[Multisystem inflammatory syndrome in children in the context of coronavirus disease 2019 pandemic]. / æ–°åž‹å† çŠ¶ç— æ¯’æ„ŸæŸ“æµè¡ŒèƒŒæ™¯ä¸‹çš„å„¿ç«¥å¤šç³»ç»Ÿç‚Žç—‡ç»¼åˆå¾.

Multisystem inflammatory syndrome in children (MIS-C) is a complex syndrome characterized by multi-organ involvement that has emerged in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak. The clinical presentation of MIS-C is similar to Kawasaki disease but predominantly presents with fever and gastrointestinal symptoms, and severe cases can involve toxic shock and cardiac dysfunction. Epidemiological findings indicate that the majority of MIS-C patients test positive for SARS-CoV-2 antibodies. The pathogenesis and pathophysiology of MIS-C remain unclear, though immune dysregulation following SARS-CoV-2 infection is considered a major contributing factor. Current treatment approaches for MIS-C primarily involve intravenous immunoglobulin therapy and symptomatic supportive care. This review article provides a comprehensive overview of the definition, epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of MIS-C.

Clinical characteristics of magnetic foreign body misingestion in children.

Magnetic foreign body misingestion (MFBM) is now occurring more frequently. It may cause remarkable mortality and morbidity in children. A retrospective analysis of the clinical data of children admitted to Xiamen Children's Hospital between March 2017 and July 2020 due to accidental MFBM. A total of 14 children who had MFBM were collected, the proportion between urban and rural areas was 8:6, and the ratio of male to female was 6:1. The age ranged from 1.2 to 8.9 years (median 4.6 years). The number of magnetic foreign bodies ingested by mistake is 1 to 17 (average 6.5). Magnetic foreign objects are divided into magnets (3 cases) + magnetic beads (11 cases). About 40% (5/14) of this patient series showed no available misingestion history. Management includes: 4 cases of open surgery (including 1 case of laparoscopic transfer to operation), 3 cases of laparoscopic surgery, 2 cases of gastroscopy, 5 cases of conservative treatment of foreign bodies discharged through the anus. Of the 7 surgical cases, 6 cases presented with intestinal obstruction and intestinal perforation (at least 1 intestinal perforation and at most 5). Abdominal sonography has limitations in the detection of magnetic foreign bodies in the digestive tract. The proportion of laparoscopic surgery in the 7 surgical cases is nearly half. All surgical cases recovered smoothly after treatment. Our experience shows that MFBM is a big issue for the small children! The early symptoms of MFBM are often atypical especially among young children and MFBM may lead to severe adverse events. We proposed a management strategy for MFBM in children. We advise pediatricians/emergency physicians, parents/children's guardians and society should raise the collaborated alertness of MFBM. Global awareness of risk prevention of magnetic material accidental ingestion cannot be overemphasized.

TM4SF1 Promotes Proliferation, Invasion, and Metastasis in Human Liver Cancer Cells.

Transmembrane 4 superfamily member 1 (TM4SF1) is a member of tetraspanin family, which mediates signal transduction events regulating cell development, activation, growth and motility. Our previous studies showed that TM4SF1 is highly expressed in liver cancer. HepG2 cells were transfected with TM4SFl siRNA and TM4SF1-expressing plasmids and their biological functions were analyzed in vitro and in vivo. HepG2 cells overexpressing TM4SF1 showed reduced apoptosis and increased cell migration in vitro and enhanced tumor growth and metastasis in vivo, whereas siRNA-mediated silencing of TM4SF1 had the opposite effect. TM4SF1 exerts its effect by regulating a few apoptosis- and migration-related genes including caspase-3, caspase-9, MMP-2, MMP-9 and VEGF. These results indicate that TM4SF1 is associated with liver tumor growth and progression, suggesting that TM4SF1 may be a potential target for treatment of liver cancer in future.

Polyinosinic-cytidylic acid as an adjuvant on natural killer- and dendritic cell-mediated antitumor activities.

