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.

Objective To explore the clinical value of the platelet count(PLT)to high-density lipoprotein cholesterol(HDL-C)ratio(PHR)in predicting poor prognosis after intravenous thrombolysis in patients with acute cerebral infarction(ACI).Methods A total of 304 patients with ACI who received intravenous thrombolytic therapy in this hospital from January 2021 to December 2023 were selected as the research sub-jects.According to the modified Rankin scale score at 6-month follow-up,the 304 patients with ACI were di-vided into the good prognosis group(n=216)and the poor prognosis group(n=88).Clinical data of all pa-tients were collected.The levels of PLT,HDL-C and PHR were compared between the two groups.The pre-dictive value of PLT,HDL-C and PHR for the prognosis of ACI patients was analyzed by using the receiver operating characteristic(ROC)curve.Binary Logistic stepwise regression analysis was used to explore the in-fluencing factors of prognosis in ACI patients.Results Compared with the good prognosis group,the HDL-C level in the poor prognosis group decreased,while the PLT level and PHR increased(P＜0.05).The results of the ROC curve showed that the area under the curve(AUC)and 95％CI of PLT,HDL-C,and PHR for pre-dicting poor prognosis after intravenous thrombolysis in ACI patients was 0.829(0.784-0.874),0.743(0.693-0.788),and 0.918(0.873-0.968),respectively.The AUC of PHR in predicting poor prognosis af-ter intravenous thrombolysis in ACI patients was higher than that of PLT and HDL-C alone(Z=13.239,10.776,P＜0.001).The proportions of National Institutes of Health Stroke Scale(NIHSS)score ≥8 points at admission,transformation of previous symptomatic hemorrhage,combined hypertension,and combined dia-betes in the poor prognosis group were all higher than those in the good prognosis group(P＜0.05).The re-sults of binary Logistic stepwise regression showed that the NIHSS score at admission(OR=2.565,95％CI:1.292-5.094),the transformation of previous symptomatic hemorrhage(OR=2.073,95％CI:1.179-8.645),and PHR(OR=3.732,95％CI:2.037-6.839)were risk factors for poor prognosis in ACI patients(P＜0.05).Conclusion PHR is expected to become an important reference index for predicting the prognosis of ACI patients after intravenous thrombolysis therapy.PHR,NIHSS score at admission,and the transforma-tion of previous symptomatic hemorrhage are all influencing factors for the prognosis of ACI patients after in-travenous thrombolysis therapy.

Objective:To observe the clinical efficacy and safety of Jianpi Bushen Jiedu Prescription combined with 5-fluorouracil (5-FU)-based chemotherapy and targeted therapy for the treatment of advanced colorectal cancer patients with liver and kidney yin deficiency combined with spleen deficiency pattern.Methods:A randomized controlled trial was conducted. A total of 72 hospitalized patients with advanced colorectal cancer treated at the Department of Oncology, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from October 2022 to January 2024 were enrolled as study subjects. Using a random number table method, they were allocated into two groups, with 36 patients in each group. The control group received the mFOLFOX6/FOLFIRI combined with bevacizumab regimen, while the treatment group was administered additional oral Jianpi Bushen Jiedu Prescription on the basis of the control group. Two weeks was a cycle in both groups, with a total of 6 cycles of treatment. Serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) were detected using electrochemiluminescence; the Karnofsky Performance Status (KPS) scale was utilized to evaluate patients' functional status; vital signs were continuously monitored, and adverse reactions were recorded. The short-term efficacy and TCM syndrome efficacy of patients were evaluated.Results:The treatment group demonstrated higher objective response rate (ORR) [31.25% (10/32) vs. 21.88% (7/32), χ2=0.72] and disease control rate (DCR) [84.38% (27/32) vs. 71.88% (23/32), χ2=1.46] compared to the control group, without statistical significance ( P>0.05). Post-treatment levels of CEA [4.09 (3.31,8.57) μg/L vs. 10.07 (4.55,22.35) μg/L, Z=-2.10] and CA72-4 [4.54 (2.04,10.99) mU/L vs. 9.48 (4.34,18.95) mU/L, Z=-2.52] in the treatment group were significantly lower than those in the control group ( P<0.05). The total effective rate of TCM syndrome was significantly higher in the treatment group [78.13% (25/32)] compared with the control group [50.00% (16/32)], with statistical significance ( χ2=5.50, P=0.019). Post-treatment KPS scores in the treatment group [80.0 (80.0, 80.0) vs. 70.0 (62.5, 80.0), Z=-2.76] were significantly higher compared with the control group ( P<0.01). During the treatment period, the treatment group showed statistical significance compared with the control group in the incidence of hemoglobin decrease ( χ2=4.66), leukopenia decrease ( χ2=4.27), and peripheral neuropathy ( χ2=3.93), with statistical significance ( P<0.05). Conclusion:The addition of Jianpi Bushen Jiedu Prescription to 5-FU-based chemotherapy combined with targeted therapy demonstrates significant clinical benefits in advanced colorectal cancer patients, including reducing tumor marker levels, alleviating clinical symptoms, improving quality of life, and mitigating treatment-related toxicities, with a good safety.

