Objective:To investigate the expression level of UBE2C in liver cancer tissues and its effect on the proliferation and invasion of hepatocellular carcinoma cells HepG2 after UBE2C silencing.Methods:The data set of liver cancer was downloaded from the TCGA database.Ac-cording to the median expression level of UBE2C mRNA in liver cancer tissues,all liver cancer pa-tients were divided into UBE2C higher(n=169)and lower expression group(n=205),respectively.The expression level of UBE2C mRNA in liver cancer tissues and its relationship with the patients prognosis was analyzed.COX regression was used to analyze the influencing factors of the liver cancer patients prognosis.The human hepatocellular carcinoma cell lines(HepG2,Huh7 and SMMC-7721)and human nromal hepatic epithelial cell line(THLE-3)were selected,and the ex-pression level of UBE2C in the four cell lines were detected by Western blot and real-time fluores-cence quantitative PCR,respectively.The HepG2 cell line was protein and mRNA expression leves divided into control group,NC group and si-UBE2C group according to UBE2C silencing.The ef-fects of UBE2C silencing on proliferation and invasion of HepG2 cell line were analyzed.Results:The expression level of UBE2C mRNA in liver cancer tissues and adjacent normal liver tissues were 4.342(3.239,5.635)and 0.905(0.587,1.230),respectively.Compared with adjacent normal liver tissues,UBE2C mRNA levels in liver cancer tissues were significantly higher(P＜0.001).The UBE2C mRNA expression levels in liver cancer tissues and paired adjacent normal liver tissues were 4.266(3.342,5.054)and 0905(0.587,1.230),respectively.Compared with paired adjacent normal liver tissues,UBE2C mRNA expression levels in liver cancer tissues were significantly higher(P＜0.001).The median survival time of UBE2C mRNA higher and lower expression groups was 48.85 months and 69.38 months.Compared with the lower expression group,the median survival time of UBE2C mRNA higher expression group was significantly shortened(P=0.045).T staging(T3/T4)and UBE2C expression(higher expression)were independent risk factors for poor prognosis in patients with liver cancer(P＜0.05).Compared with human liver epithelial cell line THLE-3,UBE2C protein and mRNA were significantly higher expressed in human hepatocellular carcinoma cell line HepG2,Huh7 and SMMC-7721(P＜0.05).The expression level of UBE2C protein and mRNA expression was the most significant in human hepatocellular carcinoma cell line HepG2 relative to cell line Huh7 and SMMC-7721.The CCK-8 results show that the cell proliferation rate in si-UBE2C group were significantly decreased protein and mRNA expression levels compared to control group and NC group at 72 h and 96 h,and the differences were significant(P＜0.05).The number of invasive cells in control group,NC group and si-UBE2C group were(23.12±3.45),(24.33±2.83)and(10.21±1.14),respectively.Compared with control group and NC group,the number of invasive cells in si-UBE2C group was significantly decreased(P＜0.05).Conclusion:UBE2C was higher expressed in liver cancer,and can be used as a biomarker for poor prognosis of patients with liver cancer.After silencing of UBE2C gene can significantly inhibit proliferation and invasion of HepG2.

