Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.

BACKGROUND: Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, but their existence and relative frequency in clinical disease are unclear, as is how to target resistance. PATIENTS AND METHODS: Longitudinal mutation and methylation profiling of circulating tumour (ct)DNA was carried out in 47 patients with metastatic BRCA1-, BRCA2- or PALB2-mutant breast cancer treated with HRD-targeted therapy who developed progressive disease-18 patients had primary resistance and 29 exhibited response followed by resistance. ctDNA isolated at multiple time points in the patient treatment course (before, on-treatment and at progression) was sequenced using a novel >750-gene intron/exon targeted sequencing panel. Where available, matched tumour biopsies were whole exome and RNA sequenced and also used to assess nuclear RAD51. RESULTS: BRCA1/2 reversion mutations were present in 60% of patients and were the most prevalent form of resistance. In 10 cases, reversions were detected in ctDNA before clinical progression. Two new reversion-based mechanisms were identified: (i) intragenic BRCA1/2 deletions with intronic breakpoints; and (ii) intragenic BRCA1/2 secondary mutations that formed novel splice acceptor sites, the latter being confirmed by in vitro minigene reporter assays. When seen before commencing subsequent treatment, reversions were associated with significantly shorter time to progression. Tumours with reversions retained HRD mutational signatures but had functional homologous recombination based on RAD51 status. Although less frequent than reversions, nonreversion mechanisms [loss-of-function (LoF) mutations in TP53BP1, RIF1 or PAXIP1] were evident in patients with acquired resistance and occasionally coexisted with reversions, challenging the notion that singular resistance mechanisms emerge in each patient. CONCLUSIONS: These observations map the prevalence of candidate drivers of resistance across time in a clinical setting, information with implications for clinical management and trial design in HRD breast cancers.

Realizing Synthetic Dimensions and Artificial Magnetic Flux in a Trapped-Ion Quantum Simulator.

Synthetic dimension is a potent tool in quantum simulation of topological phases of matter. Here we propose and demonstrate a scheme to simulate an anisotropic Harper-Hofstadter model with controllable magnetic flux on a two-leg ladder using the spin and motional states of a single trapped ion. We verify the successful simulation of this model by comparing the measured dynamics with theoretical predictions under various coupling strength and magnetic flux, and we observe the chiral motion of wave packets on the ladder as evidence of the topological chiral edge modes. We develop a quench path to adiabatically prepare the ground states for varying magnetic flux and coupling strength, and we measure the chiral current on the ladder for the prepared ground states, which allows us to probe the quantum phase transition between the Meissner phase and the vortex phase. Our work demonstrates the trapped ion as a powerful quantum simulation platform for topological quantum matter.

Placenta-derived interferon-stimulated gene 20 controls ZIKA virus infection.

Zika virus is a positive-sense single-stranded RNA virus, which can be transmitted across the placenta and has adverse effects on fetal development during pregnancy. The severity of these complications highlights the importance of prevention and treatment. However, no vaccines or drugs are currently available. In this study, we characterize the IFNß-mediated anti-viral response in trophoblast cells in order to identify critical components that are necessary for the successful control of viral replication and determine whether components of the IFN-induced response can be used as a replacement therapy for ZIKA virus infection during pregnancy. We identify and characterize interferon-stimulated gene 20 (ISG20) as playing a central role in controlling Zika virus infection in trophoblast cells and successfully establish a recombinant ISG20-Fc protein that effectively decreases viral titers in vitro and in vivo by maintaining its exonuclease activity and displaying potential immune modulatory functions. Recombinant ISG20-Fc has thus the potential to be further developed as an anti-viral treatment against ZIKA viral infection in high-risk populations, particularly in pregnant women.

Association between sarcopenia and prediabetes among non-elderly US adults.

