Home Medicine Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
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Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report

  • Hongling Li EMAIL logo , Yang He , Yongying Wang and Mengwei Xu
Published/Copyright: January 19, 2024

Abstract

Multicentric Castleman disease (MCD) is a heterogeneous, life-threatening disease. A subgroup of HIV-negative and HHV-8-negative MCD is defined as idiopathic MCD (iMCD) with a poor prognosis. Here we report an unusual case of a 47-year-old male patient with iMCD who experienced multiple treatment regimens such as chemotherapy, immunomodulatory therapy, and targeted therapy, all of which were considered ineffective. Subsequently, he was started on bortezomib in combination with dexamethasone for six cycles and he was in complete remission. The patient has survived nearly 13 years to date – the longest survival of any iMCD patient treated with bortezomib in combination with dexamethasone. Bortezomib combined with dexamethasone may be an effective salvage strategy for severe and refractory iMCD.

1 Introduction

Multicentric Castleman disease (MCD) is a heterogeneous group of chronic lymphoid tissue proliferative disorders characterized by enlarged lymph nodes. This group of diseases shares common histopathological features, including hyaline-vascular, plasma cell (PC), and hyaline-vascular plasma cell type [1,2]. MCD involves multiple lymph node sites, which is distinguished from unicentric Castleman (UCD), and often presents with systemic symptoms such as fever, night sweats, malaise, edema, anemia, and elevated C-reactive protein (CRP) and hypoproteinemia [3]. MCD can be further divided into idiopathic MCD (iMCD), human herpesvirus type 8 (HHV8)-associated MCD, and MCD with POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) [1], where the etiology of HHV8-associated MCD is well-defined and effective treatments are available [4]. In contrast, the etiology and pathogenesis of HHV-8-negative iMCD have not been clearly defined to date. iMCD is widely believed to be driven by IL-6 signaling to develop the disease, but whether other signaling pathways and cytokines are involved remain unknown. iMCD is characterized by systemic symptoms, multiregional lymph node involvement, and the typical histopathological manifestations of Castleman’s disease. Autoimmune-related symptoms are more frequently observed in iMCD than in HHV8-related MCD and UCD, mainly including arthritis or renal insufficiency with proteinuria [5]. CD3+ lymphocytes are significantly higher in the lymph nodes and CD19+/CD5+ lymphocytes appear less frequently in patients with iMCD compared to patients with UCD [6]. In addition, unlike HHV8-associated MCD, iMCD is not correlated with plasmacytoid lymphoma and Kaposi’s sarcoma [7]. iMCD has a low incidence, with a prevalence of only 1,000–1,500 cases in the United States and a slightly higher incidence in Asian countries [8]. Consequently, clinical awareness and management of the disease are lacking, and prospective clinical trials are difficult to conduct, preventing the diagnosis and treatment of the disease from gaining momentum. The diversity of its clinical manifestations makes the diagnosis of iMCD more challenging, where clinical features such as PC variant subtype, age >40 years, TAFRO subtype, organ dysfunction, and inflammation levels are significantly associated with poor prognosis [9]. In addition, iMCD patients have a variable response to treatment, with only 10–20% of iMCD patients receiving glucocorticoids and chemotherapy achieving CR, and those who achieve CR often experience disease relapse within 1–2 years [9]. Furthermore, the overall prognosis of such patients is poor, with 5-year survival rates of only 51–77% [2]. In continuous exploration and conclusion, the first international consensus on iMCD treatment was published only in 2018, continuous clinical practice is still needed to evaluate the optimal treatment options applicable to each patient.

