Rare tumors pose significant challenges to clinical research, diagnosis, and therapy due to their low incidence, high molecular heterogeneity, and the lack of preclinical models.Conventional patient-derived cell lines and patient-derived tumor xenografts have significant limitations in recapitulating the characteristics of rare tumors. As an emerging in vitro biological model, organoids preserve the molecular characteristics of original tumors and possess high biological relevance, efficient amplification capabilities, and potential for personalized medicine applications. They have currently been applied in the research of various rare tumors. This review summarizes current research on organoid models of rare tumors derived from different tissue origins, and outlines current challenges and future development directions.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective To analyze the predictive value of microRNA-34a-5p(miR-34a-5p)expression in pancreatic cancer tissue on postoperative poor prognosis.Methods The surgically resected pancreatic cancer tissues and normal tissues adjacent to cancer from 123 patients with pancreatic cancer were collected to detect the expression of miR-34a-5p.The expression of miR-34a-5p in pancreatic cancer tissues for patients with different clinicopathological characteristics were compared.The patients were divided into the poor prognosis group and the good prognosis group according to their prognosis,and the clinical data of patients between the two groups was compared.The risk factors of poor prognosis for patients with pancreatic cancer were analyzed by Cox regression model,and the predictive value of miR-34a-5p expression in pancreatic cancer tissues on poor prognosis of patients was analyzed by receiver operating characteristic(ROC)curve.Results The expression of miR-34a-5p in pancreatic cancer tissues was lower than that in normal tissues adjacent to cancer(P<0.05).There were statistically significant differences in the expression of miR-34a-5p in pancreatic cancer tissues of patients with different differentiation degrees,TNM stages,and lymph node metastasis(P<0.05).The proportions of low differentiation,TNM stage for stage Ⅲ,lymph node metastasis and incisal margin of R1,and levels of carbohydrate antigen 199(CA199),neutrophils/lymphocytes ratio(NLR)and platelet/lymphocyte ratio(PLR)for patients in the poor prognosis group were higher than those in the good prognosis group(P<0.05),while miR-34a-5p expression was lower than that in the good prognosis group(P<0.05).Cox regression analysis showed that low differentiation,TNM stage for stage Ⅲ,lymph node metastasis,incisal margin of R1,decreased expression of miR-34a-5p and increased levels of CA199,NLR and PLR were risk factors of poor prognosis for patients with pancreatic cancer(P<0.05).ROC curve analysis showed that the optimal cut-off value of miR-34a-5p expression in pancreatic cancer tissue for predicting poor prognosis of patients was 0.48,the sensitivity was 78.82%,the specificity was 89.47%and the area under the curve was 0.855,with good predictive value.Conclusion The expression of miR-34a-5p in pancreatic cancer tissue is lower than that in normal tissue adjacent to cancer,and its expression is related to the differentiation degree,TNM stage and lymph node metastasis,which is also a risk factor and predictor of poor prognosis for patients with pancreatic cancer.

Objective:To investigate the effect of LINC00641 on the viability and apoptosis of acute myeloid leukemia(AML)cells and its mechanism.Methods:RT-qPCR was applied to detect the relative expression levels of LINC00641,miR-204-5p,and MT1X in human normal bone marrow stromal cell lines HS-5 and AML cell lines,and to screen the optimal cell line THP-1 was screened for subsequent experiments.Bioinformatics,dual luciferase reporter assay,pull down assay,and RIP assay were applied to validate the targeting relationship between LINC00641,MT1X and miR-204-5p.EdU,CCK-8,flow cytometry,and Transwell assay were applied to detect cell proliferation,apoptosis,migration and invasion,respectively.Western blot was applied to detect the expression of MT1X,CyclinD1,Bcl-2,and Bax proteins.Results:Compared with HS-5 cells,the expression of LINC00641 and MT1X was obviously increased in HL60,THP-1,U937,and KG1 cells,while the expression of miR-204-5p was obviously reduced(all P＜0.05).THP-1 cells showed the most obvious changes(P＜0.05).Silencing LINC00641 or overexpressing miR-204-5p was able to obviously inhibit the proliferation,migration and invasion of THP-1 cells,as well as the expression of CyclinD1 and Bcl-2 proteins,while promote cells apoptosis and Bax protein expression(all P＜0.05).Bioinformatics analysis,dual luciferase reporter assay,pull down assay,and RIP assay all confirmed that there were targeted relationships between LINC00641,MT1X and miR-204-5p.Inhibiting miR-204-5p or overexpressing MT1X was able to respectively reverse the inhibitory effect of silencing LINC00641 or overexpressing miR-204-5p on THP-1 cells proliferation,migration and invasion,and reduce cells apoptosis.Conclusion:LINC00641 is highly expressed in AML,and inhibition of LINC00641 expression can inhibit cell proliferation,migration,and invasion and increase apoptosis by regulating the miR-204-5p/MT1X axis.

The endoplasmic reticulum is an important organelle responsible for the synthesis,folding and processing of proteins.When the endoplasmic reticulum protein folding ability is affect-ed,internal unfolded proteins or misfolded proteins accumulate in the endoplasmic reticulum accumulation,leading to endoplasmic reticulum structural dysfunction resulting in endoplasmic reticu-lum stress.Autophagy is the process by which cells selectively remove stress endoplasmic reticulum and error proteins.Under stress,the endoplasmic reticulum can maintain normal physiolog-ical functions through unfolded protein responses and autophagy.Postmenopausal osteoporosis is mainly due to an imbalance be-tween bone resorption by osteoclasts and bone formation by oste-oblasts.Endoplasmic reticulum stress and autophagy both modu-late bone cells status with consequences for bone homeostasis.This article provides a review of the progress of research on en-doplasmic reticulum stress and autophagy interaction in the path-ogenesis of postmenopausal osteoporosis.

