Home Life Sciences Metaplastic breast carcinoma with osseous differentiation: A report of a rare case and literature review
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Metaplastic breast carcinoma with osseous differentiation: A report of a rare case and literature review

  • Cong Huang , Haibo Tian , Jinming Xu , Fuyun Tong EMAIL logo and Dengyang Fang EMAIL logo
Published/Copyright: July 24, 2023

Abstract

Metaplastic matrix-producing breast carcinoma is a type of metaplastic breast carcinoma (MBC), which is a rare malignancy, accounting for 0.2–1% of breast carcinomas. A 52-year-old female visited a hospital because of a palpable painless mass in the right breast and was diagnosed with Breast Imaging Reporting and Data System (BI-RADS) category 4A via ultrasound (US) with a suspected positive lymph node at the right axillary region. Excision of the breast mass was performed and histopathologically confirmed that it was MBC with osseous differentiation. No distant metastasis was revealed before a modified radical mastectomy; however, metastasis to a lymph node of the right axillary region was observed (1/22). She received six cycles of TEC scheme chemotherapy (docetaxel, epirubicin, and cyclophosphamide, 21 days) and 5 weeks of radiotherapy (48 Gy/25 f/5 days a week), but without any follow-up examinations since radiotherapy. Twenty-four months after surgery, distant metastases to lungs and liver were confirmed and died 3 months later. This case provides valuable information for clinicians on MBC and suggests that further examination or biopsy should be performed to US BI-RADS 4A masses before surgery. In addition, regular postoperative follow-up plays important roles in detecting metastases early and improving prognosis.

Graphical abstract

1 Introduction

Metaplastic breast carcinoma (MBC) is a group of heterogeneous invasive carcinomas characterized by the differentiation of tumor cells into spindle and/or mesenchymal cells [1], accounting for 0.2–1% of breast carcinomas [2]. It was first described as a mammary carcinoma with mixed epithelial and sarcomatoid components in 1973 [3]. The etiology and pathogenesis of MBC remain unclear [4]. This heterogeneous group of MBC can be histologically classified into the following six distinct groups based on the World Health Organization 2019 classification of breast tumors: (i) low-grade adenosquamous carcinoma, (ii) fibromatosis-like metaplastic carcinoma, (iii) spindle cell carcinoma, (iv) squamous cell carcinoma, (v) metaplastic carcinoma with heterologous mesenchymal differentiation (including chondroid, osseous, and other types of mesenchymal differentiation), and (vi) mixed metaplastic carcinoma [1]. MBC with osseous differentiation is rare with great challenges in diagnosis, treatment, and prognosis. Here, we report the case of a 52-year-old female diagnosed with MBC with osseous differentiation, without any history of carcinoma or family history of breast cancer.

2 Case presentation

A 52-year-old female was admitted to our hospital with a diagnosis of MBC with osseous differentiation, based on the pathology of the excisional breast mass, without any history of carcinoma or family history of breast cancer. Three months prior, she noticed a mass in her right breast. Physical examination showed a firm, tender mass, approximately 2.5 cm size in the lower outer quarter of the right breast, without a clear boundary. No redness, swelling, pigmentation, or orange peel changes were found on the skin. No invagination, bleeding, or effusion were found in the bilateral nipple. The left breast and the bilateral axillary and supraclavicular lymph nodes were unremarkable. No obvious abnormalities were found in laboratory tests. Breast ultrasound (US) (Figure 1) showed an uneven hypoechoic mass at 9 o’clock near the nipple, and the maximum size was approximately 3.0 cm, with unclear boundary, irregular shape, posterior acoustic enhancement, and few blood flow signals inside. The mass was considered Breast Imaging Reporting and Data System (BI-RADS) category 4A, and a suspected enlarged lymph node with a slightly thickened cortical area at the right axillary region was also indicated by US.

Figure 1 
               US of MBC with osseous differentiation. US revealed that there was an uneven hypoechoic mass at 9 o’clock near the nipple, with unclear boundary, irregular shape, and posterior acoustic enhancement, and few blood flow signals inside, but without definite calcifications (a) and the suspected enlarged lymph node with a slightly thickened cortical area at the right axillary region (b).
Figure 1

US of MBC with osseous differentiation. US revealed that there was an uneven hypoechoic mass at 9 o’clock near the nipple, with unclear boundary, irregular shape, and posterior acoustic enhancement, and few blood flow signals inside, but without definite calcifications (a) and the suspected enlarged lymph node with a slightly thickened cortical area at the right axillary region (b).

