Objective:To investigate the effect of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer (MBC) patients with different expression levels of human epidermal growth factor receptor 2 (HER2) and the influencing factors of prognosis.Methods:The retrospective case series analysis and cohort study were conducted. Clinical data of 20 MBC patients with different expression levels of HER2 treated with T-DXd at Xi'an International Medical Center Hospital from August 2021 to August 2023 were retrospectively collected to analyze the efficacy and safety of T-DXd. The Cox proportional hazards model was used for multivariate analysis of prognostic factors.Results:All 20 patients were female, with a median age [ M ( Q1, Q3)] of 49 years old (40 years old, 58 years old). Of the 20 cases, 12 had low expression of HER2 [immunohistochemistry HER2+, or immunohistochemistry ++ and fluorescence in situ hybridization (FISH)-negative], and 8 had overexpression of HER2 (immunohistochemistry HER2+++, or immunohistochemistry ++ and FISH-positive); median number of lines of treatment with T-DXd was 6 lines (3 lines, 7 lines); 14 patients had partial remission, 3 patients had stable disease, and 3 patients had disease progression, with an objective remission rate (ORR) of 70% (14/20) and a disease control rate of 85% (17/20). Eight patients with overexpression of HER2 had objective remission in 6 cases, and 12 patients with low expression of HER2 had objective remission in 8 cases, and the ORR difference between the two groups was not statistically significant ( P = 1.000). The main adverse reactions of the patients were nausea (14 cases), vomiting (12 cases), leukopenia (10 cases), elevated aspartate aminotransferase (10 cases), elevated alanine aminotransferase (9 cases), anemia (8 cases), fatigue (8 cases), alopecia (8 cases), neutropenia (6 cases), and thrombocytopenia (5 cases); ≥ grade 3 adverse reactions were bone marrow suppression and gastrointestinal reactions, all with an incidence of ≤10%. The median follow-up time was 7.1 months (1.9 months, 11.5 months). The median progression-free survival (PFS) time was 6.5 months (95% CI: 3.9-9.1 months), and the median PFS time of patients with overexpression of HER2 was longer than that of patients with low expression of HER2 [7.0 months (95% CI: 6.4- 7.6 months) vs. 4.0 months (95% CI: 1.7-6.3 months)], and the difference in PFS between the two groups was statistically significant ( P = 0.025). Multivariate Cox regression analysis showed that overexpression of HER2 was an independent protective factor for PFS in MBC patients treated with T-DXd ( HR = 0.265, 95% CI: 0.075-0.945, P = 0.041). Conclusions:MBC patients with overexpression or low expression of HER2 have a good therapeutic effect and safety profile when treated with T-DXd. The overexpression of HER2 may predict good PFS in MBC patients treated with T-DXd, and may serve as a biomarker for predicting PFS in such patients, but it may not affect the ORR.

Objective:To investigate the clinical effect of high diffusion sensitivity coefficient(high b value)diffusion-weighted imaging(DWI),dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)combined with tumor carbohydrate antigen 125(CA125)in judging the nature of ovarian lesions.Methods:A total of 100 patients with ovarian lesions who were treated in Nantong Haimen People's Hospital from April 2020 to April 2022 were selected for retrospective study.All of them underwent CA125,DWI,DCE-MRI and pathologically qualitative examination.According to the pathological results,58 patients with malignant lesions of ovarian were divided into malignant group and patients with benign lesions of ovarian were divided into benign group.The CA125 levels of the two groups were analyzed and compared,and the results of the receiver operating characteristics(ROC)of different detection methods(DWI with high b value+CA125,DCE-MRI+CA125,DWI with high b value+DCE-MRI+CA125)also were analyzed and compared.Results:The CA125 index of the malignant group was significantly higher than that of the benign group,with a statistically significant difference(t=29.357,P＜0.05),and the CA125 positive rate of the malignant group was significantly better than that of the benign group,with a statistically significant difference(x2=34.456,P＜0.05).The apparent diffusion coefficient(ADC)value[(0.91±0.18)×103mm2/s]of the malignant group was significantly less than that[(33±0.21)×103mm2/s]of the benign group,while the contrast agent volume conversion constant(Ktrans),rate constant(Kep)and the extracellular space volume ratio outside of blood vessels(Ve)of the malignant group were significantly higher than those of the benign group,with significant differences(t=16.863,9.686,10.205,P＜0.05),respectively.The diagnostic accuracy,sensitivity,negative predictive value and positive predictive value of DWI with high b-value+DCE-MRI+CA125 examination method were higher than those of DWI with high b-value + CA125 or DCE-MRI+CA125 examination method in diagnosing malignant ovarian tumors.There were not significant differences in various indicators between DCE-MRI+CA125 examination method and DWI with high b-value +CA125 examination method(P＞0.05).ROC curve analysis showed that the area under curve(AUC)of the DWI with high b-value +DCE-MRI+CA125 examination method was the best(AUC=0.920).Conclusion:The combined examination method of DWI with high b-value + DCE-MRI + CA125 has better overall diagnostic efficiency,which can improve the screening ability of clinical diagnosis for malignant ovarian tumors.It has a certain clinical application value.