Currently, siltuximab and tocilizumab (an anti-IL-6 monoclonal antibody) are first-line agents for the treatment of iMCD and have been proven to be safe and effective in multiple practices. In a clinical trial, van Rhee et al. demonstrated that siltuximab significantly prolonged the life expectancy of patients with iMCD, with 34% achieving remission status, and that the incidence of adverse events associated with the drug was no higher than in the control group. It also reported no treatment-related deaths, so the drug can be considered as a safe agent [10,11]. Tocilizumab is a more personalized agent available to treat not only the disease itself but also a variety of complications in MCD patients such as thrombocytopenia, ascites, renal failure, and myelofibrosis as well as cardiomyopathy [1113]. Rituximab, which targets B lymphocytes, is used in the first-line treatment of HHV8-MCD. It is also used in combination with conventional chemotherapeutic agents (such as the R-CHOP) in the treatment of iMCD patients when anti-IL-6 agents are ineffective. The selective proteasome inhibitor bortezomib is only available as a second-line treatment option and beyond, but also offers hope for a proportion of iMCD patients [1]. Bortezomib in combination with dexamethasone, characterized by ablation of a highly activated immune system and blocking cytokine storm, is a second-line and above treatment option in patients with the worsening disease or in those who do not respond to siltuximab [5]. Of these, bortezomib is a selective and reversible class of 26S proteasome inhibitors, a drug that is thought to act by blocking the production of nuclear factor-κB-dependent cytokines, such as IL-6 [1416], which is essential in the pathogenesis of iMCD. In a prospective study [17], the bortezomib–cyclophosphamide–dexamethasone regimen has been well demonstrated for its efficacy and safety in patients with relapsed and refractory (R/R) iMCD, and such multidrug combination chemotherapy regimens may provide an additional treatment option for some patients with iMCD. Here we report an unusual case of a 47-year-old male with severe iMCD, characterized by a series of complications including anemia, pleural and peritoneal effusions, multi-organ failure, and pulmonary infections, which was successfully treated with bortezomib in combination with dexamethasone and achieved long-term survival.

2 Case presentation

A 47-year-old Chinese male was admitted to our hospital in April 2009. He reported bilateral lower limb edema with malaise for over 1 year, followed by a gradual onset of abdominal distention that lasted for 2 months. Physical examination revealed red papules on his face and an enlarged spleen with mild induration. No enlarged superficial lymph nodes were palpated and the rest of the medical history was unremarkable. His laboratory data revealed reduced levels of hemoglobin (11.7 g/dL; normal range, 12.0–16.0 g/dL) and albumin (2.65 g/dL; normal range, 3.5–5.5 g/dL), and elevated serum CRP levels (1.63 mg/dL; normal range, 0.0–0.8 mg/dL) (Figure 1). An abdominal computed tomography (CT) scan revealed hepatomegaly, splenomegaly, and effusion in the chest and abdominal cavity. Positron emission tomography-computed tomography (PET-CT) scan showed multiple enlarged retroperitoneal lymph nodes (maximum diameter 4 × 9 mm) (Figure 2). Subsequently, a bone marrow aspiration was performed and there were no significant abnormalities. As malignancy could not be completely excluded, a puncture biopsy of the enlarged abdominal lymph nodes was performed and the pathology was consistent with multicentric Castleman’s disease, PC type (Figure 3). Further examination of the patient’s peripheral blood was negative for HHV8 and HIV.

Figure 1 
               Representative laboratory data prior to and after application of different treatment regimens. Hemoglobin (a), albumin (b), CRP (c) levels, and ESR (d) improved with bortezomib combined with dexamethasone. (a: cyclophosphamide + vincristine + prednisone; b: cyclophosphamide + doxorubicin + vincristine + prednisone; c: interferon A + thalidomide; d: rituximab + interferon A + thalidomide; e: bortezomib + dexamethasone. Arrows represent the time of initiation of each treatment regimen.).
Figure 1

Representative laboratory data prior to and after application of different treatment regimens. Hemoglobin (a), albumin (b), CRP (c) levels, and ESR (d) improved with bortezomib combined with dexamethasone. (a: cyclophosphamide + vincristine + prednisone; b: cyclophosphamide + doxorubicin + vincristine + prednisone; c: interferon A + thalidomide; d: rituximab + interferon A + thalidomide; e: bortezomib + dexamethasone. Arrows represent the time of initiation of each treatment regimen.).