AIM: To explore the specific association between sarcopenia and prediabetes based on large population samples. METHODS: A total of 16,116 U.S. adults aged 20-59 with dual energy X-ray absorptiometry (DXA) was identified from the National Health and Nutrition Examination Surveys (NHANES). Sarcopenia was defined according to appendicular skeletal muscle mass (ASM) adjusted for body mass index (BMI). Multivariable binary logistic regression models were used to ascertain odds ratios (ORs) for developing prediabetes. Stratified analyses were also performed. RESULTS: Prevalence of prediabetes was higher in the sarcopenia group (n = 1055) compared with the non-sarcopenia group (n = 15,061) (45.50% vs 28.74%, P < 0.001). Sarcopenia was strongly associated with an increased risk of prediabetes after full adjustment (OR = 1.21, 95CI%: 1.05, 1.39, P = 0.009). In the stratified analysis, this association remained significant independent of obesity, triglycerides, and low-density lipoprotein cholesterol levels. When sarcopenia subjects combined with obesity especially central obesity, the risk of prediabetes was the highest (OR = 2.63, 95CI%: 2.22, 3.11, P < 0.001). Furthermore, a greater proportion of any of impaired glucose tolerance (IGT) individuals was observed in the sarcopenia group compared to the non-sarcopenia group among prediabetes population (41.72% vs 24.06%, P < 0.001). CONCLUSIONS: Sarcopenia was positively associated with prevalent prediabetes especially IGT in the non-elderly. Moreover, synergistic interactions between the sarcopenia and obesity could greatly increase the risk of prediabetes.

Phenylacetylglutamine as a novel biomarker of type 2 diabetes with distal symmetric polyneuropathy by metabolomics.

PURPOSE: Type 2 diabetes mellitus (T2DM) with distal symmetric polyneuropathy (DSPN) is a disease involving the nervous system caused by metabolic disorder, while the metabolic spectrum and key metabolites remain poorly defined. METHODS: Plasma samples of 30 healthy controls, 30 T2DM patients, and 60 DSPN patients were subjected to nontargeted metabolomics. Potential biomarkers of DSPN were screened based on univariate and multivariate statistical analyses, ROC curve analysis, and logistic regression. Finally, another 22 patients with T2DM who developed DSPN after follow-up were selected for validation of the new biomarker based on target metabolomics. RESULTS: Compared with the control group and the T2DM group, 6 metabolites showed differences in the DSPN group (P < 0.05; FDR < 0.1; VIP > 1) and a rising step trend was observed. Among them, phenylacetylglutamine (PAG) and sorbitol displayed an excellent discriminatory ability and associated with disease severity. The verification results demonstrated that when T2DM progressed to DSPN, the phenylacetylglutamine content increased significantly (P = 0.004). CONCLUSION: The discovered and verified endogenous metabolite PAG may be a novel potential biomarker of DSPN and involved in the disease pathogenesis.

Shake It Up Baby Now: The Changing Focus on TWIST1 and Epithelial to Mesenchymal Transition in Cancer and Other Diseases.

TWIST1 is a transcription factor that is necessary for healthy neural crest migration, mesoderm development, and gastrulation. It functions as a key regulator of epithelial-to-mesenchymal transition (EMT), a process by which cells lose their polarity and gain the ability to migrate. EMT is often reactivated in cancers, where it is strongly associated with tumor cell invasion and metastasis. Early work on TWIST1 in adult tissues focused on its transcriptional targets and how EMT gave rise to metastatic cells. In recent years, the roles of TWIST1 and other EMT factors in cancer have expanded greatly as our understanding of tumor progression has advanced. TWIST1 and related factors are frequently tied to cancer cell stemness and changes in therapeutic responses and thus are now being viewed as attractive therapeutic targets. In this review, we highlight non-metastatic roles for TWIST1 and related EMT factors in cancer and other disorders, discuss recent findings in the areas of therapeutic resistance and stemness in cancer, and comment on the potential to target EMT for therapy. Further research into EMT will inform novel treatment combinations and strategies for advanced cancers and other diseases.

[Clinical features and predictors of early neurological deterioration in acute isolated pontine infarction].