The patient underwent the breast mass excision surgery at that hospital without any further examinations and histopathologically (Figure 2) diagnosed with MBC with osseous differentiation, because there were two different components in the tumor; one was typical invasive ductal carcinoma (IDC) and the other was presenting as osteosarcoma with lots of immature trabeculae, and atypia osteocytes among them; there was no spindle cell component. Immunohistochemical analysis revealed that cells were CD10, CK-P and vimentin positive, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), CD34, GATA-3, HMB45, smooth muscle actin (SMA), and p63 negative; proliferative index with KI-67 was 50%. Four days later, she was admitted to our hospital for further treatment. Chest computed tomography (CT) (Figure 3) indicated that there was no metastasis in the lung and liver; emission computed tomography (ECT) findings also revealed no signs of bone metastasis. Considering that the breast mass was a high-grade malignancy, and there was a suspected metastatic lymph node at the right axillary region; doctors suggested a biopsy of the lymph node under the guidance of US. However, the patient and her families refused and requested an excision of the sentinel lymph node. Histological results showed the lymph node metastasized from breast invasive carcinoma. Immunohistochemical analysis revealed that CK5/6 and p63 were positive. Subsequently, a modified radical mastectomy was performed, and there were no other metastatic lymph nodes (0/21). Finally, she was diagnosed with MBC with osseous differentiation, staged as TxN1M0.

Figure 2 
               Pathological pictures of MBC with osseous differentiation, excision specimen. Images (a) and (b) showed components of typical IDC (a [20×]) and osteosarcoma (b [20×]). Images (c [10×]) and (d [20×]) showed immunohistochemistry of CK-P and vimentin staining, respectively; both were positive.
Figure 2

Pathological pictures of MBC with osseous differentiation, excision specimen. Images (a) and (b) showed components of typical IDC (a [20×]) and osteosarcoma (b [20×]). Images (c [10×]) and (d [20×]) showed immunohistochemistry of CK-P and vimentin staining, respectively; both were positive.

Figure 3 
               Comparing CT plans of the lung and liver before the modified radical mastectomy and 24 months after the surgery. Images (a) and (c) were CT plans of the lung and liver before the modified radical mastectomy, respectively, and revealed no metastases. Images (b) and (d) were the corresponding plans 24 months after the surgery, and metastases were indicated by the green arrows.
Figure 3

Comparing CT plans of the lung and liver before the modified radical mastectomy and 24 months after the surgery. Images (a) and (c) were CT plans of the lung and liver before the modified radical mastectomy, respectively, and revealed no metastases. Images (b) and (d) were the corresponding plans 24 months after the surgery, and metastases were indicated by the green arrows.

The patient had received six cycles of TEC chemotherapy (docetaxel, 700 mg; epirubicin, 100 mg; cyclophosphamide 500 mg; 21 days), initiated after the modified radical mastectomy, and radiotherapy (RT) at a dosage of 48 Gy/25 f/5 days a week to treat the lymph node of the right superior and inferior clavicular fossa and right chest for 5 weeks. The follow-up investigations were advised every 6 months including breast, abdomen and lymph node US, blood routine, liver and kidney function, and tumor markers and chest CT every year. However, she did not perform any checking items for 18 months since RT. Twenty-four months later after surgery, she was admitted again for dyspnea and chest discomfort; chest CT (Figure 3) revealed that there were probable metastatic lesions in lungs (maximum: 29 mm × 27 mm), liver (maximum: 12 mm × 10 mm), and mediastinal lymph nodes (maximum: 26 mm), with pleural effusion in the right thoracic cavity. The lung nodule was diagnosed as metastasis from breast invasive carcinoma by CT guided needle biopsy (Figure 4). Immunohistochemical analysis revealed that cells were ER, PR, PF-L1, SOX10, Napsin A, thyroid transcription factor-1, GCDFP-15 negative, HER-2 (2+) but in situ hybridization negative, CK-P and GATA-3 positive, proliferative index with KI-67 was 40%, and BRCA1 was local positive. The patient refused further treatment and died 3 months later. The related indicators of tests and examinations throughout the patient are presented in Table 1.

