OBJECTIVE: To screen novel diagnostic marker or therapeutic target for multiple myeloma (MM). METHODS: Sel1L, SPAG4, KCNN3 and PARM1 were identified by bioinformatics method based on GEO database as high expression genes in MM. Their RNA and protein expression levels in bone marrow mononuclear cells from myeloma cell lines U266, NCI-H929, MM.1s, RPMI8226 and leukemia cell line THP1, as well as 31 MM patients were evaluated by RT-PCR and Western blot, respectively. Meanwhile, 5 samples of bone marrow from healthy donors for allogeneic hematopoietic stem cell transplantation were employed as controls. RESULTS: Compared with leukemia cell line THP1, the expression levels of KCNN3, PARM1 and Sel1L mRNA were significantly increased in myeloma cell lines U266, NCI-H929 and MM.1s, while PARM1 was further increased in myeloma cell lines 8226. Western blot showed that the 4 genes were all expressed in the 4 myeloma cell lines. Compared with healthy controls, the expression levels of Sel1L, SPAG4, KCNN3 and PARM1 mRNA were significantly higher in MM patients (all P < 0.05). Western blot showed that the 4 genes were all expressed in MM patients, and the protein expression level of Sel1L and KCNN3 were significantly different compared with healthy donors (all P < 0.01). CONCLUSION Sel1L, SPAG4, KCNN3 and PARM1 may be potential diagnostic markers and therapeutic targets for MM.
Humans ; Multiple Myeloma/genetics* ; Cell Line, Tumor ; Proteins/metabolism* ; Computational Biology ; RNA, Messenger/genetics*

OBJECTIVE: To investigate the expression levels of EZH2 and KMT2D in patients with diffuse large B-cell lymphoma (DLBCL) and their relationship with pathological features. METHODS: 84 patients with DLBCL treated in our hospital from January 2021 to June 2022 were selected as the study subjects, and clinical characteristics such as sex, age and pathological classification of the patients were collected. Immunohistochemistry was used to detecet the expression of KMT2D and EZH2 proteins in tumor tissue cells of the DLBCL patients. The differential expression of KMT2D and EZH2 in subgroups of different sexes, ages, primary sites, clinical stages, Hans subtypes, etc. were compared. The correlation between the expression of KMT2D and EZH2 protein and BCL-6, CD79A was analyzed and validated through the interaction of protein molecular structures. We followed up and recorded the survival status of the patients for 12 months, and analyzed the factors that affect the mortality of DLBCL patients. RESULTS: The positive rate of KMT2D and EZH2 was high (over 95%) in DLBCL patients. There was no significant difference in the expression of EZH2 and KMT2D among subgroups of different sexes, ages and stages (P >0.05). However, patients with different levels of BCL-6 and CD79A expression showed differences in EZH2 and KMT2D expression (P < 0.05). EZH2 and KMT2D were positively correlated with BCL-6 (r =0.391, r =0.332) and CD79A (r =0.309, r =0.258), respectively, and there were interactions in the protein molecular structures. The risk factors for mortality in DLBCL patients include male sex (OR =1.106, 95%CI : 1.082-1.130, P < 0.001), stage II (OR =1.778, 95%CI : 1.567-2.016, P < 0.001), stage IV (OR =2.233, 95%CI : 2.021-2.467, P < 0.001), EZH2 positive (OR =2.762, 95%CI : 1.304-5.850, P =0.008), BCL-6 positive (OR =7.309, 95%CI : 1.340-39.859, P =0.022), age≥74 years (OR =3.080, 95%CI : 1.658-5.723, P < 0.001), and 63-73 years old (OR =2.400, 95%CI : 1.564-3.682, P < 0.001), while KMT2D positive (OR =0.180, 95%CI : 0.054-0.608, P =0.006) and 41-51 years old (OR =0.406, 95%CI : 0.274-0.603, P < 0.001) were factors which could reduce the risk of mortality. CONCLUSION EZH2 and KMT2D are highly expressed in patients with DLBCL, and they are positively correlated with BCL-6 and CD79A, and affect the prognosis of DLBCL patients.
Humans ; Enhancer of Zeste Homolog 2 Protein/metabolism* ; Lymphoma, Large B-Cell, Diffuse/metabolism* ; DNA-Binding Proteins/metabolism* ; Female ; Male ; Middle Aged ; Adult ; Neoplasm Proteins/metabolism* ; Aged ; Immunohistochemistry ; Proto-Oncogene Proteins c-bcl-6/metabolism* ; Prognosis

