Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2D^mutBTG2^mut had poorer OS than those with KMT2D^wt BTG2^mut (P=0.07) and KMT2D^wt BTG2^wt (P=0.05). On the contrary, patients with KMT2D^mut CD79B^mut had better OS than those with KMT2D^mut CD79B^wt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2D^mutBTG2^mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.

Objective:To study the clinical features and drug resistance profile of neonatal sepsis caused by different species of Klebsiella.Methods:From January 2009 to December 2018, cryopreserved Klebsiella strains from blood culture of neonatal sepsis cases in NICU of our hospital were reactivated. Molecular identification and antimicrobial susceptibility tests were performed. Clinical features, laboratory tests, drug resistance profile and prognosis of these patients were analyzed retrospectively.Results:A total of 29 strains of Klebsiella were reactivated. Molecular identification assigned 22 cases (75.9%) into Klebsiella pneumoniae (Kpn) group and 7 cases (24.1%) into Klebsiella quasipneumoniae (Kqu) group. Gestational age and birth weight of Kpn group were higher than Kqu group [(33.1±3.2) weeks vs. (30.6±0.9) weeks, (1 847±677) g vs. (1 416±121) g] ( P<0.05). Abdominal distension was more common in Kqu group than Kpn group [42.9% (3/7) vs. 4.5% (1/22), P<0.05]. No significant differences existed in the laboratory tests including white blood cell count, platelet count, hypersensitive C-reactive protein and procalcitonin between the two groups ( P>0.05). Kpn was 100.0% sensitive to Cefazolin-Tazobactam and Amikacinto and less sensitive to Imipenem and Cefperazone-Sulbactam, Meropenem and Ertapenem. Kqu was generally more sensitive than Kpn and the sensitivity of Kqu to Imipenem was 100.0%. No significant differences existed of the prognosis between the two groups ( P>0.05). Conclusions:Kpn is the main pathogen of neonatal Klebsiella sepsis. Kqu sepsis is more common in neonates with smaller gestational age and lower birth weight. Abdominal distention is common presenting symptom in Kpn sepsis and sensitive antibiotics should be used early.

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.
Aggrecans/metabolism* ; Animals ; Cartilage, Articular/metabolism* ; Chondrocytes/pathology* ; Cytoskeletal Proteins/metabolism* ; Mice ; Muscle Proteins/metabolism* ; Osteoarthritis/pathology* ; Temporomandibular Joint/pathology*

Objective:To explore the difference of high-risk factors between early-onset and late-onset pre-eclampsia, and to further understand high-risk factors of pre-eclampsia.Methods:Clinical data of pre-eclampsia pregnant women in 160 medical institutions in China in 2018 were retrospectively analyzed, including 8 031 cases of early-onset pre-eclampsia and 12 969 cases of late-onset pre-eclampsia. The proportion of high-risk factors, different body mass index (BMI) and age stratification between early-onset group and late-onset group were compared.Results:(1) Univariate analysis of high-risk factors: the proportions of high-risk factors in early-onset group and late-onset group were compared, and the differences were statistically significant (all P<0.05). Among them, the proportions of primipara and multiple pregnancy in early-onset group were lower than those in late-onset group, while the proportions of pregnant women with advanced age, irregular antenatal examination, obesity, family history of hypertension, pre-eclampsia, diabetes, kidney diseases, immune system diseases and assisted reproductive technology were higher than those in late-onset group. (2) Hierarchical analysis of BMI: the proportion of pregnant women with BMI≥24 kg/m 2 in early-onset group [48.2% (2 828/5 872) vs 45.5% (4 177/9 181), respectively; P=0.001] and the proportion of pregnant women with BMI ≥28 kg/m 2 in early-onset group [19.5% (1 143/5 872) vs 18.0% (1 656/9 181), respectively; P=0.028] were significantly higher than those in late-onset group. (3) Age stratification analysis: the proportion of pregnant women aged 35-39 years in the early-onset group [21.8% (1 748/8 023) vs 17.5% (2 110/12 068), respectively; P<0.01], the proportion of pregnant women 40-44 years old [6.8% (544/8 023) vs 5.4% (648/12 068), respectively; P<0.01], and the proportion of pregnant women ≥45 years old [0.7% (58/8 023) vs 0.5% (57/12 068), respectively; P=0.021] were significantly higher than those in the late-onset group. (4) Multivariate analysis: advanced age (≥35 years old), multiple pregnancy, irregular antenatal examination or transfer from other hospitals, family history of hypertension (including paternal, maternal and parental lines), previous history of pre-eclampsia, kidney diseases, immune system diseases (systemic lupus erythematosus, antiphospholipid antibody syndrome) and assisted reproductive technology pregnancy were the risk factors affecting the severity of pre-eclampsia (all P<0.05). Conclusion:Pregnant women with high risk factors such as age ≥35 years old, BMI ≥24 kg/m 2 before pregnancy, family history of hypertension, history of pre-eclampsia, chronic kidney diseases, immune diseases (mainly including systemic lupus erythematosus and antiphospholipid syndrome) and assisted reproductive technology are more likely to have early-onset pre-eclampsia.

