Purpose To investigate the distribution characteristics of tumor-associated macrophages(TAM)in different regions of breast cancer with enhanced contrast-enhanced ultrasound(CEUS),and to further explore the relationship between TAM and CEUS indicators and clinicopathology in different regions of breast cancer.Materials and Methods A total of 119 patients with suspected breast cancer admitted to the Cancer Hospital Affiliated to Xinjiang Medical University from March 2021 to March 2023 were prospectively included.CEUS was applied to the tumor,and ultrasound-guided puncture biopsy was also taken.The lesions diagnosed as breast cancer by pathology was outlined the central area,marginal area and normal area next to the cancer,and was obtained the time intensity curves of different areas.The tissues were taken for immunohistochemistry and flow cytometry,and the TAM cells were stained and distinguished.The characteristics of TAM in different regions of breast cancer and its correlation with clinical pathology were analyzed,respectively.Results By immunohistochemistry and flow cytometry,there were significant differences in the number of TAM infiltration in the border area,central area and adjacent area of breast cancer(immunohistochemistry:F=382.326,P<0.05;flow cytometry:F=24.955,P<0.05).The characteristics of CEUS in three different regions showed that the TAM in the central region of breast cancer increased when filling defect appeared(t=2.631,P<0.05),but the TAM in the peripheral region was more(t=2.999,P<0.05).After angiography,lesions showed high perfusion,and there was significantly more TAM in the edge and central area of the lesion than that in normal area next to the cancer(t=5.529,P<0.05;t=2.584,P<0.05).Clinical stage was related to the TAM in three regions.When the clinical stage was high,there were more TAM in all three regions(t=6.658,2.367,2.400,all P<0.05).Histological grading was high,and TAM in all three areas was high(F=101.151,16.922,26.822,all P<0.05).Conclusion There was a decreasing trend of TAM in the marginal area,central area and adjacent tissues of breast cancer during CEUS.The edge region has more malignant CEUS characteristics than that in the central region and the normal region adjacent to cancer;and the number of TAM is more in breast cancer with late clinical grading,poor tissue differentiation and obvious contrast-enhanced ultrasound malignant characteristics.The distribution characteristics of TAM represent the malignant degree and metastatic probability of breast cancer to a certain extent,and TAM is a factor related to the invasion of breast cancer.

Purpose To investigate the distribution characteristics of tumor-associated macrophages(TAM)in different regions of breast cancer with enhanced contrast-enhanced ultrasound(CEUS),and to further explore the relationship between TAM and CEUS indicators and clinicopathology in different regions of breast cancer.Materials and Methods A total of 119 patients with suspected breast cancer admitted to the Cancer Hospital Affiliated to Xinjiang Medical University from March 2021 to March 2023 were prospectively included.CEUS was applied to the tumor,and ultrasound-guided puncture biopsy was also taken.The lesions diagnosed as breast cancer by pathology was outlined the central area,marginal area and normal area next to the cancer,and was obtained the time intensity curves of different areas.The tissues were taken for immunohistochemistry and flow cytometry,and the TAM cells were stained and distinguished.The characteristics of TAM in different regions of breast cancer and its correlation with clinical pathology were analyzed,respectively.Results By immunohistochemistry and flow cytometry,there were significant differences in the number of TAM infiltration in the border area,central area and adjacent area of breast cancer(immunohistochemistry:F=382.326,P<0.05;flow cytometry:F=24.955,P<0.05).The characteristics of CEUS in three different regions showed that the TAM in the central region of breast cancer increased when filling defect appeared(t=2.631,P<0.05),but the TAM in the peripheral region was more(t=2.999,P<0.05).After angiography,lesions showed high perfusion,and there was significantly more TAM in the edge and central area of the lesion than that in normal area next to the cancer(t=5.529,P<0.05;t=2.584,P<0.05).Clinical stage was related to the TAM in three regions.When the clinical stage was high,there were more TAM in all three regions(t=6.658,2.367,2.400,all P<0.05).Histological grading was high,and TAM in all three areas was high(F=101.151,16.922,26.822,all P<0.05).Conclusion There was a decreasing trend of TAM in the marginal area,central area and adjacent tissues of breast cancer during CEUS.The edge region has more malignant CEUS characteristics than that in the central region and the normal region adjacent to cancer;and the number of TAM is more in breast cancer with late clinical grading,poor tissue differentiation and obvious contrast-enhanced ultrasound malignant characteristics.The distribution characteristics of TAM represent the malignant degree and metastatic probability of breast cancer to a certain extent,and TAM is a factor related to the invasion of breast cancer.

