Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.
Humans ; Neoplasms/pathology* ; Biomarkers ; Prognosis ; Oceans and Seas ; China/epidemiology*

Objective:To explore the influencing factors of acute bilirubin encephalopathy (ABE) in neonates with severe hyperbilirubinemia.Methods:A total of 123 cases of severe neonatal hyperbilirubinemia (serum total bilirubin > 342 μmol/L) in our hospital from January 2018 to May 2020 were retrospectively analyzed.According to the occurrence of ABE, they were divided into ABE group (28 cases) and non-ABE group (95 cases). The perinatal data and laboratory examination results between two groups were compared.The variables with statistical differences in univariate analysis were included in multivariate Logistic regression analysis.Results:Univariate analysis showed that the hemoglobin level and hematocrit of ABE group were higher than those of non-ABE group.The total bilirubin value, length of hospital stay, natural childbirth, mixed feeding, infection with craniocerebral hemorrhage were all higher than those in the non-ABE group, and the differences were statistically significant( P<0.05). Multivariate Logistic regression analysis showed that high hemoglobin level ( OR=1.032, 95% CI 1.007 to 1.057) and long hospital stay ( OR=1.15, 95% CI 1.007 to 1.312) were independent risk factors for ABE patients.Breastfeeding was a protective factor for ABE patients( OR=0.151, 95% CI 0.028 to 0.821). Conclusion:High hemoglobin value and long hospital stay are independent risk factors for ABE patients, and breast feeding is a protective factor for ABE.

Henoch-Schonlein purpura (HSP) is a type of systemic leucocytoclastic vasculitis mediated by IgA immune complex deposition, which mainly affects the skin, joints, gastrointestinal tract and small blood vessels in the glomeruli.It is a common systemic vasculitis in children.Due to severe complications of HSP, conventional clinical medicine has limited efficacy in some serious, even life-threatening or organ dysfunction cases, such as advanced renal insufficiency, fatal gastrointestinal bleeding, nervous vasculitis, pulmonal bleeding, etc.As an adjunctive therapy, plasma exchange has led to significant results for this type of HSP.In this paper, the status of plasma exchange in HSP treatment was reviewed.

As a member of the AFF (AF4/FMR2) family, AFF4 is a transcription elongation factor that is a component of the super elongation complex. AFF4 serves as a scaffolding protein that connects transcription factors and promotes gene transcription through elongation and chromatin remodelling. Here, we investigated the effect of AFF4 on human dental follicle cells (DFCs) in osteogenic differentiation. In this study, we found that small interfering RNA-mediated depletion of AFF4 resulted in decreased alkaline phosphatase (ALP) activity and impaired mineralization. In addition, the expression of osteogenic-related genes (DLX5, SP7, RUNX2 and BGLAP) was significantly downregulated. In contrast, lentivirus-mediated overexpression of AFF4 significantly enhanced the osteogenic potential of human DFCs. Mechanistically, we found that both the mRNA and protein levels of ALKBH1, a critical regulator of epigenetics, changed in accordance with AFF4 expression levels. Overexpression of ALKBH1 in AFF4-depleted DFCs partially rescued the impairment of osteogenic differentiation. Our data indicated that AFF4 promoted the osteogenic differentiation of DFCs by upregulating the transcription of ALKBH1.
Biomarkers ; metabolism ; Cell Differentiation ; Cells, Cultured ; Dental Sac ; drug effects ; metabolism ; Gene Expression Regulation ; Humans ; Osteogenesis ; genetics ; Repressor Proteins ; Transcription Factors ; genetics ; metabolism ; Transcriptional Elongation Factors ; metabolism