Figure 4 
               Histopathology of lung nodule (10×). This picture showed that lung nodule was metastasized from breast invasive carcinoma.
Figure 4

Histopathology of lung nodule (10×). This picture showed that lung nodule was metastasized from breast invasive carcinoma.

Table 1

The main related indicators throughout the treatment

Parameters time after surgery Breast mass excision Modified radical mastectomy Chemotherapy RT Latest hospitalized Normal reference
(month) (0) (0) 1 (0) 2 (1) 3 (2) 4 (3) 5 (4) 6 (5) (6) (24)
HGB (g/L) NA 140 103 132 132 134 130 134 130 134 115–150
WBC (109/L) NA 7.42 10.9 7.28 7.30 7.3 5.67 7.79 5.02 6.9 3.5–9.5
CEA (ng/mL) NA NA NA NA 1.65 NA NA 0.97 0.97 1.45 0–5
CA153 (U/mL) NA NA NA NA 7.94 NA NA 7.24 5.39 14.43 0–25
Breast ultrasound An uneven hypoechoic mass (sized 3.0 cm) in the right breast a suspected swollen lymph node at the right axillary region After excision of right breast mass, a suspected swollen lymph node at the right axillary region NA NA (−) NA NA (−) NA (−)
CT NA Lung, liver (−) NA NA NA NA NA Lung, liver (−) NA Lung: scattered nodules (max: 29 mm × 27 mm), pleural effusion; Liver: multiple hypo-density nodules (max: 12 mm × 10 mm); Lymph nodes: multiple mediastinal lymphadenopathy (max: 26 mm)
ECT NA (−) NA NA NA NA NA NA NA NA

Meanings of some important symbols: (−): normal; NA: this examination was not performed. Abbreviations: HGB: hemoglobin; WBC: white blood cell; CEA: carcinoembryonic antigen; CA153: carbohydrate antigen 153; CT: computed tomography; ECT: emission computed tomography; RT: radiotherapy.

  1. Informed consent: Informed consent has been obtained from all individuals included in this study.

  2. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies, and in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.

3 Discussion

Metaplastic matrix-producing carcinoma is an aggressive and rare kind of MBC, which contains invasive carcinoma displaying a transition to a cartilaginous and/or osseous stromal matrix lacking an intervening spindle cell component [5,6]. Although there are many published case series of MBC, MBC with osseous differentiation is still rare [7]. A study from India showed that 13 (2.5%) out of total 510 MBC specimens were mesenchymal differentiation, but none was osseous differentiation [8]. The same results were also found in articles including 14 Australian and 38 Turk MBC patients [9,10]. Zhang et al. reported six cases of matrix-producing MBC, but all were chondroid differentiation [11]. The histogenesis and origin of MBC are controversial [4]. The most common hypotheses regarding the histogenesis of MBC are as follows: (1) collision hypothesis, which suggests that carcinomatous and sarcomatous tissues are derived from different progenitor cells [12]; (2) monoclonal hypothesis, which suggests that the components of MBC are monoclonal, and thereby derived from a common multipotent progenitor cell [4]; and (3) epithelial–mesenchymal transition, which suggests that sarcomatous components are derived from the carcinomatous component, or myoepithelial cells due to the positivity of myoepithelial markers including CD10, p63, and SMA [13].

It is reported that MBC mostly occurs in patients aged over 50 years [14] and is characterized by rapid growth generally >2 cm [12], so was our case. The diagnosis of MBC is very difficult, because of no specificity in clinical manifestation and auxiliary examinations. Although calcifications might be detected by auxiliary examinations if there were osteosarcoma components [15,16], it is still difficult to distinguish from breast invasive carcinoma or benign neoplasms including fibroadenoma [17,18,19]. The pathological diagnosis of MBC requires the demonstration of epithelial and heterologous (chondroid or osseous), as well as the absence of spindle cell differentiation. Therefore, it can only be done on a surgical specimen [20].

