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.

Background and objective Low-dose spiral computed tomography(LDCT)has been recommended for lung cancer screening in high-risk populations.However,evidence from Chinese populations was limited due to the dif-ferent criteria for high-risk populations and the short-term follow-up period.This study aimed to evaluate the effectiveness in Chinese adults based on the Lung Cancer Screening Program in Minhang District of Shanghai initiated in 2013.Methods A total of 26,124 subjects aged 40 years or above were enrolled in the Lung Cancer Screening Program during the period of 2013 and 2017.Results of LDCT examination,and screen-detected cancer cases in all participants were obtained from the Report-ing System of the Lung Cancer Screening Program.The newly-diagnosed cases and their vital status up to December 31,2020 were identified through a record linkage with the Shanghai Cancer Registry and the Shanghai Vital Statistics.Standardized incidence ratio(SIR)and 95％CI were calculated using the local population at ages of 40 or above as the reference.Proportions of early-stage cancer(stage 0-Ⅰ),pathological types,and 5-year observed survival rates of lung cancer cases were estimated and compared between the cases derived from the screened and non-screened populations.Cox regression models were applied to evaluate the hazard ratio(HR)and 95％CI of LDCT screening with all-cause death of the lung cancer cases.Results The crude and age-standardized incidence of lung cancer in screened population were 373.3(95％CI:343.1-406.1)and 70.3 per 100,000 person-years,respectively,with an SIR of 1.8(95％CI:1.6-1.9),which was observed to decrease with following-up time.The early-stage cancer accounted for 49.4％of all lung cancer cases derived from the screened population,significantly higher than 38.4％in cases from the non-screened population during the same period(P＜0.05).The proportion of lung adenocarcinoma(40.7％vs 35.9％)and 5-year survival rate(53.7％vs 41.5％)were also significantly higher in the cases from the screened popu-lation(all P＜0.05).LDCT screening was associated with 30％(HR=0.7,95％CI:0.6-0.8)reduced all-cause deaths of the cases.Conclusion The participants of the screening program are at high-risk of lung cancer.LDCT favors the early-detection of lung cancer and improves 5-year survival of the screened cases,indicating a great potential of LDCT in reducing the disease burden of lung cancer in Chinese populations.

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.

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.

OBJECTIVETo explore the genetic basis for fetuses with cleft lip and palate.

METHODSFor 100 fetuses diagnosed with cleft lip with or without palate, G-banding chromosomal karyotyping and copy number variation sequencing (CNV-seq) were carried out on chorionic villi, amniotic fluid or cordocentesis samples.

RESULTSNo genomic abnormality was found among 49 fetuses with isolated cleft lip and palate, while 12 genomic aberrations were found among 51 fetuses with syndromic cleft lip and palate, which included 4 cases with trisomy 13, 2 cases with trisomy 18, 1 with X chromosome aneuploidy, 2 with other chromosomal aneuploidies and 3 with pathogenic CNVs.

CONCLUSIONThe incidence of genomic abnormalities in fetuses with cleft lip and palate was high. In addition to chromosomal abnormalities, attention should also be paid to pathogenic CNVs.

Objective: To discuss the application of Mohs microsurgery in nasal and facial basal cell carcinoma (BCC) and analyze the pathological and clinical features. Methods: The clinical data of 127 patients who were diagnosed by pathology as nasal and facial BCC in Qilu Hospital of Shandong University from January 2010 to January 2015 were retrospectively analysed. The value of Mohs microsurgery was discussed and the nasal & facial sites of BCC lesions, clinical and histopathology features were summarized. Results: The proportion of male and female was 1.27︰1 in 127 patients, the ages ranged from 27 to 91 years. The top three inflicted area in nasal and facial was followed by nasal dorsum, nasal root and upper lip.The most frequent clinical type was nodular ulcerative type.The most common pathological type was nodular and pigmented. Routine surgical resection was performed in 62 cases (48.8%) while Mohs micrographic surgery in 38 cases (29.9%). Follow-up duration was 37 months on average. Local recurrence occurred in 5 cases in routine surgical resection group while there was no recurrence in Mohs micrographic surgery group. There was no distant metastasis in all cases. Conclusions There are few specific clinical manifestation in nasal & facial BCC. Surgical treatment is prefered, especially by Mohs micrographic surgery, because it can strictly control the scope of surgical resection and obtain malformation repairment as well as beauty in nasal and facial region.

