Pregnancy loss in major fetal congenital heart disease: incidence, risk factors and timing.

OBJECTIVE: Fetuses with congenital heart disease (CHD) are at increased risk of pregnancy loss compared with the general population. We aimed to assess the incidence, timing and risk factors of pregnancy loss in cases with major fetal CHD, overall and according to cardiac diagnosis. METHODS: This was a retrospective, population-level cohort study of fetuses and infants diagnosed with major CHD between 1997 and 2018 identified by the Utah Birth Defect Network (UBDN), excluding cases with termination of pregnancy and minor cardiovascular diagnoses (e.g. isolated aortic/pulmonary pathology and isolated septal defects). The incidence and timing of pregnancy loss were recorded, overall and according to CHD diagnosis, with further stratification based on presence of isolated CHD vs additional fetal diagnosis (genetic diagnosis and/or extracardiac malformation). Adjusted risk of pregnancy loss was calculated and risk factors were assessed using multivariable models for the overall cohort and prenatal diagnosis subgroup. RESULTS: Of 9351 UBDN cases with a cardiovascular code, 3251 cases with major CHD were identified, resulting in a study cohort of 3120 following exclusion of cases with pregnancy termination (n = 131). There were 2956 (94.7%) live births and 164 (5.3%) cases of pregnancy loss, which occurred at a median gestational age of 27.3 weeks. Of study cases, 1848 (59.2%) had isolated CHD and 1272 (40.8%) had an additional fetal diagnosis, including 736 (57.9%) with a genetic diagnosis and 536 (42.1%) with an extracardiac malformation. The observed incidence of pregnancy loss was highest in the presence of mitral stenosis (< 13.5%), hypoplastic left heart syndrome (HLHS) (10.7%), double-outlet right ventricle with normally related great vessels or not otherwise specified (10.5%) and Ebstein's anomaly (9.9%). The adjusted risk of pregnancy loss was 5.3% (95% CI, 3.7-7.6%) in the overall CHD population and 1.4% (95% CI, 0.9-2.3%) in cases with isolated CHD (adjusted risk ratio, 9.0 (95% CI, 6.0-13.0) and 2.0 (95% CI, 1.0-6.0), respectively, based on the general population risk of 0.6%). On multivariable analysis, variables associated with pregnancy loss in the overall CHD population included female fetal sex (adjusted odds ratio (aOR), 1.6 (95% CI, 1.1-2.3)), Hispanic ethnicity (aOR, 1.6 (95% CI, 1.0-2.5)), hydrops (aOR, 6.7 (95% CI, 4.3-10.5)) and additional fetal diagnosis (aOR, 6.3 (95% CI, 4.1-10)). On multivariable analysis of the prenatal diagnosis subgroup, years of maternal education (aOR, 1.2 (95% CI, 1.0-1.4)), presence of an additional fetal diagnosis (aOR, 2.7 (95% CI, 1.4-5.6)), atrioventricular valve regurgitation ≥ moderate (aOR, 3.6 (95% CI, 1.3-8.8)) and ventricular dysfunction (aOR, 3.8 (95% CI, 1.2-11.1)) were associated with pregnancy loss. Diagnostic groups associated with pregnancy loss were HLHS and variants (aOR, 3.0 (95% CI, 1.7-5.3)), other single ventricles (aOR, 2.4 (95% CI, 1.1-4.9)) and other (aOR, 0.1 (95% CI, 0-0.97)). Time-to-pregnancy-loss analysis demonstrated a steeper survival curve for cases with an additional fetal diagnosis, indicating a higher rate of pregnancy loss compared to cases with isolated CHD (P < 0.0001). CONCLUSIONS: The risk of pregnancy loss is higher in cases with major fetal CHD compared with the general population and varies according to CHD type and presence of additional fetal diagnoses. Improved understanding of the incidence, risk factors and timing of pregnancy loss in CHD cases should inform patient counseling, antenatal surveillance and delivery planning. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

[Influence of reactive oxygen species responsive self-assembled nanomicelle loaded with pyroptosis inhibitor on full-thickness skin defects in diabetic rats].

