Risk factors for postoperative delirium in children with congenital heart disease: a prospective nested case-control study / 中国当代儿科杂志

OBJECTIVES@#To study the risk factors for postoperative delirium (POD) in children with congenital heart disease.@*METHODS@#A prospective nested case-control study was performed on children with congenital heart disease who underwent surgery in Fuwai Hospital, Chinese Academy of Medical Sciences, from December 2020 to June 2021. The clinical data were compared between the POD group (n=114) and non-POD group (n=102). A multivariate unconditional logistic regression analysis was used to investigate the risk factors for POD in children with congenital heart disease.@*RESULTS@#The multivariate logistic regression analysis showed that age (OR=0.951, P<0.001), gender (OR=2.127, P=0.049), number of invasive catheters per day (OR=1.490, P=0.017), degree of postoperative pain (OR=5.856, P<0.001), and preoperative parental anxiety level (OR=1.025, P=0.010) were independent risk factors for POD in children with congenital heart disease.@*CONCLUSIONS@#The risk of POD increases in children with congenital heart disease who are younger, male, have higher number of invasive catheters per day, higher degree of postoperative pain, or higher preoperative parental anxiety level.

Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine (KCONVAC) in Healthy Adults: Two Randomized, Double-blind, and Placebo-controlled Phase 1/2 Clinical Trials

BackgroundThe significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine, KCONVAC, in healthy adults. MethodsTwo phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in Chinese healthy adults aged 18 through 59 years. The phase 1 trial was conducted in a manner of dosage escalation. The first 30 participants were randomized in a ratio of 4:1 to receive two doses of either KCONVAC at 5 g per dose or placebo on Day 0 and Day 14, and the second 30 participants were randomized to receive either KCONVAC at 10 g per dose or placebo following the same procedures. The participants in the phase 2 trial were randomized in a ratio of 2:2:1 to receive either KCONVAC at 5 g or 10 g per dose, or placebo on Day 0 and Day 14, or Day 0 and Day 28. In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following each vaccination. Antibody response and cellular response were assayed in the phase 1 trial. In the phase 2 trial, the primary immunogenicity endpoint was the seroconversion and titre of neutralization antibody, and the seroconversion of receptor binding domain (RBD)-IgG 28 days after the second dose. FindingsIn the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-g vaccine (N=24), 10-g vaccine (N=24), or placebo (N=12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-g vaccine (N=100 for 0/14 or 0/28 regimens), 10-g vaccine (N=100 for each regimen), or placebo (N=50 for each regimen). In the phase 1 trial, 13 (54%), 11(46%), and 7 (58%) participants reported at least one adverse event (AE), of whom 10 (42%), 6 (25%), and 6 (50%) participants reported at least one vaccination-related AE after receiving 5-g vaccine, 10-g vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and 9 (18%) participants reported at least one AE, of whom 13 (13%), 17 (17%), and 6 (12%) participants reported at least one vaccination-related AE after receiving 5-g vaccine, 10-g vaccine, or placebo at the regimen of Day 0/14, respectively. Similar results were observed in the three treatment groups of Day 0/28 regimen. All the AEs were grade 1 or 2 in intensity. No AE of grade 3 or more was reported. One SAE (foot fracture) was reported in the phase 1 trial. KCONVAC induced significant antibody response. 87{middle dot}5% (21/24) to 100% (24/24) of participants in the phase 1 trial and 83{middle dot}0% (83/100) to 100% (99/99) of participants in the phase 2 trial seroconverted for neutralising antibody to live virus, neutralising antibody to pseudovirus, and RBD-IgG after receiving two doses. Across the treatment groups in the two trials, the geometric mean titres (GMTs) of neutralising antibody to live virus ranged from 29{middle dot}3 to 49{middle dot}1 at Day 0/14 regimen and from 100{middle dot}2 to 131{middle dot}7 at Day 0/28 regimen, neutralising antibody to pseudovirus ranged from 69{middle dot}4 to 118{middle dot}7 at Day 0/14 regimen and from 153{middle dot}6 to 276{middle dot}6 at Day 0/28 regimen, and RBD-IgG ranged from 605{middle dot}3 to 1169{middle dot}8 at Day 0/14 regimen and from 1496{middle dot}8 to 2485{middle dot}5 at Day 0/28 regimen. RBD-IgG subtyping assay showed that a significant part of RBD-IgG was IgG1. The vaccine induced obvious T-cell response with 56{middle dot}5% (13/23) and 62{middle dot}5% (15/24) of participants in 5-g and 10-g vaccine groups showed positive interferon-{gamma} enzyme-linked immunospot responses 14 days after the second dose in the phase 1 trial, respectively. InterpretationKCONVAC is well tolerated and able to induce robust antibody response and cellular response in adults aged 18 to 59 years, which warrants further evaluation with this vaccine in the upcoming phase 3 efficacy trial. FundingGuandong Emergency Program for Prevention and Control of COVID-19 (2020A1111340002) and Shenzhen Key Research Project for Prevention and Control of COVID-19.

