Disproportion of Corpus Callosum in Fetuses With Malformations of Cortical Development.

OBJECTIVE: To evaluate corpus callosum (CC) size in fetuses with malformations of cortical development (MCD) and to explore the diagnostic value of three CC length (CCL) ratios in identifying cortical abnormalities. METHODS: This is a single-center retrospective study in singleton fetuses at 20-37 weeks of gestation between April 2017 and August 2022. The midsagittal plane of the fetal brain was obtained and evaluated for the following variables: length, height, area of the corpus callosum, and relevant markers, including the ratios of corpus callosum length to internal cranial occipitofrontal dimension (CCL/ICOFD), corpus callosum length to femur length (CCL/FL), and corpus callosum length to cerebellar vermian diameter (CCL/VD). Intra-class correlation coefficient (ICC) was used to evaluate measurement consistency. The accuracy of biometric measurements in prediction of MCD was assessed using the area under the receiver-operating-characteristics curves (AUC). RESULTS: Fetuses with MCD had a significantly decreased CCL, height (genu and splenium), and area as compared with those of normal fetuses (P < .05), but there was no significant difference in body height (P = .326). The CCL/ICOFD, CCL/FL, and CCL/VD ratios were significantly decreased in fetuses with MCD when compared with controls (P < .05). The CCL/ICOFD ratio offered the highest predictive accuracy for MCD, yielding an AUC of 0.856 (95% CI: 0.774-0.938, P < .001), followed by CCL/FL ratio (AUC, 0.780 (95% CI: 0.657-0.904), P < .001), CCL/VD ratio (AUC, 0.677 (95% CI: 0.559-0.795), P < .01). CONCLUSION: The corpus callosum biometric parameters in fetuses with MCD are reduced. The CCL/ICOFD ratio derived from sonographic measurements is considered a promising tool for the prenatal detection of cortical malformations. External validation of these findings and prospective studies are warranted.

Transcriptomic and metabolomic profile changes in the liver of Sprague Dawley rat offspring after maternal PFOS exposure during gestation and lactation.

Epidemiological and experimental research has indicated an association between perfluorooctane sulfonate (PFOS) exposure and liver disease. However, the potential hepatotoxic effects and mechanisms of low-level prenatal PFOS exposure in offspring remain ambiguous. The objective of this research was to examine the alterations in liver transcriptomic and metabolomic profiles in offspring rats at postnatal day (PND) 30 following gestational and lactational exposure to PFOS (from gestational day 1 to 20 and PND 1 to 21). Pregnant Sprague-Dawley rats were separated into a control group (3% starch gel solution, oral gavage) and a PFOS exposure group (0.03 mg/kg body weight per day, oral gavage). Histopathological changes in liver sections were observed by hematoxylin and eosin staining. Biochemical analysis was conducted to evaluate changes in glucose and lipid metabolism. Transcriptomic and metabolomic analyses were utilized to identify significant genes and metabolites associated with alterations of liver glucose and lipid metabolism through an integrated multi-omics analysis. No significant differences were found in the measured biochemical parameters. In total, 167 significant differentially expressed genes (DEGs) related to processes such as steroid biosynthesis, PPAR signaling pathway, and fat digestion and absorption were identified in offspring rats in the PFOS exposure group. Ninety-five altered metabolites were exhibited in the PFOS exposure group, such as heptaethylene glycol, lysoPE (0:0/18:0), lucidenic acid K, and p-Cresol sulfate. DEGs associated with steroid biosynthesis, PPAR signaling pathway, fat digestion and absorption were significantly upregulated in the PFOS exposure group (P < 0.05). The analysis of correlations indicated that there was a significant inverse correlation between all identified differential metabolites and the levels of fasting blood glucose, high-density lipoprotein, and triglycerides in the PFOS exposure group (P < 0.05). Our findings demystify that early-life PFOS exposure can lead to alterations in transcriptomic and metabolomic profiles in the offspring's liver, which provided mechanistic insights into the potential hepatotoxicity and developmental toxicity associated with environmentally relevant levels of PFOS exposure.

New insights on labor progression: a systematic review.