OBJECTIVE: To analyze the cytologic characteristics fine-needle aspiration using histology as the gold standard and to evaluate its diagnostic application in classic Hodgkin lymphoma. METHODS: A retrospective analysis was conducted on 17 patients who underwent both coarse-needle aspiration and fine-needle aspiration and were histologically confirmed with classic Hodgkin lymphoma(CHL) at our hospital from December 2012 to December 2023. Clinical information of these patients was collected, and the smear morphology, immunocytochemistry and corresponding biopsies were reviewed. RESULTS: Among the 17 cases of CHL, there were 5 cases of mixed cellularity, 10 cases of nodular sclerosis and 2 cases were unsubtyped. Fifteen cases were correctly diagnosed by fine-needle aspiration, with an accuracy rate of 88.2%. The other two cases were misdiagnosed as non-Hodgkin lymphoma. Morphologically single dispersed mononuclear Hodgkin cells and multinucleated Reed-Sternberg cells were observed in a heterogenous background of lymphocytes in cytology smears, and these cells were positive for CD30 immunocytochemistry. CONCLUSION Fine needle aspiration is less invasive and quicker, and the cell morphology is better preserved as compared to histological biopsy. It is easier to recognize pathognomonic Hodgkin or Reed-Sternberg cells and it is helpful for the rapid diagnosis and clinical management of CHL.
Humans ; Hodgkin Disease/pathology* ; Biopsy, Fine-Needle ; Retrospective Studies ; Female ; Immunohistochemistry ; Male

OBJECTIVE: To investigate the expression of specific AT sequence binding protein 1 (SATB1) in diffuse large B cell lymphoma (DLBCL) and its relationship with clinicopathological features and prognosis. METHODS: A total of 68 cases of initially diagnosed with DLBCL at Guangxi Medical University Affiliated Tumor Hospital between January 2008 to December 2015 were enrolled. The expression of SATB1 were detected by Immunohistochemistry on paraffin embedded tissue of patients. The relationship between the expression of SATB1 and clinicopathological features and prognosis in patients with DLBCL was analyzed. RESULTS: SATB1 protein was mainly expressed in cytoplasm of lymphoma cell. The rate of SATB1 expression in DLBCL tissues was 66.2% (46/68). The positive rate of SATB1 in patients with ECOG score of 0-1 was higher than that in patients with ECOG score ≥2 (P <0.05). The 5-year progression-free survival (PFS) and 5-year overall survival (OS) in positive and negative SATB1 groups were 55.5% and 23.5%, respectively (P =0.045), and 65.6% and 34.9%, respectively (P <0.001). Univariate analysis showed that positive expression of SATB1 was associated with good OS of patients. Multivariate analysis showed that chemotherapy cycles less than 4 and elevated LDH were independent adverse prognostic factor for OS in DLBCL patients, with positive SATB1 expression as a protective factor. CONCLUSION The positive expression of SATB1 is closely associated with a lower ECOG score and a favorable prognosis in patients with DLBCL.
Humans ; Lymphoma, Large B-Cell, Diffuse/metabolism* ; Matrix Attachment Region Binding Proteins/metabolism* ; Prognosis ; Female ; Male ; Middle Aged ; Immunohistochemistry ; Adult