BACKGROUND: Chromosomal abnormalities are important causes of ventriculomegaly (VM). In mild and isolated cases of fetal VM, obstetricians rarely give clear indications for pregnancy termination. We aimed to calculate the incidence of chromosomal abnormalities and incremental yield of chromosomal microarray analysis (CMA) in VM, providing more information on genetic counseling and prognostic evaluation for fetuses with VM. METHODS: The Chinese language databases Wanfang Data, China National Knowledge Infrastructure, and China Biomedical Literature Database (from January 1, 1991 to April 29, 2020) and English language databases PubMed, Embase, and Cochrane Library (from January 1, 1945 to April 29, 2020) were systematically searched for articles on fetal VM. Diagnostic criteria were based on ultrasonographic or magnetic resonance imaging (MRI) assessment of lateral ventricular atrium width: ≥10 to <15 mm for mild VM, and ≥15 mm for severe VM. Isolated VM was defined by the absence of structural abnormalities other than VM detected by ultrasonography or MRI. R software was used for the meta-analysis to determine the incidence of chromosomal abnormalities and incremental yield of CMA in VM, and the combined rate and 95% confidence interval (CI) were calculated. RESULTS: Twenty-three articles involving 1635 patients were included. The incidence of chromosomal abnormalities in VM was 9% (95% CI: 5%-12%) and incremental yield of CMA in VM was 11% (95% CI: 7%-16%). The incidences of chromosomal abnormalities in mild, severe, isolated, and non-isolated VM were 9% (95% CI: 4%-16%), 5% (95% CI: 1%-11%), 3% (95% CI: 1%-6%), and 13% (95% CI: 4%-25%), respectively. CONCLUSIONS Applying CMA in VM improved the detection rate of abnormalities. When VM is confirmed by ultrasound or MRI, obstetricians should recommend fetal karyotype analysis to exclude chromosomal abnormalities. Moreover, CMA should be recommended preferentially in pregnant women with fetal VM who are undergoing invasive prenatal diagnosis. CMA cannot completely replace chromosome karyotype analysis.
Chromosome Aberrations ; Chromosomes ; Female ; Fetus ; Humans ; Hydrocephalus ; Karyotyping ; Microarray Analysis ; Pregnancy ; Prenatal Diagnosis ; Retrospective Studies ; Ultrasonography, Prenatal

