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There are two forms of myeloma: Solitary plasmacytoma and multiple myeloma. Both are malignant tumors and develop from bone marrow plasma cells, which secrete immunoglobulins. Pleural effusion secondary to myeloma is extremely rare, with an incidence of 1–2%. A 58-year-old man presented to the emergency department with a chief complaint of swelling and pain over the left side of his chest, breathlessness, generalized weakness, abdominal pain, and blood in his stool for 15 days. The chest X-ray posteroanterior view showed well-defined homogenous opacity in the left hemithorax. The patient underwent ultrasound-guided left-sided thoracocentesis. Pleural fluid was exudative, and cytology showed the presence of malignant cells. Contrast-enhanced computed tomography of the thorax and abdomen showed a well- defined soft-tissue density lesion involving the left posteriolateral chest wall with underlying rib erosion. For confirmation of malignant etiology, a USG-guided transthoracic needle biopsy was performed. A biopsy revealed a malignant round cell tumor in a histopathological review. For confirmation, a tissue sample was sent for immunohistochemistry markers, which had positivity for CD 138 and MUM 1, consistent with myeloma. Rarely, MM can present as chest wall swelling. Ultrasound is an easily available diagnostic modality that can be used for chest wall biopsy with a minimal incidence of complications.

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Background: Bone marrow examination is a vital and indispensable part for the diagnosis of hematological and non-hematological disorders. For a complete diagnosis bone marrow aspirate (BMA), imprint and biopsy must be correlated including peripheral blood examination and clinical findings so that a definite opinion could be made. Aims and Objectives: The objective of the study is to know the correlation between bone marrow cytology, imprint, and biopsy in cases of pancytopenia. Materials and Methods: A total of 121 cases presenting with pancytopenia in whom BMA, imprint, and biopsy were done were retrospective analyzed in the study. BMAs and touch imprints were stained by Leishman’s stain. Perls’ stain and cytochemical stain as required were done on BMAs, and biopsies were fixed with 10% neutral formalin and slides were stained with hematoxylin/eosin and reticulin stain. Results: Correlation between aspirate and biopsy was 78.8% and that of bone marrow imprint and biopsy were 85.3%. The most common diagnosis was aplastic anemia followed by acute leukemia. Conclusion: BMA, imprint, and biopsy are complementary to each other and if performed together result in high rate of diagnostic accuracy.

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Introducción. La leucemia es el principal tipo de cáncer infantil, con una tasa de incidencia para 2022 de 5.5 por cada 100,000 menores. La hipercalcemia maligna es una de sus manifestaciones paraneoplásica grave y poco frecuente (incidencia global del 0.4 ­ 1.3%) en la población pediátrica. Objetivo. Presentar un caso de leucemia linfoblástica aguda que debutó con hipercalcemia severa. Descripción del caso. Se trata de una preescolar femenina de 3 años que inició con cuadro clínico caracterizado por dolores óseos y limitación funcional, los hemogramas iniciales no mostraron alteración de líneas celulares, las radiografías evidenciaron osteopenia generalizada, acompañado de hipercalcemia severa, paratohormona inhibida e hipercalciuria secundaria, que fueron manejados con hidratación endovenosa, diurético, esteroide y ácido zolendrónico. Así mismo, presentó desequilibrios electrolíticos que requirieron reposición de potasio y fósforo con adecuada respuesta. Se realizaron estudios de médula ósea, confirmándose el diagnóstico de leucemia linfoblástica aguda, recibió quimioterapia protocolo ALLIC 2009 con enfermedad refractaria al final de la fase de inducción, y finalmente trasplante haploidéntico de médula que fue exitoso. Discusión. La hipercalcemia maligna es una de las urgencias oncológicas endocrinológica con una incidencia baja, que es más frecuente en la población adulta, por lo que no es la primera impresión diagnóstica para considerar en pediatría, lo que lleva a retrasos en el diagnóstico etiológico y en pronóstico. Conclusión. La hipercalcemia acompañada de lesiones osteolíticas difusas puede ser la primera y única manifestación en la población infantil con diagnóstico de leucemia linfoblástica aguda, reconocerla permitirá llevar al inicio oportuno de tratamiento, impactando en sobrevida.

Introduction. Leukaemia is the leading childhood cancer, with a 2022 incidence rate of 5.5 per 100,000 children. In the pediatric population, Hypercalcaemia maligna is one of its rare and severe paraneoplastic manifestations (overall incidence 0.4 - 1.3%). Objective. To present a case of acute lymphoblastic leukemia that debuted with severe hypercalcemia. Case description. It is about a 3-year-old female preschooler who started with a clinical picture characterized by bone pain and functional limitation; initial haemograms showed no alteration of cell lines, radiographs showed generalized osteopenia, accompanied by severe hypercalcemia, inhibited parathyroid hormone and secondary hypercalciuria, which were managed with intravenous hydration, diuretic, steroid and zoledronic acid. She also presented electrolyte imbalances that required potassium and phosphorus replacement with adequate response. Bone marrow studies were performed, confirming the diagnosis of acute lymphoblastic leukemia; she received ALLIC 2009 protocol chemotherapy with refractory disease at the end of the induction phase, and finally, a haploidentical bone marrow transplant, which was successful. Discussion. Hypercalcemia of malignancy is one of the endocrinological oncological emergencies with a low incidence, which is more frequent in the adult population. So, it is not the first diagnostic impression to be considered in pediatrics, leading to delays in aetiological diagnosis and prognosis. Conclusion. Hypercalcaemia accompanied by diffuse osteolytic lesions may be the first and only manifestation in the pediatric population with a diagnosis of acute lymphoblastic leukemia. Recognizing it will lead to the timely initiation of treatment, with an impact on survival

