showed that the accumulation of red lipid droplets of the cells in the 160 μmol /L Silibinin assay group significantly decreased ; RT-qPCR assay showed that mRNA expression of C/EBPα , C/EBPβ , PPARγ , aP2，VEGF-α , VEGFR-2，MMP-2，and MMP-9 was down-reg- ulated in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin compared with the control group (P＜0. 001) ; Western blot assay showed that protein expression of C /EBPα , C /EBPβ , PPARγ and aP2 was down-regulated in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin (P＜0. 001) ，and the phosphorylation level of p-MEK/ MEK and p-ERK/ ERK proteins was down-regulated compared with the control group (P ＜0. 001) ; ELISA assay showed that the protein concentrations of MMP-2 and MMP-9 in the cell supernatant were down-regulated (P < 0. 001) in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin． Conclusion Silibinin inhibited 3T3-F442A adipocyte differentiation and adipogenesis through inhibition of the MEK/ ERK pathway and matrix metalloproteinase activity.

Acquired cerebral amyloid angiopathy,as a cerebrovascular disease discovered in recent years,mainly spreads through iatrogenic factors.This paper focuses on acquired cerebral amyloid angiopathy and delves into the new applications and profound implications of the"toxins damaging brain collaterals"theory proposed by academician WANG Yongyan in stroke research.Starting from the perspective of"toxins damaging brain collaterals",it comprehensively analyzes the causes and pathological mechanisms of acquired cerebral amyloid angiopathy,emphasizing the importance of external toxins,latent toxins,and turbid toxins in understanding the pathogenesis of the disease.It reveals that"toxins damaging brain collaterals"is the core mechanism of acquired cerebral amyloid angiopathy.On this basis,it proposes a new connotation of"toxins damaging brain collaterals":first,"toxin"includes both internal and external toxins;second,the organic integration of"external wind theory"and"toxins damaging brain collaterals"guides the improvement of theoretical research,clinical treatment,and prevention strategies for stroke,and promotes a deeper understanding of the disease.This approach to understanding acquired cerebral amyloid angiopathy from the perspective of"toxins damaging brain collaterals"not only demonstrates the effective integration of traditional Chinese medicine theory and modern biomedical science,but also provides insights and references for the clinical diagnosis and treatment of the disease.

Objective:To compare the postoperative effects of double eyelid surgery with different exophthalmos to find its influence on the surgery and necessary changes in preoperative design and during operation.Methods:A total of 50 female patients with single eyelid seeking beauty from June 2021 to March 2022 were selected from the Department of Plastic Surgery, Affiliated Hospital of Qingdao University. The ocular protrusion was measured by HETEL ophthalmostatometer before surgery. Both eyes at 12-15 mm were taken as normal group ( n=26), both eyes at 16-18 mm as mild protrusion group ( n=14) and both eyes at 19-22 mm as severe protrusion group ( n=10). All the patients were treated with double-eyelid surgery by orbital septum and unified postoperative nursing. Results:After six months of follow-up, there was no difference in eyelid width with closed eyes (all P>0.05). The width of double eyelid with open eyes in normal group was smaller than that in mild protrusion group ( F=23.23, all P<0.05), and the width of double eyelid with open eyes in mild protrusion group was smaller than that in severe protrusion group ( F=47.70, all P<0.05). There was no difference in the improvement rate of facial aesthetics among the three groups ( P>0.05). The " feeling of meet" and scar formation in the normal group were less than those in the mild protrusion group ( F=16.92, F=33.45, all P<0.05), and the " feeling of meet" and scar formation in the mild protrusion group were less than those in the severe protrusion group ( F=27.93, F=28.53, all P<0.05). The improvement rate of normal group was higher than that of mild and severe protrusion group (χ 2=7.25, 7.89, all P<0.05). There was no difference in the improvement rate between the mild and severe protrusion groups ( P>0.05). Conclusions:In clinical practice, it is necessary to make corresponding changes in the preoperative design and operation of double eyelid surgery for patients with high eyeball protrusion.