Objective: To investigate the clinical and imaging characteristics of early neurological deterioration (END) in acute isolated pontine infarction (AIPI) and analyze the predictive factors of END. Methods: Patients with AIPI who were confirmed by magnetic resonance imaging (MRI) in Zhengzhou University People's Hospital from January 2020 to December 2021were collected and divided into END group and non-END group (NEND group). General data and imaging characteristics of the patients were compared between the two groups, the neurological function of patients was evaluated by using the modified Rankin scale (mRS) at 1 and 3 months after stroke. Multivariate binary logistic regression model was used to analyze the risk factors of END after isolated pontine infarction, and the receiver operating characteristic curve(ROC) curve was drawn. Z-test was used to compare the area under the curve to determine the best predictor of END. Results: A total of 113 patients with AIPI were enrolled, including 72 males and 41 females, aged (62±11) years, with 40 cases in the END group and 73 cases in the NEND group. The incidence of END in AIPI was 35.4% (40/113). The National Institutes of Health Stroke Scale (NIHSS) score in the END group (5.15±1.88) was higher than that in the NEND group (4.10±1.63), and the infarcts size in the END group [(2.15±0.39) mm2] was larger than that in the NEND group [(1.61±0.46) mm2] (P=0.002 and P<0.001, respectively). Multivariate binary logistic regression analysis showed that NIHSS score on admission (OR=1.393, 95%CI: 1.017-1.909, P=0.039), infarct size (OR=11.539, 95%CI: 3.574-37.255, P<0.001) were associated with END. Comparing the area of ROC curve, infarct size [area under curve (AUC)=0.787, with a sensitivity of 0.750 and specificity of 0.545] and NIHSS score on admission (AUC=0.688, with a sensitivity of 0.700 and specificity of 0.589) showed no significant difference in the value of predicting END (P=0.056). Conclusion: Patients with AIPI had higher NIHSS score and larger infarct size on admission, and both of them exhibit good predictive performance for END.

[Association between different treatment timings and adverse neonatal outcomes in pregnant women with syphilis during pregnancy].

Objective: To analyze the association between different treatment timings and adverse neonatal outcomes (premature birth, death, congenital syphilis) in syphilis-infected pregnant women. Methods: The National Management Information System for Prevention of HIV, Syphilis and HBV Mother-to-Child Transmission was used to collect information on the detection and treatment of syphilis-infected pregnant women and their newborns in Guangdong Province from October 2011 to December 2021. According to the gestational weeks of syphilis-infected pregnant women receiving penicillin treatment for the first time, they were divided into four groups: treatment in the first trimester, treatment in the second trimester, treatment in the third trimester, and no treatment during pregnancy. Multivariate logistic regression was used to analyze the association between different treatment timings and adverse neonatal outcomes in syphilis-infected pregnant women. Results: A total of 22 483 syphilis-infected pregnant women were included. The number of pregnant women who started treatment in the first trimester, second trimester, and third trimester and did not receive treatment during pregnancy were 4 549 (20.23%), 8 719 (38.78%), 2 235 (9.94%) and 6 980 (31.05%), respectively. Compared with pregnant women who started treatment in the first trimester, pregnant women who did not receive anti-syphilis treatment during pregnancy had increased risks of neonatal preterm birth (OR=1.42, 95%CI: 1.24-1.62), death (OR=4.27, 95%CI: 1.64-14.69) and congenital syphilis (OR=12.26, 95%CI: 6.35-27.45). At the same time, the risk of congenital syphilis in the newborns of pregnant women who started anti-syphilis treatment in the second trimester (OR=2.68, 95%CI: 1.34-6.16) and third trimester (OR=6.27, 95%CI: 2.99-14.80) also increased. Conclusion: Early initiation of anti-syphilis treatment during pregnancy in patients with syphilis can improve neonatal outcomes.

[Analysis of the serum bile acid profile to facilitate diagnosis and differential diagnosis of NA(+)-taurocholate cotransporting polypeptide deficiency].