The endoplasmic reticulum is an important organelle responsible for the synthesis,folding and processing of proteins.When the endoplasmic reticulum protein folding ability is affect-ed,internal unfolded proteins or misfolded proteins accumulate in the endoplasmic reticulum accumulation,leading to endoplasmic reticulum structural dysfunction resulting in endoplasmic reticu-lum stress.Autophagy is the process by which cells selectively remove stress endoplasmic reticulum and error proteins.Under stress,the endoplasmic reticulum can maintain normal physiolog-ical functions through unfolded protein responses and autophagy.Postmenopausal osteoporosis is mainly due to an imbalance be-tween bone resorption by osteoclasts and bone formation by oste-oblasts.Endoplasmic reticulum stress and autophagy both modu-late bone cells status with consequences for bone homeostasis.This article provides a review of the progress of research on en-doplasmic reticulum stress and autophagy interaction in the path-ogenesis of postmenopausal osteoporosis.

Objective To analyze the predictive value of microRNA-34a-5p(miR-34a-5p)expression in pancreatic cancer tissue on postoperative poor prognosis.Methods The surgically resected pancreatic cancer tissues and normal tissues adjacent to cancer from 123 patients with pancreatic cancer were collected to detect the expression of miR-34a-5p.The expression of miR-34a-5p in pancreatic cancer tissues for patients with different clinicopathological characteristics were compared.The patients were divided into the poor prognosis group and the good prognosis group according to their prognosis,and the clinical data of patients between the two groups was compared.The risk factors of poor prognosis for patients with pancreatic cancer were analyzed by Cox regression model,and the predictive value of miR-34a-5p expression in pancreatic cancer tissues on poor prognosis of patients was analyzed by receiver operating characteristic(ROC)curve.Results The expression of miR-34a-5p in pancreatic cancer tissues was lower than that in normal tissues adjacent to cancer(P<0.05).There were statistically significant differences in the expression of miR-34a-5p in pancreatic cancer tissues of patients with different differentiation degrees,TNM stages,and lymph node metastasis(P<0.05).The proportions of low differentiation,TNM stage for stage Ⅲ,lymph node metastasis and incisal margin of R1,and levels of carbohydrate antigen 199(CA199),neutrophils/lymphocytes ratio(NLR)and platelet/lymphocyte ratio(PLR)for patients in the poor prognosis group were higher than those in the good prognosis group(P<0.05),while miR-34a-5p expression was lower than that in the good prognosis group(P<0.05).Cox regression analysis showed that low differentiation,TNM stage for stage Ⅲ,lymph node metastasis,incisal margin of R1,decreased expression of miR-34a-5p and increased levels of CA199,NLR and PLR were risk factors of poor prognosis for patients with pancreatic cancer(P<0.05).ROC curve analysis showed that the optimal cut-off value of miR-34a-5p expression in pancreatic cancer tissue for predicting poor prognosis of patients was 0.48,the sensitivity was 78.82%,the specificity was 89.47%and the area under the curve was 0.855,with good predictive value.Conclusion The expression of miR-34a-5p in pancreatic cancer tissue is lower than that in normal tissue adjacent to cancer,and its expression is related to the differentiation degree,TNM stage and lymph node metastasis,which is also a risk factor and predictor of poor prognosis for patients with pancreatic cancer.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Aim To explore the mechanism of Guso-ngYigu decoction(GSYG)in the treatment of postm-enopausal osteoporosis(PMOP)based on the gut mi-crobiota.Methods Sixty SPF grade SD rats were ran-domly divided into Control group(Control),Model group(Model),GSYG low-dose group(GSYG-L,1.25 g·kg-1),medium-dose group(GSYG-M,2.5 g·kg-1)and high-dose group(GSYG-H,5 g·kg-1)and alendronate group(Al,0.89 mg·kg-1),with 10 rats in each group.The changes of bone histomorpholo-gy were detected by HE staining and the changes of fe-mur tissue structure were observed by micro-CT.The fecal samples from the colon of Control group,Model group,GSYG-H group were taken to extract the DNA of fecal samples.The Illumina Miseq platform was used to carry out high-throughput sequencing.Results Compared with the Control group,bone trabecula in the Model group was sparse,BV/TV,Tb.Th,Tb.N and BMD decreased(P＜0.01),while SMI and Tb.Sp increased(P＜0.01);compared with the Model group,the number of bone trabeculae in GSYG-L,GSYG-M,GSYG-H group and Al group increased,the bone microstructure was improved,BV/TV,Tb.Th,Tb.N and BMD increased significantly(P＜0.05),and SMI and Tb.Sp increased(P＜0.05).Sequencing results of gut microbiota showed that,compared with the Control group,the gut microbiota diversity of Mod-el group decreased,the flora abundance of Firmicutes decreased,while the Bacteroidetes abundance in-creased.Compared with the Model group,the Firmi-cutes abundance increased and Bacteroidetes abundance decreased in GSYG-H group.Conclusions GSYG can improve bone microstructure and increase bone mineral density,and its mechanism may be related to increasing the diversity of gut microbiota and regulating the structure of gut microbiota.