The past 20 years witnessed an invigoration of research on labor progression and a change of thinking regarding normal labor. New evidence is emerging, and more advanced statistical methods are applied to labor progression analyses. Given the wide variations in the onset of active labor and the pattern of labor progression, there is an emerging consensus that the definition of abnormal labor may not be related to an idealized or average labor curve. Alternative approaches to guide labor management have been proposed; for example, using an upper limit of a distribution of labor duration to define abnormally slow labor. Nonetheless, the methods of labor assessment are still primitive and subject to error; more objective measures and more advanced instruments are needed to identify the onset of active labor, monitor labor progression, and define when labor duration is associated with maternal/child risk. Cervical dilation alone may be insufficient to define active labor, and incorporating more physical and biochemical measures may improve accuracy of diagnosing active labor onset and progression. Because the association between duration of labor and perinatal outcomes is rather complex and influenced by various underlying and iatrogenic conditions, future research must carefully explore how to integrate statistical cut-points with clinical outcomes to reach a practical definition of labor abnormalities. Finally, research regarding the complex labor process may benefit from new approaches, such as machine learning technologies and artificial intelligence to improve the predictability of successful vaginal delivery with normal perinatal outcomes.

Mitochondrial DNA variant spectrum and the association with chronic tic disorders.

BACKGROUND AND PURPOSE: Tic disorders (TDs) are childhood onset neuropsychiatric disorders characterized by single or multiple sudden, rapid, recurrent, and motor tics and/or vocal tics. Several nuclear genes that are involved in mitochondrial functions suggest a potential role of mitochondria in TDs. METHODS: To evaluate the association of mitochondrial DNA (mtDNA) variants with TDs, we screened the whole mitochondrial genomes in 493 TD patients and 109 age- and sex-matched healthy controls using next generation sequencing technology. RESULTS: A total of 1918 mtDNA variants including 1220 variants in patients only, 154 variants in controls only, and 544 variants shared by both cases and controls were identified. We found a higher number of overall mtDNA variants in TD patients (p = 0.00028). The variant density in MT-ATP6/8 and MT-CYB coding regions showed a significant difference between TD patients and controls (p = 0.0025 and p = 0.003, respectively). Furthermore, we observed a significant association of 15 common variants with TD based on an additive model, including m.14766C > T, m.14783 T > C, m.14905G > A, and m.15301G > A in MT-CYB; m.4769A > G, m.10398A > G, m.12705C > T, and m.12850A > G in MT-ND genes; m.7028C > T in MT-CO1; m.8701A > G in MT-ATP6; two variants with m.16223C > T, m.5580 T > C in noncoding regions; and three rRNA variants with m.1438A > G and m.750A > G in RNR1, and m.2352 T > C in RNR2. CONCLUSIONS: Our data provide evidence of mtDNA variants associated with TDs. The accumulation of the heteroplasmic levels may increase the risk of TDs. Replication studies with larger samples are necessary to understand the pathogenesis of TDs.

Patients with haemophilia A with inhibitors in China: a national real-world analysis and follow-up.

The development of alloantibodies (inhibitors) against coagulation factor VIII (FVIII) is the most serious complication of FVIII replacement therapy in patients with haemophilia A (HA). We carried out a nationwide study focussing on patients with HA with inhibitors in China to evaluate the condition and management of this population. The study retrospectively analysed patient characteristics, clinical history, manifestation, treatment strategy as well as individual haemophilia care of 493 patients with inhibitors (466 with severe HA and 27 with non-severe HA) registered all over China. The median (interquartile range) age at diagnosis of FVIII inhibitors was 13 (5-28) years in patients with severe HA and 24 (10·5-39·5) years in patients with non-severe HA. Most patients (85%) had high-titre inhibitors. Prothrombin complex concentrate and recombinant activated coagulation factor VII were used respectively in 76·2% and 29·2% of patients for acute bleeding. Only 22·3% of patients underwent immune tolerance induction (ITI) treatment, of whom 64·9% achieved negative inhibitor titre. In patients who did not undergo ITI, the inhibitors turned negative in 17·7%, and patients with low peak inhibitor titre were more likely to acquire negative titre spontaneously (odds ratio 11·524, 95% confidence interval 5·222-25·432; P = 0·000). We recorded that 3·2% of the patients died from haemophilia-related life-threatening bleeding.