Objective: To investigate the influence of reactive oxygen species (ROS) responsive self-assembled nanomicelle loaded with pyroptosis inhibitor on full-thickness skin defects in diabetic rats. Methods: Experimental research methods were employed. A nucleotide-binding oligomerization domain (NOD) 1/2 inhibitor (NOD-IN-1) was encapsulated with nanomicelle polyethylene glycol-block-polypropylene sulfide (PEG-b-PPS), and the resulting product was called PEPS@NOD-IN-1. The morphology and hydration particle size of PEG-b-PPS and PEPS@NOD-IN-1 were observed by transmission electron microscope and particle size analyzer, respectively, and the encapsulation rate and drug loading rate of PEPS@NOD-IN-1 to NOD-IN-1 and the cumulative release rate of NOD-IN-1 by PEPS@NOD-IN-1 in phosphate buffer solution (PBS) alone and hydrogen peroxide-containing PBS within 40 h were measured and calculated by microplate reader, and the sample number was 3. Twenty-four male Sprague-Dawley rats aged 6-7 weeks were injected with streptozotocin to induce type 1 diabetes mellitus. Six full-thickness skin defect wounds were made on the back of each rat. The injured rats were divided into PBS group, NOD-IN-1 group, PEG-b-PPS group, and PEPS@NOD-IN-1 group with corresponding treatment according to the random number table, with 6 rats in each group. The wound healing was observed on post injury day (PID) 3, 7, and 12, and the wound healing rate was calculated. The ROS levels in wound tissue were detected by immunofluorescence method on PID 3. On PID 7, the granulation tissue thickness in wound was assessed by hematoxylin-eosin staining, the mRNA expressions of NOD1 and NOD2 were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction, and the protein expressions of NOD1, NOD2, and GSDMD-N terminals were detected by Western blotting. Six wounds from different rats in each group were taken for detection of the above indicators. Wound tissue (3 samples per group) was taken from rats in PBS group and PEPS@NOD-IN-1 group on PID 7, and transcriptome sequencing was performed using high-throughput sequencing technology platform. Differentially expressed genes (DEGs) significantly down-regulated in PEPS@NOD-IN-1 group as compared with PBS group were screened, and the enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed. The DEG heatmap of the NOD-like receptor pathway, a pyroptosis-related pathway, was made. Protein-protein interaction (PPI) analysis of DEGs in heatmap was performed through the STRING database to screen key genes of PEPS@NOD-IN-1 regulating the NOD-like receptor pathway. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, and Tukey test. Results: PEG-b-PPS and PEPS@NOD-IN-1 were in spherical structures of uniform size, with hydration particle sizes of (134.2±3.3) and (143.1±2.3) nm, respectively. The encapsulation rate of PEPS@NOD-IN-1 to NOD-IN-1 was (60±5)%, and the drug loading rate was (15±3)%. The release of NOD-IN-1 from PEPS@NOD-IN-1 in PBS alone was slow, and the cumulative release rate at 40 h was only (12.4±2.3)%. The release of NOD-IN-1 from PEPS@NOD-IN-1 in hydrogen peroxide-containing PBS within 10 h was very rapid, and the cumulative release rate at 10 h reached (90.1±3.6)%. On PID 3 and 7, the wounds of rats in the four groups were gradually healed, and the healing in PEPS@NOD-IN-1 group was better than that in the other three groups. On PID 12, the wound scab area in PBS group was large, the wound epithelialization in NOD-IN-1 group and PEG-b-PPS group was obvious, and the wound in PEPS@NOD-IN-1 group was close to complete epithelialization. Compared with those in PBS group, NOD-IN-1 group, and PEG-b-PPS group, the wound healing rates on PID 7 and 12 in PEPS@NOD-IN-1 group were significantly increased (P<0.05), the level of ROS in wound tissue on PID 3 was significantly decreased (P<0.05), the thickness of granulation tissue in wound on PID 7 was significantly thickened (P<0.05), and the mRNA expressions of NOD1 and NOD2 and the protein expressions of NOD1, NOD2, and GSDMD-N terminals in wound tissue on PID 7 were significantly decreased (P<0.05). KEGG pathway analysis showed that DEGs significantly down-regulated in PEPS@NOD-IN-1 group as compared with PBS group were significantly enriched in NOD-like receptors, hypoxia-inducible factors, mitogen-activated protein kinases, and tumor necrosis factor (TNF) pathways. In the DEG heatmap of NOD-like receptor pathway, the genes regulating pyroptosis mainly involved NOD1, NOD2, NOD-like receptor thermoprotein domain-related protein 3, Jun, signal transduction and transcriptional activator 1 (STAT1), TNF-α-induced protein 3. The PPI results showed that NOD1, NOD2, and STAT1 were the key genes of PEPS@NOD-IN-1 regulating the NOD-like receptor pathway. Conclusions: PEPS@NOD-IN-1 can down-regulate the level of local ROS in wounds and the expression of NOD1, NOD2, and GSDMD-N terminals, the key regulators of pyroptosis, thereby promoting the repair of full-thickness skin defect wounds in diabetic rats. PEPS@NOD-IN-1 can also significantly down-regulate the pyroptosis, inflammation, and hypoxia-related pathways of wounds, and regulate NOD-like receptor pathways by down-regulating key genes NOD1, NOD2, and STAT1.

