Objective To investigate the effect of percutaneous balloon mitral valvuloplasty under echocardiographic guidance for patients with moderate to severe mitral stenosis during pregnancy. Methods A retrospective observational study was conducted to include pregnant women who were diagnosed with moderate to severe mitral stenosis and underwent percutaneous balloon mitral valvuloplasty under echocardiographic guidance in Fuwai Hospital from August 2018 to June 2022, and their baseline characteristics, surgical outcomes, echocardiographic results, and follow-up results were analyzed. Results A total of 3 pregnant women aged 30-35 years, with gestational age of 19-26 weeks, and New York Heart Association (NYHA) function class Ⅲ were included. All the procedures were successfully performed. The mitral valve orifice area increased from 0.9 cm2 preoperatively to 2.1 cm2 postoperatively. The mean transvalvular pressure gradient decreased from 15.0 mm Hg preoperatively to 6.7 mm Hg postoperatively. No perioperative adverse events occurred. The follow-up time ranged from 3 to 48 months. All patients delivered uneventfully and returned to normal life, with maternal-fetal safety. Conclusion Percutaneous balloon mitral valvuloplasty under echocardiographic guidance is a feasible and effective procedure for the treatment of patients with moderate to severe mitral stenosis in pregnancy, with satisfactory maternal-fetal outcomes.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To investigate the clinical features, treatment, and prognosis of transient hyperammonemia of the newborn (THAN).Methods:Data of two infants with severe THAN admitted to the Department of Neonatology of Shanghai Children's Hospital in September 2021 and August 2022 were retrospectively investigated. Clinical data of confirmed THAN cases (blood ammonia>400 μmol/L) were collected from relevant literature retrieved from the Wanfang Database, China National Knowledge Infrastructure, Chinese Medical Journal Database, and PubMed up to July 2022. A descriptive method was used for statistical analysis.Results:A total of 24 cases were involved (two in the present study, and 22 in 12 retrieved articles), including 19 (79.2%) premature newborns and five term infants. The average birth weight was (2 237±608) g and the average onset time was 27 h (4-55 h) after birth. The early clinical symptoms included respiratory distress and hyporesponsiveness (drowsiness, lethargy, coma or hypotonia) in 18 cases (75.0%), metabolic acidosis in 11 cases (45.8%), hypocalcemia in seven cases (29.2%), pupil fixation/dilation in six cases (25.0%), convulsion in five cases (20.8%), apnea in three cases (12.5%) and sinus bradycardia in one case (4.2%). The serum ammonia levels were 1 422.8 μmol/L (547.2-4 494.1 μmol/L). Treatments included peritoneal dialysis plus exchange transfusion in eight cases (33.3%), exchange transfusion in seven cases (29.2%), continuous renal replacement therapy (CRRT) in four cases (16.7%), arginine in two cases (8.3%), peritoneal dialysis in two cases (8.3%), and CRRT+peritoneal dialysis in one case (4.2%). During follow-ups of four months (one month to six years), 13 cases (54.2%) showed no abnormalities in development; two (8.3%) had a neurodevelopmental delay, and six (25.0%) died. The follow-up of the other three cases (12.5%) were not reported in the literature.Conclusions:The early clinical manifestation of severe THAN is atypical. A good prognosis can be expected through early exclusion of possible hyperammonemia-related genetic metabolic diseases and lowering the serum ammonia level. Long-term follow-up is needed for neurological evaluation.