Objective:To investigate the expression and prognostic value of ANO1 in oral squamous cell carcinoma(OSCC)tissues.Methods:Immunohistochemistry(IHC,n=163)and Quantitative real-time PCR(qRT-PCR,n=42)were employed to detect the expression level of ANO1 protein and mRNA in OSCC tissues and paracancerous normal tissues.The relationship between ANO1 ex-pression and clinicopathological features(n=163)and prognosis(n=93)of the patients were analyzed,and the results were compared with those in TCGA database.Results:IHC and qRT-PCR confirmed that ANO1 was highly expressed in OSCC(P＜0.05),which was consistent with the results of the TCGA database.Cox regression analysis showed that ANO1 expression was significantly correlated with T stage,lymph node metastasis and TNM stage and poor prognosis(P＜0.05).By Cox regression analysis,ANO1 overexpression(P=0.002)and differentiation degree(P=0.034)were independent prognostic factors.Conclusion:ANO1 is highly expressed in OSCC and is correlated with poor prognosis,which can be used as a novel biomarker for poor prognosis of OSCC patients.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Abstract: Objective To compare the differences in the expression of interleukin-8 (IL-8) and signal transducer and activator of transcription 3 (STAT3) among three groups of individuals: patients with multi-drug resistant tuberculosis (MDR-TB), patients with drug-susceptible tuberculosis (DSP-TB), and healthy controls. By analyzing the differences between these groups, the study seeks to provide a reference basis for clinical auxiliary diagnosis of new type tuberculosis. Methods The differences in mRNA expression profiles of chip from peripheral blood mononuclear cells (PBMCs) among three groups were analyzed. MDR-TB and DSP-TB patients were selected as study subjects, with healthy individuals serving as a control group, and the serum IL-8 concentration of each group was measured using an ELISA assay to compare differences between groups. Additionally, PBMCs from all groups were isolated and total RNA was extracted for analysis of IL-8 and STAT3 mRNA expression using quantitative real-time PCR(Q-PCR). Differences in STAT3 protein expression among the groups were also compared by Western blot assay. Results The serum IL-8 concentration in the MDR-TB and DSP-TB groups was significantly higher than that in the healthy control group, with a statistically significant difference (P<0.05). The relative expression level of IL-8 mRNA in PBMCs of the MDR-TB group and DSP-TB group was also significantly higher than that of the healthy control group, with a statistical significance (P<0.05). Both Q-PCR and Western Blot results revealed that the expression of STAT3 in the healthy, DSP-TB and MDR-TB groups sequentially increased, presenting statistically significant differences between the groups (P<0.05), consistent with the mRNA chip results. Conclusions The expression of IL-8 in active tuberculosis patients (ATB) is significantly increased, which can be used as a marker to distinguish ATB from healthy populations. The changes of STAT3 concentration not only serve as a reference for the diagnosis of ATB but can also distinguish between DSP-TB and MDR-TB populations. The combined detection of IL-8 and STAT3 holds promise as a clinical auxiliary diagnostic basis for different tuberculosis patients.

Objective To analyze the transcription factor binding sites(TFBS)in the promoter region of E3 ubiquitin protein ligase 1(MIB1)gene in zebrafish,the types of MIB1 interacting genes and proteins and their roles in signaling pathways,and to investigate the regulatory mode and potential function of MIB1 gene.Methods Non-coding RNA(ncRNA)was predicted by National Genomics Data Center(NGDC).Alggen and AnimalTFDB online software were used to predict the TFBS types of MIB1 gene.GeneMANIA and STRING were used to analyze the interacting genes and proteins of MIB1.The related data were obtained through DA-VID website,and gene ontology(GO)visual analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)metabolic pathway analysis were performed.Results ncRNA could be transcribed from the promot-er region and 5'untranslated region of MIB1 gene.A total of 121 TFBS were obtained by prediction.P53 tran-scription factor could bind to the promoter region of MIB1 gene and interact with MIB1 protein.A total of 6 co-expressed genes of MIB1 were predicted online,and 20 interacting genes were screened.GO visual analysis showed that MIB1 and its interaction genes had functions in regulating the growth and differentiation of cells,tissues and organs and regulating the NOTCH signaling pathway in the biological process,and were mainly enriched in the cytoplasmic perinuclear region,cell membrane,postsynaptic dense area and so on.It had molec-ular functions such as binding NOTCH proteins and PDZ domain proteins.KEGG metabolic pathway analysis showed that MIB1 and its interacting genes were involved in 4 metabolic pathways.Conclusion MIB1 con-tains a variety of TFBS,and affects a variety of biological processes such as cell carcinogenesis and immune regulation by interacting with specific transcription factors.MIB1 may also play an important role in cell growth regulation,hematopoietic stem cell differentiation,embryonic development and neuronal information transmission through the mediation of its interacting genes and proteins.