Hyalinizing clear cell carcinoma of the salivary gland is a rare neoplasm, accounting for only less than 1% of malignancies arising from the salivary gland. It is molecularly defined by the expression of the EWSR-ATF1 fusion oncogene. To date, there has been no previous studies published yet in the Philippines regarding the existence of this tumor. In this paper, we present a case of a 70-year-old elderly female who had a 10-year history of a gradually enlarging left lateral neck mass. Histopathologic examination showed a tumor arranged of cords, nests, and trabeculae of monomorphic round cells with abundant clear to lightly eosinophilic cytoplasm surrounded by thick hyalinized collagen bundles. Immunohistochemistry and molecular studies were done which revealed a positive p63 staining, negative SMA and S100, and an EWSR1 rearrangement in Fluorescence in situ hybridization (FISH), thus, confirming the diagnosis.

BACKGROUND

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). Classification of DLBCL is often based on the cell of origin (COO), distinguishing between germinal center B-cell (GCB) and non-GCB subtypes. Although not yet recognized as a distinct entity by the World Health Organization (WHO), double expressor lymphoma (DEL), characterized by the co-expression of c-MYC and BCL2, carries an unfavorable prognosis for a subgroup of DLBCL patients. Another entity is the so-called high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit/triple-hit lymphomas) diagnosed through fluorescent in-situ hybridization (FISH) analysis.

This study aimed to determine the clinicopathologic profile and survival outcomes of Filipino DLBCL patients at the Philippine General Hospital (2016-2021), comparing double-hit versus non-double-hit and doubleexpressor versus non-double-expressor lymphomas, and assessing concordance between FISH-measured double-hit and IHC-measured double-expressor statuses.

This is a single-arm, retrospective cohort study involving all surgical pathology cases signed out, with the aid of immunohistochemistry (IHC) studies, as NHL DLBCL, GCB, or non-GCB subtype, from 2016 to 2021. A second panel of IHC studies and FISH analysis using tissue microarray was subsequently done. Most cases exhibited a nonGCB subtype and were classified as DEL on second IHC panel. Five out of eleven DEL cases were reclassified as double hit lymphoma (DHL).

Clinically, most patients with these lymphomas present at age 60 years and below, exhibit B symptoms, with elevated serum lactate dehydrogenase (LDH) levels, at least stage III-IV disease at diagnosis, and possess a high International Prognostic Index (IPI) score, collectively indicating a poor prognosis.

Survival outcomes for patients with DLBCL ranges from three to 37 months. All cases of mortality were associated with DEL, contrasting with DHL cases which had variable outcomes. Due to limited sampling, statistical significance of the results cannot be determined. A comprehensive evaluation is essential to the diagnosis of DLBCL and DHL to include a complete immunohistochemistry panel and molecular testing, notably with FISH studies.

BACKGROUND AND OBJECTIVE

Anatomical education utilizes mainly cadaver dissection, but it also depends on innovations such as novel preservation techniques, simulation models, and virtual dissection apps. There is no review on anatomical patents. This study aimed to review the worldwide landscape of existing patents on anatomical education to identify gaps and opportunities for utilization and further innovations.

We conducted a scoping review for inventions, utility models, and industrial design applications on anatomical education. We searched the following databases as of December 31, 2022 (WIPO Patentscope, Espacenet, and Derwent). We deduplicated the records, screened them for eligibility, and extracted information on characteristics of the patent application and applicant. We computed frequency and percentage according to country, type of applicant, number of inventors, type of patent, scope of patent, purpose of patent, organ system, status of patent, and time to patent granting.

Out of 667 merged records from the initial search, we removed 312 duplicates, excluded 97 records, and included 258 reports in the review. The median number of patent applications per year was 58 (range, 32, 61). Majority of the applications were from China and USA (36.0 and 34.9%, respectively), national in scope (62.8%), industry as applicant (49.6%), inventions (77.5%), usable beyond anatomy (70.9%), physical models (53.1%) and with pending status (63.6%). The median time to granting for 65 patents was 316 days (range, 40 to 1568).