Objective:To explore the effect of neutrophil-lymphocyte ratio (NLR) at the initial visit on the survival of children with newly diagnosed medulloblastoma (MB).Methods:This was a case-control study involving 61 children with newly diagnosed MB at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University from August 2018 to January 2020 .The blood cell counts, lymphocyte subsets and immunoglobulin in the periphe-ral blood were measured to calculate NLR at the initial visit.Based on the cut-off value determined by receiver opera-ting characteristic (ROC) curve, patients were divided into high NLR group (≥ 2.07, n=21) and low NLR group (<2.07, n=40). The progression-free survival (PFS) and overall survival (OS) between 2 groups were analyzed by the Kaplan-Meier method, followed by Log- rank test.The correlation between NLR at the initial visit with clinical characteristics, lymphocyte subsets and immunoglobulin of children with newly diagnosed MB was analyzed.Differences between groups were compared by the Chi- square test, Mann- Whitney U test and independent sample t test. Results:The survival analysis showed that the relapse rate (38.1% vs.10.0%, χ2=6.879, P=0.016) and mortality rate (19.0% vs.0, χ2=8.154, P=0.011) were significantly higher in high NLR group than those of low NLR group.PFS (12 months vs.19 months, χ2=9.775, P=0.002) and OS (19 months vs.20 months, χ2=8.432, P=0.004) were significantly shorter in high NLR group than those of low NLR group.No significant differences in clinical characteristics were detected between groups (all P>0.05). Compared with low NLR group, the percentage of T lymphocyte[(67.93±6.37)% vs.(73.38±8.08)%, t=2.886, df=48.865, P=0.006], T helper cells (Th)[(30.86±5.53)% vs.(34.29±7.44)%, t=2.037, df=51.981, P=0.047], and T suppressor cells (Ts)[(27.39±5.50)% vs.(30.84±6.58)%, t=2.164, df=47.581, P=0.035] were significantly lower in high NLR group.Spearman correlation analysis showed a negative correlation between NLR and T lymphocyte count ( r=-0.303, P=0.018), and Ts lymphocyte count ( r=-0.260, P=0.043). Conclusions:Children with newly diagnosed MB expressing a high level of NLR had a poor prognosis, which may be associated with T lymphocyte and Ts lymphocyte.

Objective:To explore the diagnostic value of serum cytokines and autoantibodies in children with central diabetes insipidus.Methods:A retrospective study was used.A total of 52 children diagnosed with central diabetes insipidus who were hospitalized in Qingdao municipal hospital affiliated to Qingdao Universityfrom January 2016 to January 2020 were selected as the study group, and 60 healthy children with similar gender and age were selected as the control group.The general data of the study group and the control group, 24 h urine volume, urine specific gravity and urine osmotic pressure before the start of water deprivation test, the results of pituitary magnetic resonance imaging (MRI), and the concentration of serum cytokines and autoimmune antibodies were compared to evaluate the value of serum cytokines and autoimmune antibodies in the prediction of central diabetes insipidus.Results:The 24 h urine volume in the study group (201.6 ± 9.9 mL/kg)was significantly higher than that in the control group(9.06±12.5 mL/kg). The urine specific gravity(1.006±0.002) and urine osmotic pressure((116.4±23.5) mOsm/L)were significantly lower than those in the control group((1.013±0.004) and (649.6±72.4) mOsm/L)( t=15.378, 13.298, 45.625, all P<0.001). MRI examination showed that the proportion of disappearance of high signal in posterior pituitary (46.1%(24/52)), the proportion of thickening of the pituitary stalk(32.7%(17/52))and abnormal signal in pituitary(7.7%(4/52)) in study group were significantly higher than the control group(0%(0/0)) (all P<0.05); the levels of serum IL-6, TNF-α, IFN-γ, IL-1β ((117.0±7.8), (234±21.4), (178.6±15.1), (87±6.5) ng/L)and autoimmune antibodies ((654.1±194.3) ng/L) in study group were significantly increased compared to the control((12.5±2.3), (32.5±9.7), (37.8±7.3), (22.6±4.7), (98.0±23.7) ng/L) ( t value were 17.031, 27.490, 15.670, 12.360 and 109.984, respectively; all P<0.05). Conclusion:The concentration of serum cytokines and autoimmune antibodies has a significant clinical value in the evaluation of central diabetes insipidus in children.Combined with head MRI examination, it has a certain value in the diagnosis, treatment and prognosis of central diabetes insipidus in children.