Background: and Purpose The eye-movement examination can be applied as a noninvasive method to identify multiple-system atrophy (MSA). Few studies have investigated eye movements during the early stage of MSA with predominant parkinsonism (MSA-P). We aimed to determine the characteristic oculomotor changes in the early stage of MSA-P. Methods: We retrospectively selected 17 patients with MSA-P and 40 with Parkinson’s disease (PD) with disease durations of less than 2 years, and 40 age-matched healthy controls (HCs).Oculomotor performance in the horizontal direction was measured in detail using videonystagmography. Results: We found that the proportions of patients with MSA-P and PD exhibiting abnormal eye movements were 82.4% and 77.5%, respectively, which were significantly higher than that in the HCs (47.5%, p<0.05). Compared with HCs, patients with MSA-P presented significantly higher abnormal proportions of fixation and gaze-holding (17.6% vs. 0%), without-fixation (47.1% vs. 0%), prolonged latency in reflexive saccades (29.4% vs. 5.0%), memory-guided saccades (93.3% vs. 10.0%), and catch-up saccades in smooth-pursuit movement (SPM, 41.2% vs. 0) (all p<0.05). Compared with those with PD, patients with MSA-P presented a significantly higher proportion of catch-up saccades in SPM (41.2% vs. 2.5%, p<0.001). Conclusions MSA-P presented the characteristic of catch-up saccades in SPM in the early stage, which may provide some value in differentiating MSA-P from PD.

Humans ; Pulmonary Alveolar Proteinosis/radiotherapy* ; Small Cell Lung Carcinoma/radiotherapy* ; Lung ; Bronchoalveolar Lavage ; Lung Neoplasms/radiotherapy*

Objective:Central nervous system leukemia(CNSL)is one of the main causes of recurrence and death in patients with acute leukemia.This study aims to dynamically monitor minimal residual disease(MRD)in cerebrospinal fluid and bone marrow of patients with different types of acute leukemia by flow cytometry(FCM),and to compare the timeliness and consistency of MRD detection between the 2 methods to further explore the application value of monitoring MRD in cerebrospinal fluid. Methods:A total of 199 patients with acute leukemia admitted to the Guangdong Provincial people's Hospital between October 2018 and January 2022 were retrospectively analyzed,and multiparametric FCM method was adopted to summarize and analyze MRD in cerebrospinal fluid of patients with different types of leukemia and MRD in cerebrospinal fluid and bone marrow specimens of the same patients,and its role in assessing the prognostic value of patients was discussed. Results:Among the 199 acute leukemia cases,a total of 31 cases(15.58%)were positive MRD in the cerebrospinal fluid,of which 18 cases(58%)were detected earlier than the corresponding bone marrow specimens.Among the 19 patients with acute T lymphoblastic leukemia,134 patients with acute B lymphoblastic leukemia,and 46 patients with acute myeloid leukemia counted,there were 4,18,and 9 patients with positive MRD in the cerebrospinal fluid.The Kappa value of the concordance test between the results of cerebrospinal fluid MRD and bone marrow MRD in different types of acute leukemia was only 0.156,demonstrating a low concordance between them. Conclusion:Dynamic monitoring of cerebrospinal fluid MRD by FCM can be used as a monitoring index for central nervous system leukemia,and monitoring cerebrospinal fluid can detect MRD earlier compared with bone marrow,which complements each other as a sensitive index for evaluating prognosis with significant guidance in clinic.