Pharmacokinetic, efficacy and safety evaluation of B-domain-deleted recombinant FVIII (SCT800) for prophylactic treatment in adolescent and adult patients with severe haemophilia A.

INTRODUCTION: SCT800 is a recombinant human B-domain-deleted coagulation factor VIII (BDDrFVIII) developed in China. AIM: To evaluate the repeat pharmacokinetics (PKs), efficacy, and safety of SCT800 in previously treated Chinese adolescent and adult patients with severe haemophilia A. METHODS: A phase III, multicentre, prospective, open-label, single-arm trial was conducted at 12 medical centres. Subjects received treatment for 24 weeks. PKs were assessed at the initial and repeated dosing 24 weeks later. The primary endpoint was annualized bleeding rate (ABR). Breakthrough bleeding episodes and inhibitor development were assessed. RESULTS: A total of 71 of 73 patients completed the study, and 18 were enrolled for the repeat PK investigation. Total exposure was 5643 exposure days. Overall, SCT800 showed comparable repeat PK profiles. The total ABR was 2.82 (95% confidence interval 2.01-3.96). During prophylaxis, 43.8% of patients had no bleeding episodes. The majority (89.4%) of bleeding episodes were controlled with 1-2 injections of SCT800, the success rate (defined as 'excellent' or 'good' haemostatic response) for the treatment of bleeding episodes was 92.6%. The incidence of treatment-related adverse events was 53.4%. Drug-related AE incidence was 4.1%. The observed AEs were similar to those of other coagulation factor VIII, but lower in frequency. No subject developed an inhibitor, and no other safety concerns were identified. CONCLUSIONS: SCT800 has robust PK characteristics, and is safe and efficacious for the prophylaxis and treatment of bleeding episodes in previously treated adolescent and adult patients with severe haemophilia A.

Ten years of China's new healthcare reform: a longitudinal study on changes in health resources.

BACKGROUND: China launched a new round of healthcare-system reform in 2009 and proposed the goal of equal and guaranteed essential medical and health services for all by 2020. We aimed to investigate the changes in China's health resources over the past ten years after the healthcare reform. METHODS: Data were collected from the China Statistical Yearbook and China Health Statistics Yearbook from 2009 to 2018. Four categories and ten indicators of health resources were analyzed. A descriptive analysis was used to present the overall condition. The Health Resource Density Index was applied to showcase health-resource distribution in demographic and geographic dimensions. The global and local Moran's I were used to assess the spatial autocorrelation of health resources. Concentration Index (CI) was used to quantify the equity of health-resource distribution. A Geo-Detector model and Geographic Weighted Regression (GWR) were applied to assess the association between gross domestic product (GDP) per capita and health resources. RESULTS: Health resources have increased over the past ten years. The global and local Moran's I suggested spatial aggregation in the distribution of health resources. Hospital beds were concentrated in wealthier areas, but this inequity decreased yearly (from CI=0.0587 in 2009 to CI=0.0021 in 2018). Primary medical and health institutions (PMHI) and their beds were concentrated in poorer areas (CI remained negative). Healthcare employees were concentrated in wealthier areas (CI remained positive). In 2017, the q-statistics indicated that the explanatory power of GDP per capita to beds, health personnel, and health expenditure was 40.7%, 50.3%, and 42.5%, respectively. The coefficients of GWR remained positive with statistical significance, indicating the positive association between GDP per capita and health resources. CONCLUSIONS: From 2009 to 2018, the total amount of health resources in China has increased substantially. Spatial aggregation existed in the health-resources distribution. Health resources tended to be concentrated in wealthier areas. When allocating health resources, the governments should take economic factors into account.

Unilateral and segmental distribution of facial erythema: is it a real port-wine stain?