Introdução. A leucemia é o principal tipo de câncer infantil, com uma taxa de incidência de 5.5 por 100,000 crianças em 2022. A hipercalcemia maligna é uma das suas manifestações paraneoplásicas graves e raras (incidência global de 0.4 ­ 1.3%) na população pediátrica. Objetivo. Apresentar um caso de leucemia linfoblástica aguda que teve início com hipercalcemia severa. Descrição do caso. Trata-se de uma criança pré-escolar do sexo feminino, de 3 anos, que apresentou um quadro clínico caracterizado por dores ósseas e limitação funcional. Os hemogramas iniciais não mostraram alterações nas linhas celulares, e as radiografias evidenciaram osteopenia generalizada, acompanhada de hipercalcemia severa, com paratormônio inibido e hipercalciúria secundária. O manejo incluiu hidratação endovenosa, diurético, esteroide e ácido zoledrônico. Da mesma forma, a paciente apresentou desequilíbrios eletrolíticos que exigiram reposição de potássio e fósforo, com resposta adequada. Foram realizados estudos de medula óssea, confirmando o diagnóstico de leucemia linfoblástica aguda. Ela recebeu quimioterapia seguindo o protocolo ALLIC 2009, mas apresentou doença refratária ao final da fase de indução, e, por fim, foi submetida a um transplante haploidêntico de medula, que foi bem-sucedido. Discussão. A hipercalcemia maligna é uma das urgências oncológicas endocrinológicas com baixa incidência, sendo mais comum na população adulta. Por isso, não é a primeira impressão diagnóstica a ser considerada em pediatria, o que pode resultar em atrasos no diagnóstico etiológico e no prognóstico da condição. Conclusão. A hipercalcemia acompanhada de lesões osteolíticas difusas pode ser a primeira e única manifestação na população infantil com diagnóstico de leucemia linfoblástica aguda. O reconhecimento precoce permitirá o início oportuno do tratamento, impactando positivamente na sobr evida.

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RESUMEN Las alteraciones en los recuentos celulares sanguíneos representan los hallazgos clínicos más notorios y recurrentes en pacientes que padecen enfermedad hepática, tanto aguda como crónica. Estos cambios constituyen un marcador importante de la disfunción hepática y, a menudo, desempeñan un papel crucial en la evaluación y manejo de estos pacientes. En conjunto con el alargamiento de las pruebas de coagulación, la trombocitopenia es la irregularidad más prevalente en estos individuos. Esta condición, así como las leucopenias, se le atribuye en gran medida al hiperesplenismo, una alteración en la que el bazo retiene y destruye las células sanguíneas, incluidas las plaquetas. Sin embargo, cuando el conteo plaquetario desciende por debajo de 10 x 103/µl, es fundamental considerar otras causas, como factores autoinmunitarios que pueden estar contribuyendo con la trombocitopenia. La anemia, definida como una disminución en el número de glóbulos rojos o en los niveles de hemoglobina, es otra característica constante que acompaña a la enfermedad hepática. Aunque en la mayoría de los casos la anemia es macrocítica, en algunas situaciones puede ser secundaria a eventos hemolíticos, como lo observado en el síndrome de Zieve. Esta diversidad en las manifestaciones de la anemia en pacientes hepáticos subraya la complejidad de las interacciones entre el hígado y los componentes sanguíneos. A pesar de los avances en la comprensión de las causas subyacentes de estas citopenias, las opciones del tratamiento siguen siendo limitadas. Generalmente, las opciones terapéuticas se enfocan en la administración de transfusiones de hemocomponentes para compensar las deficiencias en los recuentos celulares o en el uso de análogos de trombopoyetina (TPO) para estimular temporalmente la producción de las plaquetas en la medula ósea. No obstante, estos tratamientos tienden a abordar los síntomas más que las causas fundamentales de las alteraciones hematológicas en la enfermedad hepática. La persistencia y el empeoramiento de estas alteraciones pueden servir como indicadores tempranos de la progresión de la disfunción hepática. La relación intrincada entre el hígado y la homeostasis hematológica continúa siendo objeto de investigación, la compresión más profunda de estos mecanismos podría abrir potencialmente la puerta hacia enfoques terapéuticos más específicos y efectivos para abordar las citopenias en el contexto de la enfermedad hepática.

ABSTRACT Alterations in blood cell counts are the most prominent and recurrent clinical findings among patients suffering from both acute and chronic liver disease. These changes are an important marker of liver failure and often play a key role in the evaluation and management of these patients. Together with the prolongation of coagulation tests, thrombocytopenia is the most common disorder among these individuals. This condition, as well as leukopenia, is largely attributable to hypersplenism, a disorder in which the spleen retains and destroys blood cells, including platelets. However, when the platelet count drops below 10x103/µl, it is essential to consider other causes, such as autoimmune factors that may be contributing to the development of thrombocytopenia. Anemia, defined as a decrease in red blood cell count or hemoglobin levels, is another common characteristic of liver disease. Although in most cases macrocytic anemia occurs, in some situations it can be secondary to hemolytic events, as observed in Zieve's syndrome. This wide range of manifestations of anemia among liver patients highlights the complex interaction between liver and blood components. Despite advances in understanding the underlying causes of these cytopenias, treatment options remain limited. Therapeutic options generally focus on the transfusion of blood products to compensate for deficiencies in cell counts or on the use of thrombopoietin (TPO) analogues to temporarily stimulate platelet production in the bone marrow. However, these treatments tend to address the symptoms rather than the root causes of hematologic disorders in liver disease. The persistence and worsening of these disorders may serve as early indicators of the progression of liver failure. The complicated relationship between liver and hematological homeostasis remains the subject of research. A deeper understanding of these mechanisms could potentially open the door toward more targeted and effective therapeutic approaches to address cytopenias in the context of liver disease.