Figure 2 
               Fluorodeoxyglucose (FDG)-PET/CT scan at initial presentation revealed a mild abnormal accumulation of FDG in bilateral pleural effusion, as well as ascites, and multiple small lymph nodes (located behind the 12th thoracic and 4th lumbar vertebrae, with a diameter between 4 and 9 mm) (maximum standard uptake value: 1.8–2.2).
Figure 2

Fluorodeoxyglucose (FDG)-PET/CT scan at initial presentation revealed a mild abnormal accumulation of FDG in bilateral pleural effusion, as well as ascites, and multiple small lymph nodes (located behind the 12th thoracic and 4th lumbar vertebrae, with a diameter between 4 and 9 mm) (maximum standard uptake value: 1.8–2.2).

Figure 3 
               Lymph node biopsy showed multicentric Castleman’s disease of PC type. (a) Several lymphatic follicles were detected under light microscopy. The surrounding lymph nodes are arranged in concentric circles. The germinal center is atrophic, with a large number of PCs and a few lymphatic infiltrates in the interfollicles (hematoxylin and eosin, ×400). (b) Immunohistochemical (IHC) staining of cells by CD20 antibody, which shows positive follicular areas. (c) IHC staining CD138 PC expression is positive and shows cell membrane staining. (d) IHC staining CD3 and (e) CD68 interfollicular areas are scattered positive (IHC staining, ×20).
Figure 3

Lymph node biopsy showed multicentric Castleman’s disease of PC type. (a) Several lymphatic follicles were detected under light microscopy. The surrounding lymph nodes are arranged in concentric circles. The germinal center is atrophic, with a large number of PCs and a few lymphatic infiltrates in the interfollicles (hematoxylin and eosin, ×400). (b) Immunohistochemical (IHC) staining of cells by CD20 antibody, which shows positive follicular areas. (c) IHC staining CD138 PC expression is positive and shows cell membrane staining. (d) IHC staining CD3 and (e) CD68 interfollicular areas are scattered positive (IHC staining, ×20).

After diagnosis in April 2009, the patient was initially treated with the COP (cyclophosphamide, vincristine, and prednisone) chemotherapy regimen, which was replaced by the CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen in September 2009 due to lack of improvement in his symptoms. During the treatment period, he developed fever, cough, and worsening edema in his lower limbs, his hemoglobin dropped to 7.8 g/dL and white blood cells dropped to 2.5 × 109/L, which precluded him receiving further chemotherapy. Subsequently, the patient’s condition deteriorated dramatically, with a weight loss from 65 to 35 kg, a rapid increase in ascites and pleural effusion, and numerous episodes of anemia requiring blood transfusions with an Eastern Cooperative Oncology Group (ECOG) score of 4. In December 2009, the patient received 11 months of immunomodulatory therapy, mainly interferon A and thalidomide (100 mg/day), after which his general condition improved. Regrettably, the patient still had symptoms of anemia, no reduction in the enlarged retroperitoneal lymph nodes on CT scan, and the disease was still slowly progressing.

Hence, after discussing the treatment plan with the patient in March 2011, he received a regimen of bortezomib (1.3 mg/m2) combined with dexamethasone on Days 1, 4, 8, and 11, and repeated on Day 22. However, the patient had to interrupt his treatment after three cycles owing to the need for endoscopic retrograde cholangiopancreatography for his gallbladder stones. After surgery, the patient continued to receive three cycles of chemotherapy. At the end of treatment, a health assessment in April 2012 showed that the patient’s HB level and albumin level increased to 15.3 and 3.97 g/dL, respectively, and CRP and erythrocyte sedimentation rate (ESR) decreased to 0.809 mg/dL and 11 mm/h, respectively. His enlarged liver and spleen returned to normal size and the retroperitoneal lymph nodes were further reduced on CT images, with an ECOG score of 1. In general, the patient has well tolerated the medication with no adverse events during its administration. At the latest follow-up visit in February 2022, he had no recurrence of his disease and has returned to normal life and work.