Structural changes of the temporomandibular joint in adolescents with skeletal class III malocclusions after maxillary protraction: An X-ray measurement analysis / 中国组织工程研究

BACKGROUND: For skeletal Class III malocclusions, the positional relationship between the upper and lower jaws and abnormal occlusion can impact the shape of the condyle and the glenoid fossa, as well as the movement of the mandible and the function of the masticatory muscles. Maxillary protraction appliances are one of the effective methods for the treatment of skeletal Class III malocclusion in adolescents, which can reconstruct the positional relationship of the jaws and improve the glenoid fossa-disc-protrusion relationship in patients with skeletal Class III malocclusion. OBJECTIVE: To evaluate the temporomandibular joint changes in adolescents with skeletal Class III malocclusions treated with maxillary protraction. METHODS: Twenty-nine patients (11 girls and 18 boys; age range from 12-14, with a mean age of (12.90±0.99) years were treated with maxillary protraction. Lateral cephalograms were taken before and after treatment. A coordinate system was set to quantitatively analyze the changes of temporomandibular joint fossa, condyle and temporomandibular joint spaces in sagittal and vertical directions. RESULTS AND CONCLUSION: After maxillary protraction, no displacement of the gleniod fossa and the condyle in the sagittal direction was observed (P > 0.05). Simultaneously, in the vertical direction, there was no significant displacement of the gleniod fossa as well as no posterior and superior condyle displacement (P > 0.05). However, the anterior condyle moved upward (P 0.05). These findings indicate that maxillary protraction treatment can adaptively remodel the temporomandibular joint in adolescents with skeletal Class III malocclusion will undergo adaptive remodeling, but will not adversely affect the function of the temporomandibular joint due to the unchanged joint space.

Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials / 中华医学杂志(英文版)

BACKGROUND@#The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.@*METHODS@#Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.@*RESULTS@#In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.@*CONCLUSIONS@#Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).

Comparison of pulse pressure variation, stroke volume variation, and plethysmographic variability index in pediatric patients undergoing craniotomy / 北京大学学报(医学版)