Temporal coherence in an unbalanced SU(1,1) interferometer.

In classical coherence theory, coherence time is typically related to the bandwidth of the optical field. Narrowing the bandwidth by optical filtering will result in the lengthening of the coherence time. In the case of a delayed pulse photon interference, this will lead to pulse overlap and recovery of interference, which is otherwise absent due to time delay. However, this is changed for entangled optical fields. In this Letter, we investigate how the temporal coherence of the fields in a pulse-pumped SU(1,1) interferometer changes with the bandwidth of optical filtering. We find that the effect of optical filtering is not similar to the classical coherence theory in the presence of quantum entanglement. A full quantum theory is presented and can explain the phenomena well.

Propagation of temporal mode multiplexed optical fields in fibers: influence of dispersion.

Exploiting two interfering fields which are initially in the same temporal mode but with the spectra altered by propagating through different fibers, we characterize how the spectral profiles of temporal modes change with the fiber induced dispersion by measuring the fourth-order interference when the order number and bandwidth of temporal modes are varied. The experiment is done by launching a pulsed field in different temporal modes into an unbalanced Mach-Zehnder interferometer, in which the fiber lengths in two arms are different. The results show that the mode mismatch of two interfering fields, reflected by the visibility and pattern of interference, is not only dependent upon the amount of unbalanced dispersion but also related to the order number of temporal mode. In particular, the two interfering fields may become orthogonal under a modest amount of unbalanced dispersion when the mode number of the fields is k ≥ 2. Moreover, we discuss how to recover the spectrally distorted temporal mode by measuring and compensating the transmission induced dispersion. Our investigation paves the way for further investigating the distribution of temporally multiplexed quantum states in fiber network.

[Detection of the spontaneous blinking pattern of dry eye patients using the machine learning method].

Objective: To establish a method to record the spontaneous blink pattern with a machine learning model, and to clarify the spontaneous blink pattern in patients with dry eye. Methods: It was a cross-setional study.We selected 357 dry eye patients (102 males and 255 females), aged (46.2±13.3) years, who visited corneal specialist clinics of Beijing Tongren Eye Center in 2019, as the dry eye group. The control group enrolled 152 normal controls, including 32 males and 120 females, aged (48.1±13.9) years. All participants completed the Ocular Surface Disease Index questionnaire, blink video capture, lipid layer thickness measurement, tear break-up time measurement, corneal fluorescein staining, and Schirmer Ⅱ test. Based on the assembled model built using UNet image segmentation algorithm and ResNet image classification algorithm, single frames of the blink video were analyzed, and then the palpebral opening height of each frame was obtained in order to establish a spontaneous blink wave. Finally, the characteristics of spontaneous blinks in dry eye patients were analyzed based on different types of complete blinks (types A, B and C) and partial blinks (types Ⅰ, Ⅱ and Ⅲ). Independent sample t test and Wilcoxon rank-sum test were used to judge if there was significant difference between the dry eye group and the normal group. Results: The accuracy of the segmentation model and the classification model was 96.3% and 96.0%, respectively, and the consistency with the manual analysis was 97.9%. In dry eye patients, the number of blinks was 30 (18, 42)/min, which was higher than that in normal controls [20 (9, 46)/min] (U=18 132.50, P=0.002). The number of complete blinks in dry eye cases was significantly lower than that in normal controls [6 (3, 24)/min vs. 12 (3,33)/min; U=12 361.00, P=0.016], and the number of partial blinks was significantly higher than that in normal controls [15 (6, 27)/min vs. 3 (0, 10)/min; U=22 839.00, P<0.001]. In complete blinks, the proportion of type A blinks in dry eye patients was significantly higher than that in normal controls [53.7% (2 796/5 177) vs. 39.3% (633/1 698); χ²=101.83, P<0.001]; in partial blinks, the proportion of type Ⅱ blinks in dry eye patients was significantly higher than that in normal controls [36.0%(2 334/6 477) vs. 29.6%(126/426); χ²=6.99, P=0.007]. The average interblink interval of dry eye patients was 1.2 s, which was not significantly different from that of normal controls (1.1 s; U=15 230.00, P=0.093). The eyelid closed phase of dry eye patients was 0.8 s, which was significantly shorter than that of normal controls (1.3 s; U=16 291.50, P=0.006). There were no significant differences in eyelid closing phase, early opening phase and late opening phase between the two groups (all P>0.05). Conclusions: In dry eye patients, the number of partial blinks increased, the number of complete blinks decreased, and the duration of eyelid closed phase shortened significantly. The main blink patterns of dry eye patients included type Ⅱ partial blinks with a reduced closure amplitude and type A complete blinks with a shortened closure time.