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Hypoplastic acute leukemia (HAL), also known as smoldering leukemia, is a form of atypical leukemia. It is a rare entity and currently defined as having cellularity of < 20% in bone marrow with >20% blasts at presentation. Hypocellular acute myeloid leukemia are more frequent than hypocellular variant of acute lymphoid leukemia. Although cases of hypoplastic acute myeloid in children and younger age group have been reported in literature, they are extremely rare. These cases pose a diagnostic challenge to the hematopathologist and treating physician, as hematological features of hypoplastic acute myeloid leuckemia (AML), hypocellular myelodysplastic syndrome and aplastic anemia are similar. Therefore, it is crucial to distinguish between these diseases as treatment modalities are different for each entity. Very few reported cases are available in literature. Hereby, we report this case of hypocellular AML-M0 in a 16-years-old Indian boy.

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Caracterizar o conhecimento dos graduandos de uma instituição de ensino superior acerca do processo de doação de medula óssea. Método: Trata-se de um estudo descritivo com abordagem quantitativa. Foram entrevistados 266 graduandos, de ambos os sexos, entre 17 e 21 anos de idade. Foi utilizado um questionário estruturado, contendo perguntas sobre o conhecimento a respeito do processo de doação de medula óssea. Resultados: A maioria dos participantes não conhece o processo de cadastro e doação de medula óssea, tendo como a falta de informação a principal causa para a desinformação a respeito do tema abordado, consequentemente resultando em pouca demanda para que mais pessoas sejam cadastradas no REDOME. Conclusão: os estudantes do ensino superior desconhecem os processos que envolvem desde ao cadastro até a doação de medula óssea, devido à desinformação e pouca divulgação sobre a temática. (AU)

To characterize the knowledge of undergraduates from a higher education institution about the bone marrow donation process. Method: This is a descriptive study with a quantitative approach. 266 undergraduates were interviewed, of both sexes, between 17 and 21 years old. A structured questionnaire was used, containing questions about their knowledge about the bone marrow donation process. Results: Most participants do not know the bone marrow registration and donation process, with lack of information being the main cause for misinformation about the topic addressed, consequently resulting in little demand for more people to be registered in REDOME. Conclusion: the higher education students are unaware of the processes that involve from registration to bone marrow donation, due to misinformation and little dissemination on the subject. (AU)

Caracterizar el conocimiento de estudiantes de grado de una institución de educación superior sobre el proceso de donación de médula ósea. Método: Se trata de un estudio descriptivo con abordaje cuantitativo. Se entrevistaron 266 estudiantes universitarios, de ambos sexos, entre 17 y 21 años. Se utilizó un cuestionario estructurado que contenía preguntas sobre el conocimiento sobre el proceso de donación de médula ósea. Resultados: La mayoría de los participantes desconocen el proceso de registro y donación de médula ósea, siendo la falta de información la principal causa de la desinformación sobre el tema abordado, por lo que se genera poca demanda para que más personas se registren en REDOME. Conclusión: los estudiantes de educación superior desconocen los procesos que involucran desde el registro hasta la donación de médula ósea, debido a la desinformación y poca difusión sobre el tema. (AU)

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Background : Filariasis is one of the major health concerns of tropical country like India, where it remains undiagnosed in conventional test but accidently detected in routinely advised Fine Needle Aspiration Cytology (FNAC) and fluid analysis test for different clinical diseases. Peripheral blood smear examination is usually done to detect Microfilaria, but it is difficult to detect it in routine peripheral blood smears. This study aims to highlight the importance of cytology as very effective diagnostic tool for diagnosis of Microfilaria. Material and Methods : The study was conducted in Department of Pathology, VIMSAR Burla Sambalpur, Odisha from June, 2020 to June, 2022. FNAC smears from superficial swelling, body fluid cytology and bone marrow smears were encountered in this study. FNAC and centrifused deposit of body fluid smears were stained with Diff Quik, PAP stain. Bone marrow smears were stained with Leishman stain. Results : A total of ten cases were diagnosed with Microfilaria on microscopic examination. Out of these, maximum (4 cases) of Filariasis were from breast swelling. Conclusion : The study highlights the importance of cytology as a cost effective tool for diagnosis of Microfilaria in endemic zones.