Objective: This study focuses on Na(+)-taurocholate cotransporting polypeptide (NTCP) deficiency to analyze and investigate the value of the serum bile acid profile for facilitating the diagnosis and differential diagnosis. Methods: Clinical data of 66 patients with cholestatic liver diseases (CLDs) diagnosed and treated in the Department of Pediatrics of the First Affiliated Hospital of Jinan University from early April 2015 to the end of December 2021 were collected, including 32 cases of NTCP deficiency (16 adults and 16 children), 16 cases of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), 8 cases of Alagille syndrome, and 10 cases of biliary atresia. At the same time, adult and pediatric healthy control groups (15 cases each) were established. The serum bile acid components of the study subjects were qualitatively and quantitatively analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry. The data were plotted and compared using statistical SPSS 19.0 and GraphPad Prism 5.0 software. The clinical and bile acid profiles of children with NTCP deficiency and corresponding healthy controls, as well as differences between NTCP deficiency and other CLDs, were compared using statistical methods such as t-tests, Wilcoxon rank sum tests, and Kruskal-Wallis H tests. Results: Compared with the healthy control, the levels of total conjugated bile acids, total primary bile acids, total secondary bile acids, glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were increased in NTCP deficiency patients (P < 0.05). Compared with adults with NTCP deficiency, the levels of total conjugated bile acids and total primary bile acids were significantly increased in children with NTCP deficiency (P < 0.05). The serum levels of taurochenodeoxycholic acid, glycolithocholate, taurohyocholate, and tauro-α-muricholic acid were significantly increased in children with NTCP deficiency, but the bile acid levels such as glycodeoxycholic acid, glycolithocholate, and lithocholic acid were decreased (P < 0.05). The serum levels of secondary bile acids such as lithocholic acid, deoxycholic acid, and hyodeoxycholic acid were significantly higher in children with NTCP deficiency than those in other CLD groups such as NICCD, Alagille syndrome, and biliary atresia (P < 0.05). Total primary bile acids/total secondary bile acids, total conjugated bile acids/total unconjugated bile acids, taurocholic acid, serum taurodeoxycholic acid, and glycodeoxycholic acid effectively distinguished children with NTCP deficiency from other non-NTCP deficiency CLDs. Conclusion: This study confirms that serum bile acid profile analysis has an important reference value for facilitating the diagnosis and differential diagnosis of NTCP deficiency. Furthermore, it deepens the scientific understanding of the changing characteristics of serum bile acid profiles in patients with CLDs such as NTCP deficiency, provides a metabolomic basis for in-depth understanding of its pathogenesis, and provides clues and ideas for subsequent in-depth research.

Microwave-field sensing via electromagnetically induced absorption of Rb irradiated by three-color infrared lasers.

A microwave electric field sensing has been set up based on a three-color electromagnetically induced absorption in rubidium vapor cell via cascading transitions. All transitions are irradiated by infrared lasers: a 780 nm laser servers as probe to monitor the optical transmittancy via transition 5S1/2→P3/2;, a 776 nm laser and a 1260 nm laser are used to couple the states 5P3/2 and 5D5/2 and states 5D5/2 and 44F7/2, respectively. We find that a frequency detuning ∼2π × ( - 40) MHz of the 776 nm dressing beam prefers to a better signal-to-noise ratio for the probe beam. The off-resonance greatly depresses the double resonance pumping effect. A demonstration measurement for the electric field of microwave 1.18988 GHz, corresponding to the coupling resonance between two adjacent Rydberg states 44F7/2 and 44F9/2, gives a sensitivity of 55.79(23)nVcm-1/Hz and a smallest discernible electric field of 78.9(33) nVcm-1 in time scale of 500 ms.

Experimental Realization of the Rabi-Hubbard Model with Trapped Ions.

