Objective:To evaluate the performance of biomarkers in aneuploidy screening in the first trimester-pregnancy associated plasma protein A(PAPP-A) combined with Fetal Medicine Foundation (FMF)'s competing risk model in screening preeclampsia among our population.Methods:This study was based on a prospective cohort of singleton pregnant women who underwent aneuploidy screening in the first trimester in Nanjing Drum Tower Hospital from January 2017 to September 2020. Mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and PAPP-A were converted into multiples of median (MoM) using the algorithm disclosed on the website of the FMF (fetalmedicine.org). The predictive outcomes of maternal factors alone or in combination with MAP, UtA-PI, and PAPP-A (alone or in combination) were calculated. Chi-square test, Fisher's exact test or rank sum test were used for comparison among groups and Bonferroni method for pairwise comparisons. Receiver operating characteristic (ROC) curve was used to evaluate the screening efficiency and to calculate the sensitivities of predicting preeclampsia, term and preterm preeclampsia at false-positive rates of 5% and 10%. The predictive performance of this model was further compared to the screening strategy that was recommended in Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: a clinical practice guideline in China (2020). Results:Among the 5 144 singleton pregnancy women who were recruited in the cohort, 4 919 cases were included and analyzed in this study. A total of 223 cases were diagnosed as preeclampsia (4.5%), including 55 preterm (1.1%) and 168 term preeclampsia (3.4%). The median of MoM values of MAP, UtA-PI, and PAPP-A in the non-preeclampsia group were around 1.0±0.1. Statistical significance was observed in the difference of MAP, UtA-PI, and PAPP-A Mom between women with preterm preeclampsia and those without preeclampsia [1.061 (0.999-1.150) vs 0.985 (0.935-4.043), 1.115 (0.873-1.432) vs 1.039 (0.864-1.236), 0.820 (0.493-1.066) vs 1.078 (0.756-1.508)], which was also seen in the difference of MAP and PAPP-A Mom between women with term preeclampsia and those without preeclampsia [1.065 (1.002-1.133) vs 0.985 (0.935-4.043), 1.007 (0.624-1.393) vs 1.078 (0.756-1.508)] (all P<0.025). The combination screening with maternal factors+MAP+UtA-PI+PAPP-A was noted for the best efficiency. In predicting preeclampsia preterm and term preeclampsia at the false-positive rate of 10%, the sensitivity of the model was 53.0%, 76.4% and 44.6% respectively. Using the screening method recommended in Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: a clinical practice guideline in China(2020), the proportion of people at high risk of preeclampsia was 5.9% (290/4 919), and the sensitivity for predicting preterm preeclampsia was 25.5% (14/55), which was significantly lower than the combination screening with maternal factors+MAP+UtA-PI+PAPP-A [65.5% (36/55)] when using the same proportion of high-risk population. Conclusion:The preeclampsia screening model based on aneuploidy screening biomarkers in the first trimester--PAPP-A in combination with materral factors, MAP, UtA-PI, can effectively screen preterm preeclampsia in the local population without increasing the laboratory costs.

After decades of development,protein and peptide drugs have now grown into a major drug class in the marketplace.Target identification and validation are crucial for the discovery of protein and peptide drugs,and bioinformatics prediction of targets based on the characteristics of known target proteins will help improve the efficiency and success rate of target selection.However,owing to the developmental history in the pharmaceutical industry,previous systematic exploration of the target spaces has mainly focused on traditional small-molecule drugs,while studies related to protein and peptide drugs are lacking.Here,we systematically explore the target spaces in the human genome specifically for protein and peptide drugs.Compared with other proteins,both suc-cessful protein and peptide drug targets have many special characteristics,and are also significantly different from those of small-molecule drugs in many aspects.Based on these features,we develop separate effective genome-wide target prediction models for protein and peptide drugs.Finally,a user-friendly web server,Predictor Of Protein and Peptide drugs'therapeutic Targets(POPPIT)(http://poppit.ncpsb.org.cn/),is established,which provides not only target prediction specifically for protein and peptide drugs but also abundant annotations for predicted targets.