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SUMMARY: Senile osteoporosis is mainly caused by reduced osteoblast differentiation and has become the leading cause of fractures in the elderly worldwide. Natural organics are emerging as a potential option for the prevention and treatment of osteoporosis. This study was designed to study the effect of resveratrol on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in osteoporosis mice. A mouse model of osteoporosis was established by subcutaneous injection of dexamethasone and treated with resveratrol administered by gavage. In vivo and in vitro, we used western blot to detect protein expression, and evaluated osteogenic differentiation of BMSCs by detecting the expression of osteogenic differentiation related proteins, calcium deposition, ALP activity and osteocalcin content. Resveratrol treatment significantly increased the body weight of mice, the level of serum Ca2+, 25(OH)D and osteocalcin, ration of bone weight, bone volume/total volume, trabecular thickness, trabecular number, trabecular spacing and cortical thickness in osteoporosis mice. In BMSCs of osteoporosis mice, resveratrol treatment significantly increased the expression of Runx2, osterix (OSX) and osteocalcin (OCN) protein, the level of calcium deposition, ALP activity and osteocalcin content. In addition, resveratrol treatment also significantly increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT in BMSCs of osteoporosis mice. In vitro, resveratrol increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT, Runx2, OSX and OCN protein, the level of calcium deposition, ALP activity and osteocalcin content in BMSCs in a concentration-dependent manner, while SIRT1 knockdown significantly reversed the effect of resveratrol. Resveratrol can attenuate osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells, and the mechanism may be related to the regulation of SIRT1/PI3K/AKT pathway.

La osteoporosis senil es causada principalmente por una diferenciación reducida de osteoblastos y se ha convertido en la principal causa de fracturas en las personas mayores en todo el mundo. Los productos orgánicos naturales están surgiendo como una opción potencial para la prevención y el tratamiento de la osteoporosis. Este estudio fue diseñado para estudiar el efecto del resveratrol en la diferenciación osteogénica de las células madre mesenquimales de la médula ósea (BMSC) en ratones con osteoporosis. Se estableció un modelo de osteoporosis en ratones mediante inyección subcutánea de dexametasona y se trató con resveratrol administrado por sonda. In vivo e in vitro, utilizamos Western blot para detectar la expresión de proteínas y evaluamos la diferenciación osteogénica de BMSC detectando la expresión de proteínas relacionadas con la diferenciación osteogénica, la deposición de calcio, la actividad de ALP y el contenido de osteocalcina. El tratamiento con resveratrol aumentó significativamente el peso corporal de los ratones, el nivel sérico de Ca2+, 25(OH)D y osteocalcina, la proporción de peso óseo, el volumen óseo/ volumen total, el espesor trabecular, el número trabecular, el espaciado trabecular y el espesor cortical en ratones con osteoporosis. En BMSC de ratones con osteoporosis, el tratamiento con resveratrol aumentó significativamente la expresión de las proteínas Runx2, osterix (OSX) y osteocalcina (OCN), el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina. Además, el tratamiento con resveratrol también aumentó significativamente la expresión de SIRT1, p-PI3K/PI3K y p-AKT/AKT en BMSC de ratones con osteoporosis. In vitro, el resveratrol aumentó la expresión de las proteínas SIRT1, p-PI3K/PI3K y p- AKT/AKT, Runx2, OSX y OCN, el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina en BMSC de manera dependiente de la concentración, mientras que La caída de SIRT1 revirtió significativamente el efecto del resveratrol. El resveratrol puede atenuar la osteoporosis al promover la diferenciación osteogénica de las células madre mesenquimales de la médula ósea, y el mecanismo puede estar relacionado con la regulación de la vía SIRT1/PI3K/AKT.

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RESUMEN La primera causa de muerte por enfermedad infecto-contagiosa a nivel mundial es atribuible a la infección por Mycobacterium tuberculosis. La tuberculosis extrapulmonar representa entre un 20 % y un 25 % de los casos de enfermedad tuberculosa. Frecuentemente, para arribar al diagnóstico de dichas localizaciones, se debe recurrir a pruebas diagnósticas invasivas Se presenta el caso de un paciente de 17 años de edad con compromiso extrapulmo nar de tuberculosis en médula ósea sin inmunocompromiso conocido, con síntomas de fiebre, astenia, pérdida de peso, tricitopenia y hepatoesplenomegalia, sin otros hallazgos clínicos significativos. Se arriba al diagnóstico por cultivo positivo para tuberculosis en material de punción/ biopsia de médula ósea. Luego de un mes de tratamiento con isoniacida, pirazinamida, etambutol y rifampicina evoluciona con registros febriles aún después de recibir antibióticos por infección urinaria por Klebsiella pneumoniae, por lo cual se inicia corticoterapia oral con buena respuesta. El paciente abandona el tratamiento luego de tres meses y medio por mala adherencia a este.

ABSTRACT The leading cause of death from a contagious infectious disease worldwide is attribut able to Mycobacterium tuberculosis infection. Extrapulmonary tuberculosis accounts for 20-25 % of cases of tuberculous disease. Frequently, in order to reach the diagnosis of these sites, invasive diagnostic tests have to be used. We present the case of a 17-year-old patient with extrapulmonary tuberculosis with bone marrow involvement. The patient wasn't immunocompromised, and had the following symptoms: fever, asthenia, weight loss, tricytopenia and hepatosplenomegaly, without other significant clinical findings. The diagnosis was reached by positive culture for tuberculosis in bone marrow puncture aspiration/biopsy material After one month of treatment with isoniazid, pyrazinamide, ethambutol and rifampicin, the patient evolved with fever episodes, even after having received antibiotics for urinary tract infection caused by Klebsiella pneumoniae. Thus, oral corticosteroid therapy was started, with good response. The patient discontinued treatment after three and a half months due to poor adherence.