SU(2)-in-SU(1,1) Nested Interferometer for High Sensitivity, Loss-Tolerant Quantum Metrology.

We present experimental and theoretical results on a new interferometer topology that nests a SU(2) interferometer, e.g., a Mach-Zehnder or Michelson interferometer, inside a SU(1,1) interferometer, i.e., a Mach-Zehnder interferometer with parametric amplifiers in place of beam splitters. This SU(2)-in-SU(1,1) nested interferometer (SISNI) simultaneously achieves a high signal-to-noise ratio (SNR), sensitivity beyond the standard quantum limit (SQL) and tolerance to photon losses external to the interferometer, e.g., in detectors. We implement a SISNI using parametric amplification by four-wave mixing (FWM) in Rb vapor and a laser-fed Mach-Zehnder SU(2) interferometer. We observe path-length sensitivity with SNR 2.2 dB beyond the SQL at power levels (and thus SNR) 2 orders of magnitude beyond those of previous loss-tolerant interferometers. We find experimentally the optimal FWM gains and find agreement with a minimal quantum noise model for the FWM process. The results suggest ways to boost the in-practice sensitivity of high-power interferometers, e.g., gravitational wave interferometers, and may enable high-sensitivity, quantum-enhanced interferometry at wavelengths for which efficient detectors are not available.

[Efficacy of vaginal administration of Crinone versus Utrogestan combined with oral dydrogesterone tablets for luteal support in PGT freeze-thaw embryo transfer cycles].

OBJECTIVE: To compare the efficacy of two vaginal progesterone formulations, Crinone gel or Utrogestan capsules, combined with dydrogesterone tablets, for luteal phase support in pre-implantation genetic testing (PGT) freeze-thaw embryo transfer (FET) cycles. METHODS: We analyzed 209 FET cycles in patients undergoing PGT-blastocyst transfer in our center between June, 2017 and June, 2020. The patients received vaginal administration of either Crinone gel (n=135) or Utrogestan capsules (n=74) combined with oral dydrogesterone tablets for luteal supplementation, and the clinical pregnancy rate (CPR) and miscarriage rate (MR) were compared between the two groups. RESULTS: The Crinone gel and Utrogestan capsule groups were comparable for age, duration of infertility, AMH, AFC, BMI, basal FSH, LH, and E2 (P > 0.05). The gonadotrophin dose, duration of stimulation, levels of LH, E2, P and endometrial thickness on hCG day, and the numbers of oocytes retrieved, MII oocytes, 2PN and blastocysts did not differ significantly between two groups (P > 0.05). In FET cycles, no significant differences were observed between the two groups in the duration of endometrial preparation, P and endometrial thickness on endometrial transformation day, biochemical pregnancy rate (69.63% vs 78.38%), CPR (62.96% vs 72.97%), MR (12.94% vs 11.11%), vaginal bleeding rate in early pregnancy (20% vs 27.78%), or MR in patients with vaginal bleeding in early pregnancy (35.29% vs 20%) (P > 0.05). CONCLUSION: Crinone gel and Utrogestan capsules combined with oral dydrogesterone have similar clinical efficacy for luteal support in PGT FET cycles.

[Evaluation of the effect of free fibular flap transplantation in repairing mandibular osteoradionecrosis defect in 151 cases].

