Objective The present study was designed to explore the inhibitory effects of the ADC drug Disitamab Vedotin(RC-48)on breast cancer cells with different HER-2 expression levels by utilizing a tumor organoid culture system.Methods Within the framework of the tumor organoid culture system,the breast cancer cell lines MCF-7(characterized by low HER-2 expression,Luminal A subtype)and BT-474(exhibiting high HER-2 expression,HER-2 positive subtype)were cultured independently and in various mixed ratios.The histological characteristics,as well as the expression levels and distribution of HER-2 in MCF-7 and BT-474 organoids,were analyzed via immunohistochemistry and immunofluorescence techniques.MCF-7 and BT-474 organoids were separately treated with Vedotin(RC-48),Disitamab,and Monomethyl auristatin E(MMAE).Additionally,a drug sensitivity test of Disitamab Vedotin(RC-48)was carried out on mixed MCF-7 and BT-474 cell ratios and on patient-derived breast cancer organoids,with the assessment conducted using the 3D-Glo method.Results In the tumor organoid culture system,immunohistochemistry and immunofluorescence analyses demonstrated that HER-2 was predominantly localized in the cell membrane.Specifically,BT-474 organoids exhibited robust HER-2 expression,while MCF-7 organoids displayed relatively low expression levels.When compared with MCF-7 organoids,RC48-ADC exerted a more pronounced inhibitory effect on BT-474 organoids,with IC50 values of 109.7 μg/mL and 2.792 μg/mL,respectively.The co-culture model further confirmed the bystander effect of RC-48,revealing that the ratio of HER-2-positive to HER-2-negative cells significantly influenced drug efficacy.Additionally,treatment with RC-48 led to a reduction in HER-2 expression in breast cancer organoids with diverse HER-2 expression levels.Conclusions The tumor organoid model can accurately mirror drug sensitivity and bystander effects.Within this model,RC-48 effectively inhibited HER-2 highly-expressing breast cancer cells,augmented the killing effect through the bystander mechanism,and downregulated HER-2 expression,thereby suggesting its potential for targeting HER2-associated breast cancer.

Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

Objective The present study was designed to explore the inhibitory effects of the ADC drug Disitamab Vedotin(RC-48)on breast cancer cells with different HER-2 expression levels by utilizing a tumor organoid culture system.Methods Within the framework of the tumor organoid culture system,the breast cancer cell lines MCF-7(characterized by low HER-2 expression,Luminal A subtype)and BT-474(exhibiting high HER-2 expression,HER-2 positive subtype)were cultured independently and in various mixed ratios.The histological characteristics,as well as the expression levels and distribution of HER-2 in MCF-7 and BT-474 organoids,were analyzed via immunohistochemistry and immunofluorescence techniques.MCF-7 and BT-474 organoids were separately treated with Vedotin(RC-48),Disitamab,and Monomethyl auristatin E(MMAE).Additionally,a drug sensitivity test of Disitamab Vedotin(RC-48)was carried out on mixed MCF-7 and BT-474 cell ratios and on patient-derived breast cancer organoids,with the assessment conducted using the 3D-Glo method.Results In the tumor organoid culture system,immunohistochemistry and immunofluorescence analyses demonstrated that HER-2 was predominantly localized in the cell membrane.Specifically,BT-474 organoids exhibited robust HER-2 expression,while MCF-7 organoids displayed relatively low expression levels.When compared with MCF-7 organoids,RC48-ADC exerted a more pronounced inhibitory effect on BT-474 organoids,with IC50 values of 109.7 μg/mL and 2.792 μg/mL,respectively.The co-culture model further confirmed the bystander effect of RC-48,revealing that the ratio of HER-2-positive to HER-2-negative cells significantly influenced drug efficacy.Additionally,treatment with RC-48 led to a reduction in HER-2 expression in breast cancer organoids with diverse HER-2 expression levels.Conclusions The tumor organoid model can accurately mirror drug sensitivity and bystander effects.Within this model,RC-48 effectively inhibited HER-2 highly-expressing breast cancer cells,augmented the killing effect through the bystander mechanism,and downregulated HER-2 expression,thereby suggesting its potential for targeting HER2-associated breast cancer.