OBJECTIVE@#To compare well-known preload dynamic parameters intraoperatively including stroke volume variation (SVV), pulse pressure variation (PPV), and plethysmographic variability index (PVI) in children who underwent craniotomy for epileptogenic lesion excision.@*METHODS@#A total of 30 children aged 0 to 14 years undergoing craniotomy for intracranial epileptogenic lesion excision were enrolled. During surgery, we measured PPV, SVV (measured by the Flotrac/Vigileo device), and PVI (measured by the Masimo Radical-7 monitor) simultaneously and continuously. Preload dynamic parameter measurements were collected at predefined steps: after induction of anesthesia, during opening the skull, intraoperative electroencephalogram monitoring, excision of epileptogenic lesion, skull closure, at the end of the operation. After exclusion of outliers, agreement among SVV, PPV, and PVI was assessed using repeated measures of Bland-Altman approach. The 4-quadrant and polar plot techniques were used to assess the trending ability among the changes in the three parameters.@*RESULTS@#The mean SVV, PPV, and PVI were 8%±2%, 10%±3%, and 15%±7%, respectively during surgery. We analyzed a total of 834 paired measurements (3 to 8 data sets for each phase per patient). Repeated measures Bland-Altman analysis identified a bias of -2.3 and 95% confidence intervals between -1.9 and -2.7 (95% limits of agreement between -6.0 and 1.5) between PPV and SVV, showing significant correlation at all periods. The bias between PPV and PVI was -5.0 with 95% limits of agreement between -20.5 and 10.5, and that between SVV and PVI was -7.5 with 95% limits of agreement between -22.7 and 7.8, both not showing significant correlation. Reflected by 4-quadrant plots, the con-cordance rates showing the trending ability between the changes in PPV and SVV, PPV and PVI, SVV and PVI were 88.6%, 50.4%, and 50.1%, respectively. The concordance rate between PPV and SVV was higher (92.7%) in children aged less than 3 years compared with those aged 3 and more than 3 years. The mean angular bias, radial limits of agreement, and angular concordance rate in the polar analysis were not clinically acceptable in the changes between arterial pressure waveform-based parameters and volume-based PVI (PPV vs. PVI: angular mean bias 8.4°, angular concordance rate 29.9%; SVV vs. PVI: angular mean bias 2.4°, angular concordance rate 29.1%). There was a high concordance between the two arterial pressure waveform-based parameters reflected by the polar plot (angular mean bias -0.22°, angular concordance rate 86.6%).@*CONCLUSION@#PPV can be viewed as a surrogate for SVV, especially in children aged less than 3 years. The agreement between arterial pressure waveform-based preload parameters (PPV and SVV) and PVI is poor and these two should not be considered interchangeable. Attempt to combine PVI and PPV for improving the anesthesiologist's ability to monitor cardiac preload in major pediatric surgery is warranted.

The Chronic Kidney Disease and Acute Kidney Injury Involvement in COVID-19 Pandemic: A Systematic Review and Meta-analysis

AimThe aim of this study was to uncover whether kidney diseases were involved in COVID-19 pandemic from a systematic review. MethodsThe studies reported the kidney outcomes in different severity of COVID-19 were included in this study. Standardized mean differences or odds ratios were calculated by employing Review Manager meta-analysis software. ResultsThirty-six trials were included in this systematic review with a total of 6395 COVID-19 patients. The overall effects indicated that the comorbidity of chronic kidney disease (CKD) (OR = 3.28), complication of acute kidney injury (AKI) (OR = 11.02), serum creatinine (SMD = 0.68), abnormal serum creatinine (OR = 4.86), blood urea nitrogen (SMD = 1.95), abnormal blood urea nitrogen (OR = 6.53), received continuous renal replacement therapy (CRRT) (OR = 23.63) was significantly increased in severe group than that in nonsevere group. Additionally, the complication of AKI (OR = 13.92) and blood urea nitrogen (SMD = 1.18) were remarkably elevated in critical group than that in severe group. ConclusionCKD and AKI are susceptible to occur in patients with severe COVID-19. CRRT is applied frequently in severe COVID-19 patients than that in nonsevere COVID-19 patients. The risk of AKI is higher in critical group than that in severe group.

Early Mitotic Inhibitor 1 Regulates DNA Re-replication Mediated by Human Papillomavirus Subtype 16 E7 in Response to DNA Damage / 中国医学科学院学报

To explore the molecular mechanism of human papillomavirus subtype 16(HPV-16)E7 oncogene-induced DNA re-replication in response to DNA damage. Flow cytometry was performed to examine the cell cycle changes in RPE1 E7 cells stably expressing HPV-16 E7 and its control cell RPE1 Vector after DNA damage.Immunoblotting assay was used to evaluate the early mitotic inhibitor 1(Emi1)expression in RPE1 E7 and RPE1 Vector cells with or without DNA damage.The changes of the proportion of polyploidy was detected by flow cytometry in DNA-damaged RPE1 E7 cells interfered by Emi1 small interfering RNA. Compared with the control cells,the proportion of polyploids in RPE1 E7 cells was significantly increased in response to DNA damage(=6.397,=0.0031).Emi1 protein expression was significantly increased in DNA damaged RPE1 E7 cells(=8.241,=0.0012).The polyploid ratio of RPE1 E7 cells was significantly reduced after Emi1 was interfered by two independent small interfering RNAs(=2.916,=0.0434;=3.452,=0.0260). In response to DNA damage,Emi1 promoted DNA re-replication caused by HPV-16 E7.