Objective: To investigate the clinical effect of free fibula flap transplantation in repairing the defect of mandibular osteoradionecrosis (ORN). Methods: A total of 151 mandibular ORN patients undergoing free fibular flap transplantation were selected from August 2005 to September 2020 in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Among them, 109 patients were males and 42 patients were females, aged (54.1±10.1) (ranged 31-85) years old. The clinical data of the patients was collected and the survival rate of the flaps and postoperative function were calculated to evaluate the surgical efficacy. The χ2 test was used for difference analysis. Results: Among the 151 patients, mandibular ORN caused by radiotherapy for nasopharyngeal carcinoma accounted for 79.5% (120/151). The average time for mandibular ORN appeared was 5(6) years after radiotherapy. Facial artery [57.2%(87/152)] and superior thyroid artery [32.9%(50/152)] were the main anastomotic arteries in the recipient area. There was no significant difference in the necrosis rates of the two flaps [10.3%(9/87) and 12.5% (5/50), respectively, P=0.949]. The main anastomotic veins in the recipient area were the external jugular vein [48.4%(135/279)] and the common facial vein [26.5%(74/279)]. Twenty-five cases (16.6%) had one vein anastomosed, and 126 cases (83.44%) had two veins anastomosed. There was no significant difference in the flap necrosis rate between the two conditions [20.0%(5/25) and 7.1%(9/126), respectively, P=0.100]. Ninety-seven cases (64.2%) used the peroneal musculocutaneous-fascia composite flap to repair the maxillofacial soft and hard tissue defects. Thirteen cases (8.6%) underwent the restorations with digital virtual surgery design, of which 5 cases were repaired with dental implants at the same time. After the operations, lower respiratory tract infection occurred in 17 patients (11.3%), and upper respiratory tract obstruction occurred in 3 cases (2.0%). The survival rate of the flap after operation was 90.7% (136/151), and 21 patients (13.9%) had flap vascular crisis. Delayed healing of maxillofacial wounds occurred in 33 cases (21.9%). After 3 to 24 months of follow-ups, 110 patients (76.9%) had no fistula inside/outside the oral cavity, 118 patients (82.5%) had an improvement in opening mouth of increasing (≥0.5 cm) after surgery, 135 patients (94.4%) had pain relief, 97 cases (67.8%) could eat normal diet, semi-liquid or soft food, and 137 cases (95.8%) were satisfied or basically satisfied with the treatment effects. Conclusions: The free fibular flap transplantation is an effective method to repair mandibular ORN defects. Preoperative vascular assessment is helpful for the selection of recipient vessels. Facial artery, superior thyroid artery, external jugular vein and common facial vein can be used as the main recipient vessels. The repair of the peroneal musculocutaneous-fascia composite flap facilitates the closure of internal and external fistulas. Digital technology can help to restore the maxillofacial shape more accurately, improve the patient's occlusal and chewing function and enhance the quality of life of mandibular ORN patients.

[XBP1 modulates hypoxia/reoxygenation injury in mouse renal tubular epithelial cells through TXNIP-NLRP3 signaling pathway].

Objective: To investigate the role and regulation mechanism of X box binding protein 1 (XBP1) for hypoxia/reoxygenation(H/R) injury in mouse renal tubular epithelial cells (TCMK-1) through thioredoxin interacting protein (TXNIP)-nucleotide-binding domain (NOD)-like receptor protein (TXNIP-NLRP3) signaling pathway. Methods: The cells were divided into 4 groups: si-NC group transfected with negative control siRNA (si-NC), si-XBP1 group transfected with siRNA targeting XBP1 (si-XBP1), si-NC+H/R group transfected with si-NC and exposed to H/R, and si-XBP1+H/R group transfected with si-XBP1 and exposed to H/R. The Annexin Ⅴ/PI double-staining method was used to detect cell apoptosis; The mitochondrial membrane potential (MMP) was determined by using JC-1 dye; The mitochondrial reactive oxygen species (mROS) was assessed by using MitoSOX™ dye. The interference efficiency of XBP1 was tested by Western blotting and quantitative real-time polymerase chain reaction. The expression levels of TXNIP, NLRP3 and IL-1ß protein were detected by Western blotting. The colocalization of mitochondria and TXNIP was detected by double-labeling immunofluorescent staining. The intergroup difference was compared by using an independent samples t-test. Results: Compared with the si-NC group, more mROS, apoptosis and lower MMP were observed in si-NC+H/R group. Compared with the si-NC+H/R group, less apoptosis (12.08±0.51 vs 19.01±1.80, P<0.05), mROS (34.63±0.64 vs 48.17±1.84, P<0.01) and higher MMP (1.03±0.11 vs 0.45±0.08, P<0.05) were observed in si-XBP1+H/R group. Down-regulation of XBP1U (protein: 1.31±0.18 vs 0.23±0.02, P<0.01; mRNA: 1.12±0.07 vs 0.38±0.01, P<0.001) and XBP1S (protein: 1.13±0.17 vs 0.28±0.07, P<0.01; mRNA: 8.39±0.63 vs 2.45±0.22, P<0.001) inhibited expression of TXNIP (0.15±0.02 vs 0.04±0.01, P<0.01), NLRP3 (1.13±0.12 vs 0.51±0.12, P<0.05) and IL-1ß (1.02±0.04 vs 0.19±0.06, P<0.001) during H/R. Meanwhile, TXNIP exhibited significantly much less colocalization with mitochondria in the si-XBP1+H/R group. Conclusion: Supression of XBP1 expression can effectively alleviate H/R-induced TCMK-1 cells injury, whose mechanism may be inhibition of TXNIP-induced NLRP3 inflammasome activation.