According to National Comprehensive Cancer Network (NCCN) guidelines of breast cancer screening and diagnosis [21], BI-RADS 4A breast masses should be performed for further examinations or biopsy. Although this case was accurately diagnosed with MBC with osseous differentiation through surgical specimens at the beginning, we still recommend biopsies of the mass and suspicious metastatic lymph node before surgery. Comprehensive preoperative relevant examinations including chest CT, mammogram, magnetic resonance imaging, and emission computed tomography are crucial for clinicians to stage the MBC patient, make a therapeutic regimen, and evaluate the progression and prognosis. The lack of comprehensive preoperative examinations including mammogram of the mass is a limitation of this case report. It has been reported that ER, PR, and HER-2 are negative in more than 90% of MBC, which is similar to the biological characteristics of triple-negative breast cancer (TNBC) [22], while at least one of keratin, including AE1/3, CK7, CK5, CK14, and CK15, is positive. Vimentin, p63, and SMA are other potentially positive markers [14,23]. Findings of our case were consistent with this, and the presence of epithelial components of positive CK-P staining differentiated it from the primary osteosarcoma.

Although the optimal management for this rare malignancy remains unclear, total mastectomy with surgical axillary staging is necessary for the follow-up treatment [24,25,26]. Currently, surgical management guidelines of MBC parallel the recommendation for IDC [27]. Breast-conserving surgery could be performed in patients with early-stage MBC; however, it is reported that modified radical mastectomy is often the preferred option for definitive surgical intervention due to larger tumor size, higher tumor grade, and hormone receptor negativity compared with IDC [28,29,30]. Axillary management is still important. It is reported that MBC patients with positive lymph nodes are associated with poor prognosis [21,31], although only 15–20% of MBC presents axillary nodal metastases [32], less frequently than hematogenous metastasis [12,33]. Therefore, a positive biopsy is recommended when US indicates a suspicious metastatic lymph node. In our case, a modified radical mastectomy was performed, with one axillary node metastasis in total (1/22).

Systemic therapy and/or RT have been received as components of the definitive treatment in most MBC patients, due to the negative prognosis associated with the histology and the increased likelihood of advanced-stage disease at presentation, although the optimal regimen remains undefined [25,34]. Studies have demonstrated variable responses to systemic therapy, it is reported that some MBC cases responded poorly to systemic chemotherapy and had a poor prognosis [35], while some [12,29,36] demonstrated better outcomes with chemotherapy, but no association between RT and prognosis of MBC. However, many studies have reported that postoperative RT is independently associated with improved overall survival and disease-specific survival in MBC patients [37,38,39,40]. In addition, a study of Polamraju et al. revealed that adjuvant chemotherapy and RT improved the prognosis of MBC patients [41]. Considering that the patient we reported was ER- and HER-2-negative MBC with 3.0 cm in size and one positive axillary node, according to the NCCN guidelines [24] and Chinese Society of Clinical Oncology guidelines [42], chemotherapy scheme of TEC and RT to infraclavicular region, supraclavicular area, and any part of the axillary bed at risk were sequentially performed.

The prognosis of MBC is poor [25]. A study comparing outcomes of 5,142 MBC and 50,705 TNBC patients suggested that the 5-year overall survival rate of MBC was 55%, which was less than that of TNBC with an overall survival rate of 72% [41]. It has been reported that approximately 50% of MBC patients present distant metastases after the primary surgery, with lungs and brain being the organs most commonly involved [39,43]. Similarly, the patient in our case was diagnosed with multiple organ metastases from breast invasive carcinoma 24 months later after surgery, including the liver and lungs, and died 3 months later.

For this case, first, it was a rare malignancy with ER, PR, and HER-2 negativity, and high proliferative index with Ki-67 (50%), and 3.0 cm in size and positive axillary lymph node; all the indicators implicated a poor prognosis. Secondly, the patient was advised to review breast carcinoma-related items every 6 months. However, she did not perform any checking items for 18 months since RT and admitted again for dyspnea and chest discomfort, and chest CT revealed scattered metastases to lungs, liver, and mediastinal lymph nodes. It is suggested that regular review plays a crucial role in early detecting metastases; simultaneously, active lifestyle, healthy diet, and timely intervention are important for improving prognosis.