Objective To investigate the relationship among circulating soluble major histocompatibility complex class Ⅰ-related chain A(sMICA),soluble major histocompatibility complex class Ⅰ-related chain B(sMICB),the activity of systemic lupus erythematosus(SLE)and autoantibodies.Methods A total of 156 SLE patients(SLE group)and 103 healthy volunteers(control group)who underwent physical examination in outpatient physical examination center were selected from the Qianjiang Hospital Affiliated to Chongqing University from January 2020 to January 2023.According to SLE disease activity score(SLEDAI),these SLE patients were divided into mild activity group(n=43),moderate activity group(n=69),and severe activity group(n=44).Serum levels of sMICA and sMICB,and the proportion of autoantibodies and peripheral blood NK cells were detected.Spearman or Pearson method was used to analyze the correlation among sMICA,sMICB,score,autoantibodies and peripheral blood NK cells proportion.Receiver operating characteristics(ROC)curve was used to evaluate the value of sMICA and sMICB in the diagnosis of SLE activity.Results Serum sMICA(173.65±23.92 pg/ml)and sMICB(96.35±15.74 pg/ml)levels in SLE group were higher than those in control group(32.51±6.27 pg/ml,12.03±2.47 pg/ml),while the proportion of CD3-CD56+NK cells(12.02％±2.65％)in peripheral blood was lower than that in control group(18.35％±3.71％),and the differences were statistically significant(t=58.498,53.897,-16.010,all P＜0.05).Serum sMICA and sMICB levels in severe active group were higher than those in moderately active group and mildly active group(t=8.192,12.352;19.652,23.742,all P＜0.05),and the proportion of CD3-CD56+NK cells in peripheral blood was lower than that in moderate and mild active groups(t=8.154,10.658,P＜0.05).The differences in positive rates of anti-dsDNA antibody,anti-nuclear antibody,anti-nucleosome antibody and anti-histone antibody in SLE patients with different disease activities were significant(x2=8.795,7.216,7.539,8.946,all P＜0.05).Serum sMICA and sMICB levels in SLE patients were positively correlated with SLED AI score,anti-dsDNA antibody,anti-nuclear antibody,anti-nucleosome antibody and anti-histone antibody(r=0.206～0.402,all P＜0.05),and negatively correlated with the proportion of CD3-CD56+NK cells in peripheral blood(r=-0.563,-0.427,all P＜0.05).The areas under the curve of SLE in severe active group diagnosed by sMICA and sMICB alone were 0.652 and 0.704,respectively.The area under the curve of SLE in severe active group diagnosed by sMICA and sMICB combined with SLE was 0.812,which was higher than that by the single diagnosis(Z=3.050,2.346,all P＜0.05).Conclusion The increased serum sMICA and sMICB levels in SLE patients were associated with the increased positive rate of SLE autoantibodies,the decreased proportion of NK cells in peripheral blood and the enhanced disease activity,which could be used as potential markers of SLE.

Lipids,including fats(triglycerides)and lipoids(phospholipids and sterols),not only serve as an energy source for the body but also play a pivotal role throughout the reproductive process,particularly in the establishment and maintenance of early pregnancy.This encompasses the regulate of early embryonic development and uterine tolerance,and the facilitation of embryo implantation.Given the diversity of lipids,this review focuses on extensively studied lipid mediators such as polyunsaturated fatty acids,endocannabinoids,prostaglandins,lysophosphatidic acid,sphingolipids and steroid hormones.It systematically elaborates on the regulatory effects of fatty acid,phospholipid,and cholesterol metabolism on the formation of endometrial receptivity and embryo implantation,as well as the potential underlying mechanisms.The review aims to provide new insights and feasible intervention approaches for predicting and improving the outcomes of natural pregnancy and/or assisted reproductive technology.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

OBJECTIVE: The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model. METHODS: Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model. RESULTS: On the 10th day after inoculation, hCD45⁺ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3⁺ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks. CONCLUSION Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.
Humans ; Animals ; Mice ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Heterografts ; Bone Marrow ; Disease Models, Animal ; T-Lymphocytes ; Mice, SCID

Humans ; Sarcoma, Alveolar Soft Part/secondary* ; Lung Neoplasms/pathology* ; Soft Tissue Neoplasms/pathology*

Objective: To investigate the diagnosis and treatment of Chiari malformation patients with hoarseness and other otorhinolaryngological symptoms. Methods: The clinical data of 18 patients of Chiari malformation with hoarseness were retrospectively collected, which was composed of 5 men and 13 women, aged 3-71 with median age of 52. All the patients were admitted to the Affiliated Hospital of Qingdao University from January 1989 to January 2020. All patients underwent brain MRI and laryngoscopy. The patient's symptoms and first diagnosis department, diagnosis time, total course of disease, hoarseness course, diagnosis and treatment, and postoperative recovery time were summarized. Follow-up time was 3-16 years, with median follow-up time of 6.5 years. Descriptive methods were used for analysis. Results: The first visit departments of 18 patients included neurology (9 cases), otorhinolaryngology head and neck surgery (5 cases), pediatrics (2 cases), orthopedics (1 case) and respiratory department (1 case). Except for the 7 cases in neurology department, the other 11 patients were not diagnosed in time. The disease duration of 18 patients with Chiari malformation ranged from 2 months to 5 years, and hoarseness was present from 20 days to 5 years. After diagnosis, 9 patients underwent posterior fossa decompression surgery, and 1 of them underwent syrinx drainage at the same time. The symptoms of 8 cases improved significantly after operation, with the improvement time from 1 to 30 days. In addition, 9 patients chose conservative treatment, among whom 8 had no improvement in symptoms and 6 progressed. Conclusions: Posterior fossa decompression is an effective treatment for Chiari malformation, and the prognosis is good. Timely diagnosis and treatment can improve the prognosis of patients.
Male ; Humans ; Female ; Child ; Hoarseness/etiology* ; Retrospective Studies ; Conservative Treatment ; Drainage ; Laryngoscopy