Objective To examine the association of pre-pregnancy obesity, excessive gestational weight gain (GWG) and gestational diabetes mellitus (GDM) with the risk of large for gestational age (LGA), and assess the dynamic changes in population attributable risk percent (PAR%) for having these exposures. Methods A retrospective cohort study was conducted to collect data on pregnant women who received regular health care and delivered in Beijing Obstetrics and Gynecology Hospital from January to December in 2011, 2014 and 2017, respectively. Information including baseline characteristics, metabolic indicators during pregnancy, pregnancy complications, and pregnancy outcomes were collected. Multivariate logistic regression model was constructed to assess their association with LGA delivery. Adjusted relative risk and prevalence of these factors were used to calculate PAR%and evaluate the comprehensive risk. Results (1) The number of participants were 11 132, 13 167 and 4 973 in 2011, 2014 and 2017, respectively. Corresponding prevalence of LGA were 15.19% (1 691/11 132), 14.98% (1 973/13 167) and 16.21% (806/4 973). No significant change in the prevalence of LGA was observed across all years investigated (all P>0.05). (2) According to results from multivariate logistic regression model, advanced maternal age, multiparity, pre-pregnancy overweight or obesity, GWG, GDM and serum triglyceride level≥1.7 mmol/L in the first trimester were associated with high risk of LGA (all P<0.05). Among these factors, pre-pregnancy overweight or obesity, excessive GWG and multiparity were common risk factors of LGA. GDM was not associated with risk of LGA in 2017 database. (3) Dynamic change of PAR% in these years were notable. PAR% of GWG for LGA decreased (32.6%, 27.2% and 22.2% in 2011, 2014 and 2017, respectively), while PAR% of pre-pregnancy overweight or obesity showed an upward trend (4.2%, 3.3% and 8.4%). In addition, PAR% of multiparity increased as well (3.5%, 6.3% and 15.9%). (4) Further analysis showed that excessive GWG in the first and second trimesters contributed the most (20.2% and 19.0% in 2014 and 2017). Conclusions Excessive GWG, pre-pregnancy overweight or obesity and multiparity are the important risk factors what contribute to LGA. PAR% of excessive GWG for LGA decrease in recent years. However, GWG in the first and second trimesters is a critical factor of LGA. Appropriate weight management in pre-pregnancy, the first or second trimester is the key point to reduce the risk of LGA.

Objective: To examine the association of pre-pregnancy obesity, excessive gestational weight gain (GWG) and gestational diabetes mellitus (GDM) with the risk of large for gestational age (LGA), and assess the dynamic changes in population attributable risk percent (PAR%) for having these exposures. Methods: A retrospective cohort study was conducted to collect data on pregnant women who received regular health care and delivered in Beijing Obstetrics and Gynecology Hospital from January to December in 2011, 2014 and 2017, respectively. Information including baseline characteristics, metabolic indicators during pregnancy, pregnancy complications, and pregnancy outcomes were collected. Multivariate logistic regression model was constructed to assess their association with LGA delivery. Adjusted relative risk and prevalence of these factors were used to calculate PAR%and evaluate the comprehensive risk. Results: (1)The number of participants were 11 132, 13 167 and 4 973 in 2011, 2014 and 2017, respectively. Corresponding prevalence of LGA were 15.19% (1 691/11 132), 14.98% (1 973/13 167) and 16.21% (806/4 973). No significant change in the prevalence of LGA was observed across all years investigated (all P>0.05). (2)According to results from multivariate logistic regression model, advanced maternal age, multiparity, pre-pregnancy overweight or obesity, GWG,GDM and serum triglyceride level≥1.7 mmol/L in the first trimester were associated with high risk of LGA (all P<0.05). Among these factors, pre-pregnancy overweight or obesity, excessive GWG and multiparity were common risk factors of LGA. GDM was not associated with risk of LGA in 2017 database. (3) Dynamic change of PAR% in these years were notable. PAR% of GWG for LGA decreased (32.6%, 27.2% and 22.2% in 2011, 2014 and 2017, respectively), while PAR% of pre-pregnancy overweight or obesity showed an upward trend (4.2%, 3.3% and 8.4%). In addition, PAR% of multiparity increased as well (3.5%, 6.3% and 15.9%). (4) Further analysis showed that excessive GWG in the first and second trimesters contributed the most (20.2% and 19.0% in 2014 and 2017). Conclusions Excessive GWG, pre-pregnancy overweight or obesity and multiparity are the important risk factors what contribute to LGA. PAR% of excessive GWG for LGA decrease in recent years. However, GWG in the first and second trimesters is a critical factor of LGA. Appropriate weight management in pre-pregnancy, the first or second trimester is the key point to reduce the risk of LGA.