Objective:To evaluate the effects of cellulift ? administered intradermally by mesotherapy on collagen synthesis in D-galactose induced aging model of rats. Methods:The study was conducted between April and October in 2014 in the Department of Anatomy, Qindao University. 30 male rats were randomly allocated to three groups: aging treatment group, aging control group and normal group; each group had ten rats. Aging treatment group and the control group were subcutaneously injected with D-galactose prepared in saline 125 mg·kg -1·d -1 for 42 day. Normal group was injected with saline for 42 d with same method and dose. From the 18th day after shaving their hair, the dermis of two sides hip skin marked zone of aging treatment group were injected cellulift at a dose of 1 ml per week for 4 weeks. Meanwhile, the aging control group was administrated the same volume of saline with same method. In vivo skin collagen alterations were investigated by reflectance confocal microscopy 3 days after every treatment. Skin specimens were obtained in 42 days. In order to measure the dermal collagen density and dermal thickness, HE and Masson trichrome staining were performed, respectively. Immunohistochemical staining for TGFβ1 and proliferating cell nuclear antigen (PCNA) was performed. Also, the level of TGFβ1, Smad3, types Ⅰ and Ⅲ pro-collagen mRNA expression was assessed by real-time quantitative polymerase chain reaction. Results:As revealed by RCM, collagen density of aging treatment group increased gradually after treatments, while in aging control group it decreased with time. Measurement of dermal thickness, hydroxyproline content and TGFβ-1 mRNA and protein expression in treatment group increased significantly as compared with that in aging control group, but were significantly lower than that in normal group (F values were 25.45, 98.90, 37.94 and 21.35, respectively; P<0.05). Measurement of dermal collagen density, the mRNA expression of type I pre-collagen and Smad3 elevated over that of aging control group with significant difference (F values were 44.46, 29.54 and 10.01, respectively; P<0.05), and there was no difference between normal and aging treatment group ( P>0.05). The difference of PCNA expression between aging control and treatment groups was not significant ( P>0.05), and both were lower than normal group ( P<0.05) . Conclusions:Cellulift ? shows anti-aging effects by activating collagen synthesis and eventually causing dermal thickening. This effect is probably mediated by TGF-β1/Smad3 signaling pathway.

Objective: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized high-risk T lymphoblastic leukemia subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL are poorly characterized. In this study, we explore the efficacy and outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ETP-ALL. Methods: The clinical data of 23 patients with ETP-ALL receiving allo-HSCT from 2010 to 2018 were retrospectively analyzed. Patients with ETP-ALL were diagnosed based on the characteristic immunophenotypes. Second-generation sequencing was done in all patients. As to the donors, 12 patients had haploidentical donors (Haplo-HSCT) , 7 HLA-matched sibling donors (Sib-HSCT) and 4 HLA-matched unrelated donors (URD-HSCT) . Before transplantation, 19 patients achieved complete remission (CR) and 4 patients without. Results: The main clinical features of ETP-ALL included high white blood cell counts in 5 patients, splenomegaly in 14, lymphadenopathy in 19, and thymus masses in 5. According to cytogenetic and molecular characteristics, 11 patients had gene mutations related to myeloid tumors, and 7 with high risk Karyotype. After first induction regimen, 14/23 patients achieved CR. 5 patients reached CR after more than 2 cycles of chemotherapy, while another 4 patients did not reach CR. After allo-HSCT, 22 patients were successfully implanted. The median time of granulocyte and platelet reconstitution was +12 and +19 days. One patient died of transplant-related infection at +14 days. The estimated 18-month overall survival (OS) and relapse-free survival (RFS) rates were (55.0±14.4) % and (48.1±14.7) % respectively. Transplant-related mortality was 4.3%. The median OS in patients achieving CR before transplantation was 20 months, however, that in patients without CR was only 13 months. OS and RFS between haplo-HSCT and sib-HSCT were comparable (P=0.460 and 0.420 respectively) . Conclusions Allo-HSCT is an effective therapy in some patients with ETP-ALL. Salvage HSCT cannot overcome the poor outcome. Haplo-HSCT and sib-HSCT in ETP-ALL patients have the similar clinical outcome.

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.

