Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

New-onset refractory status epilepticus is a rare and special clinical manifestation with high mortality. About half of the patients have no clear cause. At present, the pathogenesis is unclear, and the treatment plan is controversial. In recent years, it has been found that inflammatory and immune responses of the body may be involved in the pathogenic process, and it is called “inflammatory-immune mediated epileptic encephalopathy” based on the perspective of pathogenesis. There have also been many treatment attempts based on the inflammatory and immunological mechanisms, some of which have achieved satisfactory results. However, most of them are based on the review of small sample cases, and relevant guidelines are still lacking at present. In this paper, the definition, etiology, pathogenesis, clinical manifestations and treatment of persistent status of new-onset refractory status epilepticus are reviewed.

Anti-contactin associated protein-like 2 (CASPR2) antibody encephalitis is a rare autoimmune encephalitis with variable clinical symptoms and atypical imaging manifestations. The prognosis of the patients with severe disease is poor. Reversible posterior leukoencephalopathy syndrome is rarely reported in autoimmune encephalitis. The clinical data, diagnosis and treatment of a patient with anti-CASPR2 antibody encephalitis complicated with reversible posterior encephalopathy syndrome were reported, in order to improve the understanding of clinicians on the rare disease complicated with atypical imaging manifestations.

Objective:To investigate the characteristics of pregnancy with pre-excitation syndrome and its influence on pregnancy outcomes.Methods:A retrospective analysis was made on the clinical data of 62 cases of pregnancy complicated with pre-excitation syndrome in Beijing Anzhen Hospital from Jan. 2008 to Dec. 2008. According to whether there was a supraventricular tachycardia (SVT) in pregnancy, they were divided into two groups. There were 16 pregnant women in the SVT seizure group during pregnancy, and 46 pregnant women in no SVT seizure group, with a multi-disciplinary comprehensive diagnosis and treatment model. SPSS software was used to analyze the data and compare the gestational age, age and weight of the newborn, and then compare the pregnancy outcomes.Results:(1) The total number of deliveries in Beijing Anzhen Hospital during the study period was 21 786, and the patients with pregnancy combined with pre-excitation syndrome account for 0.28% (62/21 786). (2) Totally 44 patients (71%, 44/62) were diagnosed with pre-excitation syndrome before pregnancy, and 18 patients (29%, 18/62) were diagnosed for the first-time during pregnancy. Among patients diagnosed with pre-excitation syndrome before pregnancy, 16 patients (36%, 16/44) had seizures before pregnancy, 28 patients (64%, 28/44) had asymptomatic before pregnancy, and 4 of asymptomatic patients had SVT during pregnancy. (3) Of the 16 pregnant women in the SVT seizure group during pregnancy, 2 patients (2/16) had SVT episodes in the first trimester, 5 patients (5/16) had SVT episodes in the second trimester, 9 patients (9/16) had SVT episodes in the third trimester. In the SVT seizure group, 8 patients (8/16) had SVT episodes before pregnancy, and 8 patients (8/16) had no SVT episodes before pregnancy. There were 46 patients in the SVT seizure-free group during pregnancy, including 9 patients with SVT attacks before pregnancy and 37 patients without SVT before pregnancy. (4) Compared with the pregnant women in the SVT seizure group, the age, weight gained during pregnancy, delivery gestation week, newborn weight, and the time of the first and second labors were not statistically different between the two groups of pregnant women (all P>0.05). However, the total duration of labor in the SVT seizure group during pregnancy was shorter and pre-pregnancy weight was lower (all P<0.05). The rate of cesarean section in pregnant women with SVT attack was 12/16, and the rate of cesarean section in pregnant women without SVT was 50% (23/46; P=0.051). No pregnant woman had an arrhythmia during delivery. Conclusions:SVT episode in patients during pregnancy most occurs in the third trimester. Patients who are asymptomatic before pregnancy may also have SVT during pregnancy. Pre-excitation syndrome patients with SVT attacks during pregnancy increase adverse pregnancy outcomes. Multidisciplinary comprehensive management could effectively control pregnant women with pre-excitation syndrome, effectively reduce the occurrence of serious arrhythmia risk events during pregnancy, so that most patients could get good pregnancy outcomes.