  1. Informed consent: Informed consent has been obtained from the patient.

3 Discussion

Until now, iMCD has been known for over 10 years, but its etiology and pathogenesis remain elucidated [1]. Various studies have shown that overproduction of cytokines (IL-6 and vascular endothelial growth factor [VEGF]), viral infections other than HHV-8, and immune diseases play a critical role in the pathogenesis of some cases [3,18]. Targeting different treatment regimens for the cause of the disease has also been refined, including combination chemotherapy, B-cell depleting agents, immunomodulators, and anti-IL-6 targeting monoclonal antibodies. Owing to the heterogeneous and rare nature of iMCD, however, there is variability in the response to treatment in different individuals [19].

According to the consensus iMCD treatment guidelines [5] published in 2018, our case was identified as severe iMCD with a PC subtype of pathology and an unfavorable prognosis. With respect to the choice of the best treatment for this patient was a clinical challenge we faced. The results of a study [20] showed that CHOP regimen had an overall response rate of approximately 90% in iMCD, with 50% showing complete remission. In another prospective study [21], of the ten patients with iMCD treated with COP or CHOP, one had a complete remission and six had a partial remission, which was a more significant treatment effect. In our case, based on our experience with non-Hodgkin’s lymphoma, the patient was treated sequentially with a chemotherapy regimen of COP and CHOP. However, he only obtained a treatment response of disease stabilization and we abandoned this regimen. Subsequently, considering that iMCD may be due to an unexplained viral infection, the patient was treated with antiviral and immunomodulatory therapy. Interferon A and thalidomide, not only have immunomodulatory, antiviral, and anti-angiogenic effects but also have the property of inhibiting the production of the pro-inflammatory cytokines IL-1, IL-6, and IL-12 [19,22]. Unfortunately, only a partial response was achieved in our patients. The anti-CD20 drug rituximab, which is considered to be therapeutic that can cause lasting remission [23], did not yield any positive response in our patients. Siltuximab, an anti-IL-6 targeting monoclonal antibody, is currently the first-line therapy of choice for iMCD, but we did not have access to this drug.

Ultimately, the patient was started on bortezomib in combination with dexamethasone for a total of six cycles. Bortezomib is the first selective proteasome inhibitor to enter clinical practice and is currently used in the treatment of a variety of hematological disorders. One of the most successful applications is the treatment of adult multiple myeloma, with significant anti-tumor activity in both untreated and refractory/recurrent multiple myeloma (MM) patients [2426]. The drug inhibits the growth of MM tumor cells by inhibiting the activity of NF-κB and blocking the production of cytokines such as IL-6 and VEGF. In combination with dexamethasone, this inhibitory effect with synergy will play an even greater role [17,27]. IL-6 is also considered to be the main pathogenic mechanism of iMCD, causing B symptoms in the organism and also inhibiting albumin synthesis, which leads to pleural and abdominal effusions in patients [23]. To this extent, this may explain the initial clinical manifestations of our patient. IL-6 is thought to be intensively associated with the pathogenesis of PC tumors. Overexpression of IL-6 in IL-6 transgenic mice or introduction of IL-6-containing retroviruses into stem cells will induce iMCD [28], and monoclonal antibodies against IL-6 or IL-6 receptors developed at this stage against this target may attenuate the clinical manifestations associated with iMCD patients. The blockade of IL-6 by bortezomib may be part of what allowed our patients to achieve a good outcome.