Capillary malformation-arteriovenous malformations (CM-AVMs) caused by a RASA-1 or EPHB4 mutation are characterized as hereditary sporadic or multifocal capillary malformations (CMs), associated with potential fast-flow vascular anomalies underlying erythema lesions. Because of the similar phenotype, CM-AVMs should be considered in the differential diagnosis of isolated CMs as well as other disorders with an erythema phenotype, such as hereditary hemorrhagic telangiectasia (HHT).Herein, we report a male patient with facial erythema. Red lesions were located in the V1 region of his left face, the V2 and V3 regions on his right side, and the nasal back. The patient was initially thought to have PWSs because of the unilateral and segmental distribution of his red facial lesions. In contrast to a previous diagnosis, we diagnosed the child with capillary malformation-arteriovenous malformation type 2 (CM-AVM2) based on a family history of erythema, the results of physical examination and ultrasound raising potential fast-flow lesions, and a genetic study revealing a germline EPHB4 mutation. This study emphasizes the importance of differential diagnosis for PWS and CM-AVM. A single clinical diagnosis can be limited, and molecular diagnosis is recommended to provide more information for the evaluation of the potential risk of fast-flow lesions underlying erythema lesions if necessary.

Novel genetic alteration in congenital melanocytic nevus: MAP2K1 germline mutation with BRAF somatic mutation.

Congenital melanocytic nevus (CMN) represent a benign proliferative skin disease in the epidermis and dermis. CMN are historically known to be associated with activating NRAS or BRAF mutations. Melanoma frequently harbors the BRAF p.Val600Glu mutation, which is also commonly found in benign nevi. A recent study reported mutation of MAP2K1, a downstream effector of the RAS-RAF-MEK pathway, in melanoma with an overall frequency of 8%. Later, in 2019, Jansen P detected one activating MAP2K1 mutation in acral nevi. However, it is unknown whether MAP2K1 mutations are common in CMN, and how MAP2K1 contributes to the pathogenesis of CMN remains to be determined.In this study, we report one patient clinically and histologically diagnosed with CMN, with the MAP2K1 germline mutation and a BRAF p.Val600Glu somatic hit in the lesion. To the best of our knowledge, this is the first report of the coexistence of mutated BRAF and MAP2K1 in CMN, which may suggest that MAP2K1 mutations contribute to the occurrence and development of nevus expanding our knowledge of the genetics of CMN.

Outcome of CARE: a 6-year national registry of acquired haemophilia A in China.

Acquired haemophilia A (AHA) is a rare haemorrhagic disorder caused by autoantibodies directed against the functional epitopes of coagulation factor VIII (FVIII). Its management relies on prompt diagnosis, control of bleeding and eradication of the inhibitor by immunosuppression. China Acquired Hemophilia Registry (CARE), a nationwide multicentre registry, was intended to survey the status of AHA and standardize its diagnosis and therapy in China. One hundred and eighty-seven registered patients had an average age of 52 years. Diagnosis was delayed in 46·5% patients. There was a significant delay from diagnosis to immunosuppressive therapy in 68·3% patients. Bleeding control was significantly higher in patients treated with prothrombin complex concentrate (PCC) versus FVIII replacement therapy (84·6% vs. 34·4%; P < 0·001). Inhibitor eradication with a combination of steroids and cyclophosphamide showed a higher partial remission (PR) rate (92·2% vs. 70·3%) and stable complete remission (CR) rate (82·8% vs. 48·6%) than with steroids alone. Logistic regression model showed age and malignancy were significantly related to survival at final follow-up. The mean age for the survivors [51 years (IQR, 35-65 years)] was significantly lower than that of the non-survivors [79 years (IQR, 67-86 years)] (P < 0·001). Overall survival was higher in non-malignancy group than malignancy group (94·9% vs. 70%) (OR = 1·313; 95% CI, 0·913-1·889, P = 0·015).

Characterization of the B Cell Receptor Repertoire in the Intestinal Mucosa and of Tumor-Infiltrating Lymphocytes in Colorectal Adenoma and Carcinoma.

