Fibroblast growth factor 21 (FGF21) attenuates tacrolimus-induced hepatic lipid accumulation through transcription factor EB (TFEB)-regulated lipophagy / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Tacrolimus (TAC), also called FK506, is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation. However, it has been proved to be associated with post-transplant hyperlipemia. The mechanism behind this is unknown, and it is urgent to explore preventive strategies for hyperlipemia after transplantation. Therefore, we established a hyperlipemia mouse model to investigate the mechanism, by injecting TAC intraperitoneally for eight weeks. After TAC treatment, the mice developed hyperlipemia (manifested as elevated triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c), as well as decreased high-density lipoprotein cholesterol (HDL-c)). Accumulation of lipid droplets was observed in the liver. In addition to lipid accumulation, TAC induced inhibition of the autophagy-lysosome pathway (microtubule-associated protein 1 light chain 3β (LC3B) II/I and LC3B II/actin ratios, transcription factor EB (TFEB), protein 62 (P62), and lysosomal-associated membrane protein 1 (LAMP1)) and downregulation of fibroblast growth factor 21 (FGF21) in vivo. Overexpression of FGF21 may reverse TAC-induced TG accumulation. In this mouse model, the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome pathway. We conclude that TAC downregulates FGF21 and thus exacerbates lipid accumulation by impairing the autophagy-lysosome pathway. Recombinant FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.

Clinical Characteristics of Children with Hemophagocytic Syndrome with Different EB Virus DNA Loads / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics of hemophagocytic syndrome (HLH) children with different EB virus (EBV) DNA loads, and to explore the relationship between differential indicators and prognosis.@*METHODS@#Clinical data of 73 children with HLH treated in our hospital from January 2015 to April 2022 were collected. According to EBV DNA loads, the children were divided into negative group (≤5×102 copies/ml), low load group (>5×102-<5×105 copies/ml) and high load group (≥5×105copies/ml）. The clinical symptoms and laboratory indexes of the three groups were compared, and the ROC curve was used to determine the best cut-off value of the different indexes. Cox regression model was used to analyze the independent risk factors affecting the prognosis of children, and to analyze the survival of children in each group.@*RESULTS@#The proportion of female children, the swelling rate of liver and spleen lymph nodes and the involvement rate of blood, liver, circulation and central nervous system in the high load group were higher than those in the negative group. The incidence of disseminated intravascular coagulation(DIC) and central nervous system(CNS) involvement in the high load group were higher than those in the low load group. The liver swelling rate and circulatory system involvement rate in the low load group were higher than those in the negative group(P<0.05). PLT counts in the high load group were significantly lower than those in the negative group, and the levels of GGT, TBIL, CK-MB, LDH, TG, SF, and organ involvement were significantly higher than those in the negative group. The levels of CK, LDH, SF and the number of organ involvement in the high load group were significantly higher than those in the low load group. The levels of GGT and TBIL in low load group were significantly higher than those in negative group. In terms of treatment, the proportion of blood purification therapy in the high and low load group was significantly higher than that in the negative group(P<0.01). ROC curve analysis showed that the best cut-off values of PLT, LDH, TG and SF were 49.5, 1139, 3.12 and 1812, respectively. The appellate laboratory indicators were dichotomized according to the cut-off value, and the differential clinical symptoms were included in the Cox regression model. Univariate analysis showed that LDH>1139 U/L, SF>1812 μg/L, dysfunction of central nervous system, number of organ damage, DIC and no blood purification therapy were the risk factors affecting the prognosis of children (P<0.05); Multivariate analysis shows that PLT≤49.5×109/L and dysfunction of central nervous system were risk factors affecting the prognosis of children (P<0.05). Survival analysis showed that there was no significant difference in the survival rate among the three groups.@*CONCLUSION@#The incidence of adverse prognostic factors in children with HLH in the EBV-DNA high load group is higher, and there is no significant difference in the survival rate of the three groups after blood purification therapy. Therefore, early identification and application of blood purification therapy is of great significance for children with HLH in the high load group.

Advances in treatment and prognosis of MiT family translocated renal cell carcinoma / 中华泌尿外科杂志

MiT family translocation renal cell carcinoma mainly includes Xp11.2/TFE3 gene fusion-related renal cell carcinoma (TFE3 RCC)and t(6; 11)/TFEB gene fusion-related renal cell carcinoma(TFEB RCC), which is rare and there is no standard treatment plan yet, and the prognosis is still controversial. For localized lesions, surgery is the first choice for treatment, and systemic treatment such as targeted drugs and immune checkpoint inhibitors can be combined when there is metastasis. The application of gene testing provides the basis for personalized treatment. TFE3 RCC is highly invasive and has a poor prognosis, while TFEB RCC usually has a biological behavior of inertia and a better prognosis.