Previously, we demonstrated that treatment with E7(44-62) and the adjuvant polyinosinic-cytidylic acid (poly(I:C)) in a rodent model generates antitumor immune responses, but the effect of E7(44-62) with poly(I:C) on natural killer (NK)- and dendritic cell (DC)-mediated antitumor activities is still unclear. Our goal was to examine the antitumor effects of E7(44-62) with poly(I:C). We examined the ability of E7(44-62) with poly(I:C) to induce toll-like receptor 3 (TLR3) expression, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) mRNA expression, and tumor cell-killing activity in human NK cells as well as its ability to induce CD11c and CD86 expression and proliferation in human DCs. We found that E7(44-62) with poly(I:C) treatment markedly increased TLR3 expression and cytotoxicity against HeLa cells in human NK92 cells. Moreover, treatment with E7(44-62) and poly(I:C) markedly up-regulated IFN-γ and TNF-α mRNA expression in NK92 cells. Human patients with cervical cancer exhibited a marked decrease in the frequency of DCs; however, ex vivo treatment with E7(44-62) and poly(I:C) restored DC frequency. Stimulation of human DCs in patients with E7(44-62) and poly(I:C) led to high levels of CD11c and CD86 expression. Our data reveal the involvement of E7(44-62) combined with poly(I:C) in potentiating antitumor cytotoxicity and cytokine-producing activities in human NK92 cells and DCs.

The antitumor effect of the toll-like receptor 3 ligand polyinosinic-cytidylic acid as an adjuvant.

Although polyinosinic-polycytidylic acid (poly(I:C)) has been applied in tumor immunity as a Toll-like receptor 3 (TLR3) ligand, the interaction between poly(I:C) and TLR3 is still unclear, as are the mechanisms underlying the antitumor effect of poly(I:C). Our aim was to investigate the interaction between poly(I:C) and TLR3, as well as the mechanisms underlying the antitumor effect of poly(I:C). NK92 cells were maintained in medium (untreated group), or medium containing E7(44-62) (E7 group) or E7(44-62)+poly(I:C) (poly(I:C)/E7 group), and we measured the expression of TLR3 mRNA, p-p65, and IκB-α protein. The cells were first incubated in medium alone or medium containing TLR3 monoclonal antibody, and then in medium containing poly(I:C)/E7. Finally, we measured the level of interferon-beta (INF-ß) in the supernatant and determined the tumor cell-killing effect of the NK92 cells. At 1 h, the expression of TLR3 mRNA in the poly(I:C)/E7 group was markedly higher than that in the untreated and E7 groups (P < 0.05). When compared with the poly(I:C)/E7 group, the expression of IκB-α was dramatically increased in the E7 and untreated groups, and the expression of p-p65 was dramatically decreased in the E7 and untreated groups (all P < 0.05). At 24 h, INF-ß content and tumor cell-killing activity in the poly(I:C)/E7 group were markedly higher than those in the untreated group (P < 0.001, <0.05, respectively). Treatment with TLR3 monoclonal antibody significantly inhibited poly(I:C)/E7-induced INF-ß secretion and tumor cell-killing activity in NK92 cells (P < 0.001, <0.05, respectively). The interaction between poly(I:C) and TLR3 plays an important role in the antitumor immunity of NK92 cells. In addition, the interaction between poly(I:C) and TLR3 increases INF-ß expression, which may be attributed to the activation of NFκB.

Combined detection of mRNA expression of Alpha-fetoprotein in peripheral blood and telomerase activity of monocytes in hepatocellular carcinoma patients.