The B cells inhabited in mucosa play a vital role in mediating homeostasis with autoantigens and external Ags. Tumor-infiltrating lymphocytes are potential prognostic markers and therapeutic agents for cancer. However, the spatial heterogeneity of the B cell repertoire in intestinal mucosa and the tumor-infiltrating lymphocytes in colorectal cancer (CRC) remain poorly understood. In this study, we developed an unbiased method to amplify the IgH repertoire, as well as a bioinformatic pipeline to process these high-throughput sequencing data. With biopsies from seven intestinal mucosal segments, we uncovered their strong spatial homogeneity among the large intestine, where the clone overlap rate was up to 62.21%. The heterogeneity between terminal ileum and large intestine was also observed, including discrepant isotype distribution and low clone overlap rate. With tumor and adjacent normal mucosal tissues from CRC and colorectal advanced adenoma (AD) patients, we observed a similar IgH profile between tumor and adjacent normal mucosal tissues in AD, as well as a slight difference in CRC. Interestingly, we found distinct repertoire properties in the CRC tumor from AD and normal mucosa. Finally, we identified 1445 public clones for the normal mucosa, and 22 public clones for the CRC tumor with characteristic features. These data may be of potential use in clinical prognosis, diagnosis, and treatment of CRC.

Validation of fetal DNA fraction estimation and its application in noninvasive prenatal testing for aneuploidy detection in multiple pregnancies.

OBJECTIVE: To analyze the fetal fraction, fetal sex, and chromosomal aneuploidy in multiple pregnancies using noninvasive prenatal testing (NIPT). METHOD: A total of 362 pregnant women including 203 singleton pregnancies, 69 twins, and 90 higher-order multiple pregnancies were recruited. Fetal fractions estimated by size ratio-based and Y chromosome-based approaches in singleton pregnancies with male fetus were used as source data to establish the model. The model was then applied to multiple pregnancies for fetal fraction estimation. By comparing the fetal fractions estimated by size ratio to those estimated by Y chromosome or autosomal chromosomes, fetal sex and chromosomal aneuploidy can be analyzed. RESULTS: The size ratio-based approach has been well established in estimating fetal fractions for twin and higher-order multiple pregnancies. Fetal fraction had a positive correlation with gestational age in twin and triplet pregnancies. Fetal sex was determined with accuracies of 98.6% (95% CI, 92.19%-99.96%) in twins and 97.6% (95% CI, 91.76%-99.71%) in triplet pregnancies. Four trisomy 21, one trisomy 18, and one trisomy 13 cases were detected by NIPT. Two trisomy 21 singleton pregnancies and one trisomy 21 twin pregnancy were confirmed by karyotyping. CONCLUSION: Fetal sex and chromosomal aneuploidy in multiple pregnancies can be determined using NIPT.

Neonatal alloimmune thrombocytopenia caused by anti-HPA antibodies in pregnant Chinese women: a study protocol for a multicentre, prospective cohort trial.

BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT), caused by maternal antibodies raised against alloantigens carried on foetal platelets, is a very common haematological abnormality in newborns worldwide. However, baseline data on NAIT in China are lacking. Therefore, this study seeks to explore the incidence of alloantibody against the human platelet antigen (HPA) in pregnant women and its associations with NAIT in China. METHODS: A multicentre, prospective cohort study design will be used, and 55,497 pregnant women will be recruited for the first screening of the anti-HPA antibody at 12 to 28 weeks of gestational age. Subjects who are positive in the first screening for the anti-HPA antibody will be included in the exposure group. Re-tests of the antibody titre, antigen-specificity and genotyping of HPA and HLA will be conducted during admission. A ratio of 1:1 paired individuals with the same ethnicity and parity but testing negative for the anti-HPA antibody will be randomly selected to be included in the non-exposure group. NAIT will be diagnosed in the newborns on day one of the birth. The HPA of the neonates in the exposure group will also be genotyped by sequencing. Associations of maternal HLA with the occurrence of the anti-HPA antibody and correlation of the severity of NAIT with the titre of the anti-HPA antibody will be further analysed. DISCUSSION: The study is expected to provide baseline data on NAIT in China. Besides, we hope to find out a population who expresses particular HLA molecules has significant higher risk of HPA alloimmunization in Chinese individuals. We also hope to find a Chinese-specific cut-off antibody titre for the prediction of the severity of NAIT and to provide a means to evaluate the necessity of antenatal treatment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02934906 (date registered: 13.10.2016).

Residential greenspace counteracts PM2.5 on the risks of preterm birth subtypes: A multicenter study.