Objective:To investigate the effects of gestational weight gain (GWG) at different stages on pregnancy complications such as preeclampsia, gestational hypertension, gestational diabetes mellitus(GDM), small for gestational age (SGA), and large for gestational age (LGA).Methods:This was a prospective longitudinal cohort study. Singleton pregnancies at 11-13 +6 weeks of gestation in the Affiliated Drum Tower Hospital, Medical School of Nanjing University from January 2017 to November 2019 were recruited. The maternal height, weight, blood pressure, and fetal ultrasonic parameters were measured at 19-23 +6, 29-34 +6, and 35-40 +6 weeks of gestation by face-to-face interview and the pregnancy outcomes were followed up. All participants were grouped by body mass index (BMI) in the first trimester, with <18.50 kg/m 2 as underweight group, 18.50-23.99 kg/m 2 as normal group, ≥24.00 kg/m 2 as overweight/obesity group. Chi-square test and rank-sum test were adopted for comparison among groups. Weekly weight gain was converted into Z scores, and insufficient, appropriate, and excessive weight gain were respectively defined when Z<-1, -1≤ Z≤1, and Z>1. The effect of weekly weight gain at different gestational trimesters on pregnancy complications was analyzed by binary logistic regression. Results:Totally, 4 143 pregnant women entered the cohort. After excluding 327 cases, 3 816 were finally included in the analysis, with 394 in underweight group, 2 668 in normal group, and 754 in overweight/obesity group. Excessive weekly weight gain in the early second trimester was a risk factor for LGA( aOR=1.78, 95% CI:1.31-2.42, P<0.001), and in the later second trimester it was associated with preterm preeclampsia ( aOR=3.00, 95% CI: 1.26-7.10, P=0.013), gestational hypertension ( aOR=2.38, 95% CI: 1.44-3.94, P=0.001), and LGA ( aOR=1.59, 95% CI: 1.15-2.22, P=0.005). In the third trimester, excessive weekly weight gain was associated with higher risks of term preeclampsia ( aOR=2.70, 95% CI: 1.61-4.54, P<0.001) and gestational hypertension ( aOR=1.84, 95% CI: 1.05-3.21, P=0.033); while insufficient weekly weight gain was a risk factor for SGA ( aOR=1.58, 95% CI: 1.01-2.48, P=0.045), but a protective factor for term preeclampsia ( aOR=0.37, 95% CI: 0.14-0.97, P=0.041). Insufficient and excessive weekly weight gain in the early second trimester were not related to GDM (both P>0.05). Conclusions:GWG at different stages has different effects on pregnancy complications. A more relaxed control of GWG in the early second trimester combined with strict control in both the later second trimester and the third trimester may be a reasonable strategy to reduce the risk of preeclampsia without increasing the risk of SGA.

Objective: To explore the relationship between fetal nuchal translucency (NT) in the first trimester and pregnancy outcome. Methods: A prospective cohort study was conducted in Nanjjing Drum Tower Hospital from December 2015 to December 2018, 4 958 singleton pregnant women were enrolled to screen fetal ultrasound structure and serology in the first trimester, ultrasound in the second trimester and neonatus physical examination 28 days after birth. According to the results of NT, 167 cases of fetus with increased NT (≥3.0 mm) and 4 791 cases of normal NT were divided, moreover, 86 cases with isolate increased NT and 81 cases of increased NT combined with structural abnormality. The prognosis of fetuses with different NT thickness was analyzed, and the pregnancy outcome of fetuses with isolate increased NT or combined with structural abnormality were analyzed. In the first trimester, if the fetal structure was abnormal or the serological screening result was high risk, the chromosomal microarray analysis (CMA) would be performed by chorionic villus sampling to determine the prenatal diagnosis. Results: (1) The pregnancy outcome for fetus of normal NT: there were 4 791 cases with normal NT. Totally, 4 726 cases with normal NT and no structural abnormalities were screened out in the firsttrimester. In this group, 5 cases of aneuploidies were diagnosed based on high risk of maternal serum biomarkers and 83 cases of structural abnormalities were screened out in the subsequent ultrasound scan and the neonatal examination. Another 65 cases with normal NT present complicated with structural anomalies were screened out in the first trimester and 4 cases were diagnosed as aneuploidies. (2) The pregnancy outcome for fetus of isolate increased NT: 66 (76.7%, 66/86) cases of isolated increased NT were performed CMA, 3 cases were diagnosed as trisomy 21 and terminated pregnancy. Another 4 cases were terminated pregnancy privately without cytogenetic diagnosis. No further anomalies were found in 79 cases till 6 to 21 months postnatally. (3) The pregnancy outcome for fetus of increased NT with structural anomalies: increased NT present with structural anomalies were screened out by detailed anomaly scan in the first trimester and 32 of them were confirmed as aneuploidies. In this group, 70 cases terminated pregnancy, 2 cases had spontaneous miscarriages and 9 cases had liveborns (1 newborn was found ventricular septal defect). (4) The pregnancy outcome for fetus of increased NT with or without structural anomalies: the percentage of aneuploidies in fetuses with isolated increased NT (3.5%, 3/86) was significantly lower than those with structural abnormalities (39.5%,32/81). The healthy survival rate in fetuses with isolated increased NT (91.9%,79/86) was significantly higher than those with structural abnormalities (9.9%, 8/81). Conclusions A detailed first-trimester anomaly scan could improve prenatal screening efficiency of birth defects. Compared to the fetuses with increased NT combined with structural abnormalities, the healthy survival rate of fetuses with isolated increased NT based on detailed first-trimester anomaly scan is higher and the percentage of fetal aneuploidies is lower.