Humans ; COVID-19 ; Quarantine ; Renal Dialysis ; SARS-CoV-2 ; Hospitals

To explore the different chloroplast genome characteristics of Sinopodophyllum hexandrum, five chloroplast genome sequences of S. hexandrum were compared. Its genome map, repeat sequence, codon preference, inverted repeat (IR)/single-copy (SC) boundary, alignment of chloroplast genome sequences and phylogenetic were analyzed using bioinformatics tools. The results showed that: the total length of five chloroplast genomes of S. hexandrum, with a typical tetrad structure, were 157 203-157 940 bp, and a total of 133-137 genes were annotated, reflecting the diversity of chloroplast genomes of S. hexandrum. Different chloroplast genomes of S. hexandrum has different simple sequence repeat (SSR), where simple repeat of single nucleotide of A/T were the majority among the SSR detected. The interspersed repetitive sequences included direct, palindromic and inverted repeats. The value of effective number of codon (ENc) which was analyzed by using codon bias was 51.14~51.17, the proportion of GC and GC3s was less than 50%, the codon usage pattern tended towards frequently use of A/U-ending bases. Genome sequences and the IR/SC boundaries of five chloroplast genomes of S. hexandrum were relatively conservative. Phylogenetic analysis showed that S. hexandrum and Podophyllum pettatum had the closest genetic relationship. In summary, the chloroplast genome characteristics and evolutionary relationship of different chloroplast genomes of S. hexandrum were obtained, which may facilitate the utilization, protection, variety identification and genetic evolution of S. hexandrum resources.
Phylogeny ; Genome, Chloroplast ; Chloroplasts/genetics* ; Genomics ; Evolution, Molecular

Objective:To understand the main adverse event (AE) related to denosumab and the risks and provide reference for the safe use of the drug in clinic.Methods:The AE reports on denosumab included in the US FDA Adverse Event Reporting System from the second quarter of 2010 to the first quarter of 2021 were collected, and the AE risk signals was explored using proportional reporting odds ratio ( PRR) method. AEs with ≥3 reports, PRR value ≥2, and χ2≥4 were defined as positive risk signals. AEs were counted and classified using the preferred system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities 24.0. The PTs of top 50 adverse event reports and signal intensity were selected and analyzed. Results:A total of 132 764 AE reports with denosumab as the primary suspected drug were collected, involving 5 571 PTs, and 641 positive risk signals were selected. After the second screening, the top 50 PTs in the number of AE reports and the top 50 PTs with great PRR values were obtained, and 93 PTs were included in the analysis after sifting out the repeated, involving 114 617 AE reports. The top 5 PTs in the number of AE reports were off-label use (28.7%, 32 863/114 617), death (14.2%, 16 230/114 617), osteonecrosis of the jaw (6.0%, 6 861/114 617), arthralgia (4.7%, 5 420/114 617), and limb pain (4.1%, 4 727/114 617). The top 5 PTs with the high signal intensity were giant-cell tumour of bone ( PRR=402.7), malignant giant-cell tumour of bone ( PRR=325.2), C-telopeptide increase ( PRR=169.4), exostosis of jaw ( PRR=163.2), and ionised calcium abnormal ( PRR=158.1). The top 5 SOC involving AE reports were injury, poisoning and procedural complications (35.9%, 41 757/114 617), musculoskeletal and connective tissue disorders (32.7%, 37 455/114 617), general disorders and administration site conditions (18.2%, 20 814/114 617), surgical and medical procedures (4.1%, 4 744/114 617), and investigations (2.9%, 3 290/114 617). Forty-four PTs were not included in the drug instructions, of which 23 were related to the oral cavity. Conclusions:Denosumab AE with the most reports were off-label use and osteonecrosis of the jaw. The risk signals of osteonecrosis of the jaw and recurrence or deterioration of giant-cell tumor of bone was strong. Most of the AE risk signals that were not included in the instructions are oral problems.