A Contrast-Enhanced MDCT Study on the Morphology of Renal Vessels, Their Variations and Clinical Implications

Introduction: The kidneys—the main organs of the excretory system, are supplied by a paired renal artery, originating from the Abdominal Aorta at the level of a disc between L1 and L2 and drained by a paired renal vein exiting from the hilum of the kidney to the Inferior vena cava. Aim: To evaluate the morphology of renal vessels, their variations & clinical implications during renal surgeries in the subjects of the North India population by contrast-enhanced MDCT. Materials and Method: The present study was conceptualized & carried out in the Department of Anatomy, in collaboration with the Department of Radiodiagnosis, Santosh Medical College & Hospital, Ghaziabad and from Dr. O.P Gupta Imaging Centre, Meerut. This study was performed on the 108 patients who were referred for abdominal CECT examination with suspected abdominal pathologies. Contrast-enhanced MDCT scan images of the Abdomen were reviewed for normal anatomy of renal vessels and their variants. Result: Out of 108 patients, anatomical variations of the renal vessel were found in 72 (66.66%) patients. Variations of the renal artery were found in 56 patients (51.85%). Out of these 56 patients, 47 had supplementary renal artery, 17 had early branching of the renal artery and 8 patients had both supplementary and early branching of the renal artery. Supplementary renal arteries were seen in 15 patients on the right side, 16 patients on the left side & 16 patients bilaterally. Earlier branching of the renal artery was found in 9 patients on the right side, 10 patients on the left side and in 2 patients bilaterally. Variations of the renal vein were more commonly found on the right side, late renal vein confluence was seen in 28 (25.92%) patients and supplementary renal veins in 9 (8.3%) patients. On the left side, 2 (1.85%) patients had late renal vein confluence and 2 (1.85%) patients had retroaortic vein. Conclusion: Variations of the renal artery are found frequently. Morphological evaluation of renal vessels is useful for planning and performing the endovascular, laparoscopic and urological procedure.

Clinical analysis of 252 children with Epstein-Barr virus infection / 中国基层医药

Objective:To investigate the clinical manifestations of Epstein-Barr virus infection in children and the efficacy of interferon combined with ganciclovir.Methods:A total of 252 children with Epstein-Barr virus infection who received treatment in Liaocheng Maternal and Child Health Hospital from June 2018 to February 2020 were included in this study. They were randomly assigned to undergo treatment either with ganciclovir alone (control group, n = 126) or interferon combined with ganciclovir (experimental group, n = 126). General condition, clinical manifestation, clinical outcomes, and clinical efficacy were compared between the two groups. Results:The 252 children with Epstein-Barr virus infection were divided into four groups according to different age brackets: infancy (3.97%), early childhood (53.57%), preschool (28.97%), school age (13.49%). Children at the early childhood and preschool ages accounted for high proportions. Their clinical manifestations included fever, pharyngeal congestion, cervical lymph node swelling, and pharyngeal pain. Children with hepatosplenomegaly accounted for the highest proportion (44.12%) among those at the school age, and children with binocular edema accounted for the highest proportion (10.37%) among those at the early childhood age. The time to defervesce, eyelid edema, and lymph node regression in the experimental group were (3.55 ± 1.58) hours, (3.82 ± 1.17) hours, and (9.55 ± 1.60) hours respectively, which were significantly shorter than those in the control group [(4.40 ± 1.80) hours, (5.33 ± 1.58) hours, (10.44 ± 1.66) hours, t = 3.64, 2.47, 2.67, P < 0.001, P = 0.024, 0.009]. The total response rate was significantly higher in the experimental group than in the control group [96.03% (107/126) vs. 84.92% (121/126), χ2 = 9.03, P = 0.003]. Conclusion:Epstein-Barr virus infection has different clinical manifestations in children at different ages. Interferon combined with ganciclovir is more effective on Epstein-Barr virus infection than ganciclovir alone.

Effects of oxidative stress, PSMB5, TFEB, and lysosomes on sodium arsenite-induced liver injury in rats / 环境与职业医学