Quantum simulation provides important tools in studying strongly correlated many-body systems with controllable parameters. As a hybrid of two fundamental models in quantum optics and in condensed matter physics, the Rabi-Hubbard model demonstrates rich physics through the competition between local spin-boson interactions and long-range boson hopping. Here, we report an experimental realization of the Rabi-Hubbard model using up to 16 trapped ions and present a controlled study of its equilibrium properties and quantum dynamics. We observe the ground-state quantum phase transition by slowly quenching the coupling strength, and measure the quantum dynamical evolution in various parameter regimes. With the magnetization and the spin-spin correlation as probes, we verify the prediction of the model Hamiltonian by comparing theoretical results in small system sizes with experimental observations. For larger-size systems of 16 ions and 16 phonon modes, the effective Hilbert space dimension exceeds 2^{57}, whose dynamics is intractable for classical supercomputers.

Observation of Non-Markovian Spin Dynamics in a Jaynes-Cummings-Hubbard Model Using a Trapped-Ion Quantum Simulator.

The Jaynes-Cummings-Hubbard (JCH) model is a fundamental many-body model for light-matter interaction. As a leading platform for quantum simulation, the trapped ion system has realized the JCH model for two to three ions. Here, we report the quantum simulation of the JCH model using up to 32 ions. We verify the simulation results even for large ion numbers by engineering low excitations and thus low effective dimensions; then we extend to 32 excitations for an effective dimension of 2^{77}, which is difficult for classical computers. By regarding the phonon modes as baths, we explore Markovian or non-Markovian spin dynamics in different parameter regimes of the JCH model, similar to quantum emitters in a structured photonic environment. We further examine the dependence of the non-Markovian dynamics on the effective Hilbert space dimension. Our Letter demonstrates the trapped ion system as a powerful quantum simulator for many-body physics and open quantum systems.

Quantum Simulation of the Two-Dimensional Weyl Equation in a Magnetic Field.

Quantum simulation of 1D relativistic quantum mechanics has been achieved in well-controlled systems like trapped ions, but properties like spin dynamics and response to external magnetic fields that appear only in higher dimensions remain unexplored. Here we simulate the dynamics of a 2D Weyl particle. We show the linear dispersion relation of the free particle and the discrete Landau levels in a magnetic field, and we explicitly measure the spatial and spin dynamics from which the conservation of helicity and properties of antiparticles can be verified. Our work extends the application of an ion trap quantum simulator in particle physics with the additional spatial and spin degrees of freedom.

Serum fibrinogen-like protein 1 as a novel biomarker in polycystic ovary syndrome: a case-control study.

PURPOSE: To investigate the relationship between fibrinogen-like protein 1 (FGL-1) concentrations and various metabolic characteristics in patients with polycystic ovary syndrome (PCOS) and explore whether FGL-1 could be a predictive biomarker for PCOS. METHODS: This case-control study included 136 patients with PCOS and 34 normal controls recruited in the Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital between May 2017 and June 2021. Anthropometric characteristics, metabolic parameters, and reproductive hormones were collected. Serum FGL-1 measurement was conducted using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Serum FGL-1 concentrations were higher in patients with PCOS than in control subjects in body mass index (BMI) subgroups, insulin resistance (IR) subgroups, and hepatic function subgroups, respectively. Serum FGL-1 concentrations were significantly associated with BMI, glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), high-density lipoprotein cholesterol (HDL-c), and serum uric acid (SUA) in all individuals. The receiver operating characteristic (ROC) curve analysis revealed that the best cutoff value for FGL-1 levels to predict PCOS was 21.02 ng/ml with a sensitivity of 74.3% and a specificity of 70.6%. Both univariate and multiple logistic regressions indicated that the odds ratio (OR) for PCOS significantly increased in the subjects with high levels of FGL-1. CONCLUSION: In our study, FGL-1 was associated with serum aminotransferase and various metabolic indexes. Moreover, the high risk of PCOS was independently associated with the increased FGL-1 levels, which suggested that FGL-1 could be a predictive biomarker for PCOS.

[Establishment and validation of a predictive model for neurogenic urinary tract injury in children].