In the iMCD PC subtype, IL-6 produced by lymph nodes may induce paracrine secretion of VEGF from PCs and vascular proliferation in the intercapsular region of the affected lymph nodes [27]. We speculate that bortezomib may exert a therapeutic effect in iMCD by inhibiting the above processes. We speculate that inhibition of the above processes by bortezomib is another reason for the therapeutic effect.

Nevertheless, about half of the iMCD patients failed to respond to IL-6 inhibition, suggesting that there may be other unknown cytokines and signaling pathways involved in the development of the disease [1]. There are other hypotheses proposed for the disease, partly iMCD patients overlap with autoimmune diseases [29], yet the patients we reported had no significant abnormalities in autoantibodies and therefore could not be tested from this aspect. The hypothesis that tumor cells drive iMCD is also interesting [29], but additional data are required to support this opinion.

Previously, cases of bortezomib combined with dexamethasone successfully treating MCD combined with myeloma have been reported, achieving excellent partial remission [15,30]. Sobas et al. [19] reported that bortezomib was effective in refractory MCD associated with POEMS. This suggests that this combination therapy may be a boon for patients with severe, refractory iMCD and that further clinical studies could be conducted to assess its potential therapeutic value.


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


Acknowledgements

The authors thank the patient and his family, as well as all the doctors at Gansu Provincial Hospital.

  1. Funding information: This study was supported by grants from the Hospital Internal Scientific Research Foundation of Gansu Province Hospital (No. 19SYPYA-3,20YF8WA096).

  2. Author contributions: H.L., Y.H., and Y.W. contributed equally to this work. H.L. treated the patient and revised the manuscript. Y.H. wrote the manuscript. Y.W. and M.X. were responsible for data collection. All authors have read and approved the final version of the manuscript and agreed to be responsible for all aspects of the manuscript.

  3. Conflict of interest: All authors declare that they have no competing interests.

  4. Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Received: 2022-10-26
Revised: 2023-07-04
Accepted: 2023-07-04
Published Online: 2024-01-19