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Objective To investigate the targeted differentiation ability of mouse bone marrow derived mesenchymal stem cells(BM-MSCs)and adipose-derived mesenchymal stem cells(AD-MSCs).Methods BM-MSCs and AD-MSCs were isolated and cultured from bone marrow of femur and white adipose tissue of groin of C57BL/6J mice respectively,and the two types of cells were induced by osteogenic,chondrogenic and adipogenic differentiation medium respectively.Alizarin red,alcian blue and oil red O staining were used to detect the differentiated degree of osteogenic,chondrogenic and lipogenic differentiation.Real-time fluorescence quantitative PCR(qPCR)was used to identify MSCs and detected expression levels of directed differentiation-related genes Runx2,Sp7(osteoblast),Sox9,Col2a1(chondroblast),Pparg and Cebpa(lipogenesis)to determine the directed differentiation ability of cells.Based on gene expression profiles of mouse and human BM-MSCs and AD-MSCs in GEO database GSE43804 and GSE122778,the differentially expressed genes and their enrichment signal pathways were analyzed.Results The cell morphology of BM-MSCs and AD-MSCs obtained by isolation and culture was different,and spindle-shaped morphology was more obvious in AD-MSCs.Both cells expressed CD29,CD44 and CD90,but did not express CD34 and CD45.AD-MSCs showed higher osteogenic and lipogenic differentiation than those of BM-MSCs after directed induction,while chondrogenic differentiation was lower in AD-MSCs than that of BM-MSCs(P＜0.05).After directional induction,expression levels of Runx2,Pparg and Cebpa mRNA were higher in AD-MSCs than those in BM-MSCs,and Sox9 mRNA expression levels were lower than those in BM-MSCs(P＜0.05).Highly expressed genes of AD-MSCs in mice and human were enriched in PPAR and WNT signaling pathways.Highly expressed genes of BM-MSCs were enriched in cartilage and bone developmental signaling pathways.Conclusion The osteogenic and adipogenic differentiation ability of mouse AD-MSCs is stronger than those of BM-MSCs,while the chondrogenic differentiation ability AD-MSCs is weaker than that of BM-MSCs.The activation status of PPAR,WNT,cartilages and skeletal system development signaling pathways plays an important regulatory role in determining the different directional differentiation potential of AD-MSCs and BM-MSCs.

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BACKGROUND:Medical hydrogels are new functional polymer materials with three-dimensional structural networks and excellent biocompatibility,which have been widely studied in the field of tissue engineering and drug carriers,but the research on the combination of medical hydrogels and Chinese medicine for the treatment of diseases based on tissue engineering is still in the early exploration stage.Therefore,through the analysis of the mechanism of the role of medical hydrogels,the integration of medical hydrogels and Chinese medicine in the research of the joint application of the article,can better provide ideas for scientific researchers,and the joint application of Chinese medicine and medical hydrogels is of great significance. OBJECTIVE:To explore the strategy and significance of Chinese medicine combined with medical hydrogel for disease treatment based on tissue engineering research. METHODS:PubMed and CNKI were used to retrieve articles about the application of Chinese medicine combined with medical hydrogel in tissue engineering from January 2010 to November 2022,with the Chinese and English search terms"hydrogel,traditional Chinese medicine,drug carrier,tissue engineering".After the initial screening of all articles according to the inclusion and exclusion criteria,the 61 articles with high relevance were retained for review. RESULTS AND CONCLUSION:(1)Although the application of Chinese medicine combined with medical hydrogel is involved in intra-articular,intra-tissue organ,soft tissue wounds,tissue engineering,etc.,except for the clinical application of Chinese medicine combined with hydrogel dressing for soft tissue injury,other aspects are still in the experimental stage.(2)The development of Chinese medicine combined with medical hydrogel has great potential and development prospects,but there is a certain difficulty in the manufacture of the gel with high-performance requirements,and it is difficult to master the physical and chemical properties precisely.(3)At present,the comprehensive view of injectable hydrogel with the characteristics of easy to use,its joint use of Chinese medicine can be extended to a wider range,can be used for joint,organ,tissue engineering-related disease treatment.Smart hydrogel has high sensitivity and reversible transformation can also meet the use of the special environment.During the combined use of Chinese medicine,it also needs to understand the mechanism of action of Chinese medicine components.(4)The strategy of combining Chinese medicine with medical hydrogels for disease treatment should start with matching the therapeutic effects of Chinese medicine on organs,tissues and cells combined with appropriate types of medical hydrogels to make up for the shortcomings of traditional Chinese medicine delivery methods and frequent drug delivery.In tissue engineering,hydrogels can be loaded with stem cells after Chinese medicine intervention,or with both Chinese medicine and stem cells for disease treatment.(5)In future research of combined Chinese medicine and medical hydrogel application,we also need to consider:we should ensure that the biological properties of medical hydrogel can be quantified,and grasp the characteristics of hydrogel with different manufacturing processes of different materials to produce the required medical hydrogel that meets the application conditions.In Chinese medicine,we need to comprehensively understand and analyze the therapeutic effects and application mechanisms of known Chinese medicine monomer and Chinese medicine compound extracts,so as to achieve a more perfect combination between Chinese medicine and medical hydrogel under a more clear mechanism.With the continuous improvement of medical science and technology innovation,the medical hydrogel can be innovatively combined with other traditional treatment methods of Chinese medicine,such as acupuncture,massage,cupping and so on,to be used from multiple angles.