To evaluate immune efficacy of the recombinant Lactobacillus casei, we constructed pLA-Newcastle disease virus (NDV)-F/L. casei and obtained the expression products. PCR amplified the NDV F gene carrying part of the major epitopes. The target gene was inserted to the shuttle plasmid pLA, and then transformed into Escherichia coli BL21 (DE3) in order to screen positive recombinant plasmid. The positive recombinant plasmid was transformed into L. casei by electroporation to construct pLA-NDV-F/L. casei. The positive strains were identified by PCR. The reactivity of the recombinant bacteria was identified by Western blotting and the protein expression was detected by indirect immunofluorescence, flow cytometry and laser confocal microscopy. The 14-day-old chickens in each group were vaccinated by oral plus nose drops. The pLA-NDV-F/L. casei twice immunization group and three times immunization group, the commercial vaccine group, the pLA/L. casei group, the unchallenge PBS and the challenge PBS group were established. IgG in serum and sIgA in the lavage fluid of intestinal, nasal and lung were detected by ELISA. The protection rate of chickens was evaluated. The results showed that 94.10% of the recombinant bacteria expressed the F protein. The recombinant protein was highly expressed on the surface of L. casei with a protein size of 62 kDa, which specifically bound to anti-NDV serum. The levels of anti-F IgG and sIgA antibodies in each test group were significantly higher than those in the control groups. The duration of antibody in the pLA-NDV-F/L. casei three-time immunization group lasted 28 days longer than that in the twice immunized group, and there was no significant difference between antibody peak values. The attack protection rates in each group of immunized pLA-NDV-F/L. casei three times, twice, attenuated vaccine, pLA/L. casei and PBS were 80%, 80%, 90%, 0% and 0%, respectively. Therefore, the antigenic protein of NDV F was successfully expressed by L. casei expression system, which has of reactogenicity and immunogenicity, and could induce protective immune responses in chickens.
Animals ; Antibodies, Viral ; Chickens ; Immunization ; Lactobacillus casei ; Newcastle disease virus ; Vaccines, Attenuated ; Viral Vaccines

Objective: To investigate the expression of metastasis-associated protein 2 (MTA2) in human bladder cancer tissues and its effect on the malignant biological behaviors of bladder cancer T24 cells, as well as to explore the effect of MTA2 on the progression of bladder cancer. Methods: Sixty-two cases of human bladder cancer tissues and 28 cases of normal bladder tissues (from patients with cystitis, and pathologically confirmed as normal tissue) were collected at People’s Hospital of Hebei Province during December 2012 and December 2014. The expression of MTA2 in bladder cancer tissues and normal bladder tissues was detected by immunohistochemical staining, and the correlation between MTA2 expression and clinicopathological characteristics of patients was also analyzed. The bladder cancer T24 cell line stably expressing MTA2 was constructed. The effects of MTA2 on the proliferation, colony formation, migration and invasion of bladder cancer T24 cells were detected by MTS, clone formation, scratch healing and Transwell assay, respectively. Results: Immunohistochemical staining showed that MTA2 expression was significantly up-regulated in bladder cancer tissues as compared with normal bladder tissues (P<0.01). The high expression of MTA2 in bladder cancer tissues was not related to gender, age and tumor volume (P>0.05), but was associated with higher TNM stage, histological grade, and lymphatic infiltration and metastasis (all P<0.05). After over-expression of MTA2 in bladder cancer T24 cell line, the proliferation activity of the cells was significantly increased (P<0.05), and the colony formation, scratch healing, migration and invasion ability were significantly increased (all P<0.01). Conclusions: MTA2 is up-regulated in human bladder cancer tissues and can promote the proliferation, tumor formation, migration and invasion of T24 cells.

Objective: To explore the clinical features, the serotype distribution and drug resistance of the isolates in patient with invasive pneumococcal disease (IPD). Methods: By retrieving the laboratory information system in 18 children′s hospitals from 2012 to 2017, the children with IPD were enrolled. Streptococcus pneumoniae (Spn) must be isolated from the sterile sites (blood, cerebrospinal fluid, hydrothorax and joint effusion etc.). The clinical characteristics, serotype, drug resistance, treatment and prognosis were reviewed and analyzed. According to the telephone follow up results, the patients were divided into death group and recovered group. The index as an independent risk factor of mortality was demonstrated by multivariate logistic regression analysis. Results: There were 1 138 children with IPD, including 684 male and 454 female. The proportion of male to female was 1.5∶1. The age ranged from one day to 16 years. The median age was 1 year 3 month. The majority was under 5 years of age (89.3%, n= 1 016), especially under 2 years of age (61.9%, n=704). In all cases, 88.2% (n=1 004) were community acquired infection. The infections included meningitis (n=446, 39.2%), pneumonia with bacteremia (n=339, 29.8%), and bacteremia without focus (n=232, 20.4%). Underlying diseases were found in 242 cases (21.3%). Co-infections were determined in 62 cases (5.4%) with mycoplasma, 27 cases (2.4%) with adenovirus and 34 cases with influenza virus (3.0%). The penicillin insensitivity (PNSP) rates in meningitis and non-meningitis isolates were 69.5% (276/397) and 35.9% (221/615), respectively. There were 81 strains serotyped, in which 93.8% (76/81) were covered by 13-valent protein-polysaccharide conjugate vaccine (PCV13). In the 965 patients who were followed up by phone call, 156 cases (16.2%) were confirmed dead. The independent risk factors for the death were under 2 years of age (OR=2.143, 95%CI 1.284-3.577, P=0.004), meningitis (OR=3.066, 95%CI 1.852-5.074, P<0.01), underlying disease (OR=4.801, 95%CI 2.953-7.804, P<0.01), septic shock(OR=3.542, 95%CI 1.829-6.859, P<0.01), disseminated intravascular coagulation (DIC) (OR=4.150, 95%CI 1.468-11.733, P=0.007), multiple organ failure (OR=12.693, 95%CI 6.623-24.325, P<0.01) and complications of central nervous system (OR=1.975, 95%CI 1.144-3.410, P=0.015). Conclusions Most children with IPD were under 5 years of age, having underlying diseases and acquired the infection in community. The independent risk factors for death were under two years old, meningitis, underlying diseases and multiple organ failure. The problem of drug resistance was severe. The universal immunization of PCV13 would be effective to prevent IPD in Chinese children.