Objective:To evaluate the characteristics and risk factors for blood transfusion in very low birth weight infants(VLBWI).Methods:Clinical data of one hundred VLBWI, hospitalized from July, 2016 to June, 2019, were studied retrospectively.The infants were divided into two groups according to whether they received blood transfusion.The general information, incidence of diseases and treatment measures were compared between two groups.The risk factors influencing the blood transfusion were analyzed.Results:Of the one hundred VLBWI, sixty-nine cases needed blood transfusion.The first time of blood transfusion ranged from one to four weeks after birth, and average number of transfusions was 6 times.Maternal anemia during pregnancy, birth weight, gestational age, hemoglobin and hematocrit at birth, volume of blood taking within two weeks after birth, duration of hospitalization, duration of paraenteral nutrition, delivery method, need for intubation and neonatal respiratory distress syndrome, apnea, bronchopulmonary dysplasia, patent ductus arteriosus showed significant differences between the two groups( P<0.05). Logistic regression analysis revealed that lower gestation( OR=0.386, 95% CI 0.212-0.704, P=0.002), longer duration of hospital stay( OR=2.177, 95% CI 1.170-4.049, P=0.014), prolonged parenteral nutrition( OR=1.195, 95% CI 1.083-1.319, P<0.001), greater volume of blood taking within two weeks after birth ( OR=1.269, 95% CI 1.083-1.487, P=0.003)and cesarean delivery( OR=5.513, 95% CI 1.056-28.770, P=0.043) were associated with increasing risk of blood transfusion in VLBWI. Conclusion:The gestational age, length of hospital stay, blood intake within two weeks after birth, duration of paraenteral nutrition and delivery method all affected the risk of blood transfusion to varying degrees.

TORCH, which is considered as a series of pathogens, including the Toxoplasma gondii, Rubella virus, Cytomegalovirus or Herpes simplex virus, often infects the pregnant women to induce the the fetus or newborn infection by transplacental infection or exposure to contaminated genital tract secretions at delivery. Increasing evidence have been confirmed that the infection of TORCH may cause the miscarriage, premature birth, malformed fetus, stillbirth, intrauterine growth retardation, neonatal multiple organ dysfunction and other adverse pregnancy outcomes. For most TORCH-infections cases may lacking the effective treatments during pregnancy, and it is important to achieve the effacing monitoring of TORCH infections before and during pregnancy. The laboratory testing of TORCH has the great significance. However, the consensus opinions still need to improve the the standardization of TORCH testing process and the correct interpretation. Based on the characteristics of the TORCH detection method, this article gives a consensus opinion on the standardized detection and clinical application of TORCH from the laboratory perspective according to the characteristics and types of infection of different pathogens.

Objective To investigate the effects of inhaling high concentration of hydrogen gas on the expressions of endoplasmic reticulum stress(ERS) related protein glucose regulated protein 78 (GRP78),Caspase-12 and the neural cell apoptosis and related proteins Bcl-2 and Bax in the rats with focal cerebral ischemia reperfusion(I/R) injury.Methods Seventy-two healthy SPF male Sprague-Dawley rats were selected and then randomly divided into the control group(Ⅰ:without any treatment),sham operation group (Ⅱ),cerebral IRI group (Ⅲ) and hydrogen gas treatment group (Ⅳ),18 cases in each group.Focal cerebral ischemia reperfusion injury (IRI) model was induced by using the suture-occluded method.The neurological deficits score (NDS) was assessed at 24 h after cerebral reperfusion in four groups.The cerebral infarction severity and size were detected by TTC staining and neuronal apoptosis of brain cortex were tested by TUNEL technique.The apoptosis index (AI) was calculated.Then the expressions of GRP78,Caspase-12,Bcl-2 and Bax were assessed by Western blot and immunohistochemistry.Results As compared with the group Ⅰ and Ⅱ,NDS score,cerebral infarction size,AI and the expressions of GRP78,Caspase-12 and Bax in cerebral cortex in the group Ⅲl and Ⅳ were significantly increased,while the expression of Bcl-2 in cerebral cortex was markedly decreased(P＜0.05);compared with the group Ⅲ,NDS score,brain infarction size,AI and the expression of Caspase-12 and Bax in cerebral cortex in the group Ⅳ were markedly decreased,while the expressions of GRP78 and Bcl-2 were dramatically increased (P＜0.05).Conclusion Inhaling high concentration of hydrogen gas has a certain protective effect on cerebral IRI in rats through increasing endoplasmic reticulum GRP78 protein expression after IRI and inhibiting Caspase-12 activation,thus inhibiting ERS and promoting the repair function of endoplasmic reticulum.