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BACKGROUND:Recent studies have shown that the occurrence and prevention of osteoporosis often focus on the cellular molecular level,and the mechanism of related signaling pathways is an important way to further understand osteoporosis.At present,traditional Chinese medicine has been proved to play a significant role in alleviating osteoporosis.Kaempferol as an emerging Chinese herbal extract has become the focus of clinical and basic research due to its anti-osteoporosis effectiveness and mechanism of action. OBJECTIVE:To further understand the mechanism underlying the anti-osteoporosis effect of kaempferol active monomer through regulation of related signaling pathways by analyzing and collating domestic and foreign literature. METHODS:"Kaempferol,osteoporosis,osteoblasts,osteoclasts,bone marrow mesenchymal stem cells,signaling pathways"were used as Chinese and English search terms to search CNKI,WanFang,VIP,PubMed,Web of Science and Embase databases for relevant literature published from database inception to February 2023. RESULTS AND CONCLUSION:Kaempferol affects the occurrence and progression of osteoporosis to varying degrees by participating in the regulation of differentiation,proliferation and apoptosis of bone marrow mesenchymal stem cells,osteoblasts and osteoclasts.Kaempferol can prevent and treat osteoporosis by regulating various signaling pathways.Kaempferol can promote the proliferation and differentiation of osteoblasts and inhibit the formation of osteoclasts by interfering with the Wnt/β-catenin signaling pathway to regulate β-catenin protein counting and the formation of β-catenin-TCf/LEF complex.Kaempferol interferes with the RANK/RANKL pathway to maintain the dynamic balance of osteoclasts and bone homeostasis.Kaempferol can promote bone formation by intervening with the PI3K/Akt signaling pathway to upregulate the levels of related osteogenic factors Runx2 and Osterix and promote bone cell calcification.Kaempferol interferes with osteoclast differentiation and inhibits reactive oxygen species activity by regulating the ER/ERK pathway.Kaempferol inhibits the expression of ERK,JNK,p38/MAPK and decreases reactive oxygen species production by interfering with the MAPK pathway,thus protecting osteogenesis.Kaempferol enhances the expression of osteogenic factors,bone morphogenetic protein-2,p-Smad1/5/8,β-catenin and Runx2,inhibits the expression of Peroxisome proliferation-activated receptor,and promotes the differentiation and proliferation of osteoblasts through the BMP/Smad pathway.

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BACKGROUND:The pathogenesis of osteoporosis is complex,and its essence is the weakening of bone formation and the enhancement of bone absorption caused by various reasons,resulting in the imbalance of bone metabolism.In recent years,N6-methyladenosine has been found(N6-methyladenosine,m6A)methylation can prevent and treat osteoporosis by regulating bone metabolism. OBJECTIVE:Taking the regulation of bone metabolism by m6A methylation as an entry point,to systematically sort out and summarize the research progress of m6A methylation in osteoporosis,so as to provide certain theoretical reference bases for the search of new therapeutic targets for osteoporosis. METHODS:CNKI,WanFang,VIP,PubMed,MEDLINE,Nature,and Cochrane databases were retrieved for relevant literature published from database inception to 2023.The keywords were"osteoporosis,m6A methylation,bone metabolism,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts"in Chinese and English.Duplicates and obsolete non-referenced documents were excluded,and a total of 73 standard papers were included for further review. RESULTS AND CONCLUSION:m6A methylation can affect the activity and differentiation of bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts through various pathways to regulate bone metabolism and prevent osteoporosis.The regulatory process of m6A methylation is extremely complex,and its related proteins play different roles in different cells.Even in the same kind of cells,the same type of proteins may have radically different roles,regulating different physiological and pathological processes.

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BACKGROUND:Osteoarthritis is one of the most common senile chronic degenerative diseases in China.Due to its complex pathogenesis and cellular molecular communication pathways,there is currently no effective method to slow down the progression of osteoarthritis.Studies have found that transforming growth factor-β is one of the key factors in the maintenance and regulation of joint stability and plays a significant role in the formation of early joints,as well as the development of bone and cartilage,and the remodeling of joints at various stages. OBJECTIVE:To review the regulatory role of the transforming growth factor-β subfamily in the occurrence and development of osteoarthritis,both domestically and internationally in recent years,to analyze the impacts it has at different stages of osteoarthritis,and to explore the potential application prospects of transforming growth factor-β in the clinical treatment of osteoarthritis,with a view to informing clinical treatment protocols.. METHODS:The relevant articles were searched by computer from CNKI Database and PubMed Database.The search terms were"osteoarthritis,transforming growth factor,signaling pathway,bone remodeling,cartilage degeneration,angiogenesis,treatment"in Chinese and English,respectively.Finally,57 articles were included for review. RESULTS AND CONCLUSION:The pathogenesis of osteoarthritis remains a subject of ongoing exploration with no unified consensus.Numerous studies highlight the close correlation between osteoarthritis and cytokines,focusing on the transforming growth factor-β superfamily as a pivotal mechanism and therapeutic breakthrough.Transforming growth factor-β plays a crucial role in early joint cartilage formation and maintenance,promoting cartilage repair.However,post-joint formation,its protective effect weakens,leading to potential destructive consequences.This dual regulatory role is a current clinical treatment focus,necessitating further research to delineate its application scope for standardized protocols.Highly active transforming growth factor-β participates in the regulation of bone cells,osteoblasts,and osteoclasts under mechanical stress,and intervenes in the subsequent remodeling of bone microstructure.Specific inhibitors present potential targeted therapeutics,yet their safety and efficacy in clinical settings require refinement.Vascular proliferation may serve as a potential disruptive pathway in transforming growth factor-β-mediated cartilage degeneration and subchondral bone remodeling.Abnormal communication pathways can further disrupt the homeostasis of the microenvironment of osteochondral units,thereby accelerating key pathological progressions of osteoarthritis.Research on transforming growth factor-β in osteoarthritic contexts is comprehensive,holding broad clinical application prospects.Drugs related to transforming growth factor-β are in clinical trial phases,but addressing potential impacts on other tissues and precise control of targeted delivery are critical concerns.As research advances,there is optimism for innovative breakthroughs in slowing the progression of osteoarthritis in the future.