Effect of acupuncture on CXCL8 receptors in rats suffering from embryo implantation failure / 华中科技大学学报（医学）（英德文版）

To observe the effect of acupuncture on CXCL8 receptors (CXCR1 and CXCR2) in rat endometrium experiencing embryo implantation failure, 72 pregnant rats were randomly divided into four groups: normal group (N), embryo implantation failure group (M), acupuncture treatment group (A), and progestin treatment group (W). Then the rats in each group were equally randomized into a day-6 (D6) group, a day-8 (D8) group, and a day-10 (D10) group. The rats in group M, group A, and group W were treated with mifepristone-sesame oil solution on day 1, while the rats in group N were injected with the same amount of sesame oil. Meanwhile, "Housanli" and "Sanyinjiao" were selected for acupuncture. From day 1 to the time of death, the rats in group A were fastened up and then acupuncture was administered while the rats in group N and group M were only fixed, and the rats in group W were given progestin. The number of implanted embryos was calculated. The expression of CXCR1 and CXCR2 in rat endometrium was detected by immunohistochemistry, Western blotting and real-time PCR. Compared to group N, the average number of implanted embryos, the protein and mRNA expression of CXCR1 (D6, D8 and D10), and the protein and mRNA expression of CXCR2 (D8 and D10) in rat endometrium were significantly decreased in group M. Compared to group M, there was significant elevation in the average number of implanted embryos, the protein expression (D6, D8 and D10) and mRNA expression (D8) of CXCR1 in rat endometrium of group A, and the protein expression (D8 and D10) and mRNA expression (D8) of CXCR2 in rat endometrium of group W. These findings indicated that acupuncture can increase the number of implanted embryos in rats of embryo implantation failure, which may be relevant with up-regulation the expression of CXCR1 and CXCR2 at maternal-fetal interface of rats with embryo implantation failure.

Effect of acupuncture on CXCL8 receptors in rats suffering from embryo implantation failure / 华中科技大学学报（医学）（英德文版）

To observe the effect of acupuncture on CXCL8 receptors (CXCR1 and CXCR2) in rat endometrium experiencing embryo implantation failure, 72 pregnant rats were randomly divided into four groups: normal group (N), embryo implantation failure group (M), acupuncture treatment group (A), and progestin treatment group (W). Then the rats in each group were equally randomized into a day-6 (D6) group, a day-8 (D8) group, and a day-10 (D10) group. The rats in group M, group A, and group W were treated with mifepristone-sesame oil solution on day 1, while the rats in group N were injected with the same amount of sesame oil. Meanwhile, "Housanli" and "Sanyinjiao" were selected for acupuncture. From day 1 to the time of death, the rats in group A were fastened up and then acupuncture was administered while the rats in group N and group M were only fixed, and the rats in group W were given progestin. The number of implanted embryos was calculated. The expression of CXCR1 and CXCR2 in rat endometrium was detected by immunohistochemistry, Western blotting and real-time PCR. Compared to group N, the average number of implanted embryos, the protein and mRNA expression of CXCR1 (D6, D8 and D10), and the protein and mRNA expression of CXCR2 (D8 and D10) in rat endometrium were significantly decreased in group M. Compared to group M, there was significant elevation in the average number of implanted embryos, the protein expression (D6, D8 and D10) and mRNA expression (D8) of CXCR1 in rat endometrium of group A, and the protein expression (D8 and D10) and mRNA expression (D8) of CXCR2 in rat endometrium of group W. These findings indicated that acupuncture can increase the number of implanted embryos in rats of embryo implantation failure, which may be relevant with up-regulation the expression of CXCR1 and CXCR2 at maternal-fetal interface of rats with embryo implantation failure.