BACKGROUND: The association between residential greenspace and preterm birth (PTB) risk remained inconclusive. The PTB subtypes have been ignored and the effect of co-exposure of PM2.5 on PTB risk is still unclear. OBJECTIVE: To investigate the independent, interactive, and mixed effects of residential greenspace and PM2.5 on the risk of PTB subtypes. METHODS: A total of 19,900 singleton births from 20 hospitals in Shanghai, China, from 2015 to 2017 were included. The Normalized Difference Vegetation Index (NDVI) within 500 m and 1000 m buffers of the maternal residence and a combined geoscience-statistical model-derived PM2.5 and its six components were used as the exposure measures. PTB (<37 completed weeks of gestation) were divided into early PTB (24-33 weeks) vs. late PTB (34-36 weeks) and into spontaneous PTB (sPTB), preterm premature rupture of the fetal membranes (PPROM), and iatrogenic PTB. Multivariable logistic regression models were applied to assess the independent and interactive effects of NDVI and PM2.5 on PTB in each trimester. The quantile g-computation approach was employed to explore the mixture effect of PM2.5 components and greenspace across the pregnancy and to determine the main contributors. RESULTS: Levels of PM2.5 and greenspace were associated with increased [aOR (95%CI) ranging from 1.18 (1.07, 1.30) to 3.36 (2.45, 4.64)] and decreased risks [aORs (95%CI) ranging from 0.64 (0.53, 0.78) to 0.86 (0.73, 0.99)] of PTB subtypes, respectively. At the same PM2.5 level, higher residential greenspace was associated with lower risks, and vice versa. All these associations were more pronounced in late pregnancy. Early PTB and PPROM were the main affected subtypes, and the main drivers in PM2.5 were black carbon and ammonium. CONCLUSIONS: Residential greenspace may mitigate the PTB risks due to PM2.5 exposure during pregnancy.

In utero exposure to perfluoroalkyl substances and early childhood BMI trajectories: A mediation analysis with neonatal metabolic profiles.

BACKGROUND: In utero perfluoroalkyl substances (PFAS) exposure has been associated with childhood adiposity, but the mechanisms are poorly known. OBJECTIVE: To investigate the potential mediating role of neonatal metabolites in the relationship between prenatal PFAS exposure and childhood adiposity trajectories in the first four years of life. METHODS: We analyzed the data for 1671 mother-child pairs from the Shanghai Birth Cohort study. We included those with PFAS exposure information in early pregnancy, neonatal metabolites data and at least three child anthropometric measurements at 6, 12, 24 and/or 48 months. Body mass index (BMI) z-score trajectories were identified using latent class growth mixture modeling. The associations between PFAS concentrations and trajectory classes were assessed using multinomial logistic regression. Screening and penalization-based selection was used to identify neonatal amino acids and acylcarnitines with significant mediation effects. RESULTS: Three BMI z-score trajectories in early childhood were identified: a persistent increase trajectory (Class 1, 2.2 %), a stable trajectory (Class 2, 66 %), and a transient increase trajectory (Class 3, 32 %). Increased odds of being in Class 1 were observed in association with one log-unit increase in concentrations of perfluorooctane sulfonate (odds ratio [OR], 1.76 [95 % CI, 0.96-3.23], Class 2 as reference; OR, 2.36 [95 % CI, 1.27-4.40], Class 3 as reference), perfluorononanoic acid (OR, 1.90 [95 % CI, 0.97-3.72], Class 2 as reference; OR, 2.23 [95 % CI, 1.12-4.42], Class 3 as reference) and perfluorodecanoic acid (OR, 1.95 [95 % CI, 1.12-3.38], Class 2 as reference; OR, 2.14 [95 % CI, 1.22-3.76], Class 3 as reference). The effect of prenatal PFAS exposure on being in Class 1 was significantly but partly mediated by octanoylcarnitine (2.64 % for perfluorononanoic acid and 3.70 % for sum of 10 PFAS). CONCLUSIONS: In utero PFAS exposure is a risk factor for persistent growth in BMI z-score in early childhood. The alteration of neonatal acylcarnitines suggests a potential molecular pathway.

Comparison of joint status using ultrasound assessments and Haemophilia Joint Health Score 2.1 in children with haemophilia.