Insomnia symptom is one of the most common types of sleep disturbances.Apart from being a risk factor for psychiatric disorders, insomnia symptom has been found to affect the course of psychiatric disorders and increase the relapse rate of psychiatric disorders.Therefore, insomnia treatment is beneficial to mitigate the psychiatric symptoms among chronic insomnia patients, which may help prevent mental health disorders.On the other hand, insomnia treatment for psychiatric patients is conductive to reduce the harm consequence in social function, which can help improving the prognosis of psychiatric disorders.Cognitive behavior therapy for insomnia (CBT-I) is a first-line treatment for chronic insomnia.This paper reviews the research progress on the efficiency of CBT-I on the psychiatric symptoms of chronic insomnia patients, as well as its application in comorbid psychiatric conditions.Findings from previous research suggested that CBT-I is effective to improve the psychiatric symptoms of insomnia patients through insomnia improvement, and it can also promote the remission of depression and anxiety symptoms, reduce the risk of substance disorder and suicide behaviors, and reduce the impairment of life quality and costs of treatment through insomnia improvement among psychiatric patients comorbid with insomnia, which indicated that CBT-I is a safe and effective treatment for insomnia symptoms in psychiatric patients.Moreover, this paper listed the contraindications and the decision-to-treat algorithm of CBT-I among psychiatric patients, as well as the CBT-I availability and adherence that limited the clinical application.More understanding of CBT-I is beneficial to provide support for a broad clinical application in mental health services.

The clinical data of a child with bronchial Dieulafoy disease treated in Wuhan Children′s Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, was analyzed retrospectively.The patient was a 9-month-old boy, who was admitted to hospital due to " intermittent hematemesis vomiting blood for 6 hours" . Chest CT suggested ground-glass opacity in both lungs.Electronic bronchoscopy showed that the neoplasm bulged into the lumen at the opening of the right inferior lobar bronchus, and fresh blood oozed from the basal segment of the neoplasm during the operation.Bronchial arteriography and transcatheter bronchial artery embolization were performed due to recurrent hemoptysis, during which the patient was diagnosed with bronchial arterial vascular malformation and finally diagnosed with bronchial Dieulafoy disease after consulting the relevant literatures.The disease is infrequent and characterized by rupture hemorrhage of bronchial submucosal malformed artery, the etiology and pathogenesis of which are still unclear, and it may be related to congenital vascular malformation in children.Bronchoscopy for hemoptysis of unknown cause in children should be performed with caution.If small and smooth protruded nodular lesions are seen under the bronchoscope, the bronchial Dieulafoy disease should be considered, and the lesions should not be touched too much or subjected to biopsy blindly.Fatal massive hemorrhage can be avoided by bronchial arteriography and bronchial artery embolization.

Objective:To analyze the surgical methods of operable breast cancer and analyze the follow-up results.Methods:A retrospective analysis of the clinical and pathological data of 636 operable breast cancer patients admitted to Zibo First Hospital from July 2008 to April 2018, including the clinical stage, pathological staging. Analyze of the proportion of four surgical methods, and through follow-up, analyze the treatment effect of different surgical methods.Results:All patients are female, aged 26-80 years, the clinical stage of 636 patients: Tis 18 cases, stage Ⅰ 143 cases, stage Ⅱ 354 cases, stage Ⅲ 114 cases, stage Ⅳ 7 cases. There are four types of surgery: ① breast conserving surgery + sentinel lymph node biopsy in 124 cases (19.50%); ② breast conserving surgery + axillary lymph node dissection in 39 cases (6.13%); ③ mastectomy + sentinel lymph node biopsy in 163 cases (25.63%); ④ modified radical surgery in 310 cases (48.74%). Sentinel lymph node biopsy in 427 cases (67.14%), success in 404 patients (94.61%); all patients with lymph node negative 384 cases (60.38%). Follow-up for 1 to 9 years, 11 cases of local recurrence after breast-conserving surgery, It accounted for 6.75% of breast-conserving surgery; 43 cases of local recurrence of chest wall after mastectomy, accounting for mastectomy 9.09%; 33 cases of recurrence and metastasis of axillary lymph nodes and supraclavicular lymph nodes, 4 cases of axillary recurrence after sentinel lymph node biopsy.Conclusions:The proportion of breast-conserving surgery in this group of patients was high and the local recurrence rate of breast-conserving surgery was less than that of mastectomy group; the proportion of simple modified radical surgery declined further; patients with axillary lymph node metastasis were less in the whole group. The choice of reasonable operation method is an important factor to improve the prognosis of breast cancer.

Objective:To explore the status quo and development trends of clinical practice ability research of Chinese nursing graduate students.Methods:Articles about the clinical practice ability of nursing graduate students were searched from China National Knowledge Infrastructure (CNKI) , Chinese BioMedical Database (CBM) , Wanfang and VIP databases. Bibliometric analysis was performed over the year, journal, author, region and institution, fund, methods and contents of these articles.Results:Totally 67 valid articles were included, including 46 studies. 41 journal articles were distributed in 18 journals, and Chinese Nursing Research had the largest number of papers. There were 10 core authors, accounting for a co-authorship rate of 64.18% and a cooperation degree of 2.72. The first authors came from 16 provinces, municipalities and autonomous regions, and most of the research institutions were medical schools. The fund support rate was 52.17%. The top 7 keywords were professional degree, clinical practice model, Delphi method, training model, education, evaluation indicator and analytical hierarchy process. Research topics could be divided into 5 categories.Conclusions:The study of the clinical practice ability of Chinese graduate nursing students generally shows an upward trend, and the distribution of research regions and institutions is imbalanced. The core author group has not yet been formed, and the degree of cooperation research is not high. The research content is rich, but the quality and depth of research still needs to be improved.