Background Liver damage presented in endemic arsenic poisoning is usually serious. Studies have shown that oxidative stress, proteasome beta 5 subunit (PSMB5), regulatory transcription factor EB (TFEB), and lysosomes are associated with liver injury, but their specific links to arsenic-induced liver injury remain unclear. Objective Using a sodium arsenite (NaAsO2)-induced rat liver injury model established earlier by the research group, the expressions of PSMB5, TFEB, and lysosomal associated membrane protein 1 (LAMP1) in liver tissues were detected. Methods Twenty-four SPF Wistar rats were randomly divided into control group, and low, medium, and high dose groups, with 6 rats in each group, half male and half female. The exposure concentrations were 0, 25, 50, and 100 mg·L−1 NaAsO2 solutions for 24 weeks. At the end of the experiment, liver was dissected after rats were anesthetized. The levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), total bile acid (TBA), and catalase (CAT) in liver tissues were detected by chemical colorimetry, and the levels of lipid peroxide (LPO), 4-hydroxynonenal (4-HNE), LAMP1, and cathepsin D (CTSD) in liver tissues were detected by enzyme-linked immunosorbent assay (ELISA); the transcriptional expression levels of PSMB5 and TFEB in liver tissues were detected by real-time fluorescence quantitative PCR (RT-qPCR), and the protein expressions of PSMB5, TFEB, and phosphorylated TFEB (p-TFEB) in liver tissues were detected by immunohistochemistry. Results The results of chemical colorimetry and ELISA showed that compared with the control group, the liver homogenate levels of ALP, TBA, and LAMP1 of each arsenic-exposed group, the ALT and LPO in the medium and high concentration groups, the 4-HNE and CTSD in the high concentration group were increased, while the CAT activity of each arsenic-exposed group was decreased (P<0.05). The results of real-time fluorescence quantitative PCR showed that the transcription levels of PSMB5 and TFEB in the liver tissues of each arsenic-exposed group were decreased compared with those of the control group (P<0.05). The results of immunohistochemistry showed that compared with the control group, the expression of PSMB5 of each arsenic-exposed group were decreased, the expression of TFEB in the medium and high concentration groups was decreased, while the expression of p-TFEB of each arsenic-exposed group was increased (P<0.05). The expression of TFEB protein gradually decreased in the nucleus, while the expression of p-TFEB protein gradually increased in the cytoplasm, but no expression of p-TFEB was found in the nucleus. The results of Pearson correlation analysis showed that PSMB5 in liver tissues was positively correlated with CAT (r=0.818, P＜0.05), and negatively correlated with 4-HNE and p-TFEB (r=−0.582, r=−0.899; P＜0.05); TFEB was negatively correlated with CTSD and LAMP1 (r=−0.457, r=−0.564; P＜0.05); CTSD was positively correlated with ALT and ALP (r=0.529, r=0.485; P＜0.05). Conclusion Long-term exposure to NaAsO2 can induce oxidative stress, inhibit the expression of PSMB5 and TFEB, promote the accumulation of p-TFEB in the cytoplasm, decrease the nuclear entry of active TFEB, damage the lysosome, and cause liver damage.

Morphological Characteristics of Bone Marrow Cells in Patients with EB Virus Infection / 中国实验血液学杂志

OBJECTIVE@#Review and analyze the characteristics of bone marrow cell morphology in patients with Epstein-Barr virus (EBV) infection, and explore the diagnostic value of bone marrow cell morphology for the early identification of EBV infection.@*METHODS@#A total of 33 patients with EBV-DNA positive detection in the First Affiliated Hospital of Guangxi Medical University from January 2018 to May 2021 were collected as the research objects. Bone marrow cell morphology and peripheral blood cell analysis were performed, and the significance in disease diagnosis was analyzed by statistical methods.@*RESULTS@#The sampling satisfaction of 33 patients with EBV infection was 100%. In the clinical diagnosis of all cases, 7 cases were IM, 17 cases were EBV-HLH, 3 cases were lymphoma, 2 cases were EBV-associated lymphoid hyperplasia, and 4 cases were not diagnosed. Among them, 31 patients had active bone marrow hyperplasia or above, 26 patients had active granulocytic hyperplasia or above, 21 patients had active erythroid hyperplasia or above, and 17 cases of megakaryocyte production platelet function decreased. The abnormal components of bone marrow mainly indude atypical lymphocyte cells (33 cases), hemophagocytic cells (22 cases), abnormal histiocyte (10 cases).@*CONCLUSION@#According to the proliferation of granulocytes, erythrocytes and megakaryocytes in the bone marrow, and the emergence of abnormal components such as atypical lymphocytes, hemophagocyte, abnormal histiocyte. Bone marrow cell morphological examination can indicate the possibility of EBV infection, which is certain diagnostic value for early identification of EBV infection.

Curcumin alleviates the manganese-induced neurotoxicity by promoting autophagy in rat models of manganism / 北京大学学报(医学版)