[Effects of sleep quality and mood of patients with Parkinson's disease on their caregivers].

Objectve: To evaluate the relationship of Parkinson's disease(PD) patients' sleep quality and depression with burden, quality of life, and depression of their caregivers. Methods: A total of 120 PD patients (68 males and 52 females) and their caregivers (48 males and 72 females) from Changshu Hospital Affiliated to Nanjing University of Chinese Medicine between January 2017 and June 2019 were recruited. Patients' sleep quality, depression and quality of life was evaluated. Burden, quality of life, quality of sleep, and depression of caregivers were assessed by the Caregivers Burden Questionnaire (CBI), Health Survey Brief (SF-36), Pittsburgh Sleep Quality Index (PQS1) and Hamilton Depression Scale (HAMD), meanwhile, the correlation between relevant factors was analyzed. Results: The CBI of caregivers was positively correlated with the unified Parkinson's disease rating scale (UPDRS)-Ⅲ scores of PD patients (r=0.436, P<0.05). The CBI, SF-36GH, SF-36MH, HAMD and PSQI scores of caregivers were positively correlated with Parkinson's disease sleep scale (PDSS) scores of PD patients (r=0.546, 0.762, 0.528, 0.562 and 0.522, respectively, all P<0.01). The caregiver's CBI score was positively correlated with PD patients' Epworth sleepiness score (ESS) score (r=0.442, P<0.05), and caregiver's CBI, SF-36GH, SF-36MH, HAMD, PSQI scores were positively correlated with PD patients' HAMD scores (r=0.765, 0.813, 0.635, 0.884 and 0.601, respectively, all P<0.01). The caregiver's CBI score was positively correlated with the PDQ-39 score of PD patients (r=0.834, 0.452, 0.463, 0.421 and 0.387, respectively, all P<0.05). Multiple regression analysis indicated that the caregiver's CBI score was significantly correlated with the patient's PDQ-39, PDSS and HAMD scores (r=0.512, 0.645 and 0.635, respectively, all P<0.01), and the caregiver's SF-36GH score was significantly correlated with the patient's PDQ-39, PDSS and HAMD scores (r=0.452, 0.682 and 0.506, respectively, all P<0.01). The caregiver's SF-36MH score was significantly correlated with the patient's PDQ-39, PDSS and HAMD scores (r=0.426, 0.608 and 0.598, respectively, all P<0.01). There was significant correlations between the caregiver's HAMD score and the patient's PDSS and HAMD scores (r=0.568 and 0.496, both P<0.01), and the PSQI score of the caregiver was significantly correlated with the PDSS and HAMD scores of the patient (r=0.532 and 0.461, both P<0.01). Conclusions: This current study underscores the presence of a significant relationship of patient's sleep quality with caregiver's burden, quality of life, depression and sleep quality. Specifically, sleep quality and depression of the patients are independent predictors for burden, quality of life and sleep quality of the caregivers.

[Intellectual developmental disorder with cardiac arrhythmia syndrome in a family caused by GNB5 variation and literature review].