Objective: To assess the effectiveness in optimizing resources and shortening critical children′s waiting time in pediatric emergency department (PED) with five-level pediatric emergency triage system (PETS). Methods: This retrospective study was conducted in the First Affiliated Hospital of Xiamen University after PETS was applied. The data of patients who visited the pediatric emergency department from January 2015 to December 2017 were collected and analyzed, including age, sex, diseases, visiting time, triage rate and destination. Results: A total of 375 985 patients were included, among whom males were 225 308 (59.9%) and females were 150 677 (40.1%), all younger than 14 years of age. The number of critical cases (level Ⅰ, level Ⅱ and level Ⅲ) was increased from 4 719 (3.7%) in 2015, 12 209 (10.2%) in 2016 to 16 188 (12.7%) in 2017. The number of non-critical patients (level Ⅴ) decreased year by year, as from 98 213 (76.8%) in 2015 to 75 210 (62.6%) in 2016 and 78 857 (61.7%) in 2017. The patients who classified as level Ⅰ or levelⅡaccording to the PETS were seen immediately by physician (n=1855, 0.5%). Overall, 119 738 patients (98.3%) who were classified as level Ⅲ or level Ⅳ could be seen by physician in a timely manner according to triage guidelines, while 2 112 patients (1.7%) could not. The mean waiting time was 9.09 min in level Ⅲ, 17.7 min in level Ⅳ, and 55.76 min in level Ⅴ patients, respectively. The critical cases admitted to the intensive care units were 175 (36.2%) in 2015, 350 (62.8%) in 2016 and 374 (66.2%) in 2017. The etiologies were respiratory diseases (73.3%), gastrointestinal diseases (15.8%) and infectious diseases (3.1%). Conclusion The application of PETS could optimize emergency resources and shorten the waiting time of critically ill children.

Objective To explore the neurological development of fetal with ventriculomegaly at 1 year after birth by systematically reviewing the domestic and international literature about prognosis of fetal ventriculomegaly. Methods Wanfang database, CNKI, CBM, PubMed, EMBASE and the Cochrane Library were online searched to collect relevant literature published from January 1st, 1980 to November 22th, 2017. Literature were extracted based on the Newcastle-Ottawa Scale(NOS), and analyzed by R software for meta-analysis. The corresponding model was selected according to the results of heterogeneity test to comprehensively analyze the prognosis of the fetus with ventriculomegaly. Results Five studies were included in the meta analysis, all of them were of high quality(scores>5).(1)The good prognosis rate of nervous system was 88％(95％CI:0.77-0.95)in fetus with mild ventriculomegaly,was 57％(95％CI:0.18-0.91)in those with moderate ventriculomegaly, and was 36％(95％CI: 0.16-0.59)in those with severe ventriculomegaly.(2)The good prognosis rate of the nervous system was 86％(95％CI:0.75-0.94)in fetus with the isolated ventriculomegaly, while was 58％ (95％CI: 0.20-0.91) in those with non-isolated ventriculomegaly.Theincidenceofchromosomalabnormalitieswas 7％(95％CI:0.05-0.09)inventriculomegaly. The improvement rate of lateral ventricle width in pregnancy was 41％(95％CI:0.27-0.57). Conclusions The prognosis of nervous system with mild ventriculomegaly is better than that of moderate and severe ventriculomegaly. The prognosis of nervous system with isolated ventriculomegaly is better than that of non-isolated ventriculomegaly. Fetal ventriculomegaly may be associated with fetal chromosomal abnormalities and intrauterine infection. The variation of fetal lateral ventricular width should be monitored regularly during pregnancy, the risk of poor prognosis should be informed, and pediatrician should be asked for evaluation.

Medical simulation training as a modern medical education has been used for decades in developed countries. Simulation based team training for obstetric emergency provides opportunities to re-hearse without risks to patients and helps overcome some limitations of the current medical education to improve the ability of medical staff to deal with obstetric emergencies, and improve adverse pregnancy out-comes. Simulation training is still at early stage in China. The Simulation Training Center of Beijing Ob-stetrics&Gynecology Hospital was established in June 2013. There are 100 medical staffs from our hospital and 406 from other hospitals who are trained using simulations to respond to acute obstetrical emergencies, including postpartum hemorrhage, neonatal recovery, shoulder dystocia and amniotic fluid embolism. Through introduction—on-scene simulation training—task report, we focus on learning, practical operation, emer-gency team and multidisciplinary coordination and communication skills training and through training, help learners understand the medical simulation training mode, and improve personal and team's ability to deal with the obstetric emergency. There is no doubt that simulation training will be further developed in China. Further research is required to investigate the application significance and feasibility of simulation training and access effectiveness of it.