OBJECTIVE@#To investigate the protective effects of curcumin(CUR) and its mechanism on a rat model of neurotoxicity induced by manganese chloride (MnCl2), which mimics mangnism.@*METHODS@#Sixty male SD rats were randomly divided into 5 groups, with 12 rats in each group. Control group received 0.9% saline solution intraperitoneally (ip) plus double distilled water (dd) H2O intragastrically (ig), MnCl2 group received 15 mg/kg MnCl2(Mn2+ 6.48 mg/kg) intraperitoneally plus dd H2O intragastrically, CUR group received 0.9% saline solution intraperitoneally plus 300 mg/kg CUR intragastrically, MnCl2+ CUR1 group received 15 mg/kg MnCl2 intraperitoneally plus 100 mg/kg curcumin intragastrically, MnCl2+ CUR2 group received 15 mg/kg MnCl2 intraperitoneally plus 300 mg/kg CUR intragastrically, 5 days/week, 4 weeks. Open-field and rotarod tests were used to detect animals' exploratory behavior, anxiety, depression, movement and balance ability. Morris water maze (MWM) experiment was used to detect animals' learning and memory ability. ICP-MS was used to investigate the Mn contents in striata. The rats per group were perfused in situ, their brains striata were removed by brains model and fixed for transmission electron microscope (TEM), histopathological and immunohistochemistry (ICH) analyses. The other 6 rats per group were sacrificed. Their brains striata were removed and protein expression levels of transcription factor EB (TFEB), mammalian target of rapamycin (mTOR), p-mTOR, Beclin, P62, microtubule-associated protein light chain-3 (LC3) were detected by Western blotting. Terminal deoxynucleotidyl transterase-mediated dUTP nick end labeling (TUNEL) staining was used to determine neurocyte apoptosis of rat striatum.@*RESULTS@#After exposure to MnCl2 for four weeks, MnCl2-treated rats showed depressive-like behavior in open-field test, the impairments of movement coordination and balance in rotarod test and the diminishment of spatial learning and memory in MWM (P < 0.05). The striatal TH+ neurocyte significantly decreased, eosinophilic cells, aggregative α-Syn level and TUNEL-positive neurocyte significantly increased in the striatum of MnCl2 group compared with control group (P < 0.05). Chromatin condensation, mitochondria tumefaction and autophagosomes were observed in rat striatal neurocytes of MnCl2 group by TEM. TFEB nuclear translocation and autophagy occurred in the striatum of MnCl2 group. Further, the depressive behavior, movement and balance ability, spatial learning and memory ability of MnCl2+ CUR2 group were significantly improved compared with MnCl2 group (P < 0.05). TH+ neurocyte significantly increased, the eosinophilic cells, aggregative α-Syn level significantly decreased in the striatum of MnCl2+ CUR2 group compared with MnCl2 group. Further, compared with MnCl2 group, chromatin condensation, mitochondria tumefaction was alleviated and autophagosomes increased, TFEB-nuclear translocation, autophagy was enhanced and TUNEL-positive neurocyte reduced significantly in the striatum of MnCl2+ CUR2 group (P < 0.05).@*CONCLUSION@#Curcumin alleviated the MnCl2-induced neurotoxicity and α-Syn aggregation probably by promoting TFEB nuclear translocation and enhancing autophagy.

Application of expertise-based pragmatic randomized controlled trial in acupuncture-moxibustion clinical research / 中国针灸

According to clinical practice, the characteristics and issues of pragmatic randomized controlled trial(PRCT) and expertise-based randomized controlled trial (EBRCT) in acupuncture-moxibustion clinical research were summarized. The characteristics of expertise-based pragmatic randomized controlled trial (EB-PRCT), which is the combination of above two, and its application in acupuncture-moxibustion clinical trial were explored. PRCT emphasizes the clinical practice, the positive control of standard therapy and the the blind performance on data collection and statistics. PRCT has the advantage of flexible grouping, nevertheless, it also has shortcomings such as higher cost and lack of typical subjects. EBRCT emphasizes the participation of professional acupuncturists, so that the therapeutic effect is ensured, the compliance of subjects and the bias of manipulation are improved. Thus, the replacement scheme of acupuncturists is essential in EBRCT. Having the complementary advantages, EB-PRCT provides a superior research method for acupuncture-moxibustion clinical trial, and leads to convincing results.

Effect of atorvastatin on autophagy and cholesterol level in foam cells by activating transcription factor EB / 医学研究生学报