Objective:To preliminarily study the feasibility, safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with selective portal vein embolization (SPVE) before surgical resection in the treatment of large liver cancer.Methods:A retrospective study was conducted on the clinical data of 17 patients with large liver cancer treated with TACE combined with SPVE from January 2016 to December 2019 at the Department of Hepatobiliary Surgery, the Sixth Medical Center of PLA General Hospital. The study included 15 males and 2 females, aged (59.17±10.30) years. The levels of alanine aminotransferase, tumor changes and patient survival were analyzed before operation, after TACE, and after SPVE.Results:Among the 17 patients, the levels of alanine aminotransferase on the 1st and 3rd day after SPVE was significantly higher than those after TACE [191.4 (30.5-1966.4) IU/L vs 125.3 (35.7-846.2) IU/L on the first day, and 298.5 (24.6-1334.2) IU/L vs 208.6 (21.6-775.6) IU/L on the 3rd day], all P<0.05. One month after the two combined embolism, among the 6 patients with a tumor diameter of 5-10 cm, 2 patients (33.3%) had complete remission, 3 patients (50.0%) had partial remission, and 1 patients (16.6%) had stable disease. For the tumor’s longest diameter, among the 11 patients with tumors >10 cm, 1 patient had complete remission (9.1%), 4 patients had partial remission (36.4%), 5 patients had stable diseases (45.5%), and 1 patient had disease progression (9.1%). Eventually, 11 patients underwent surgical exploration. The median residual liver volume before treatment was 329.5 (284.9-365.7) ml, and after the combined procedure 415.6 (354.7-718.8) ml. The median hyperplasia ratio was 28.1% (14.1%-51.3%). Eight patients finally underwent surgical resection. There was no death in the perioperative periods. The median tumor-free survival time was 17 (7-42) months, and the median survival time was 27 (7-42) months. Conclusion:For patients with large liver cancer with insufficient remnant liver volume, preoperative TACE+ SPVE has certain value in controlling tumor progression, promoting remnant liver hyperplasia, increasing surgical resection rate and improving prognosis.

Objective:To study the correlations of neonatal hemodynamic parameters with gestational age (GA) and birth weight (BW) using non-invasive ultrasound cardiac output monitor (USCOM).Method:From March to September 2019, neonates with stable hemodynamics admitted to the Department of Neonatology of our hospital were enrolled in this prospective study. According to their GA, they were assigned into <29 w group, 29~33 w group, 34~36 w group and ≥37 w group. According to their BW, they were assigned into <1 000 g group, 1 000~1 499 g group, 1 500~2 499 g group and ≥2 500 g group. Cardiac output (CO), cardiac index (CI), stroke volume (SV), myocardial contractility (inotropy, INO), flow time corrected (FTC), systemic vascular resistance index (SVRI) and heart rate (HR) were measured using USCOM. The univariate linear regression method was used to analyze the correlation of hemodynamic parameters with different GA and BW.Result:A total of 120 neonates with stable hemodynamics were enrolled, including 69 males and 51 females. The average GA was (34.2±3.8)w and the average BW was (2 221±860) g. SV ( r=0.489, P<0.001), CO ( r=0.681, P<0.001), CI ( r=0.348, P<0.001), FTC ( r=0.266, P=0.003), INO ( r=0.446, P<0.001)and HR ( r=-0.322, P<0.001) showed significant linear correlations with GA. No linear correlation existed between SVRI ( r=-0.052, P=0.574) and GA. SV ( r=0.603, P<0.001), CO ( r=0.852, P<0.001), CI ( r=-0.390, P<0.001), INO ( r=0.576, P<0.001) and HR ( r=-0.440, P<0.001) showed significant linear correlations with BW. No significant linear correlations existed between SVRI ( r=-0.076, P=0.409) or FTC ( r=0.090, P=0.329) and BW. Conclusion:USCOM can monitor neonatal hemodynamic parameters in real-time.Hemodynamic parameters including SV, CO, CI and INO are significantly different among newborns with different GA and BW and these parameters are linearly correlated with GA and BW.

【Objective】 Aim of this study was to evaluate performance of two chemiluminescence immunoassay (CLIA) reagents for hepatitis C virus antibodies (anti-HCV) detection, focusing on the feasibility of blood screening for blood donors. 【Methods】 The sero-panel samples from NCCL and the donor samples were tested with CLIA, ECLIA and two ELISA (A: double antigen sandwich method, B: indirect method) reagents synchronously to evaluate their performances respectively, and the sensitivity, specificity and CV of the four reagents were compared. 【Results】 CLIA, ECLIA, A and B reagents showed sensitivities of 99.06%(315/318), 99.69%(317/318), 99.06%(315/318) and 99.69%(317/318), and clinical specificities was 99.06%(315/318), 99.69%(317/318), 99.06%(315/318) and 99.69%(317/318), respectively. Between-run and within-run precision for ECLIA reagent ranged (both CV<8%) was better than two ELISA reagents (between-run: CV <15% and within-run: CV <20%), and the CLIA reagent also met the requirement in blood screening (CVs <14%). 【Conclusion】 This ECLIA reagent showed high sensitivity and good reproducibility together with acceptable specificity in routine sample screening, which proved its further application in blood screening. This CLIA reagent has high specificity and the same sensitivity as indirect ELISA reagent. This CLIA reagent could be used in combination with other reagents with high sensitivity to screen anti-HCV in blood donors.