BACKGROUND/AIMS: The detection of hepatocellular carcinoma (HCC) cells in the peripheral blood is not only important for the diagnosis of FICC, but is also of critical importance for early detection of hematogenous metastasis of HCC. The purpose of this study was to measure Alpha-fetoprotein (AFP) mRNA in the peripheral blood and telomerase activity in peripheral blood monocytes to determine their utility, in isolation and concert, in the early diagnosis of HCC. METHODOLOGY: Nested RT-PCR was employed to detect the mRNA expression of AFP in the peripheral blood, and PCR-ELISA was used to measure the telomerase activity of peripheral blood mononuclear cells (PBMCs) in patients with HCC, benign hepatic tumors, chronic liver diseases and healthy subjects. RESULTS: Of the 30 HCC patients, 22 (73.3%) were positive for AFP, and 28/30 (93.3%) HCC patients were positive for telomerase activity. The mRNA expression of AFP was positively correlated with telomerase activity in HCC patients (r=0.6742, p<0.05). CONCLUSIONS: Detection of both mRNA expression of AFP in the peripheral blood and telomerase activity in PBMCs may prove to play an important role in achieving an early diagnosis of HCC.

Protective effect of low-molecular-weight heparin on pancreatic encephalopathy in severe acute pancreatic rats.

BACKGROUND AND AIMS: Pancreatic encephalopathy (PE) is a severe complication and significant cause of death in patients with severe acute pancreatitis (SAP). We have reported previously that low-molecular-weight heparin (LMWH) treatment could reduce incidence of PE in SAP patients. Our objective here was to investigate the protective effect of LMWH and its mechanism on PE in SAP rats. METHODS: SD rats were randomly divided into three groups: (1) Sham-operation (S) group, (2) SAP group, and (3) LMWH treatment (LMWH) group. LMWH was administrated 4 h after the SAP model conducted. The levels of serum amylase, myelin basic protein (MBP), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), brain water content, occurrence of apoptosis, and pathological changes of pancreas and brain were measured at 1 day after models were set up in the SAP and S groups, and 1 day after LMWH treatment was administrated in the LMWH group. RESULTS: (1) The levels of serum amylase, TNF-α, and IL-6 in the SAP group were increased significantly more than those in the S and LMWH groups (all P < 0.001), as were the levels of serum MBP in the SAP group compared to those in the S and LMWH groups (P < 0.01, <0.05 respectively). However, while the level of serum amylase and IL-6 in the LMWH group were significantly increased compared to those in the S group (P < 0.05, <0.001 respectively), the levels of TNF-α and MBP showed no significant difference between the LMWH and S groups (all P > 0.05). (2) The brain water content in the SAP group was significantly increased compared to the S group and LMWH group (P < 0.01, <0.05 respectively). (3) Neuronal apoptosis, demyelination, and mitochondrial vacuolation in neuronal cells were observed in the SAP group; in contrast, in the LMWH group, significantly lower rates of neuronal apoptosis, demyelination and mitochondrial edema were observed in neuronal cells. CONCLUSIONS: The protective effect of LMWH on PE progression in SAP rats might result from inhibition of inflammatory activation and reduction of the occurrence of neuronal apoptosis.

Randomized controlled study of plasma exchange combined with molecular adsorbent re-circulating system for the treatment of liver failure complicated with hepatic encephalopathy.

BACKGROUND/AIMS: To evaluate the use of plasma exchange (PE) combined with the molecular adsorbent re-circulating system (MARS) for the treatment of liver failure complicated with hepatic encephalopathy. METHODOLOGY: A prospective randomized controlled study was conducted to compare the therapeutic effect of MARS treatment (MARS group, n=60) with that of PE combined with MARS treatment (PE+MARS group, n=60) in patients with liver failure complicated with hepatic encephalopathy. RESULTS: The serum total bilirubin and blood ammonia levels were significantly decreased compared with pretreatment levels after 3 days of both the MARS treatment (p=0.0001, p<0.001) and PE+MARS treatment (both p<0.0001) and the Glasgow coma scale score was significantly increased (both p<0.0001). The 30-day mortality rate was 10.0% (6/60) in the MARS group and 11.7% (7/60) in the PE + MARS group. The per capita cost of treatment was significantly lower in the PE + MARS group than in the MARS group (p=0.0003). CONCLUSIONS: Both MARS and PE + MARS therapy can safely and effectively be used to treat liver failure complicated with hepatic encephalopathy, but PE + MARS therapy reduces serum total bilirubin level more effectively and is more cost-effective.