OBJECTIVE To analyze the dose-adjusted concentrations of Posaconazole oral suspension in patients undergoing hematopoietic stem cell transplantation （HSCT） and their influential factors. METHODS Data were collected from hospitalized HSCT patients admitted to the First Affiliated Hospital of Shandong First Medical University （Shandong Provincial Qianfoshan Hospital） from January 2021 to April whtwhm@yeah.net 2023 who took Posaconazole oral suspension for the prevention of invasive fungal disease （IFD） and received blood concentration of posaconazole. The rate of concentration attainment and clinical failure rate of posaconazole for the prevention of IFD were evaluated， and one-way and multiple linear regression analyses were performed for the influential factors of dose-adjusted concentrations （C0/D） of posaconazole. RESULTS A total of 44 patients were enrolled； the mean C0 of posaconazole in patients was （0.99±0.94） µg/mL， and 20 patients had a C0≥0.7 μg/mL， with a concentration attainment rate of 45.45% for the prevention of IFD； 13 cases were clinical failures， with a clinical failure rate of 29.55%. Of 24 patients who did not achieve C0/D of posaconazole for IFD prophylaxis， one patient was a clinical failure despite timely dose adjustment of posaconazole in seven patients； seven of the thirteen patients who did not undergo dose adjustment were clinical failures； and the remaining four patients were switched to other antifungal agents. The results of univariate analysis showed that gender， body mass index （BMI）， renal function， combined use of sodium phenytoin， omeprazole and metoclopramide had a significant effect on the C0/D of posaconazole （P＜0.05）； the results of multivariate linear regression analysis showed that gender， BMI and combined use of sodium phenytoin were the independent factors affecting the C0/D of posaconazole （P＜0.05）. CONCLUSIONS Significant individual differences are reflected in the blood concentration of Posaconazole oral suspension； gender， BMI and combined use of sodium phenytoin are independent factors affecting the C0/D of posaconazole.

Mendelian Randomization Analysis ; Bone Density ; Genome-Wide Association Study ; Minerals ; Life Expectancy ; Polymorphism, Single Nucleotide

To explore the influencing factors of perceived stress among frontline nurses during COVID-19, and the role of positive psychological capital in anxiety sensitivity and stress perception, so as to provide evidence for reducing the perceived stress of frontline nurses. From December 2021 to January 2022, 475 frontline nurses from 8 hospitals in X city were investigated by general data questionnaire, positive psychological capital, anxiety sensitivity index and perceived stress scale. The results showed that there were significant differences in nurses’ perceived stress in age, working years, professional title and salary. Perceived stress was positively correlated with anxiety sensitivity, negatively correlated with positive psychological capital, and anxiety sensitivity was negatively correlated with positive psychological capital. Anxiety sensitivity can not only directly predict perceived stress, but also negatively affect perceived stress through positive psychological capital. Therefore, during the epidemic prevention and control in COVID-19, nurses can obtain effective stress coping strategies by strengthening their positive psychological capital, thus reducing their anxiety and perceived stress, and better providing high-quality nursing services for patients.

Objective: To explore the relationship between family background and parental support and adolescents physical activity and motor skills, and to provide a corresponding theoretical basis for the health promotion of children and adolescents in China. Methods: From November to December 2019, 140 junior high school students aged 12-14 years in a junior high school in Shanxi Province were selected, and physical activity was recorded for 7 days using an ActiGraph GT3X+ accelerometer. The Activity Support Scale for Children (ACTS CN) was used to evaluate parents support and attitude towards children s activities and behaviors. The Canadian Agility and Movement Skill Assessment (CAMSA) was used to evaluate the motor ability development of adolescents. Results: The daily participation time in moderate to vigorous physical activity (MVPA) was (40.57±13.54) and (31.65± 9.98 ) min for males and females, respectively, with a statistically significant difference ( t =4.44, P <0.05); The average motor skill scores were (10.8±1.9) and (10.1±1.9), and completion times were (17.7±2.8) and (19.1±2.5)s, respectively; regression analyses showed that mothers education, monthly household income, mothers attention to children s exercise and fathers support for club participation were all significantly associated with adolescents MVPA ( B =-0.28,-0.16,-0.16, 0.18, P <0.05). Parental provision of exercise space was significantly associated with motor ability ( r =0.17, 0.17, P <0.05). Conclusion Parents with higher levels of education have a more positive influence on their children s physical activity participation. Parental presence can contribute to a certain extent to the level of physical activity of adolescents, and a supportive environment provided from parents can positively influence the level of motor skills of adolescents.