Objective To explore the value of MR T2 mapping imaging in evaluation of the effection of Zhitong-Jiangu recipes in treatment of cartilage injury in osteoarthritis.Methods The models of osteoarthritis in the knee of New Zealand white rabbits were made with intra-articular injection of papain.Totally 48 New Zealand white rabbits were randomly divided into normal control group,model control group,glucosamine hydrochloride treatment group and Zhitong-Jiangu recipes treatment group.MR T2 mapping was performed on the knee and the content of MMP-1 in articular cartilage was analyzed with immunohistochemistry 4 weeks after treatment.The differences of T2 value and MMP-1 content of articular cartilage among the four groups were compared.The correlation among the different intervention methods,MMP-1 content of articular cartilage and the T2 value of articular cartilage were analyzed.Results T2 value of articular cartilage in the model control group was significantly higher than that in the other three groups (all P＜0.01),and there was no significant difference of T2 value among the other three groups.The MMP-1 content of articular cartilage in glucosamine hydrochloride treatment group and Zhitong-Jiangu recipes treatment group was lower than that in model control group (both P＜0.05),and was higher than that in normal control group (both P＜0.05).There was no significant difference between the two groups.The relationship between MMP-1 content and T2 value of articular cartilage was nonlinear.With the increase of MMP-1 content,T2 value first increased slowly and then increased rapidly (P＜0.05).Conclusion MR T2 mapping imaging is helpful to evaluating the efficacy of Zhitong-Jiangu recipes in treatment of cartilage injury in osteoarthritis in rabbit models.The relationship between MMP-1 content and T2 value of articular cartilage may be nonlinear.

OBJECTIVE:To evaluate the efficacy and safety of the application of airway secretions expurgation cluster manage-ment in oxygen-driven aerosol inhalation. METHODS:280 patients with chronic obstructive pulmonary disease in the Respiratory Second Division of our hospital from Mar. 2012 to Dec. 2013 were randomly divided into group A,B,C and D,with 70 cases in each group.Group A and B were treated with compound isopropyl bromide 2 ml+nomal saline 5 ml,10 min/time,twice a day,and 6 L/min oxygen-driven aerosol inhalation for 7 days;group C and Dreceived Ambroxol hydrochloride injection 15 ml+normal saline 5 ml,10 min/time,twice a day,and 6 L/min oxygen-driven aerosol inhalatiom for 7 days. group A and C were treatment groups, group B and D were control groups. Two treatment groups inhaled compound medications while the application of airway secretions expurgation cluster management. Two control groups inhaled compound medications with single effective cough guidance. RE-SULTS:Compared with control groups,the patients in treatment groups eliminated more phlegm,had lower (PaCO2)and higher (PaO2),also had a shorter hospitalization period,with significant difference(P<0.05). CONCLUSIONS:Airway secretions expur-gation cluster management technology is a simple,safe and effective method,especially in patients with chronic obstructive pulmo-nary disease in oxygen-driven inhalation therapy.

Objective To investigate the application effects of ultrasonic scalpel combined with bipolar coag-ulation tweezers on open thyroid surgery.Methods 80 cases of thyroidectomy patients were randomly selected.These patients were divided into two groups by random cluster sampling method,whch were the study group (n =40)and control group (n =40).The control group of patients were given ultracision ligature methods combined with traditional therapy,while the study group of patients were given ultrasonic scalpel combined with bipolar coagulation tweezers treatment.And then the surgical related indicators and complications of the two groups of patients were statistically an-alyzed.Results Compared with the control group of (90.5 ±3.6)min,(6.5 ±0.6)d,(40.5 ±2.0)mL,(50.3 ± 1.4)mL and (6.6 ±0.5)cm,the operative time and length of stay of the study group of patients[(58.5 ±5.4)min and (3.4 ±0.2)d]were significantly shorter (t =6.965,3.143,all P <0.05);the blood loss and postoperative drainage of (5.0 ±1.4)mL and (1.0 ±0.6)mL were significantly less (t =4.541,3.747,all P <0.05);the cut diameter of (3.8 ±0.3)cm was significantly shorter (t =3.365,P <0.05);the complication rate of 2.5% (1 /40) was significantly lower than the control group 10.0%(4 /40)(χ2 =9.35,P <0.05).Conclusion The application effects of ultrasonic scalpel combined with bipolar coagulation tweezers on open thyroid surgery are obvious.