Objective To investigate the role of phosphatidylinositol 3?kinase∕protein kinase B∕glycogen synthase kinase?3β ( PI3K∕Akt∕GSK?3β) signaling pathway in hydrogen?induced inhibition of neuronal ap?optosis induced by focal cerebral ischemia?reperfusion ( I∕R) in rats. Methods One hundred and twenty
healthy adult male Sprague?Dawley rats, weighing 200-220 g, were divided into 5 groups ( n=24 each) u?sing a random number table: sham operation group ( group S); cerebral I∕R group ( group I∕R); hydrogen group (group H2); LY294002 (specific PI3K inhibitor) group (group LY); LY294002+hydrogen group ( group LY+H2 ) . Focal cerebral I∕R was induced by occlusion of the middle cerebral artery for 1 h followed by 24 h reperfusion. In H2 and H2+LY groups, the animals inhaled 67% H2+33% O2 for 2 h starting from onset of reperfusion, and then inhaled H2 for 2 h every 6 h. In LY and LY+ H2 groups, LY294002 ( 10 mmol∕L) 10 μl was injected into the lateral cerebral ventricle at 10 min before reperfusion. Neurologic defi?cit was evaluated and scored ( NDS) at 24 h of reperfusion. The rats were then sacrificed, and the brains were removed for measurement of the cerebral infarct size ( by TTC staining) and apoptosis in cortical neu?rons ( by TUNEL) and for determination of the expression of Akt in the ischemic cerebral cortex, phospho?rylated Akt ( p?Akt) , GSK?3β and phosphorylated GSK?3β ( p?GSK?3β) and Bcl?2 and Bax positive cell count in the ischemic cerebral cortex ( by immuno?histochemistry) . The apoptosis index ( AI) , p?Akt∕Akt ratio and p?GSK?3β∕GSK3?β ratio were calculated. Results Compared with group S, the NDS, cerebral infarct size, AI, p?Akt∕Akt ratio, p?GSK?3β∕GSK?3β ratio and Bax positive cell count were significantly increased, and the Bcl?2 positive cell count was significantly decreased in group I∕R ( P<0?05) . Compared with group I∕R, the NDS, cerebral infarct size, AI and Bax positive cell count were significantly de?creased, and the p?Akt∕Akt ratio, p?GSK?3β∕GSK?3β ratio and Bcl?2 positive cell count were significantly increased in group H2 ( P <0?05) , and no significant changes were found in the parameters mentioned a?bove in LY and LY+H2 groups ( P>0?05) . Compared with group H2 , the NDS, cerebral infarct size, AI and Bax positive cell count were significantly increased, and the p?Akt∕Akt ratio, p?GSK?3β∕GSK?3βratio and Bcl?2 positive cell count were significantly decreased in group LY+H2 ( P<0?05) . Conclusion The mechanism by which hydrogen inhibits focal cerebral I∕R?induced neuronal apoptosis is associated with the activation of PI3K∕Akt∕GSK?3β signaling pathway in rats.