Angiogenesis is an essential process in tumor growth, invasion and metastasis. VEGF receptor 2 (VEGFR2) inhibitors targeting tumor angiogenic pathway have been widely used in the clinical cancer treatment. However, most of currently used VEGFR2 kinase inhibitors are multi-target inhibitors which might result in target-associated side effects and therefore limited clinical toleration. Highly selective VEGFR inhibitors are still highly demanded from both basic research and clinical application point of view. Here we report the discovery and characterization of a novel VEGFR2 inhibitor (CHMFL-VEGFR2-002), which exhibited high selectivity among structurally closed kinases including PDGFRs, FGFRs, CSF1R, etc. CHMFL-VEGFR2-002 displayed potent inhibitory activity against VEGFR2 kinase in the biochemical assay (IC = 66 nmol/L) and VEGFR2 autophosphorylation in cells (ECs ∼100 nmol/L) as well as potent anti-proliferation effect against VEGFR2 transformed BaF3 cells (GI = 150 nmol/L). In addition, CHMFL-VEGFR2-002 also displayed good anti-angiogenesis efficacy and exhibited good PK (pharmacokinetics) profile with bioavailability over 49% and anti-angiogenesis efficacy in both zebrafish and mouse models without apparent toxicity. These results suggest that CHMFL-VEGFR2-002 might be a useful research tool for dissecting new functions of VEGFR2 kinase as well as a potential anti-angiogenetic agent for the cancer therapy.

Objective To explore the efficacy of continuous renal replacement therapy (CRRT) in the treatment of neonatal acute kidney injury (AKI).Methods Totally 17 critically ill neonates treated with CRRT were selected who were hospitalized at Department of Neonatology,Shanghai Children's Hospital,Children's Hospital Affiliated to Shanghai Jiaotong University,from June 2012 to June 2017,and among them there were 15 cases with AKI,and the clinical data of these 15 patients were retrospectively analyzed,while 15 AKI neonates were treated with CRRT combined with conventional treatment.The model for CRRT was continuous veno-venous hemofiltration dialysis (CVVH-DF) in 13 cases,plasma exchange (PE) in 2 cases.The changes of blood pressure(BP),renal function,electrolyte,acid-base balance index and hemodynamic indicators were analyzed respectively before CRRT treatment,12 h,24 h,48 h after treatment and by the end of CRRT treatment.The efficacy of CRRT treatment was evaluated in these 15 AKI neonates.Results Gestational age of 15 AKI newborns was 33 +4-40 +1 weeks,admission day age was 2-28 days,birth weight was 2.25-4.00 kg.Primary diseases were severe asphyxia in 6 cases,neonatal septicemia in 5 cases,congenital hereditary metabolic disease in 2 cases,traumatic asphyxia in 1 case,and liver failure in 1 case.CRRT treatment persisted for 49-190 hours.BP value [(50.8 ± 6.57) mmHg(1 mmHg =0.133 kPa)] could reach normal level after 12 h CRRT treatment,and blood pH value (7.31 ± 0.25) increased significantly after 12 h CRRT treatment,while blood K+[(5.51 ±1.86) mmoL/L],urea nitrogen (BUN) [(9.5 ±3.7) mmol/L],creatinine(Cr) [(93± 14)μmol/L] significantly decreased after 12 h CRRT treatment,and reached the normal range [K + (4.78 ± 2.95)mmol/L,BUN (7.5 ±2.1) mmol/L,Cr (54 ± 13) μmol/L] after 24 h treatment,but urine volume[(0.8 ±0.2)mL/(kg· h)] significantly increased after 24 h treatment.Partial pressure of oxygen/fraction of inspired oxygen reached 200 mmHg after 12 h treatment and more than 300 mmHg after 24 h treatment.CRRT treatment of 15 AKI neonates turned out to be effective.Conclusions CRRT can effectively improve the internal environment of AKI neonates and reduce the death rate of neonatal AKI,which can provide an effective adjuvant treatment measures for the treatment of AKI neonates.