© 2024 the author(s), published by De Gruyter

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

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  45. Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1
  46. Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model
  47. Clinical analysis of incomplete rupture of the uterus secondary to previous cesarean section
  48. Abnormal sleep duration is associated with sarcopenia in older Chinese people: A large retrospective cross-sectional study
  49. No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study
  50. Identification and validation of autophagy-related genes in SSc
  51. Long non-coding RNA SRA1 suppresses radiotherapy resistance in esophageal squamous cell carcinoma by modulating glycolytic reprogramming
  52. Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study
  53. The possible role of oxidative stress marker glutathione in the assessment of cognitive impairment in multiple sclerosis
  54. Compilation of a self-management assessment scale for postoperative patients with aortic dissection
  55. Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation
  56. Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study
  57. Clinical characteristics and assessment of risk factors in patients with influenza A-induced severe pneumonia after the prevalence of SARS-CoV-2
  58. Analgesia nociception index is an indicator of laparoscopic trocar insertion-induced transient nociceptive stimuli
  59. High STAT4 expression correlates with poor prognosis in acute myeloid leukemia and facilitates disease progression by upregulating VEGFA expression
  60. Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study
  61. HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis
  62. Mesenchymal stem cell-derived exosomal miR-26a induces ferroptosis, suppresses hepatic stellate cell activation, and ameliorates liver fibrosis by modulating SLC7A11
  63. Endovascular thrombectomy versus intravenous thrombolysis for primary distal, medium vessel occlusion in acute ischemic stroke
  64. ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis
  65. Prognostic value of EIF5A2 in solid tumors: A meta-analysis and bioinformatics analysis
  66. The role of enhanced expression of Cx43 in patients with ulcerative colitis
  67. Choosing a COVID-19 vaccination site might be driven by anxiety and body vigilance
  68. Role of ICAM-1 in triple-negative breast cancer
  69. Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2
  70. HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells
  71. Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome
  72. Efficacy of tacrolimus monotherapy in primary membranous nephropathy
  73. Mechanisms of Tripterygium wilfordii Hook F on treating rheumatoid arthritis explored by network pharmacology analysis and molecular docking
  74. FBXO45 levels regulated ferroptosis renal tubular epithelial cells in a model of diabetic nephropathy by PLK1
  75. Optimizing anesthesia strategies to NSCLC patients in VATS procedures: Insights from drug requirements and patient recovery patterns
  76. Alpha-lipoic acid upregulates the PPARγ/NRF2/GPX4 signal pathway to inhibit ferroptosis in the pathogenesis of unexplained recurrent pregnancy loss
  77. Correlation between fat-soluble vitamin levels and inflammatory factors in paediatric community-acquired pneumonia: A prospective study
  78. CD1d affects the proliferation, migration, and apoptosis of human papillary thyroid carcinoma TPC-1 cells via regulating MAPK/NF-κB signaling pathway
  79. miR-let-7a inhibits sympathetic nerve remodeling after myocardial infarction by downregulating the expression of nerve growth factor
  80. Immune response analysis of solid organ transplantation recipients inoculated with inactivated COVID-19 vaccine: A retrospective analysis
  81. The H2Valdien derivatives regulate the epithelial–mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway
  82. Clinical efficacy of dexamethasone combined with isoniazid in the treatment of tuberculous meningitis and its effect on peripheral blood T cell subsets
  83. Comparison of short-segment and long-segment fixation in treatment of degenerative scoliosis and analysis of factors associated with adjacent spondylolisthesis
  84. Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway
  85. Methylation regulation for FUNDC1 stability in childhood leukemia was up-regulated and facilitates metastasis and reduces ferroptosis of leukemia through mitochondrial damage by FBXL2
  86. Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
  87. Risk factors of postoperative airway obstruction complications in children with oral floor mass
  88. Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction
  89. Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022
  90. Evaluating anemia in HIV-infected patients using chest CT
  91. Ponticulus posticus and skeletal malocclusion: A pilot study in a Southern Italian pre-orthodontic court
  92. Causal association of circulating immune cells and lymphoma: A Mendelian randomization study
  93. Assessment of the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals on treating renal fibrosis: A systematic review and meta-analysis
  94. Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer
  95. New target-HMGCR inhibitors for the treatment of primary sclerosing cholangitis: A drug Mendelian randomization study
  96. Population pharmacokinetics of meropenem in critically ill patients
  97. Comparison of the ability of newly inflammatory markers to predict complicated appendicitis
  98. Comparative morphology of the cruciate ligaments: A radiological study
  99. Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator
  100. Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study
  101. SHP-1 mediates cigarette smoke extract-induced epithelial–mesenchymal transformation and inflammation in 16HBE cells
  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
  107. Analysis of the risk factors of the radiation-induced encephalopathy in nasopharyngeal carcinoma: A retrospective cohort study
  108. Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
  109. Evaluation of upper airway ultrasonographic measurements in predicting difficult intubation: A cross-section of the Turkish population
  110. Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer
  111. Postural stability after operative reconstruction of the AFTL in chronic ankle instability comparing three different surgical techniques
  112. Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis
  113. Frequency and clinicopathological correlation of gastrointestinal polyps: A six-year single center experience
  114. ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation
  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
  116. Effectiveness of nutritional support for clinical outcomes in gastric cancer patients: A meta-analysis of randomized controlled trials
  117. The relationship between IFN-γ, IL-10, IL-6 cytokines, and severity of the condition with serum zinc and Fe in children infected with Mycoplasma pneumoniae
  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
  119. Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case–control study
  120. Dioscin protects against chronic prostatitis through the TLR4/NF-κB pathway
  121. Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population
  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
  137. The unusual location of primary hydatid cyst: A case series study
  138. Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation
  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
  217. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment
  218. Special Issue Advancements in oncology: bridging clinical and experimental research - Part I
  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
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