Objective To investigate the effect of high concentration hydrogen gas on neurons in the rat hippocampus CA1 region during global cerebral ischemic/reperfusion injury (GCIR) Methods Four-vessel occlusion was used to establish rat model with GCIR injury. One hundred and five healthy male Sprague-Dawley rats were randomly divided into sham operation group(SH group, n = 15), model group(4-VO group, n = 45) and treatment group(4-VO+H2 group,n = 45). After 72 h and 9 d reperfusion, hippocampal CA1 region pyramidal neurons in every group were detected with Nissle staining , immunohistochemical neuron-specific nuclear protein (NeuN), specific protein antibody microglial cells (Iba1) staining and the relationship of position between neurons and microglia was observed through fluorescence double staining. We used Morris water maze to test the space orientation ability and the learning and memory ability in rats after 9 d reperfusion. Results Compared with those of 4-VO group,the neurons of hippocampus CA1 region were closer to normal in 72 h and 9 d in 4-VO+H2 group and neuron form and the number of neuron survival were increased significantly (P < 0.05);immunohistochemical staining showed that the number of neuron survival in 4-VO+H 2 group was obviously higher than that in 4-VO group (P < 0.05) and the number of microglia in 4-VO group was obviously higher than that in 4-VO+H2 group (P < 0.05). Water maze experiment showed that the swimming time in quadrant Ⅳ in 4-VO+H2 group was longer than that in 4-VO group (P < 0.05). Conclusion Inhalation of high concentration hydrogen gas has prominent protective effect on neurons of rat hippocampal CA1 region during reperfusion. The mechanism may be related with inhibiting the microglia excitation and activation during GCIR.

Objective To explore the protective effect of in-taking high concentration hydrogen gas on neurons and dendritic spines in hippocampus CA1 region of rats after globe cerebral ischemia/reperfusion (I/R) injury and its mechanism.Methods Four-vessel occlusion (4VO) was used to establish the models of global cerebral I/R injury in rats.One hundred and twenty healthy male Sprague-Dawley rats were randomly divided into 3 groups using a random number table:sham-operated group (inhaled 67％ N2 and 67％ O2,n=40),model group (inhaled 67％ N2 and 67％ O2 during reperfusion,n=40),and treatment group (inhaled 67％ H2 and 67％ O2 during reperfusion,n=40).After 72 h,5 and 9 d reperfusion,neuron-specific nuclear (NeuN) protein expression in the pyramidal neurons of the hippocampal CA1 region was detected with immumohistochemical staining and the positive cells were counted.And the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in serum were tested with colorimetry.Water maze test was used to measure the spatial orientation and memory function and Golgi staining to detect the number of dendritic spines in neurons 9 d after reperfusion.Results (1) Immunohistochemical staining of NeuN results showed that as compared with those in the model group,the neurons ofhippocampus CA1 region were significantly closer to normal with relatively intact structure,and the number of positive neurons was significantly increased in the treatment group 72 h,5 d,and 9 d after reperfusion (P＜0.05).With the reperfusion time being prolonged,the number of NeuN stained positive neurons at different time points of reperfusion in model group was gradually decreased (P＜0.05),and the numeric of the NeuN stained positive neurons at different time points of reperfusion in treatment group was slightly declined without significant difference (P＞0.05).(2) The serum SOD activity in the treatment group was significantly higher than that in the model group and sham-operated group (P＜0.05),while the MDA content in the treatment group was significantly lower than that in model group 72 h,5 d,and 9 d after reperfusion (P＜0.05).And with the reperfusion time being prolonged,the SOD activity at different time points of reperfusion showed no significant difference among the difference groups (P＞0.05).But the MDA content at different time points ofreperfusion between model group and treatment group was significantly different (P＜0.05);with the reperfusion time being prolonged,the MDA content was gradually decreased in both groups.(3) Nine d after reperfusion,water maze test found that the incubation period of treatment group was significantly shorter than that of model group (P＜0.05);the IV quadrant swimming time of space exploration in the treatment group was significantly longer than that in the model group (P＜0.05).(4) Golgi staining showed that the complexity of the neuronal dendrites branch and the number of dendritic spines of neurons in the hippocampal CA1 region of treatment group were increased than those in the model group;high-power oil microscopy indicated that the density of dendritic spines in the treatment group was significantly higher than that in the model group (P＜0.05).Conclusion In-taking of high concentrations hydrogen gas during reperfusion can definitely protect neurons in hippocampal CA1 region after globe cerebral I/R injury,and improve learning and memory function,whose mechanism may be related to hydrogen protecting the structure and function of neurons and dendritic spines,and inhibiting oxidative stress to reduce oxidative damage.