Genomics of hepatitis B virus-related hepatocellular carcinoma and adjacent noncancerous tissues with cDNA microarray.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common primary cancer frequently associated with hepatitis B virus (HBV) infection. However, whether these identified genes are particularly associated with HBV-related HCC remains unknown. The aim of this study was to investigate the differential gene expression between HBV-related HCC tissues and adjacent noncancerous tissues. METHODS: cDNA microarray was used to detect the differential gene expression profile in the HBV-related HCC tissues and adjacent noncancerous tissues, and reverse transcription-polymerase chain reaction (RT-PCR) was performed to verify the differential expression of candidate genes obtained from cDNA microarray experiment. RESULTS: In this study, 1369 genes or expressed sequence tags (ESTs) including 121 genes or ESTs with at least two-fold expression alterations between cancerous and noncancerous tissues were identified. Special AT-rich sequence binding protein 1 (SATB-1) expression was positive in 73% (16/22) of cancerous tissues and negative (0/22) in all noncancerous tissues of HBV-related HCC patients. Transmembrane 4 superfamily member 1 (TM4SF-1) expression was positive in 86% (19/22) of cancerous tissues and negative (0/22) in all noncancerous tissues. Suppression of tumorigenicity 14 (ST-14) expression was positive in 73% (16/22) of noncancerous tissues in patients with HBV-related HCC and negative in all HCC tissues (0/22). CONCLUSION: This study provided the gene expression profile of HBV-related HCC and presented differential expression patterns of SATB-1, TM4SF-1 and ST-14 between cancerous and noncancerous tissues in patients with HBV-related HCC.

Biorthonormal transfer-matrix renormalization-group method for non-Hermitian matrices.

A biorthonormal transfer-matrix renormalization-group (BTMRG) method for non-Hermitian matrices is presented. This BTMRG produces a dual set of biorthonormal bases to construct the renormalized transfer matrix with only half the dimensions of the matrix of a conventional transfer-matrix renormalization group (TMRG). We show that under generic conditions, such biorthonormal bases always exist. Based on a special E·S·E scheme (where S and E represent the system and environment blocks, respectively, and the two dots in between represent two additional physical sites), the BTMRG method can achieve zero truncation of any reduced state in describing both current left and right Perron states so as to reach a high degree of efficiency and accuracy. We believe that the BTMRG constitutes a more powerful and robust tool than conventional TMRG for non-Hermitian matrices and that it would allow us to better understand the collective behaviors and emerging phenomena of strongly correlated many-body systems. We also show that this scheme is particularly adapted to the calculation of the two-site correlation function of a one-dimensional quantum or two-dimensional classical lattice model.

Recognition of microcalcifications in digital mammograms based on Markov random field and deterministic fractal modeling.

We studied the performance of microcalcifications (MCs) recognition in digital mammograms using the combination of 4th order Markov random field (MRF) and deterministic fractal model (FM). Fifty 88 x 88 ROI samples are selected for computer experiments, among which 25 samples are attributed to class MCs and another 25 samples to class normal. We employed a three-layer backpropagation neural network (BPNN) and the leave-one-out method to test the proposed method. The receiver operating-characteristic (ROC) analysis and the area under the ROC curve (AUC) are used to analyze the performance of recognition. We first demonstrated that 4th order MRF has a superior performance with AUC=0.87 to MRF of order lower than 4. By combining the 4th order MRF and FM modeling, the AUC is further elevated to 0.90. Our results highlight the potential benefit of MRF and FM modeling in the recognition of MCs in digital mammograms.

Effect of low molecular weight heparin on pancreatic micro-circulation in severe acute pancreatitis in a rodent model.