For the period 2018-2022, there were 258 patent applications related to anatomical education, both as a basic science and in clinical applications, were mostly inventions, applied for by industry, contributed by US and China, only national in scope, physical 3D models (mostly musculoskeletal, head/neck and sensory organs, and whole body), and usable beyond basic anatomy. The majority of patent applications are still pending with only 65 granted patents. Plastinated specimens, and the urinary, reproductive, and pulmonary organ system models were least represented.

BACKGROUND

The COVID-19 pandemic resulted in the lack of traditional cadaveric dissection among first year medical students in Anatomy courses in the University of the Philippines College of Medicine. The Learning Enhancement in Anatomy Program (LEAP) was implemented as a bridging program to enhance knowledge and understanding of gross anatomy and histology. As part of this program, a novel multi-strategy teaching method was conducted for the Integumentary and Musculoskeletal Anatomy Module.

This case study described a novel multi-strategy teaching method on Integumentary and Musculoskeletal anatomy for first year medical students which was done after the COVID-19 pandemic wherein there was a shortage of cadavers. By describing this multi-strategy teaching method, this case study aims to present a potential alternative teaching method in a situation where there is an unexpected shortage of human cadavers.

A retrospective review of documents related to this teaching method among first year medical students at the University of the Philippines College of Medicine was conducted from November 15, 2023, to January 15, 2024. The novel teaching method for the Integumentary and Musculoskeletal station was taught using five different methods: proctor demonstration, a prosected lower extremity with a self-directed manual, dissection education videos viewed on a large screen, skeletons for osteology, and individual light microscopes with a self-directed laboratory histology manual. We described the data and analyzed according to strengths and limitations, and formulated recommendations to improve the module.

The Integumentary and Musculoskeletal Module of the LEAP provided an interactive, hands-on experience in anatomy education. The five-pronged method facilitated a multifaceted approach to learning through cadaveric prosections, self-directed manuals, dissection videos, osteology exercises, and microscopic study. There was active engagement, overall positive student feedback, and increased post-test scores. However, certain limitations, such as the lack of direct cadaveric dissection, potential underutilization of histology components, and reliance on faculty guidance, highlight areas for improvement.

The Integumentary and Musculoskeletal Module of the LEAP has demonstrated significant strengths in enhancing anatomical education through a multimodal approach that fosters active learning, improves knowledge retention, and provides a structured curriculum adaptable to various resource constraints. Student feedback and test performance support the effectiveness of the module, particularly in gross anatomy. Addressing challenges in future iterations will be crucial in refining the program and expanding its applicability to different educational contexts. By building on its strengths and mitigating its weaknesses, this five-pronged method can continue to serve as a model for innovative and effective anatomy education. 

Gliomatosis peritonei (GP) is a condition characterized by the dissemination of mature glial tissues throughout the peritoneal cavity. It is usually associated with immature ovarian teratoma but presents with mature cystic teratoma (MCT) in 1% of cases. GP, associated with MCT, is a benign disorder. The majority of cases remain asymptomatic and rarely recur. Here, we present a case of a 22-year-old woman with a history of abdominal enlargement and severe abdominal pain who underwent exploratory laparotomy, peritoneal fluid cytology, bilateral salpingo-oophorectomy, appendectomy, omental biopsy, and Jackson-Pratt drain insertion with histopathologic result of GP with MCT. A month later, the patient had a recurrence of abdominal enlargement, necessitating a second surgery. Immunohistochemistry for histopathologic evaluation and diagnostic imaging are crucial in confirming the diagnosis and guiding the treatment strategy. A multidisciplinary team approach in monitoring and comprehensive support is significant in optimizing outcomes for patients with aggressive GPs associated with MCT. Further research and clinical experience are essential to establish a standardized guideline to improve the management and clinical outcome of this condition.

BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Humans ; Female ; Polycystic Ovary Syndrome/metabolism* ; Endometrium/metabolism* ; Sirtuin 3/genetics* ; Oxidative Stress/genetics* ; Adult ; Animals ; Mice ; Apoptosis/physiology* ; Immunohistochemistry ; Cell Proliferation/physiology*