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Fluorine is an important element widely present in nature, and moderate intake can prevent dental caries and promote bone development. However, long-term excessive intake can lead to fluorosis, damaging tissues or organs such as teeth, bones, heart muscle, and blood vessels. Bone marrow mesenchymal stem cells (BMSCs) play an important role in the repair process of bone injury due to their excellent multi-directional differentiation potential. Therefore, studying BMSCs is of great value in the treatment of fluorosis caused by fluoride poisoning. This article summarize the progress on the effect of fluoride on BMSCs, providing new ideas for the study of the pathogenesis and clinical treatment of fluorosis.

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Objective To investigate the molecular mechanism of sulforaphane(Sul)promoting bone marrow stem cells(BMSCs)differentiating into osteoblasts.Methods BMSCs were divided into the control group(without any treatment),induction group(induction of osteogenic differentiation),and induction+Sul group(induction of osteogenic differentiation with the addition of 40 μmol/L of Sul).The adenovirus-shRNA-Mock,-shRNA-TET1,-shRNA-TET2,and-shRNA-TET3 were transfected into BMSCs as the shRNA-Mock group,shRNA-TET1 group,shRNA-TET2 group,and shRNA-TET3 group.BMSCs were cultured in cell culture medium containing osteogenic differentiation induction medium and 40 μmol/L of Sul,and then transfected with adenovirus-shRNA-TET1,-shRNA-TET2,-shRNA-TET3,and-shRNA-Mock as the induction+Sul+shRNA-TET1 group,induction+Sul+shRNA-TET2 group,induction+Sul+shRNA-TET3 group,and induction +Sul+shRNA-Mock group.The mRNA and protein expression levels of Runx2 after BMSCs differentiated into osteoblasts were determined by qPCR and Western blot.The DNA content of Runx2 promoter region bound to Histone H3 after BMSCs differentiated into osteoblasts was determined by chromatin immunocoprecipitation(ChIP).The methylation level of Runx2 promoter region of BMSCs differentiated into osteoblasts was determined by HpaⅡenzyme and MspⅠenzyme digestion combined with qPCR.The degree of BMSCs differentiated into osteoblasts was determined by alizarin red staining.Results Compared with the induction group,the mRNA and protein expression levels of Runx2 in the induction+Sul group were significantly increased(P<0.05);the content of DNA in the Runx2 promoter region bound to Histone H3 was increased(P<0.05),the methylation level of Runx2 promoter region was reduced(P<0.05),and the alizarin red staining score was elevated(P<0.05).Compared with the induction+Sul group,the content of DNA in the Runx2 promoter region bound to Histone H3 in the induction+Sul+shRNA-TET1 group was decreased(P<0.05),the methylation level of Runx2 promoter region was increased(P<0.05),and the alizarin red staining score was decreased(P<0.05).While there was no significant change among the induction+Sul+shRNA-TET2 group,induction+Sul+shRNA-TET3 group,induction+Sul+shRNA-Mock group(P>0.05).Conclusion Sul can promote the differentiation of BMSCs into osteoblasts through promoting DNA demethylation of Runx2 promoter region by TET1.

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Objectives:To investigate the relationships between vertebral marrow fat in lumbar spine and age and gender in adults using iterative decomposition of water and fat with echo asymmetry and least-squares estimation image quantitation(IDE AL-IQ)magnetic resonance imaging technology.Methods:The IDEAL-IQ fat fraction images from 298 subjects(Male:138,Female:160,age range:20-69 years old)were collected.All the patients were divided into 5 groups based on age,with each group spanning a range of 10 years:age range 20-29 years(Twenties):24 males,20 females;30-39 years(Thirties):47 males,39 females;40-49 years(Forties):36 males,47 females;50-59 years(Fifties):20 males,37 females;60～69 years(Sixties):11 males,17 females.The bone marrow proton density fat fration(PDFF)were measured using GE ADW4.6 processing work station.Results:In the same age group,there were differences in vertebral bone marrow PDFF between gen-ders.PDFF of L1-L5 vertebrae was significantly higher in males than females in twenties,thirties and forties(P＜0.05).In the fifties,there was no statistically significant difference in the L1-L5 vertebrae PDFF between males and females(P＞0.05);while in the sixties,the PDFF of the L1-L5 vertebrae was lower in males than that in females(P＜0.05).The PDFF of lumbar vertebral bone marrow was positively correlated with age,with a higher correlation observed in females(r=0.72,P＜0.05)than that in males(r=0.32,P＜0.05).From the age of 20 to 69,the L4 vertebra PDFF in males had the highest growth rate(21.08％),while the L1 vertebra PDFF in female had the highest growth rate(65.68％).For males,the growth of PDFF was primarily concentrated in the thirties and fifties;The PDFF of L1,L4,and L5 vertebrae showed the largest increase in the fifties,while that of L2 and L3 vertebrae had the highest increase rate in the thirties.For females,vertebral PDFF showed a slight decrease trend in the group of thirties,which gradually increased subsequently in all vertebare in the group of forties,fifties,and sixties,with the largest increase rate observed in the fifties.Conclusions:There are differences in vertebral fat distribution between males and females across different age groups,and the growth rates of vertebral PDFF also vary;the PDFF of vertebral bodies in different segments of the lumbar spine is positively correlated with age.