Objective To explore the clinical application effect of multiple end-to-side anastomosis in free anterolateral thigh perforator flap transplantation.Methods From January,2013 to October,2017,29 cases were applied the technology of multiple end-to-side anastomosis to the same recipient vessel in anterolateral thigh perforator flap transplantation for wound repair.Fifteen cases treated with multiple end-to-side anastomosis on flap arteries,and 2-3 arteries were anastomosed,with the average of 2.13.Nine cases were treated with venous multiple end-to-side anastomosis,and 2-4 veins were anastomosed,with the average of 3.11.Five cases treated with arterial and venous multiple end-to-side anastomosis,and 4-6 vessels were anastomosed,with the average of 5.20.Distribution of wounds:10 cases with hands and wrists wounded,15 cases with forearms and elbow joints wounded,and 4 cases with lower legs and feet wounded.The soft tissue defect size was 5 cm×13 cm-11 cm×27 cm,and the flap area was 6 cm× 15 cm-12 cm×29 cm.Postoperative followed-up was performed every 3-6 months to review flap survival.Results All flaps of 29 cases survived.Venous congestion occurred in 2 flaps within 48 h after the operation,among which,1 was overcomed after released the dressing and sutures,and the other underwent surgical exploration.The venous end-to-side anastomotic stomas were unobstructed,and hematoma was formed.After the hematoma compression was removed,circulation was recovered and the flap survived.With followed-up for 6 months to 2.5 years,both donor site and recipient site of the flaps healed well and the injured distal limbs had no hemodynamic disorder.Conclusion The application of multiple end-to-side anastomosis to the same recipient vessel for free transplantation of anterolateral thigh perforator flaps is safe and reliable.