4 Conclusion

MBC with osseous differentiation is an extremely rare type of MBC, with a prognosis poorer than that of TNBC. The origin of this disease remains unclear. Auxiliary examinations cannot provide specific information, and a final diagnosis is based on meticulous pathological and comprehensive immunohistochemical examinations. It is still controversial in operation selection, management of axillary lymph nodes, the role of adjuvant chemoradiotherapy, and RT. Further researches regarding the origin, imaging findings, and effective treatment methods are required to improve prognosis.


# These authors contributed equally to this work and share last authorship.


Acknowledgments

The authors thank the patient’s family members for allowing us to publish this case report. Meanwhile, we would like to thank Yuanyuan Shen and Yu Jiang for their assistance in supporting the US pictures.

  1. Funding information: Authors state no funding involved.

  2. Author contributions: Guarantor of integrity of the entire case study: H.C., T.H.B., X.J.M., T.F.Y., and F.D.Y. Study concepts and design: T.F.Y. and F.D.Y. Literature research: H.C., X.J.M., and F.D.Y. Imaging and data analysis: T.H.B. and X.J.M. Manuscript preparation: H.C. and F.D.Y. Manuscript revision: H.C., T.H.B., T.F.Y., and F.D.Y. All authors contributed to the article and approved the submitted version.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: All data generated or analyzed during this study are included in this published article.

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Received: 2023-02-25
Revised: 2023-05-11
Accepted: 2023-05-22
Published Online: 2023-07-24