ObjectiveRecent studies revealed that the transcription factor EB (TFEB) plays an important role in regulating autophagy, reducing intracellular lipids, and inhibiting atherosclerosis. This study aims to explore the effects of atorvastatin (ATV) on autophagy and cholesterol levels of foam cells by activating TFEB.MethodsHuman mononuclear cell line THP-1 was cultured in vitro and induced to differentiate into macrophages using phorbol ester. Oxidized low-density lipoprotein (oxLDL) was added to macrophages, which were induced for 48 hours to establish a foam cell model. The experiment was divided into four groups: blank group, model group (oxLDL group), oxLDL+ Chloroquine (CQ) group, oxLDL+ ATV group, and oxLDL+CQ+ ATV group. Cells in each group were treated with drugs for 48 h. The toxicity of ATV and chloroquine on the cells was detected by the CCK8 method. Oil red O staining was used to test the level of lipid droplets. Oxidase method was used to detect levels of intracellular free cholesterol (FC), total cholesterol (TC) and others related to. Cholesterol efflux fluorescence analysis was used to determine the cholesterol efflux rate of the cells. Expression of I, P62, TFEB, LAMP 1 protein was determined by Western blot.ResultsThe results of the CCK8 method showed that the cell survival rate decreased significantly with the increase of ATV and CQ concentrations (P<0.01). Compared to the blank group, the levels of lipid droplets, FC, TC, and CE/TC in the model group significantly increased (P<0.05), and the cholesterol outflow rate significantly decreased (P<0.05). Compared to the model group, the intracellular lipid droplets, FC, TC, and CE/TC levels in the oxLDL+CQ group elevated significantly (P<0.05), while the cholesterol outflow rate decreased significantly (P<0.05). The intracellular lipid droplets, FC, TC, and CE/TC contents in the oxLDL+ATV group decreased significantly (P<0.05), and the cholesterol outflow rate increased significantly (P<0.05). Compared to the oxLDL+CQ group, the intracellular lipid droplets, FC, TC, and CE/TC content in the oxLDL+CQ+ATV group decreased significantly (P<0.05), while the cholesterol outflow rate increased significantly (P<0.05). Western blotting results showed that protein expression levels of LC3II/I, P62 and TFEB were decreased in the model histone in comparison to the blank group (P<0.05). Compared to the expression levels of LC3II/I, P62, TFEB and LAMP1 ((1.006±0.052), (0.183±0.013), (0.333±0.020), and (0.957±0.026)) in the model group, the expression levels of oxLDL+CQ histamine ((1.594±0.017), (0.257±0.006), (0.477±0.024), and (0.957±0.026)) were significantly higher (P<0.05).The protein expression levels of LC3II/I, TFEB and LAMP1 in oxLDL+ATV group ((1.146±0.060), (0.540±0.031), and (1.027±0.054)) were increased, while the protein expression levels of P62 (0.115±0.009) were decreased (P<0.05). Compared to LC3II/I and P62 in oxLDL+CQ group, the expression level of oxLDL+CQ+ATV histone was decreased ((1.419±0.036) and (0.165±0.006)), and the difference was statistically significant (P< 0.05).ConclusionATV can increase the cholesterol outflow rate of macrophages, reduce the level of cholesterol and lipid droplets in macrophages, and reduce the formation of foam cells. The mechanisms behind this are still unknown, which may be related to the activation of TFEB by ATV and influencing the process of autophagy.

Overexpression of transcription factor EB regulates mitochondrial autophagy to protect lipopolysaccharide-induced acute lung injury / 中华医学杂志(英文版)

Background@#Acute lung injury (ALI) is characterized by an acute inflammatory process, and oxidative stress in the lung tissue leads to a lack of effective therapeutics. This study aimed to identify whether the overexpression of transcription factor EB (TFEB) regulates mitophagy to protect against lipopolysaccharide (LPS)-induced ALI.@*Methods@#We detected the expression of inflammatory factors, cytochrome c (Cyt.c) and nicotinamide adenine dinucleotide phosphate (NADPH), and autophagy-related proteins and observed the changes in lung histopathology induced by ALI in rats and the changes in the cell ultrastructure of primary alveolar type II epithelial cells induced by changing the expression of TFEB in the context of ALI.@*Results@#The overexpression of TFEB could reduce the expression of proinflammatory factors, such as IL-1 and IL-6, and increase the expression of anti-inflammatory factors, such as IL-10, both in vitro and in vivo. In addition, the overexpression of TFEB could reduce the Cyt.c and NADPH levels both in vivo and in vitro. The overexpression of TFEB could upregulate the expression of autophagy-related proteins, such as lysosomal-associated membrane protein 1 (LAMP1), microtubule-associated protein light chain 3B (LC3B), and Beclin both in vivo and in vitro, and promote mitochondrial autophagy. The overexpression of TFEB significantly improved the histopathologic changes induced by LPS-induced ALI in rats. However, low TFEB expression produced the opposite results.@*Conclusion@#TFEB overexpression can decrease inflammation and mitochondrial damage in the lung tissue and alveolar epithelial cells through regulating mitochondrial autophagy to protect against LPS-induced ALI. Therefore, TFEB is likely a potential therapeutic target in LPS-induced ALI.

Analysis of clinical prognosis and mutant gene phenotype in children with hemophagocytic lymphohistiocytosis / 中国小儿急救医学