ObjectiveTo investigate the cost-effectiveness and cost-benefit of five screening strategies for Down syndrome (DS) to optimize prenatal screening strategy.MethodsA retrospective analysis was conducted in 26803 gravidas, who underwent the second trimester maternal serum screening ( maternal serumα-fetoprotein andβ-human chorionic gonadotropin) from 2002 to 2003, whom were classified into three groups according to the results of serum DS screening: high risk group (≥1/270), borderline risk group (≥1/1000-<1/270) and elderly gravida group (age at expected date of confinement≥35 years old). TreeAge Pro 2011 sofware was used to set up the decision tree model for cost-effectiveness and cost-benefit analysis. Strategy 1: Maternal serum screening was carried out on all gravidas, and then prenatal diagnosis was performed for women in high risk group. Strategy 2: Non-invasive prenatal testing (NIPT) was carried out on all gravidas, and then prenatal diagnosis was offered for women with positive or suspected results. Strategy 3: NIPT was only carried out on gravidas of advanced maternal age and maternal serum screening was performed on the rest population. Gravidas with positive or suspected positive results in NIPT or classified into the high risk group underwent prenatal diagnosis. Strategy 4: Maternal serum screening was carried out on all gravidas. Those at high risk received prenatal diagnosis, while those at borderline risk underwent NIPT first and followed by prenatal diagnosis if positive or suspected positive NIPT results were identified. Strategy 5: Maternal serum screening was carried out on all gravidas. Those at high or borderline risk would undergo NIPT followed by prenatal diagnosis if they were positive or suspected positive for NIPT.Results(1) Among 26803 gravidas, 1244 were at high risk group (4.64％) with five having trisomy 21; 3925 were at bordelrine risk (14.64％) with four having trisomy 21; 300 women were of advanced age (1.12％) with one having trisomy 21. (2) Cost-effectiveness analysis: the incremental cost-effectiveness ratios of strategy 3 and 4 were negative and that of strategy 1 was 0 with a cost-effectiveness ratio of 15833764.53. The incremental cost-effectiveness ratio of strategy 2 was 49865746.10, which was far greater than that of strategy 5 (63049.56). The cost-effectiveness ratio of strategy 4 is 586703.63, which was less than those of strategy 1,2 and 3 but higher than that of strategy 5. The average cost-effectiveness ratio of strategy 5 was the lowest (508431.20) among these five strategies, which meant that for every diagnosis of DS, strategy 5 had the lowest cost (508400 yuan). (3) Cost-benefit analysis: The benefits of strategy 4 and 5 were greater than their costs. Strategy 5 had the highest benefit-cost ratio, followed by strategy 4, 2, 3 and 1. (4) When other factors remained unchanged and only the acceptance rate of prenatal diagnosis was adjusted from 50％ to 100％, strategy 1 had the least cost expectation, followed by strategy 3, 5, 4 and 2. When the cost of NIPT was below 82.4 yuan, the cost expectation of strategy 2 that performed on all gravidas was the lowest, while when it was between 82.4 and 1827.2 yuan, the screening cost of strategy 5 was the lowest.ConclusionsStrategy 5 has the best cost-effectiveness and cost-benefit. It would be the best screening strategy for DS, if the cost of NIPT is between 82.4-1827.2 yuan.

Objective To investigate the causes and prevention of postoperative pain of laparoscopic transabdominal preperitoneal (TAPP) and Lichtensteinrepair in the treatment of adult recurrent inguinal hernia.Methods Sixty adult recurrent inguinal hernia patients were enrolled in this study.They were divided into TAPP group and Lichtenstein group by random digits table,with 30 cases in each group.At 6 h Mter operation,the pain degree was evaluated by visual analogue scale (VAS) and compared between two groups.The level of VAS in TAPP group was (3.76 ± 1.47) scores,in Lichtenstein group was (6.36 ± 1.54) scores,and there was significant difference (t =-5.978,P =0.000).In TAPP group,pain was mainly moderate (17 cases,56.67％) and mild (11 cases,36.67％).In Lichtenstein group,pain was mainly moderate (14 cases,46.66％) and severe (13 cases,43.33％).Postoperative follow-up ranged from 6 to 48 months.No chronic pain appeared in TAPP group.There were 4 cases with chronic pain in Lichtenstein group,and the incidence rate of chronic pain was 13.3％.Conclusions The operation of TAPP in the treatment of recurrent inguinal hernia in adult patients has the advantage of shorter operation time,less postoperative pain,faster postoperative recovery,and can effectively reduce the incidence of postoperative pain.