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  12. Immunological responses of septic rats to combination therapy with thymosin α1 and vitamin C
  13. High glucose and high lipid induced mitochondrial dysfunction in JEG-3 cells through oxidative stress
  14. Pharmacological inhibition of the ubiquitin-specific protease 8 effectively suppresses glioblastoma cell growth
  15. Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1
  16. Age-related changes in peripheral T-cell subpopulations in elderly individuals: An observational study
  17. Single-cell transcription analysis reveals the tumor origin and heterogeneity of human bilateral renal clear cell carcinoma
  18. Identification of iron metabolism-related genes as diagnostic signatures in sepsis by blood transcriptomic analysis
  19. Long noncoding RNA ACART knockdown decreases 3T3-L1 preadipocyte proliferation and differentiation
  20. Surgery, adjuvant immunotherapy plus chemotherapy and radiotherapy for primary malignant melanoma of the parotid gland (PGMM): A case report
  21. Dosimetry comparison with helical tomotherapy, volumetric modulated arc therapy, and intensity-modulated radiotherapy for grade II gliomas: A single‑institution case series
  22. Soy isoflavone reduces LPS-induced acute lung injury via increasing aquaporin 1 and aquaporin 5 in rats
  23. Refractory hypokalemia with sexual dysplasia and infertility caused by 17α-hydroxylase deficiency and triple X syndrome: A case report
  24. Meta-analysis of cancer risk among end stage renal disease undergoing maintenance dialysis
  25. 6-Phosphogluconate dehydrogenase inhibition arrests growth and induces apoptosis in gastric cancer via AMPK activation and oxidative stress
  26. Experimental study on the optimization of ANM33 release in foam cells
  27. Primary retroperitoneal angiosarcoma: A case report
  28. Metabolomic analysis-identified 2-hydroxybutyric acid might be a key metabolite of severe preeclampsia
  29. Malignant pleural effusion diagnosis and therapy
  30. Effect of spaceflight on the phenotype and proteome of Escherichia coli
  31. Comparison of immunotherapy combined with stereotactic radiotherapy and targeted therapy for patients with brain metastases: A systemic review and meta-analysis
  32. Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation
  33. Association between the VEGFR-2 -604T/C polymorphism (rs2071559) and type 2 diabetic retinopathy
  34. The role of IL-31 and IL-34 in the diagnosis and treatment of chronic periodontitis
  35. Triple-negative mouse breast cancer initiating cells show high expression of beta1 integrin and increased malignant features
  36. mNGS facilitates the accurate diagnosis and antibiotic treatment of suspicious critical CNS infection in real practice: A retrospective study
  37. The apatinib and pemetrexed combination has antitumor and antiangiogenic effects against NSCLC
  38. Radiotherapy for primary thyroid adenoid cystic carcinoma
  39. Design and functional preliminary investigation of recombinant antigen EgG1Y162–EgG1Y162 against Echinococcus granulosus
  40. Effects of losartan in patients with NAFLD: A meta-analysis of randomized controlled trial
  41. Bibliometric analysis of METTL3: Current perspectives, highlights, and trending topics
  42. Performance comparison of three scaling algorithms in NMR-based metabolomics analysis
  43. PI3K/AKT/mTOR pathway and its related molecules participate in PROK1 silence-induced anti-tumor effects on pancreatic cancer
  44. The altered expression of cytoskeletal and synaptic remodeling proteins during epilepsy
  45. Effects of pegylated recombinant human granulocyte colony-stimulating factor on lymphocytes and white blood cells of patients with malignant tumor
  46. Prostatitis as initial manifestation of Chlamydia psittaci pneumonia diagnosed by metagenome next-generation sequencing: A case report
  47. NUDT21 relieves sevoflurane-induced neurological damage in rats by down-regulating LIMK2
  48. Association of interleukin-10 rs1800896, rs1800872, and interleukin-6 rs1800795 polymorphisms with squamous cell carcinoma risk: A meta-analysis
  49. Exosomal HBV-DNA for diagnosis and treatment monitoring of chronic hepatitis B
  50. Shear stress leads to the dysfunction of endothelial cells through the Cav-1-mediated KLF2/eNOS/ERK signaling pathway under physiological conditions
  51. Interaction between the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count in rats with LPS-induced pulmonary infection
  52. Meta-analysis of the rs231775 locus polymorphism in the CTLA-4 gene and the susceptibility to Graves’ disease in children
  53. Cloning, subcellular localization and expression of phosphate transporter gene HvPT6 of hulless barley
  54. Coptisine mitigates diabetic nephropathy via repressing the NRLP3 inflammasome
  55. Significant elevated CXCL14 and decreased IL-39 levels in patients with tuberculosis
  56. Whole-exome sequencing applications in prenatal diagnosis of fetal bowel dilatation
  57. Gemella morbillorum infective endocarditis: A case report and literature review
  58. An unusual ectopic thymoma clonal evolution analysis: A case report
  59. Severe cumulative skin toxicity during toripalimab combined with vemurafenib following toripalimab alone
  60. Detection of V. vulnificus septic shock with ARDS using mNGS
  61. Novel rare genetic variants of familial and sporadic pulmonary atresia identified by whole-exome sequencing
  62. The influence and mechanistic action of sperm DNA fragmentation index on the outcomes of assisted reproduction technology
  63. Novel compound heterozygous mutations in TELO2 in an infant with You-Hoover-Fong syndrome: A case report and literature review
  64. ctDNA as a prognostic biomarker in resectable CLM: Systematic review and meta-analysis
  65. Diagnosis of primary amoebic meningoencephalitis by metagenomic next-generation sequencing: A case report
  66. Phylogenetic analysis of promoter regions of human Dolichol kinase (DOLK) and orthologous genes using bioinformatics tools
  67. Collagen changes in rabbit conjunctiva after conjunctival crosslinking
  68. Effects of NM23 transfection of human gastric carcinoma cells in mice