Objective@#To investigate the clinical manifestations, prognosis and gene mutation phenotypes of hemophagocytic lymphohistiocytosis(HLH)in children of our hospital.@*Methods@#The clinical data of 42 patients with HLH from April 2013 to December 2018, and the genetic data of 8 patients with familial HLH(FHL)were collected retrospectively.The age, clinical manifestation, laboratory examination, prognosis and the characteristics of gene mutation phenotype of patients with HLH and FHL were analyzed emphatically.Furthermore, the clinical manifestations and prognosis of patients with HLH were analyzed according to whether EB virus was infected.@*Results@#Among these 42 patients with HLH, the onset age was ranged from 1 month to 13 years old and most of them were younger than 5 years old.The main clinical manifestations included cytopenia, prolonged fever, enlargement of liver and spleen and lymph nodes enlargement and serosal effusion.Laboratory examination showed that lactate dehydrogenas, ferritin, erythrocyte sedimentation rate and triglyceride increased significantly.The survival rate of the group in ferritin exceeding 4 500 μg/L and non-chemotherapy was lower than that of the group of ferritin less than 4 500 μg/L and chemotherapy in clinical prognosis(P<0.05). Ten patients of them survived after chemotherapy, and 2 patients survived for 5 to 6 months after hematopoietic stem cell transplantation in FHL.Patients with EB virus infection were older than those without EB virus infection.They had longer fever duration and higher proportion of lymph nodes enlargement and ferritin more than 4 500 μg/L(P values were 0.01, 0.04, 0.03, 0.03 respectively). However, there was no significant difference in survival time between the two groups.Eight patients had mutations in UNC13D(50.00%), PRF1(25.00%), PRKDC(12.50%)and IL2RG(12.50%)genes respectively, and most of the mutations were complex heterozygous mutations(62.50%). All the mutations were originated from their parents.@*Conclusion@#HLH is characterized by cytopenia, prolonged fever, enlargement of liver and spleen.HLH is more common in children under 5 years old.The clinical manifestations of HLH with EB virus infection are more severe while the prognosis is not statistically significant.The incidence of FHL is higher.There are more UNC13D gene mutations and complex heterozygous mutations.Children with HLH should be detected and treated with standardized therapy as soon as possible.Hematopoietic stem cell transplantation is a good treatment for HLH, especially for FHL patients.

Clinical characteristics, diagnosis and efficacy of primary lymphoepithelial carcinoma of the parotid gland / 中华放射肿瘤学杂志

Objective@#To analyze the clinical features, diagnosis and prognosis of patients with primary lymphoepithelial carcinoma of the parotid gland.@*Methods@#Clinical data of 13 patients diagnosed with lymphoepithelial carcinoma of the parotid gland in our hospital from 2009 to 2017 were retrospectively analyzed. The median follow-up time was 38.5 months. All patients received radiotherapy after operation.@*Results@#Of 13 patients, 9 cases were male and 4 female. The median age was 33 years. At the initial diagnosis, 9 cases had primary lesions limited to the parotid gland, and 4 cases of lymph node metastases located in Ⅰb and Ⅱ regions of the neck. According to UICC2010 staging, 1 case was classified as stage Ⅰ, 1 as stage Ⅱ, 6 as stage Ⅲ and 5 as stage Ⅳ, respectively. Eleven surgically pathological specimens were tested with EBER in-situ, and 10 cases were positive for EBER. No patient died in the whole group. The 3-year overall survival rate was 100%. The 3-year progression-free survival rate was 76%. The 3-year local control rate was 92%. The 3-year metastasis-free survival rate was 84%.@*Conclusions@#The incidence of lymphoepithelial carcinoma of the parotid gland is relatively low. The pathological features are associated with EB virus. It is prone to present with cervical lymph node metastasis. The possibility of lymph node metastasis of nasopharyngeal carcinoma to the parotid gland should be excluded before treatment. At present, surgery combined with postoperative radiotherapy is the main treatment. The overall survival is favorable. Local recurrence and distant metastasis are the main causes of treatment failure.

Analysis of clinical prognosis and mutant gene phenotype in children with hemophagocytic lymphohisti-ocytosis / 中国小儿急救医学

Objective To investigate the clinical manifestations,prognosis and gene mutation pheno-types of hemophagocytic lymphohistiocytosis(HLH)in children of our hospital. Methods The clinical data of 42 patients with HLH from April 2013 to December 2018,and the genetic data of 8 patients with familial HLH(FHL)were collected retrospectively. The age,clinical manifestation,laboratory examination,prognosis and the characteristics of gene mutation phenotype of patients with HLH and FHL were analyzed emphatical-ly. Furthermore,the clinical manifestations and prognosis of patients with HLH were analyzed according to whether EB virus was infected. Results Among these 42 patients with HLH,the onset age was ranged from 1 month to 13 years old and most of them were younger than 5 years old. The main clinical manifestations in-cluded cytopenia,prolonged fever,enlargement of liver and spleen and lymph nodes enlargement and serosal effusion. Laboratory examination showed that lactate dehydrogenas,ferritin,erythrocyte sedimentation rate and triglyceride increased significantly. The survival rate of the group in ferritin exceeding 4 500 μg/L and non- chemotherapy was lower than that of the group of ferritin less than 4 500 μg/L and chemotherapy in clinical prognosis(P<0. 05). Ten patients of them survived after chemotherapy,and 2 patients survived for 5 to 6 months after hematopoietic stem cell transplantation in FHL. Patients with EB virus infection were older than those without EB virus infection. They had longer fever duration and higher proportion of lymph nodes enlargement and ferritin more than 4 500 μg/L(P values were 0. 01,0. 04,0. 03,0. 03 respectively). Howev-er,there was no significant difference in survival time between the two groups. Eight patients had mutations in UNC13D(50. 00%), PRF1 ( 25. 00%), PRKDC ( 12. 50%) and IL2RG ( 12. 50%) genes respectively, and most of the mutations were complex heterozygous mutations(62. 50%). All the mutations were originated from their parents. Conclusion HLH is characterized by cytopenia,prolonged fever,enlargement of liver and spleen. HLH is more common in children under 5 years old. The clinical manifestations of HLH with EB virus infection are more severe while the prognosis is not statistically significant. The incidence of FHL is higher. There are more UNC13D gene mutations and complex heterozygous mutations. Children with HLH should be detected and treated with standardized therapy as soon as possible. Hematopoietic stem cell transplantation is a good treatment for HLH,especially for FHL patients.