Objective:To analyze the risk of diabetes mellitus related to immune checkpoint inhibitors (ICI).Methods:The adverse event (AE) reports on fulminant type 1 diabetes mellitus (FT1DM), type 1 diabetes mellitus (T1DM), diabetic ketoacidosis (DKA), which were related to duvalizumab, pabolizumab, nivolumab, and atezolizumab in the US FDA Adverse Event Reporting System from the first quarter of 2004 to the second quarter of 2021, were collected.The correlation between the 4 drugs and FT1DM, T1DM,and DKA were evaluated using proportional reporting odds ratio ( PRR) method.AE with reports ≥3, PRR value≥2, and χ2≥4 were judged to have statistical correlations with drugs. The greater the PRR value, the stronger the correlation between AE and drugs and the stronger the risk signals. Results:A total of 1 468 AE reports on diabetes mellitus were collected, 53, 386, 957, and 72 of which were related toduvalizumab, pabolizumab, nivolumab, and atezolizumab, respectively. For duvalizumab, pabolizumab, nivolumab, and atezolizumab, the PRR reflecting the correlation with FT1DM were 21.97 ( χ2=40.71), 71.50 ( χ2=3 531.21), 294.30 ( χ2=4 3915.75), and 33.58 ( χ2=279.70), respectively; the PRR reflecting correlation with T1DM were 12.12 ( χ2=162.08), 21.04 ( χ2=3391.17), 20.99 ( χ2=5816.11), and 9.71 ( χ2=224.81), respectively; the PRR reflecting correlation with DKA were 6.93 ( χ2=161.26), 4.78 ( χ2=426.52), 6.82 ( χ2=1797.15), and 3.04 ( χ2=41.84), respectively. The 4 drugs were statistically correlated with their corresponding AE. The order of risk signal intensity for corresponding AE was FT1DM > T1DM > DKA. The order of risk signal intensity for FT1DM were nivolumab > pabolizumab > duvalizumab > atezolizumab, for T1DM were pabolizumab ≈ nivolumab > duvalizumab > atezolizumab, for DKA were duvalizumab ≈ nivolumab > pabolizumab > atezolizumab. Conclusions:Duvalizumab, pabolizumab, nivolumab, and atezolizumab all can cause diabetes mellitus. The risk signal intensity was the strongest for FT1DM, followed by T1DM and DKA in order.

Objective:To analyze the risk of diabetes mellitus related to immune checkpoint inhibitors (ICI).Methods:The adverse event (AE) reports on fulminant type 1 diabetes mellitus (FT1DM), type 1 diabetes mellitus (T1DM), diabetic ketoacidosis (DKA), which were related to duvalizumab, pabolizumab, nivolumab, and atezolizumab in the US FDA Adverse Event Reporting System from the first quarter of 2004 to the second quarter of 2021, were collected.The correlation between the 4 drugs and FT1DM, T1DM,and DKA were evaluated using proportional reporting odds ratio ( PRR) method.AE with reports ≥3, PRR value≥2, and χ2≥4 were judged to have statistical correlations with drugs. The greater the PRR value, the stronger the correlation between AE and drugs and the stronger the risk signals. Results:A total of 1 468 AE reports on diabetes mellitus were collected, 53, 386, 957, and 72 of which were related toduvalizumab, pabolizumab, nivolumab, and atezolizumab, respectively. For duvalizumab, pabolizumab, nivolumab, and atezolizumab, the PRR reflecting the correlation with FT1DM were 21.97 ( χ2=40.71), 71.50 ( χ2=3 531.21), 294.30 ( χ2=4 3915.75), and 33.58 ( χ2=279.70), respectively; the PRR reflecting correlation with T1DM were 12.12 ( χ2=162.08), 21.04 ( χ2=3391.17), 20.99 ( χ2=5816.11), and 9.71 ( χ2=224.81), respectively; the PRR reflecting correlation with DKA were 6.93 ( χ2=161.26), 4.78 ( χ2=426.52), 6.82 ( χ2=1797.15), and 3.04 ( χ2=41.84), respectively. The 4 drugs were statistically correlated with their corresponding AE. The order of risk signal intensity for corresponding AE was FT1DM > T1DM > DKA. The order of risk signal intensity for FT1DM were nivolumab > pabolizumab > duvalizumab > atezolizumab, for T1DM were pabolizumab ≈ nivolumab > duvalizumab > atezolizumab, for DKA were duvalizumab ≈ nivolumab > pabolizumab > atezolizumab. Conclusions:Duvalizumab, pabolizumab, nivolumab, and atezolizumab all can cause diabetes mellitus. The risk signal intensity was the strongest for FT1DM, followed by T1DM and DKA in order.