  69. Oral nifedipine and phytosterol, intravenous nicardipine, and oral nifedipine only: Three-arm, retrospective, cohort study for management of severe preeclampsia
  70. Case report of hepatic retiform hemangioendothelioma: A rare tumor treated with ultrasound-guided microwave ablation
  71. Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling
  72. Rare presentation of double-clonal Waldenström macroglobulinemia with pulmonary embolism: A case report
  73. Giant duplication of the transverse colon in an adult: A case report and literature review
  74. Ectopic thyroid tissue in the breast: A case report
  75. SDR16C5 promotes proliferation and migration and inhibits apoptosis in pancreatic cancer
  76. Vaginal metastasis from breast cancer: A case report
  77. Screening of the best time window for MSC transplantation to treat acute myocardial infarction with SDF-1α antibody-loaded targeted ultrasonic microbubbles: An in vivo study in miniswine
  78. Inhibition of TAZ impairs the migration ability of melanoma cells
  79. Molecular complexity analysis of the diagnosis of Gitelman syndrome in China
  80. Effects of maternal calcium and protein intake on the development and bone metabolism of offspring mice
  81. Identification of winter wheat pests and diseases based on improved convolutional neural network
  82. Ultra-multiplex PCR technique to guide treatment of Aspergillus-infected aortic valve prostheses
  83. Virtual high-throughput screening: Potential inhibitors targeting aminopeptidase N (CD13) and PIKfyve for SARS-CoV-2
  84. Immune checkpoint inhibitors in cancer patients with COVID-19
  85. Utility of methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses
  86. Integrated analysis of the microbiome and transcriptome in stomach adenocarcinoma
  87. Berberine suppressed sarcopenia insulin resistance through SIRT1-mediated mitophagy
  88. DUSP2 inhibits the progression of lupus nephritis in mice by regulating the STAT3 pathway
  89. Lung abscess by Fusobacterium nucleatum and Streptococcus spp. co-infection by mNGS: A case series
  90. Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis
  91. Granulomatous polyangiitis involving the fourth ventricle: Report of a rare case and a literature review
  92. Studying infant mortality: A demographic analysis based on data mining models
  93. Metaplastic breast carcinoma with osseous differentiation: A report of a rare case and literature review
  94. Protein Z modulates the metastasis of lung adenocarcinoma cells
  95. Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro
  96. TAK-242, a toll-like receptor 4 antagonist, against brain injury by alleviates autophagy and inflammation in rats
  97. Primary mediastinum Ewing’s sarcoma with pleural effusion: A case report and literature review
  98. Association of ADRB2 gene polymorphisms and intestinal microbiota in Chinese Han adolescents
  99. Tanshinone IIA alleviates chondrocyte apoptosis and extracellular matrix degeneration by inhibiting ferroptosis
  100. Study on the cytokines related to SARS-Cov-2 in testicular cells and the interaction network between cells based on scRNA-seq data
  101. Effect of periostin on bone metabolic and autophagy factors during tooth eruption in mice
  102. HP1 induces ferroptosis of renal tubular epithelial cells through NRF2 pathway in diabetic nephropathy
  103. Intravaginal estrogen management in postmenopausal patients with vaginal squamous intraepithelial lesions along with CO2 laser ablation: A retrospective study
  104. Hepatocellular carcinoma cell differentiation trajectory predicts immunotherapy, potential therapeutic drugs, and prognosis of patients
  105. Effects of physical exercise on biomarkers of oxidative stress in healthy subjects: A meta-analysis of randomized controlled trials
  106. Identification of lysosome-related genes in connection with prognosis and immune cell infiltration for drug candidates in head and neck cancer
  107. Development of an instrument-free and low-cost ELISA dot-blot test to detect antibodies against SARS-CoV-2
  108. Research progress on gas signal molecular therapy for Parkinson’s disease
  109. Adiponectin inhibits TGF-β1-induced skin fibroblast proliferation and phenotype transformation via the p38 MAPK signaling pathway
  110. The G protein-coupled receptor-related gene signatures for predicting prognosis and immunotherapy response in bladder urothelial carcinoma
  111. α-Fetoprotein contributes to the malignant biological properties of AFP-producing gastric cancer
  112. CXCL12/CXCR4/CXCR7 axis in placenta tissues of patients with placenta previa
  113. Association between thyroid stimulating hormone levels and papillary thyroid cancer risk: A meta-analysis
  114. Significance of sTREM-1 and sST2 combined diagnosis for sepsis detection and prognosis prediction
  115. Diagnostic value of serum neuroactive substances in the acute exacerbation of chronic obstructive pulmonary disease complicated with depression
  116. Research progress of AMP-activated protein kinase and cardiac aging
  117. TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5
  118. Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target
  119. Metastasis from small cell lung cancer to ovary: A case report
  120. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury
  121. The effect of NK cell therapy on sepsis secondary to lung cancer: A case report
  122. Erianin alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation
  123. Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features
  124. Signalling pathways in the osteogenic differentiation of periodontal ligament stem cells
  125. Crosstalk between lactic acid and immune regulation and its value in the diagnosis and treatment of liver failure
  126. Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma
  127. Traumatic brain injury and rTMS-ERPs: Case report and literature review
  128. Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling
  129. Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
  130. The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles
  131. Inflammation-related signaling pathways in tendinopathy
  132. CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review