Objective:The study aimed to validate the Neuroception of Psychological Safety Scale (NPSS) in terms of reliability and validity among individuals with mental disorders in China.Methods:The Study followed Brislin′s translation principles to adapt the scale into Chinese. From February to June 2023, a total of 638 hospitalized patients with mental disorders (477 with schizophrenia and 161 with mood disorders) were selected through gender-stratified simple random sampling from the Shanghai Pudong New Area Mental Health Center and the Shanghai Baoshan Mental Health Center. The Chinese version of the NPSS and the Security Questionnaire (SQ) were administered. The reliability of the scale was measured using split-half reliability and test-retest reliability. Validity was assessed through content validity, structural validity, convergent validity, and discriminative validity analyses. In addition, SQ was used as a criterion tool to test the validity of the criterion through Pearson correlation analysis.Results:The Chinese version of the NPSS contained 29 items, with total scores ranging from 29 to 145. Higher total scores indicated greater psychological safety. Item analysis showed a decider value of 10.58 to 20.80 (>3), and the correlation between items and total scores ranged from 0.579 to 0.749 (all P<0.05). The item-level content validity index (I-CVI) for the items ranged from 0.86 to 1.00, while the average scale-level content validity index (S-CVI/Ave) was 0.99. Exploratory factor analysis extracted three common factors: social participation, empathy, and bodily sensations, which is consistent with the structure of the original scale, explaining a cumulative variance contribution rate of 62.551%. Confirmatory analysis revealed a satisfactory model fit, with average variance extracted (AVE) values for the three dimensions ranging from 0.523 to 0.645, and composite reliability(CR) ranging from 0.905 to 0.938. The standard loading coefficients for the items ranged from 0.608 to 0.859, and inter-factor correlation coefficients were all smaller than the square roots of their respective AVE values. Pearson correlation analysis indicated significant positive relationships between the Chinese NPSS and SQ ( r=0.822-0.846, P<0.01). Reliability analysis showed Cronbach′s alpha coefficients of 0.903-0.959 for the total scale and subscales. After a 3-week interval, test-retest reliability (70 patients) ranged from 0.874 to 0.983, and split-half reliability was 0.869-0.969. All model fit indices met established criteria. Conclusions:The Chinese version of the NPSS demonstrates good reliability and validity, making it suitable for both research and clinical applications in assessing psychological security among individuals with schizophrenia and mood disorders.

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.

Objective:The study aimed to validate the Neuroception of Psychological Safety Scale (NPSS) in terms of reliability and validity among individuals with mental disorders in China.Methods:The Study followed Brislin′s translation principles to adapt the scale into Chinese. From February to June 2023, a total of 638 hospitalized patients with mental disorders (477 with schizophrenia and 161 with mood disorders) were selected through gender-stratified simple random sampling from the Shanghai Pudong New Area Mental Health Center and the Shanghai Baoshan Mental Health Center. The Chinese version of the NPSS and the Security Questionnaire (SQ) were administered. The reliability of the scale was measured using split-half reliability and test-retest reliability. Validity was assessed through content validity, structural validity, convergent validity, and discriminative validity analyses. In addition, SQ was used as a criterion tool to test the validity of the criterion through Pearson correlation analysis.Results:The Chinese version of the NPSS contained 29 items, with total scores ranging from 29 to 145. Higher total scores indicated greater psychological safety. Item analysis showed a decider value of 10.58 to 20.80 (>3), and the correlation between items and total scores ranged from 0.579 to 0.749 (all P<0.05). The item-level content validity index (I-CVI) for the items ranged from 0.86 to 1.00, while the average scale-level content validity index (S-CVI/Ave) was 0.99. Exploratory factor analysis extracted three common factors: social participation, empathy, and bodily sensations, which is consistent with the structure of the original scale, explaining a cumulative variance contribution rate of 62.551%. Confirmatory analysis revealed a satisfactory model fit, with average variance extracted (AVE) values for the three dimensions ranging from 0.523 to 0.645, and composite reliability(CR) ranging from 0.905 to 0.938. The standard loading coefficients for the items ranged from 0.608 to 0.859, and inter-factor correlation coefficients were all smaller than the square roots of their respective AVE values. Pearson correlation analysis indicated significant positive relationships between the Chinese NPSS and SQ ( r=0.822-0.846, P<0.01). Reliability analysis showed Cronbach′s alpha coefficients of 0.903-0.959 for the total scale and subscales. After a 3-week interval, test-retest reliability (70 patients) ranged from 0.874 to 0.983, and split-half reliability was 0.869-0.969. All model fit indices met established criteria. Conclusions:The Chinese version of the NPSS demonstrates good reliability and validity, making it suitable for both research and clinical applications in assessing psychological security among individuals with schizophrenia and mood disorders.