Objective To investigate the dynamic changes of blood-brain barrier(BBB) permeability after acute cerebral ischemia in rats with middle cerebral artery occlusion (MCAO) by dynamic contrast-enhanced(DCE)-MRI. Methods Sixty MCAO rat models were established by suture-occlusion method. All rats were divided randomly into twelve groups with different ischemia duration (3 hours, 6 hours, permanent) and reperfusion times (2, 6, 12 and 24 hours after reperfusion). Each group was examined by MRI at the time points. The BBB permeability parameters(Ktrans, Ve, Kep, rKtrans, rVe, rKep) were calculated by Siemens workstation and compared with Evans blue(EB) extravasation results. Multivariate analysis of variance (M-ANOVA), one-way analysis of variance (one-way ANOVA), Pearson analysis were respectively used to verify the influences of ischemia duration and reperfusion time on BBB permeability parameters, EB extravasation and relationships between parameters. Results In 3 hours and 6 hours ischemia duration groups, change of BBB permeability after reperfusion appeared biphasic. At 2 hours and 6 hours after reperfusion, BBB permeability increased, while rKtrans values and rVe values rose and rKep values dropped. BBB permeability decreased at 12 hours and increased again at 24 hours after reperfusion. The highest BBB permeability was observed at 6 hours after reperfusion. However, BBB permeability in permanent ischemia groups had uniphasic change, as its increase was rather mild as ischemia time went on. rKtrans values(1.99± 0.79)were positively correlated with rVe values(2.88 ± 1.78) (r=0.93, P<0.01) and negatively correlated with rKep values(0.66 ± 0.21) (r=-0.84, P<0.01). The negative correlation between rVe values and rKep valueswas also significant(r=- 0.80, P<0.01). EB extravasation results were consistent with MRI findings. Conclusions BBB permeability change was biphasic in reperfusion groups, while it was uniphasic in permanent ischemia groups. DCE-MRI may accurately reflect the changes of BBB permeability after acute cerebral ischemia. Both ischemic duration and reperfusion time had influences on BBB permeability. With prolongation of ischemic time, the duration of BBB permeability increase became shorter, BBB damage appeared earlier, with increased degree of ischemic damage.

Objective To investigate the influence of gestational weight gain (GWG) on the incidence of macrosomia, and to establish the reference ranges of GWG based on the incidence of macrosomia. Methods A multicenter, cross-sectional study was conducted. Totally, 112485 women were recruited from 39 hospitals in 14 provinces in China. Totally, 61149 cases were eligible with singleton pregnancies and non-premature deliveries. The associations of pre-pregnancy body mass index (BMI), GWG, newborn gender and gestational diabetes with macrosomia were analyzed with logistic regression. The normal GWG ranges were calculated in all maternal BMI subgroups, based on the normal incidence of macrosomia was set as the range of 5.0% to 10.0%. Results In this study, the incidence of macrosomia was 7.46%(4563/611149). The macrosociam was positive related with maternal height, delivery week,pre-pregnancy BMI, GWG, gestational diabetes, primipara, and male babies significantly (P<0.05), based on unadjusted and adjusted logestic regression. The normal range of GWG 20.0-25.0, 10.0-20.0, 0-10.0 and 0-5.0 kg in subgroups of underweight (pre-pregnancy BMI<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2) and obese (≥30.0 kg/m2), respectively. Conclusion The reference range of GWG in China based on the incidence of macrosomia is established.

Objective To investigate the performance of MicroScan WalkAway 96 Plus (MSW) system in detection of carbapenem-resistant Enterobacteriaceae (CRE).Methods A total of 81 stock CRE strains were used in this study. Bacterial identification and antimicrobial susceptibility test were performed by MSW system. Beta-lactamases genes blaKPC,blaIMP,blaVIM, blaOXA-48 and blaNDM were amplified by PCR and subjected to sequencing analysis. Disk diffusion method and PCR were used as gold standard to evaluate the performance and reliability of MSW system in identifying carbapenem-resistant and carbapenemase-producing Enterobacteriaceae.Results Overall, 69.1 % (56/81) of the Enterobacteriaceae strains were identified as CRE by the MSW system. The results of PCR showed that 48 strains were carbapenemase-producing Enterobacteriaceae. When carbapenemase-producing Enterobacteriaceae strains were identified by the instrument using an advanced expert system, the sensitivity was 93.8 % and specificity was 42.4 %. The positive predictive value was 70.3 %, the negative predictive value was 82.4 % and the predictive accuracy value was 72.8 %.Conclusions The MicroScan WalkAway 96 Plus system has shown good performance in detection of CRE.