Clinical characteristics, diagnosis and efficacy of primary lymphoepithelial carcinoma of the parotid gland / 中华放射肿瘤学杂志

Objective To analyze the clinical features,diagnosis and prognosis of patients with primary lymphoepithelial carcinoma of the parotid gland.Methods Clinical data of 13 patients diagnosed with lymphoepithelial carcinoma of the parotid gland in our hospital from 2009 to 2017 were retrospectively analyzed.The median follow-up time was 38.5 months.All patients received radiotherapy after operation.Results Of 13 patients,9 cases were male and 4 female.The median age was 33 years.At the initial diagnosis,9 cases had primary lesions limited to the parotid gland,and 4 cases of lymph node metastases located in Ⅰb and Ⅱ regions of the neck.According to UICC2010 staging,1 case was classified as stage Ⅰ,Ⅰ as stage Ⅱ,6 as stage Ⅲ and 5 as stage Ⅳ,respectively.Eleven surgically pathological specimens were tested with EBER in-situ,and 10 cases were positive for EBER.No patient died in the whole group.The 3-year overall survival rate was 100％.The 3-year progression-free survival rate was 76％.The 3-year local control rate was 92％.The 3-year metastasis-free survival rate was 84％.Conclusions The incidence of lymphoepithelial carcinoma of the parotid gland is relatively low.The pathological features are associated with EB virus.It is prone to present with cervical lymph node metastasis.The possibility of lymph node metastasis of nasopharyngeal carcinoma to the parotid gland should be excluded before treatment.At present,surgery combined with postoperative radiotherapy is the main treatment.The overall survival is favorable.Local recurrence and distant metastasis are the main causes of treatment failure.

Expression of MAGEA4 and EB1 proteins in lung cancer tissues and their correlation with clinicopathological features and prognosis / 实用肿瘤学杂志

Objective The aim of this study was to investigate the expression of MAGEA4 and EB1 proteins in lung cancer tissues and their correlation with clinicopathological features and prognosis. Methods A total of 136 patients with lung cancer in our hospital were enrolled. The expression levels of MAGEA4 and EB1 at levels of mRNA and protein were measured by real-time fluo-rescence reverse transcription and immunohistochemistry. The correlation between MAGEA4 and EB1 expression and clinical patholog-ical features,and prognosis were analyzed by χ2 test and Cox regression analysis. Results The expression of MAGEA4 and EB1 mR-NA in lung cancer tissues was higher than those in adjacent tissues(P<0. 05). The positive rates of MAGEA4 and EB1 in lung canc-er tissues were higher than those in adjacent tissues(P<0. 05). The expression of MAGEA4 and EB1 proteins in lung cancer tissues was higher than those in adjacent tissues(P<0. 05). The positive rates of MAGEA4 and EB1 proteins were not significantly correlated with age(P>0. 05),but they were related to the maximum diameter,pathological grade,TNM stage,infiltration depth,lymphatic vas-cular infiltration,lymph node metastasis and recurrence(P<0. 05). The 3-year survival rate and total survival time of MAGEA4 and EB1 negative group were significantly higher than those of MAGEA4 and EB1 positive group(P<0. 05). Lymphatic vascular infiltra-tion,lymph node metastasis,MAGEA4 positive and EB positive were independent risk factors for prognosis of patients with lung cancer (P<0. 05). Conclusion The positive expression rates of MAGEA4 and EB1 proteins in lung cancer tissues are increased,and their high expression may be related to the occurrence and development of lung cancer. Lung cancer patients with negative expression of MAGEA4 and EB1 proteins can obtain better prognosis.