BACKGROUND: Alleviation of microcirculation disorders in severe acute pancreatitis (SAP) can improve survival rates, and low molecular weight heparin (LMWH) is well known to have potent ameliorative effect on microcirculation disorders caused by anti-coagulant activity. The aim of this study was to investigate the effects of LMWH on pancreatic microcirculation in SAP in rats. METHODS: SD rats were randomly divided into 3 groups: sham operation (S) group, SAP group, and LMWH treatment (LT) group. The concentrations of serum amylase, tumor necrosis factor-alpha (TNF-alpha), endothelin-1 (ET-1), pancreatic ultrastructure were examined at 24 hours after the models were set up in each group. RESULTS: Compared with S group, the concentration of serum amylase, ET-1, and TNF-alpha in SAP group were significantly increased (P < 0.001); After LMWH treatment, the concentration of serum amylase, ET-1, TNF-alpha were decreased significantly compared with SAP group (P < 0.001, 0.01, 0.001, respectively). On electron microscopy, the microthrombosis in LT group was significantly less than that in SAP group. The 3-day survival rate in SAP group (25.0%) was significantly lower than that in S group (100.0%, P < 0.05) and in LT group (87.5%, P < 0.05). CONCLUSIONS: The disorder of pancreatic microcirculation may be involved in the inflammatory response of rats with SAP. LMWH can effectively improve the survival rate of SAP, and alleviate the severity of microcirculation disorders through its antithrombin effects and down-regulate the levels of serum ET-1 and TNF-alpha.

Detection of microcalcifications in digital mammograms using wavelet filter and Markov random field model.

Clustered microcalcifcations (MCs) in digitized mammograms has been widely recognized as an early sign of breast cancer in women. This work is devoted to developing a computer-aided diagnosis (CAD) system for the detection of MCs in digital mammograms. Such a task actually involves two key issues: detection of suspicious MCs and recognition of true MCs. Accordingly, our approach is divided into two stages. At first, all suspicious MCs are preserved by thresholding a filtered mammogram via a wavelet filter according to the MPV (mean pixel value) of that image. Subsequently, Markov random field parameters based on the Derin-Elliott model are extracted from the neighborhood of every suspicious MCs as the primary texture features. The primary features combined with three auxiliary texture quantities serve as inputs to classifiers for the recognition of true MCs so as to decrease the false positive rate. Both Bayes classifier and back-propagation neural network were used for computer experiments. The data used to test this method were 20 mammograms containing 25 areas of clustered MCs marked by radiologists. Our method can readily remove 1341 false positives out of 1356, namely, 98.9% false positives were removed. Additionally, the sensitivity (true positives rate) is 92%, with only 0.75 false positives per image. From our experiments, we conclude that, with a proper choice of classifier, the texture feature based on Markov random field parameters combined with properly designed auxiliary features extracted from the texture context of the MCs can work outstandingly in the recognition of MCs in digital mammograms.

[Preliminary study on proteomic patterns in hepatic tissue to identify HBV related hepatocellular carcinoma].

OBJECTIVE: To identify proteomic patterns in hepatic tissues for diagnosing early HBV related HCC. METHODS: Proteomic spectra were generated by two-dimensional gel electrophoresis (2-DE), A preliminary "raining" set of spectra derived from analysis of 14 cancer tissues and 14 non-cancer tissues, a proteomic patterns that completely discriminated cancer from non-cancer was identified. The discovered pattern was then used to classify an independent set of 48 masked samples: 24 from cancer tissues, and 24 from non-cancer tissues. RESULTS: The discriminatory pattern correctly identified all cancer tissues and non-cancer tissues in the masked set. This result yielded a sensitivity of 100%, specificity of 100%. CONCLUSION: Further analysis on these proteins in the proteomic pattern will be helpful to screen tumor markers for HBV related HCC. These findings justify a prospective assessment of proteomic pattern technology as a screening tool for cancer in high-risk and general populations.