  133. Clinical analysis of severe Chlamydia psittaci pneumonia: Case series study
  134. Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane
  135. Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility
  136. Catharanthus roseus (L.) G. Don counteracts the ampicillin resistance in multiple antibiotic-resistant Staphylococcus aureus by downregulation of PBP2a synthesis
  137. Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia
  138. Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
  139. TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data
  140. Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway
  141. Ferroptosis: A potential target of macrophages in plaque vulnerability
  142. Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches
  143. Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins
  144. HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway
  145. IL-17 in osteoarthritis: A narrative review
  146. Circadian cycle and neuroinflammation
  147. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
  148. Hemorrhagic meningioma with pulmonary metastasis: Case report and literature review
  149. SPOP regulates the expression profiles and alternative splicing events in human hepatocytes
  150. Knockdown of SETD5 inhibited glycolysis and tumor growth in gastric cancer cells by down-regulating Akt signaling pathway
  151. PTX3 promotes IVIG resistance-induced endothelial injury in Kawasaki disease by regulating the NF-κB pathway
  152. Pancreatic ectopic thyroid tissue: A case report and analysis of literature
  153. The prognostic impact of body mass index on female breast cancer patients in underdeveloped regions of northern China differs by menopause status and tumor molecular subtype
  154. Report on a case of liver-originating malignant melanoma of unknown primary
  155. Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer
  156. The fibroblast growth factor–Klotho axis at molecular level
  157. Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations
  158. A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
  159. Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft
  160. Small breast epithelial mucin as a useful prognostic marker for breast cancer patients
  161. Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage
  162. Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
  163. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report
  164. Case report of atypical undernutrition of hypoproteinemia type
  165. Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer
  166. Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis
  167. Research progress of serum eosinophil in chronic obstructive pulmonary disease and asthma
  168. Clinicopathological characteristics of co-existing or mixed colorectal cancer and neuroendocrine tumor: Report of five cases
  169. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis
  170. Precisional detection of lymph node metastasis using tFCM in colorectal cancer
  171. Advances in diagnosis and treatment of perimenopausal syndrome
  172. A study of forensic genetics: ITO index distribution and kinship judgment between two individuals
  173. Acute lupus pneumonitis resembling miliary tuberculosis: A case-based review
  174. Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm
  175. Fractalkine modulates pulmonary angiogenesis and tube formation by modulating CX3CR1 and growth factors in PVECs
  176. Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function
  177. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms
  178. Evaluation of effects of small-incision approach treatment on proximal tibia fracture by deep learning algorithm-based magnetic resonance imaging
  179. An online diagnosis method for cancer lesions based on intelligent imaging analysis
  180. Medical imaging in rheumatoid arthritis: A review on deep learning approach
  181. Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach
  182. Utility of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in predicting acute-on-chronic liver failure survival
  183. A biomedical decision support system for meta-analysis of bilateral upper-limb training in stroke patients with hemiplegia
  184. TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
  185. Stochastic gradient descent optimisation for convolutional neural network for medical image segmentation
  186. Comparison of the prognostic value of four different critical illness scores in patients with sepsis-induced coagulopathy
  187. Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development
  188. Hepatobiliary surgery based on intelligent image segmentation technology
  189. Value of brain injury-related indicators based on neural network in the diagnosis of neonatal hypoxic-ischemic encephalopathy
  190. Analysis of early diagnosis methods for asymmetric dementia in brain MR images based on genetic medical technology
  191. Early diagnosis for the onset of peri-implantitis based on artificial neural network
  192. Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy
  193. Forecast of pain degree of lumbar disc herniation based on back propagation neural network
  194. SPA-UNet: A liver tumor segmentation network based on fused multi-scale features
  195. Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image
  196. Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke
  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
  198. ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis
  199. Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model
  200. Lung nodule segmentation via semi-residual multi-resolution neural networks
  201. Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI
  202. A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis
  203. Markov model combined with MR diffusion tensor imaging for predicting the onset of Alzheimer’s disease
  204. Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method
  205. Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis
  206. Monitoring and evaluation of anesthesia depth status data based on neuroscience
  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
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