I-Evans blue: evaluation of necrosis targeting property and preliminary assessment of the mechanism in animal models

Necrosis is a form of cell death, which is related to various serious diseases such as cardiovascular disease, cancer, and neurodegeneration. Necrosis-avid agents (NAAs) selectively accumulated in the necrotic tissues can be used for imaging and/or therapy of related diseases. The aim of this study was to preliminarily investigate necrosis avidity of I-evans blue (I-EB) and its mechanism. The biodistribution of I-EB at 24 h after intravenous administration showed that the radioactivity ratio of necrotic to viable tissue was 3.41 in the liver and 11.82 in the muscle as determined by counting in model rats. Autoradiography and histological staining displayed preferential uptake of I-EB in necrotic tissues. nuclear extracts from necrotic cells exhibited 82.3% of the uptake in nuclei at 15 min, as well as 79.2% of the uptake at 2 h after I-EB incubation. The DNA binding study demonstrated that evans blue (EB) has strong binding affinity with calf-thymus DNA (CT-DNA) (=5.08×10 L/(mol/L)). Furthermore, the accumulation of I-EB in necrotic muscle was efficiently blocked by an excess amount of unlabeled EB. In conclusion, I-EB can not only detect necrosis by binding the DNA released from necrotic cells, but also image necrotic tissues generated from the disease clinically.

Progress of EB virus related lymphomas / 白血病·淋巴瘤

The occurrence and development of some lymphomas are closely related to EB virus, including B cell lymphoma, NK/T cell lymphoma, Hodgkin lymphoma and post-transplant lymphoproliferative disorder. Many studies have shown that some gene expression products that related to EB virus latent infection play a crucial role in the development of lymphoma. In this paper, the structure and biological characteristics of EB virus, its gene expression products, the mechanism of tumorigenesis and the related lymphomas are reviewed.

Virus infection and limbic encephalitis: Clinical analysis of 5 cases of anti-N-methyl-D-aspartic receptor encephalitis and literature review / 中华实验和临床病毒学杂志

Objective@#To have a profound understanding of anti-N-methyl-D-aspartic receptor (anti-NMDAR) encephalitis, through the clinical analysis of 5 cases of anti-NMDAR encephalitis, and literature review.@*Methods@#This is a retrospective analysis. Five cases of anti-NMDA receptor encephalitis treated from May 2010 to June 2015, in the Department of Neurology, Beijing Friendship Hospital affiliated to Capital Medical University, were included in this study. The clinical data, including clinical manifestation, past history, radiological features, serum and cerebral spinal fluid examinations, treatment and prognosis, were analyzed.@*Results@#Among the 5 cases, 3 young female and 2 middle-to old-aged male. The clinical features of the onset was mental and behavior disorder, as well as seizure and extrapyramidal features, like facial and limbic involuntary movements or tremor. Coma and hypopnea was severe in 3 young female cases, needing assistance of mechanical ventilator, while the manifestation of 2 male patients was much mild, need not assisted respiration. 1 case had teratoma of ovary, 1 case had Vogt-Koyanagi-Harada syndrome. The anti-NMDA receptor antibody was positive in cerebraospinal fluid of all 5 cases, but in serum of 3 cases, serum and CSF Epstein-Barr virus (EBV) IgM antibody was positive in 1 case, while herpes simplex I virus (HSV-1) IgM antibody positive in another case, and anti-myelin oligodendrocyte glycoprotein (MOG) antibody was seen in serum and CSF in 1 case. The time interval from the onset to treatment was 10-37 d (18.8±9.8 d). IVIG was used in all of the 5 cases, glucocoticoid in 4 cases, and plasma exchange in 3 cases. One case with Vogt-Koyanagi-Harada syndrome, having a long time before diagnosis and treatment, died, while the other 4 cases had good prognosis, and had no relapse.@*Conclusions@#Mental and behavior disturbance is common at onset of anti-NMDAR encephalitis. The radiological and lab examination may be normal. It may be accompanied with HSV-1 or EBV infection, anti-MOG antibody may be positive in this disease. Active treatment is important.

TFEB regulation:new insight into treatment of kidney diseases / 中国病理生理杂志

Transcription factor EB(TFEB)is a member of the MiTF/TFE family and plays an important role in cell stress,metabolism,cancer and so on.There are relatively few studies on the role of TFEB in renal diseases.TFEB was initially found to be highly expressed in TFEB-fusion renal cell carcinoma and plays a key role in the development of re-nal cell carcinoma.Blocking the downstream signaling pathway activated by TFEB would be a promising treatment for TFEB-fusion renal cell carcinoma.On the contrary,the expression of TFEB in renal intrinsic cells is decreased in diabetic kidney disease,leading to a blockage in the autophagy-lysosome pathway.TFEB enhances the ability of cell stress and self-repair,and then delays the progress of diabetic kidney disease.In cystine nephropathy,TFEB expression is reduced in re-nal tubular epithelial cells and compensatory activation is insufficient as well.TFEB over-expression effectively eliminates intracellular cystine and repairs damaged lysosome,which is expected to alleviate or cure the Fanconi syndrome.In summa-ry,TFEB plays a key role in different kidney diseases,and targeted regulation of TFEB provides new hope for the treatment of kidney diseases.