Objective To investigate the changes of the platelet function in APP/PS-1/tau(3xTg) mice, a murine model for Alzheimer''s disease,and explore its mechanisms.Methods We assessed the change of function of platelet in 3xTg-AD mice by flow cytometry.Adhesion assay and Western blotting were used to compare with the data of wild type mice.Results Platelets from aged 3xTg-AD mice were normal in number and glycoprotein expression (P>0.05), but adhere more avidly on matrices such as fibrinogen, compared with the platelets from age-matching wild type mice (P<0.05).The washed platelets of 3xTg-AD mice were adherent to fibrinogen, and also showed increased phosphorylation of selected signaling proteins, including PI3 kinase effector Akt and p38MAP kinase (P<0.05).In contrast, activation induced by several agonists in 3xTg-AD mice was similar to that of wild type platelets (P>0.05).Conclusions These results demonstrate that Alzheimer''s mutations result in a significant hyper-activated adhesion state of circulating platelets, evident with the progression of the disease.

Objective To study the polymorphism of glucocerebrosidase ( GBA) gene of N370S, V394L, L444P, R120W, R359X, R496H, R353W and RecNcil in the patients with Parkinson's disease ( PD) in Han, Uygur and Kazak in Xinjiang and to investigate the relationship between GBA gene polymorphism and Parkinson's disease.Methods GBA gene polymorphism was analyzed by improved multiplex ligation detection reaction technique in 294 sporadic PD patients (100 cases of Uygur, 134 cases of Han, 60 cases of Kazak) and 305 healthy controls (109 cases of Uygur, 122 cases of Han, 74 cases of Kazak) in Xinjiang area.Results There were two L444P loci polymorphisms that were heterozygous mutations in 294 cases of PD patients and the mutation frequency was 0.7%.Three hundred and five cases of control group did not show L 444P polymorphism.There were no significant differences in L 444P genotype and allele frequency distribution between PD group and control group ( AA:99.3%vs 100.0%, GA:0.7%vs 0, P>0.05;G:0.3%vs 0, A:99.7%vs 100.0%, P>0.05);L444P genotype and allele frequency distribution in Han and Uygur patients with PD showed no significant differences ( AA:99.3% vs 99.0%, GA:0.7%vs 1.0%, P>0.05;G:0.4%vs 0.5%, A:99.6%vs 99.5%,P>0.05);N370S, V394L, R120W, R359X, R496H, R353W, RecNcil loci polymorphisms were not found in the PD and control groups.Conclusion The GBA gene of N370S, V394L, R120W, R359X, R496H, R353W, RecNcil showed no polymorphism in Xinjiang Han and Uygur population and there was no association of L 444P polymorphism with Parkinson's disease in Han and Uygur populations in Xinjiang .

[Abstract ] Objective C reactive protein (CRP), an in-flammatory maker, increased significantly among diabetes mellitus and other metabolic diseases.Meanwhile, adiponectin plays a vital role in anti-atherogenic, anti-inflammatory and anti-diabetic poten-tials.Further, it decreased in diabetes mellitus.To investigate the effects of C-reactive protein in the expression of high-molecular-weight adiponectin ( HMWA) and adiponectin multimerization. Methods The fully differentiated 3T3-L1 cells were respectively treated with 50μg/mL CRP for 0 h、6 h、12 h and 24 h , and different doses of CRP with 0μg/mL、5μg/mL、25μg/mL、50μg/mL for 24 h.The expres-sion of HMWA was further detected by Western blot.Additionally,
the mRNA expressions of adiponectin assembly related genes ( Ero1-L、DsbA-L、ERp44 ) were detected by Real time PCR after 50μg/mL CRP treatment for 24 h. Results After 24 h treatment, 25μg/mL CRP and 50μg/mL CRP resulted in a substantial reduction ( [70 ±7]%vs [44 ±7]%, P<0.05) while 5μg/mL CRP revealed no change.With the dose of 50μg/mL CRP treated, the ex-pression of HWMA were both inhibited after the 12 h and 24 h CRP treatment ([71 ±6]%vs [48 ±11]%, P<0.05), but for the 6 h CRP treatment group, HWMA remained unchanged.Additionally, CRP inhibited Ero1-L(86 ±10)%and DsbA-L(72 ±6)%gene expression and upregulated the expression of ERp44(141 ±23)%. Conclusion CRP decreases HMWA expression in a dose and time-dependent manner and inhibits the multimerization of adiponectin, thus weaken the benefits of adiponectin in diabetes.