Objective:To explore the mechanism of exacerbating chronic graft versus host disease (GVHD) in mice with inflammatory status and enhancing immune injury in mice with PD-1.Method:Bone marrow and spleen cells of DBA/2 mice were injected into BALB/C mice pretreated with chemotherapy regimen (Flu+Bu) for constructing a chronic GVHD model. The animals were assigned into two groups of zymosan (100M SPL+10M BM+Zymosan) and control (100M SPL+10M BM+ PBS). After transplantation, two groups of mice were observed for weight changes, survival status and chronic GVHD manifestations. Target organ tissues were harvested for pathological scoring. Flow cytometry was employed for detecting cell subpopulations and surface co-stimulatory molecules in target organs. PD-1 monoclonal antibody was injected into inflammatory murine model. Mice were observed and target organ cells were harvested for subsets and co-stimulatory factors.Result:In in vivo experiments, zymosan group showed more significant changes of chronic GVHD with higher mortality rate, faster weight loss and more severe symptoms of GVHD. At Week 2 post-transplantation, hematoxylin-eosin stain of target organ tissue was performed for pathology examination. Zymosan group showed more lymphocyte infiltration, more severe inflammation and more significant tissue injury with higher GVHD pathological score. The proportion of M2 in liver/lung of zymosan group was significantly lower than that of control group ( P<0.05) and no significant difference existed in the proportion of M1. In in vivo experiments, M1 ratio of splenic cell spiked markedly in zymosan group as compared to control group while M2 ratio declined greatly. The secretions of IL-4 and IL-10 dropped significantly while co-stimulatory molecules CD80 and CD86 rose obviously. Conclusion:The worsening graft-versus-host disease in inflammatory mice with anti-PD1 treatment is associated with a decline of Treg proportion.

The construction of a medication safety culture is important for medication safety management and rational drug use.The construction of medication safety culture standards is formulated based on relevant national policies and regulations,accreditation standards for hospitals,expert opinions,the current situation,and the development trend of the healthcare industry.With scientificity,general applicability,instructive guidance,and practicality,they standardized basic requirements,management processes,and improvement of the construction of medication safety culture.To facilitate understanding and the implementation of the standards,we describe the process of standards formulation and explain the key points of the standards.

The banana Fusarium wilt (BFW) caused by Fusarium oxysporum f. sp. cubense tropical race4 (FocTR4) is difficult to control worldwide, which causes a huge economic losse to banana industry. The purpose of this study was to screen Trichoderma strains with antagonistic activity against FocTR4, to isolate and purify the active compound from the fermentation broth, so as to provide important biocontrol strains and active compound resources. In this work, Trichoderma strains were isolated and screened from the rhizosphere soil of crops, and the strains capable of efficiently inhibiting FocTR4 were screened by plate confrontation, and further confirmed by testing inhibition for the conidial germination and mycelial growth of FocTR4. The phylogenetic tree clarified the taxonomic status of the biocontrol strains. Moreover, the active components in the fermentation broth of the strains were separated and purified by column chromatography, the structure of the most active component was analyzed by nuclear magnetic resonance spectroscopy (NMR), the BFW control effect was tested by pot experiments. We obtained a strain JSHA-CD-1003 with antagonistic activity against FocTR4, and the inhibition rate from plate confrontation was 60.6%. The fermentation broth of JSHA-CD-1003 completely inhibited the germination of FocTR4 conidia within 24 hours. The inhibition rate of FocTR4 hyphae growth was 52.6% within 7 d. A phylogenetic tree was constructed based on the ITS and tef1-α gene tandem sequences, and JSHA-CD-1003 was identified as Trichoderma brevicompactum. Purification and NMR identification showed that the single active compound was trichodermin, and the minimum inhibitory concentration (MIC) was 25 μg/mL. Pot experiments showed that the fermentation broth of strain JSHA-CD-1003 was effective against BFW. The control rate of leaf yellowing was 47.4%, and the rate of bulb browning was 52.0%. Therefore, JSHA-CD-1003 effectively inhibited FocTR4 conidial germination and mycelium growth through producing trichodermin, and showed biocontrol effect on banana wilt caused by FocTR4, thus is a potential biocontrol strain.
Fusarium ; Musa ; Phylogeny ; Trichodermin ; Hypocreales