Objective: To establish a predictive model for upper urinary tract damage in children with neurogenic bladder and verify its efficacy. Methods: From January 2011 to December 2021, 143 children with NB in the Children's Hospital of Chongqing Medical University and 84 children with NB in the First Affiliated Hospital of Zhengzhou University were selected as the research objects. The former is set as the training set and the latter is set as the validation set, and the general parameters of the two are compared. The independent risk factors of upper urinary tract damage in children with NB were screened out by Lasso regression, and multivariate logistic regression analysis and a nomogram prediction model was established. The models were validated internally and externally on the training set and validation set, respectively, and the area under the receiver operating curve (ROC) was used to verify the accuracy of the model. Results: A total of 227 children with NB were included in this study, including 121 males and 106 females, aged (10.2±3.8) years. There was no significant difference in other parameters except age between the training set and validation set (all P>0.05); Lasso regression and multivariate logistic regression analysis showed that detrusor leakage point pressure (DLPP) ≥ 40 cmH2O (OR=4.76, 95%CI: 2.01-11.26, 1 cmH2O=0.098 kPa), overactive bladder (OAB) (OR=3.08, 95%CI: 1.34-7.04), bladder compliance (BC)<20 ml/cm H2O (OR=3.65, 95%CI: 1.41-9.47), history of previous urinary tract infection (OR=2.73, 95%CI: 1.09-6.81), and abdominal pressure/other voiding patterns (OR=2.86, 95%CI: 1.20-6.82) were risk factors for upper urinary tract damage in children with NB (all P<0.05). The above parameters were used to establish a nomogram model of upper urinary tract damage in children with NB. The internal and external validation results show that the AUC values for the training and validation sets were 0.84 (95%CI: 0.77-0.91) and 0.86 (95%CI: 0.79-0.94), respectively. Conclusion: The prediction model of upper urinary tract damage in children with NB constructed in this study has high discrimination, accuracy and clinical applicability, which can help clinicians identify high-risk patients and make individualized treatment design for these patients.

[A multicenter, double-blind, randomized controlled clinical trial comparing ergometrine with oxytocin and oxytocin alone for prevention of postpartum hemorrhage at cesarean section].

Objective: To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS). Methods: This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1∶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration. Results: (1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant (P<0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P<0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P>0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups (P>0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant (P<0.05), but the blood pressure of the two groups were in the normal range. Conclusion: The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.

[A survey of the current status of research on the diagnosis and treatment of hepatitis C virus antibody-positive pregnant women].

Objective: To analyze the screening, diagnosis, epidemiology, pregnancy outcomes and treatment status in hepatitis C virus antibody-positive pregnant women, in order to provide clinical evidence for further improving prevention and control of maternal and infant safety. Methods: Data of 246 HCV antibody-positive pregnant women admitted to the Second Hospital of Nanjing from January 2014 to December 2019 were analyzed by epidemiological survey research method. Statistical analysis was performed according to different data using t-test, χ2 test, corrected χ2 test or Fisher's exact test. Results: 80 of 246 HCV antibody-positive women had confirmed infection before pregnancy. Of these, 85% were HCV RNA positive, and 16 became pregnant after antiviral therapy. Prenatal examination during pregnancy found that 166 cases were HCV RNA positive, and the HCV RNA positive rate was 81.93%. In the relationship between infection route and birth cohort in HCV antibody-positive pregnant women, there was a statistically significant differences in the proportions of transmission route among birth cohort (χ2=115.6, P＜0.001). With the delay of birth cohort, the proportion of infection through drug use was decreased (P＜0.001), while the proportion of acupuncture-associated infection (P=0.043) and infant hospitalization history were increased (P=0.005). Among pregnancy complications, HCV antibody-positive pregnant women in HCV RNA＜5.0 E+02 IU/ml and ≥5.0 E+02 IU/ml groups had intrahepatic cholestasis of pregnancy (χ2=4.73, P=0.030) and gestational hypertension (χ2=8.65, P=0.003), and the difference in incidence was statistically significant. Postpartum treatment strategy data analysis showed that the treatment rate was highest in the first year of postpartum, and then showed an upward trend year by year, with a statistically significant difference (χ2=17.26,P =0.004). Conclusion: Anti-HCV screening rates are lower among pregnant and reproductive age women. HCV screening should be used as an important supplementary means to strengthen maternal safety and health education management during pregnancy. Active postpartum antiviral therapy, with particularly emphasis on management within the first year after delivery, can significantly improve the treatment rate among women of child bearing age.