Objective: To explore the clinical characteristics of intellectual developmental disorder with cardiac arrhythmia syndrome (IDDCA) in a family caused by GNB5 gene variation and to review the literature. Methods: The clinical and genetic data of an infant with IDDCA, who visited Shenzhen Children's Hospital in September 2018, were collected and analyzed. His parents' and brother's gene analysis was also done by the next-generation sequencing and confirmed by Sanger sequencing. Related literature up to March 2020 was searched in Online Mendelian Inheritance in Man (OMIM), PubMed, CNKI and Wanfang databases with "GNB5" "IDDCA" "LADCI" "intellectual developmental disorder with cardial arrhythmia" "language delay and attention deficit-hyperactivity disorder or cognitive impairment with or without cardiac arrhythmia" as the key words. The related papers were retrieved and analyzed to summarize the clinical and genetic characteristics of this disorder. Results: The proband was an 11-month-old boy who presented with mental and motor developmental retardation, accompanied with convulsion and muscle weakness. Sinus arrest was also detected. His electroencephalogram (EEG) and flash visual evoked potential (FVEP) were both abnormal. Genetic analysis identified the homozygous frameshift variation of GNB5 gene (c.136delG, p.Glu46Argfs*8) in this infant and heterozygous variation in his parents, confirmed the diagnosis of IDDCA. The same GNB5 variation was identified in his brother, who was 4 years and 8 months old and had developed the similar clinical manifestations after birth. There were only 7 papers reporting this disease in the literature review, with a total of 27 patients from 14 families. Including these 2 cases, there were 29 patients in total, whose age of diagnosis ranged from 5.5 months to 23 years. Among all the patients, 20 cases (69%) were diagnosed as IDDCA, while 8 cases (28%) as LADCI; and 11 (38%) were males while 18 (62%) females. Regarding the clinical features, 66% (19/29) had mental retardation, 41% (12/29) had seizures, 79% (23/29) developed language delay and 62%（18/29） had sinus node dysfunction. Genetic tests showed that 4 patients from 3 families had complex heterozygous variation, and 25 patients (86%) from 12 families had homozygous variation. Seventeen patients from 8 families were consanguineous. Among the total 12 variations, there were 4 nonsense, 3 frameshift, 2 missense and 2 shear mutations, and 1 shear disorder caused by synonymous mutation. Conclusions: IDDCA caused by GNB5 gene variations mainly manifests as general developmental delay or severe mental retardation, and sinus node dysfunction. GNB5 associated syndromes have phenotypic heterogeneity and are inherited in an autosomal recessive manner.

Direct Temporal Mode Measurement for the Characterization of Temporally Multiplexed High Dimensional Quantum Entanglement in Continuous Variables.

Field-orthogonal temporal mode analysis of optical fields has recently been developed for a new framework of quantum information science. However, so far, the exact profiles of the temporal modes are not known, which makes it difficult to achieve mode selection and demultiplexing. Here, we report a novel method that measures directly the exact form of the temporal modes. This, in turn, enables us to make mode-orthogonal homodyne detection with mode-matched local oscillators. We apply the method to a pulse-pumped, specially engineered fiber parametric amplifier and demonstrate temporally multiplexed multidimensional quantum entanglement of continuous variables in telecom wavelength. The temporal mode characterization technique can be generalized to other pulse-excited systems to find their eigenmodes for multiplexing in the temporal domain.

[Current consensus and controversy in neoadjuvant therapy for pancreatic cancer].

Pancreatic cancer is malignant and has a poor prognosis.At present, the treatment mode has changed from "Surgery First" to systemic therapy under multi-disciplinary team, but surgical resection is still the only way to cure pancreatic cancer. In systemic treatment of pancreatic cancer, the effect of postoperative adjuvant therapy is significant, and preoperative neoadjuvant therapy has gradually attracted widespread attention. Neoadjuvant therapy can improve the rate of R0 resection in patients with pancreatic cancer.There is a consensus on neoadjuvant therapy for patients who with borderline resectable and locally advanced, but for the patients who with resectable remains controversial.

[Clinical analysis of carotid artery stenting with severe stenosis and extracranial distortion under proximal protection technique].