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Objective To analyze the value of magnetic resonance proton density-weighted fat-saturated(PDWI-FS)sequence in the diagnosis of bone marrow edema(BME)in osteoarticular injury.Methods A total of 150 patients with bone and joint trauma were enrolled in the study.All patients underwent sagittal PDWI-FS sequence scan and conventional MRI sequence scan.The BME detection,signal intensity,image quality,and the signal-to-noise ratio and contrast-to-noise ratio of the lesions were compared between two methods.Results Both methods revealed that there were 225 sites of BME signs in 134 out of the 150 patients,with a higher prevalence in knee joint trauma patients.The signal intensity of the lesions was mainly grade 3 on PDWI-FS sequence and grade 2 on conventional MRI sequence,accounting for 97.78%(220/225)and 43.11%(97/225),indicating that the two methods graded signal intensity differently(Z=15.919,P<0.05).PDWI-FS sequence and conventional sequence had scores of 4.09±0.45 vs 3.88±0.39,3.65±0.42 vs 3.41±0.36,3.25±0.37 vs 3.14±0.35 and 4.21±0.38 vs 3.97±0.34 on lesion clarity,spatial resolution,anamorphosis and diagnostic confidence,and the former scored higher(t=4.319,5.314,2.645,5.765;P<0.05).The signal-to-noise ratio and contrast-to-noise ratio of the lesions on PDWI-FS sequence were 2.07±0.23 and 5.52±0.64,higher than 2.01±0.22 and 5.17±0.59 on conventional sequence,and the differences were statistically significant(t=2.309,4.925;P<0.05).Conclusion Compared with conventional MRI sequence,magnetic resonance PDWI-FS sequence can effectively enhance image quality and display lesions more clearly,providing more accurate information for the diagnosis of BME in osteoarticular injury.

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【Objective】 To investigate the effect and mechanism of musk-containing serum on the migration of bone marrow mesenchymal stem cells (BMSCs). 【Methods】 Sixty SD rats were randomly divided into four groups: musk-high-, medium- and low-dose groups and blank control group; medicated serum was prepared. Fifteen SD rats were isolated and cultured with BMSCs, and the third generation of BMSCs were identified by morphology, phenotype, osteogenic and adipogenic induction. BMSCs received medicinal healing intervention with high-, medium- and low- (16.8, 8.4, and 4.2 μL/100 g) musk, and the cell proliferation rate was detected by MTT assay. Under the intervention of the protein kinase C (PKC) signaling pathway (GF109203X), the effect of musk with pharmacition on the migration of BMSCSs was detected with the Transwell test. 【Results】 The rat BMSCs were attached to the wall, with orderly arrangement and good cell viability. Phenotypic identification revealed that the expressions of CD44 and CD90 were positive, while the expressions of CD45 and CD34 were negative, and the cells could differentiate into osteoblasts and adipocytes. The proliferation rates of BMSCSs with different concentrations at different time periods were higher than those in the blank control group (P0.05). 【Conclusion】 The mechanism of musk-containing serum in promoting BMSCs migration may be related to the activation of PKC signaling pathway.

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Objective:To investigate the effect of time-restricted feeding (TRF) on bone marrow fat of proximal femur in obese rats induced by high-fat diet (HFD) using proton density fat fraction (PDFF).Methods:Totally 30 male Sprague-Dawley rats were stratified and randomly sampled into 6 subgroups according to body weight, with 5 rats each. Then 2 subgroups were combined into one group, and there were totally 3 groups. The rats in the control group were fed with normal diet, and the rats could eat as much as they wanted for 24 h; the rats in the HFD group were fed with high-fat diet, and the rats could eat as much as they wanted for 24 h; the rats in the HFD+TRF group were fed with high-fat diet only between 9 AM (2 h after light) and 17 PM. One subgroup of rats from each group was examined with MRI on the femur on day 28 of the experiment, and the other subgroup from each group was examined on day 56 to measure the bone marrow PDFF of proximal femur based on mDixon-Quant quantitative sequence images. The rats were executed at the end of the scanning period, and blood samples were collected to measure serum levels of leptin. One-way ANOVA or Kruskal-Wallis H test was used to compare the differences in body weight, PDFF, and serum levels of leptin among 3 groups. The LSD- t test was used for multiple comparisons. Results:On day 28 of the experiment, the differences in body weight, PDFF, and serum leptin among the 3 groups of rats were not statistically significant ( P>0.05). On day 56, the bone marrow PDFF of proximal femur of the rats in the control group, HFD group, and HFD+TRF group were (7.2±1.4)%, (9.7±2.4)%, and (11.2±3.6)%, respectively. The differences in body weight, PDFF, and serum levels of leptin among the 3 groups of rats were statistically significant ( F=6.95, P=0.010, F=5.98, P=0.007, F=4.54, P=0.034). The results of multiple comparisons showed that the body weight in the HFD group was higher than those in the control group (LSD- t=52.96, P=0.036) and the HFD+TRF group (LSD- t=82.74, P=0.003). The values of bone marrow PDFF of proximal femur in the HFD+TRF group was higher than that in the control group (LSD- t=4.01, P=0.012). The serum levels of leptin in the HFD group were higher than those in the control group (LSD- t=1.45, P=0.030) and the HFD+TRF group (LSD- t=1.62, P=0.018). Conclusion:TRF induces an increase in the values of bone marrow PDFF of proximal femur in conjunction with weight loss in obese rats induced by HFD, and the increase in bone marrow fat may be related to the decrease in serum leptin.