Cytochrome P4502J2 (CYP2J2) metabolizes arachidonic acid (AA) to cardioprotective epoxyeicosatrienoic acids (EETs). Dronedarone, an antiarrhythmic drug prescribed for treatment of atrial fibrillation (AF) induces cardiac adverse effects (AEs) with poorly understood mechanisms. We previously demonstrated that dronedarone inactivates CYP2J2 potently and irreversibly, disrupts AA-EET pathway leading to cardiac mitochondrial toxicity rescuable via EET enrichment. In this study, we investigated if mitigation of CYP2J2 inhibition prevents dronedarone-induced cardiac AEs. We first synthesized a deuterated analogue of dronedarone (termed poyendarone) and demonstrated that it neither inactivates CYP2J2, disrupts AA-EETs metabolism nor causes cardiac mitochondrial toxicity in vitro. Our patch-clamp experiments demonstrated that pharmacoelectrophysiology of dronedarone is unaffected by deuteration. Next, we show that dronedarone treatment or CYP2J2 knockdown in spontaneously beating cardiomyocytes indicative of depleted CYP2J2 activity exacerbates beat-to-beat (BTB) variability reflective of proarrhythmic phenotype. In contrast, poyendarone treatment yields significantly lower BTB variability compared to dronedarone in cardiomyocytes indicative of preserved CYP2J2 activity. Importantly, poyendarone and dronedarone display similar antiarrhythmic properties in the canine model of persistent AF, while poyendarone substantially reduces beat-to-beat variability of repolarization duration suggestive of diminished proarrhythmic risk. Our findings prove that deuteration of dronedarone prevents CYP2J2 inactivation and mitigates dronedarone-induced cardiac AEs.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

OBJECTIVE: To investigate the abnormality and distribution of plasma cholesterol levels in single-center hospitalized children. METHODS: The blood lipid levels of children aged 2-18 years who had blood lipid test results in Peking University First Hospital from June 2016 to June 2019 were etrospectively analyzed. Cholesterol oxidase method was used for total cholesterol, and high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were detected by clearance method. The counting data were compared with chi-square test. RESULTS: The survey had involved 11 829 children (7 087 were boys and 4 742 were girls). 1 822 (15.4%) children were with elevated total cholesterol, 1 371 (11.6%) children with elevated low-density lipoprotein cholesterol, and 2 798 (23.7%) children with high-density lipoprotein cholesterol reduction. The total number of the children with abnormal cholesterol levels was 4 427 (37.4%). Among the 7 835 children who visited hospital due to the disease not commonly inducing dyslipidemia, 731 (9.3%) had elevated TC, 561 (7.2%) had elevated LDL-C, 1 886 (24.1%) had decreased HDL-C, and 2 576 (32.9%) had abnormal cholesterol levels. Among the children with different diseases, the difference in the incidence of abnormal cholesterol was statistically significant. The top three main groups of the children with increased total cholesterol and low-density lipoprotein cholesterol were "dyslipidemia", "urinary tract disease", and "nutritional disease"; The top three main groups of the children with reduced high-density lipoprotein cholesterol were "respiratory diseases", "dyslipidemia", "hematological diseases and malignant tumors". Among the 1 257 blood li-pid test results sent by other departments, 300 cases had abnormal cholesterol levels (23.8%). Among them, there were 70 children with hypercholesterolemia (5.6%), 44 children with increased low-density lipoprotein cholesterol (3.5%), and 224 children with reduced high-density lipoprotein cholesterol (17.8%). There were 365 (4.6%) children with low-density lipoprotein cholesterol ≥140 mg/dL (3.6 mmol/L) who needed to further exclude familiar hypercholesterolemia among the children who visited hospitals due to the disease not commonly inducing dyslipidemia. CONCLUSION Children in hospitals have a high incidence of cholesterol abnormalities. Doctors need to pay more attention to the cholesterol diagnosis and management regardless of the discipline, which not only helps to control secondary hypercholesterolemia, but also provides the possibility of detecting familial hypercholesterolemia in time.
Child ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Dyslipidemias/epidemiology* ; Female ; Humans ; Hypercholesterolemia/epidemiology* ; Incidence ; Lipids ; Male ; Triglycerides