Objective: To investigate the feasibility, efficacy and safety of endovascular reconstruction of the carotid artery with severe stenosis and extracranial distortion under proximal protection. Methods: A retrospective analysis of 21 patients with severe carotid stenosis and extracranial distortion who were admitted to the Second Affiliated Hospital of Soochow University between January 2011 and August 2017, of which 16 patients were symptomatic stenosis with acute ischemic stroke. All the patients were treated with carotid artery stenting under (CAS) proximal protection technique, and assessed with the National Institutes of Health Stroke Scale (NIHSS) before the treatment and hospital discharge. The clinical outcome and vascular morphology were followed-up regularly after the treatment. Results: Twenty-one patients were successfully completed the CAS procedure under the proximal protection technique, the average blocking time was 241.0 (232.5-261.0) seconds. Nine patients received 1block attempt, 6 patients received 2 block attempts, and the other 6 patients received 3 block attempts. Three patients experienced transient ischemic attack (TIA) during the procedure, the maximum duration of TIA was 10 minutes. In 16 patients with symptomatic stenosis, there were no significant differences in NIHSS score before CAS procedure and hospital discharge (P>0.05). The residual stenosis rate of the carotid artery after stenting was(13±6)%, compared with preoperative (87±16)%, which appeared a significant difference (t=19.948, P<0.05). All the patients had no adverse events such as myocardial infarction, recurrent ischemic stroke and death in the follow-up period. Restenosis was assessed in 6 patients by DSA or CTA and no restenosis was found. Conclusion: Endovascular reconstruction of the carotid artery with severe stenosis and extracranial distortion under proximal protection technique has been proven as a safe and effective therapy.

Pulsed entanglement measured by parametric amplifier assisted homodyne detection.

Balanced homodyne detection relies on a beam splitter to superpose the weak signal input and strong local oscillator. However, recent investigation shows that a high gain phase sensitive amplifier (PSA) can be viewed as homodyne detector, in which the strong pump of PSA serves as the local oscillator [1]. Here, we analyze a new method of measuring the continuous variable entanglement by assisting a balanced homodyne detector with the PSA and implement it experimentally. Before measuring quadrature amplitude with the balanced homodyne detectors, two entangled fields generated from a pulse pumped fiber optical parametric amplifier are simultaneously coupled into the PSA. We find that the normalized noise for both the difference and sum of the quadrature amplitudes of the two entangled fields fall below the shot noise limit by about 4.6 dB, which is the record degree of entanglement measured in optical fiber systems. The experimental results illustrate that the advantages of the new measurement method include but not limit to tolerance to detection loss and characterizing entanglement with only one homodyne detector. The influence of mode-mismatching due to multi-mode property of entanglement on the measured noise reduction can also be greatly mitigated, indicating the new method is advantageous over the traditional measurement in multi-mode case.

Versatile and precise quantum state engineering by using nonlinear interferometers.

The availability of photon states with well-defined temporal modes is crucial for photonic quantum technologies. Ever since the inception of generating photonic quantum states through pulse pumped spontaneous parametric processes, many exquisite efforts have been put on improving the modal purity of the photon states to achieve single-mode operation. However, because the nonlinear interaction and linear dispersion are often mixed in parametric processes, limited successes have been achieved so far only at some specific wavelengths with sophisticated design. In this paper, we resort to a different approach by exploiting an active filtering mechanism originated from interference fringe of nonlinear interferometer. The nonlinear interferometer is realized in a sequential array of nonlinear medium, with a gap in between made of a linear dispersive medium, in which the precise modal control is realized without influencing the phase matching of the parametric process. As a proof-of-principle demonstration of the capability, we present a photon pairs source using a two-stage nonlinear interferometer formed by two identical nonlinear fibers with a standard single mode fiber in between. The results show that spectrally correlated two-photon state via four wave mixing in a single piece nonlinear fiber is modified into factorable state and heralded single-photons with high modal purity and high heralding efficiency are achievable. This novel quantum interferometric method, which can improve the quality of the photon states in almost all the aspects such as modal purity, heralding efficiency, and flexibility in wavelength selection, is proved to be effective and easy to realize.

Non-Hermitian Magnon-Photon Interference in an Atomic Ensemble.

The interference of photons in a lossy beam splitter (BS) exhibits anticoalescence, which is surprising for bosons. Such a non-Hermitian system involving open quantum dynamics is of particular interest for quantum information processing and metrology. The Hermiticity of photonic devices is generally fixed according to the material, but is controllable at the interface of photons and atomic systems. Here, we demonstrate a tunable non-Hermitian BS for the interference between traveling photonic and localized magnonic modes. The crossover from a Hermitian to a non-Hermitian magnon-photon BS is achieved by controlling the coherent and incoherent interaction mediated by the excited levels of atoms, which is reconfigurable via the detuning of a control laser. A correlated interference pattern between the photons and magnons is demonstrated by such a non-Hermitian BS. Our system has the potential to operate with photons and magnons at the single-quanta level, and it provides a versatile quantum interface for studying the non-Hermitian quantum physics and parity-time symmetry.