Measurement of the Cosmic Ray Helium Energy Spectrum from 70 GeV to 80 TeV with the DAMPE Space Mission.

The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.

Stillbirths in China: a nationwide survey.

OBJECTIVE: To estimate a stillbirth rate at 24 or more gestational weeks in 2015-2016 and to explore potentially preventable causes in China. DESIGN: A multi-centre cross-sectional study. SETTING: Ninety-six hospitals distributed in 24 (of 34) provinces in China. POPULATION: A total of 75 132 births at 24 completed weeks of gestation or more. METHODS: COX Proportional Hazard Models were performed to examine risk factors for antepartum and intrapartum stillbirths. Population attributable risk percentage was calculated for major risk factors. Correspondence analysis was used to explore region-specific risk factors for stillbirths. MAIN OUTCOME MEASURES: Stillbirth rate and risk factors for stillbirth. RESULTS: A total of 75 132 births including 949 stillbirths were used for the final analysis, giving a weighted stillbirth rate of 13.2 per 1000 births (95% CI 7.9-18.5). Small for gestational age (SGA) and pre-eclampsia/eclampsia increased antepartum stillbirths by 26.2% and 11.7%, respectively. Fetal anomalies increased antepartum and intrapartum stillbirths by 17.9% and 7.4%, respectively. Overall, 31.4% of all stillbirths were potentially preventable. Advanced maternal age, pre-pregnant obesity, chronic hypertension and diabetes mellitus were important risk factors in East China; low education and SGA were major risk factors in Northwest, Southwest, Northeast and South China; and pre-eclampsia/eclampsia and intrapartum complications were significant risk factors in Central China. CONCLUSIONS: The prevalence of stillbirth was 13.2 per 1000 births in China in 2015-2016. Nearly one-third of all stillbirths may be preventable. Strategies based on regional characteristics should be considered to reduce further the burden of stillbirths in China. TWEETABLE ABSTRACT: The stillbirth rate was 13.2 per 1000 births in China in 2015-2016 and nearly one-third of all stillbirths may be preventable.

Comparing the bone mineral density among male patients with latent autoimmune diabetes and classical type 1 and type 2 diabetes, and exploring risk factors for osteoporosis.

AIMS: This study aimed to compare the bone mineral densities (BMDs) among male patients with latent autoimmune diabetes in adults (LADA), classical type 1 diabetes (T1DM), and type 2 diabetes (T2DM), and to examine the risk factors for developing low BMD in these patients. PATIENTS AND METHODS: Between January 2017 and October 2020, a total of 57, 67, and 223 male patients with LADA, classical T1DM, and T2DM, respectively, were recruited from the endocrinology department of Shanghai Tenth People's Hospital. Hormonal markers of bone metabolism, lipid profiles, uric acid, glycosylated hemoglobin A1c (HbA1c), and beta-cell function were measured using blood samples. BMD was measured at the lumbar spine, femoral neck, and right hip by dual-energy X-ray absorptiometry. RESULTS: The mean BMD values from all three skeletal sites in male patients with LADA were comparable to those with classical T1DM but were much lower than those with T2DM. After adjusting for confounding factors, multiple linear regression analysis demonstrated that in all male patients with diabetes, body mass index (BMI), uric acid, and fasting C-peptide showed significant positive associations with BMD at all three skeletal sites; however, osteocalcin showed a negative association at all three sites. CONCLUSIONS: Compared with male patients with T2DM, lower BMDs were observed in patients with LADA and T1DM. Low BMI, uric acid, C-peptide levels, and high osteocalcin levels are risk factors for developing low BMD in male patients with diabetes.