Objective: To investigate the effect of interleukin-8 (IL-8) on esophageal cancer cell line KYSE170, and to preliminarily explore its mechanism. Methods: siRNA targeting IL-8 was in vitro synthesized and transfected into KYSE170 cells by lipofectamine 2000. The efficiency of silencing was determined by Real-time PCR, Western blotting and ELISA. Morphological changes of KYSE170 cells were observed microscopically. Scratch assay was performed to observe the cell migration ability. CCK-8 assay was used to detect the cell proliferation ability. Western blotting was used to detect the expressions of IL-8 receptor and JAK2-STAT3 signaling pathway related proteins. Results: Compared with the negative control group, the mRNA and protein expressions of IL-8 in KYSE170 cells were all significantly decreased after IL-8 silencing (P<0.01), and IL-8 secretion was significantly reduced (P<0.01).After IL-8 gene silencing, the migration capacity of KYSE170 cells was significantly weakened (P<0.01), while no significant changes in cell proliferation was detected. The expression of IL-8 receptor 2 (CXCR2) and transfer-related protein WASF3 were significantly decreased (P< 0.05), while the expression of IL-8 receptor 1 (CXCR1) was not significantly changed; the expressions of p-JAK2 and p-STAT3 protein in JAK2-STAT3 signaling pathway were significantly decreased (all P<0.01). Conclusion: Knock-down of IL-8 inhibits the migration of esophageal cancer KYSE170 cells, and the mechanism may be related with the alteration of CXCR2 and its downstream JAK2STAT3 signaling pathway.

Objective To design perinatal grief scale ( PGS) for single intrauterine fetal death( sIUFD) and evaluate its reliability and validity, so as to provide reference for psychological nursing of this kind of pregnant women. Methods Scale development study group was established, with the PGS as a framework, 24 items were enrolled after brainstorming, expert consultation and preliminary experiments. From January 2013 to December 2015, 100 pregnant women with sIUFD were enrolled from this hospital. Internal consistency reliability, retest reliability, content validity, and receiver operating characteristic curve ( ROC) were used to analyze the sensitivity, specificity, etc. Results Cronbach′s α coefficient and split-half reliability of the scale were 0. 896 and 0. 806. Test-retest reliability and content validity index were 0. 901 and 0. 92. Except for the fifteenth item,the other items had a good correlation with total score (r = -0. 263 -0. 779). With PGS as calibration, PGS of sIUFD had a good correlation with PGS (r =0. 845, P <0. 001). The sensitivity and specificity of PGS of sIUFD were 0. 71 and 0. 72. The cut-off value was 72 points. Conclusions The PGS of sIUFD has good reliability, validity and sensitivity. It has an important clinical value on assessing the sad mood of sIUFD.

OBJECTIVETo analyze the implement performance of China Infectious Diseases Automated-alert and Response System (CIDARS) of 31 provinces in mainland China, and to provide the evidences for further promoting the application and improvement of this system.

METHODSThe amount of signals, response situation and verification outcome of signals related to 32 infectious diseases of 31 provinces in mainland China in CIDARS were investigated from 2011 to 2013, the changes by year on the proportion of responded signals and timeliness of signal response were descriptively analyzed.

RESULTSA total of 960 831 signals were generated nationwide on 32 kinds of infectious diseases in the system, with 98.87% signals (949 936) being responded, and the median (the 25(th) percentile to the 75(th) percentile (P25-P75) ) of time to response was 1.0 (0.4-3.3) h. Among all the signals, 242 355 signals were generated by the fixed-value detection method, the proportion of responded signals was 96.37% (62 349/64 703), 98.75% (68 413/69 282) and 99.37% (107 690/108 370), respectively, and the median (P25-P75) of time to response was 1.3 (0.3-9.7), 0.8(0.2-4.9) and 0.7 (0.2-4.2) h, respectively. After the preliminary data verification, field investigation and laboratory test by local public health staffs, 100 232 cases (41.36%) were finally confirmed.In addition, 718 476 signals were generated by the temporal aberration detection methods, and the average amount of signal per county per week throughout the country were 1.53, and 8 155 signals (1.14%) were verified as suspected outbreaks. During these 3 years, the proportion of signal response was 98.89% (231 149/233 746), 98.90% (254 182/257 015) and 99.31% (226 153/227 715), respectively, and the median (P25-P75) of time to response was 1.1 (0.5-3.3), 1.0 (0.5-2.9) and 1.0 (0.5-2.6) h, respectively.

CONCLUSIONFrom 2011 to 2013, the proportion of responded signals and response timeliness of CIDARS maintained a rather high level, and further presented an increasing trend year by year. But the proportion of signals related to suspected outbreaks should be improved.