Objective To compare the clinical efficacy of laparoscopic repair of laparoscopic transabdominal preperitoneal(TAPP)and Lichtenstein tension-free repair herniorrhaphy in the treatment of recurrent inguinal hernia in adults,and to explore the clinical advantages of TAPP in the treatment of recurrent inguinal hernia.Methods A retrospective analysis was conducted in 54 adult patients with recurrent inguinal hernia from December 2010 to January 2015.The patients were randomly divided into TAPP group and Lichtenstein group.The operation time,intraoperative bleeding volume,postoperative hospitalization time,cost of hospitalization,postoperative complications,early postoperative pain and the recurrence of hernia were compared between the two groups.Results All patients were successfully completed surgery.The operation time of TAPP group (47.2 ±9.4)min was significantly shorter than (73.1 ±10.4)min of Lichtenstein group (t=-2.503,P=0.034).The median amount of bleeding during operation of TAPP group was 40(15 -110)ml,which was significantly less than 73(11 -130)ml in Lichtenstein group (t=-6.018,P=0.000). Postoperative hospital stay of TAPP group[(6.5 ±1.4)d]was shorter than (8.2 ±1.6)d of the Lichtenstein group (t=-2.613,P=0.028).Early postoperative pain score of TAPP group[(1.8 ±1.2)points]was better than (2.9 ± 1.4)points in Lichtenstein group (t=-7.006,P=0.000),the difference was statistically significant.However,the hospitalization cost of TAPP group[(8 842.8 ±415.2)yuan]was higher than (6 676.9 ±327.6)yuan of the Lichtenstein group,the difference was statistically significant(t=6.782,P<0.05).In TAPP group,2 cases had complications after operation,which were less than 5 cases of Lichtenstein group.Postoperative follow up ranged from 6 to 48 months,1 case of recurrence in Lichtenstein group,the recurrence rate was 3.8%.There was no recurrence in the TAPP group.Conclusion TAPP has the advantages of short operation time,less bleeding,rapid postoperative recovery,less postoperative pain and so on.It can be used as a recommended procedure for the treatment of recurrent inguinal hernia in adults.

Objective To investigate the feasibility of prophylactic cranial irradiation with hippocampal avoidance (HA-PCI) in non-small cell lung cancer (NSCLC).Methods The clinical data of 56 patients with brain metastases of NSCLC who were treated from 2011 to 2014 were collected.Brain metastases and the hippocampus were delineated on T1 W1 contrast-enhanced MRI,and the distance between brain metastases and the hippocampus was analyzed;an HA-PCI regimen was also developed,and the distribution of the metastases in planning target volume (PTV) low-dose regions around the hippocampus was analyzed.Results None of the 139 metastases involved the hippocampus.There were 6(4.3％) and 18 (12.9％) metastases within 5 mm and 10 mm,respectively,outside the hippocampus.In the HA-PCI regimen,the D50％ and D2％ of PTV were 25.6 Gy and 27.1 Gy,respectively.Dmean and D2％ for the hippocampus were 7.4 Gy and 9.9 Gy,respectively;D50％ within 0-5.0 mm,5.1-10.0 mm,and 10.1-15.0 mm outside the hippocampus was 10.3 Gy,15.1 Gy,and 20.5 Gy,respectively.Conclusions HA-PCI may be feasible theoretically,but this needs to be confirmed by the intracranial failure pattern in patients with long-term survival.

Pig copper zinc superoxide dismutase (CuZnSOD) is an important antioxidant enzyme. Some studies focused on the function of CuZnSOD gene, but the transcriptional regulation of the CuZnSOD gene is not yet fully elucidated. Therefore, the aims of the study were to determine the core promoter region and to explore its mechanism of transcriptional regulation. The 853 bp DNA sequence of 5'-flanking promoter was amplified by performing PCR. A series of CuZnSOD promoter fragments with gradually truncated 5'-end were produced by nested PCR and inserted into pGL3-Basic vector. The activities of the promoters were measured by the dual-luciferase assay system after transient transfection into the NIH/3T3 cells. The results demonstrated that there were 2 potential transcription start sites in the regions from initiation codon to -87 bp and -266 bp, respectively. The region from -383 bp to +67 bp in CuZnSOD gene promoter showed higher activity than other regions, and further deletion analysis demonstrated that the region from -75 bp to -32 bp contained an essential promoter sequence for pig CuZnSOD gene transcription. In addition, several potential transcription factor binding sites were predicted with bioinformatics method. These results suggest that these transcription factor binding sites may be involved in the transcriptional regulation of CuZnSOD gene.
Animals ; Cloning, Molecular ; Gene Expression Regulation ; Genetic Vectors ; Mice ; NIH 3T3 Cells ; Promoter Regions, Genetic ; Superoxide Dismutase ; genetics ; Swine ; Transfection