Introduction: Ultrasound (US) has gained popularity in the evaluation of haemophilic joint diseases because it enables the imaging of soft-tissue lesions in the joints and bone-cartilage lesions. We aimed to determine the correlation between US evaluations and clinical assessments performed using HJHS 2.1 and to evaluate their respective characteristics in assessing early haemophilic arthropathy. Methods: A total of 178 joints (32 knees, 85 elbows, and 61 ankles) in 45 haemophilia A patients (median age, 10 years; range, 6-15) were assessed using US and HJHS 2.1. Ultrasonographic scoring was performed in consensus assessments by one imager by using the US scores. Results: The total HJHS 2.1 and US scores showed a strong correlation (rS=0.651, P=0.000, CI: 0.553-0.763), with an excellent correlation for the elbows (rS=0.867, P=0.000, CI: 0.709-0.941) and a substantial correlation for the knees (rS=0.681, P=0.000, CI: 0.527-0.797). The correlation for the ankles was relatively moderate (rS=0.518, P=0.000, CI: 0.308-0.705). Nine subjects (15.5%) without abnormalities, as indicated by HJHS 2.1, showed haemophilic arthropathy in US scoring. All nine joints showed moderate (1/9) to severe (8/9) synovial thickening in the ankle (5/9) and elbow joints (4/9). In contrast, 50 joints (50.5%) showed normal US scores and abnormal changes as indicated by HJHS 2.1. S scores correlated well with HJHS 2.1 for overall and individual joints. Discussion: US could identify some early pathological changes in joints showing normal clinical findings, but still cannot replace the HJHS; however, it can serve as an imaging examination complementing HJHS 2.

Dietary Lactobacillus reuteri SL001 Improves Growth Performance, Health-Related Parameters, Intestinal Morphology and Microbiota of Broiler Chickens.

It was assumed that dietary inclusion of Lactobacillus reuteri SL001 isolated from the gastric contents of rabbits could act as an alternative to feed antibiotics to improve the growth performance of broiler chickens. We randomly assigned 360 one-day-old AA white-feathered chicks in three treatments: basal diet (control), basal diet plus zinc bacitracin (antibiotic), and basal diet plus L. reuteri SL001 (SL001) treatment. The results showed the total BW gain and average daily gain (ADG) of broilers in SL001 treatment increased significantly (p < 0.05, respectively) compared with the control group from day 0 to 42. Moreover, we observed higher levels of immune globulins in both the SL001 group and the antibiotic group. Total antioxidant capacity and levels of antioxidant factors were also significantly increased (p ≤ 0.05, respectively) in the SL001 treatment group, while the interleukin 6, interleukin 4, creatinine, uric acid, total cholesterol, triglyceride, VLDL, LDL and malondialdehyde were remarkably decreased (p < 0.05, respectively). In the ileum of SL001 treatment broilers, the height of villi and the ratio of villi height to crypt depth were significantly increased (p < 0.05). Meanwhile, the crypt depth reduced (p < 0.01) and the ratio of villi height to crypt depth increased (p < 0.05) in the jejunum compared to the control. The abundance of microbiota increased in the gut of broilers supplemented with SL001. Dietary SL001 significantly increased the relative abundance of Actinobacteria in the cecal contents of broilers (p < 0.01) at the phylum level. In conclusion, L. reuteri SL001 supplementation promotes the growth performance of broiler chickens and exhibits the potential application value in the industry of broiler feeding.

Epidemiology of placenta accreta spectrum disorders in Chinese pregnant women: A multicenter hospital-based study.

INTRODUCTION: Placenta accreta spectrum disorder (PASD) is a life-threatening obstetric complication. China still lacks high-quality data on the epidemiology of PASD. We intend to examine the major risk factors for PASD, explore the association of PASD with severe adverse perinatal outcomes and describe the geographical variations in China. METHODS: We used data from the China Labor and Delivery Survey, which included a total of 75,132 births from 96 hospitals in 24 provinces in China in 2015 and 2016. Each participating hospital randomly selected 6-10 weeks within a 12-month period. In the selected weeks, all births with gestational age ≥24 weeks or birth weight ≥500 g were included. We analyzed the demographic characteristics and prevalence of PASD in pregnant women. Multivariable logistic regression was used to examine the association of previous caesarean section (CS) and repeated surgical abortion with PASD. We explored the association of PASD with severe adverse perinatal outcomes, which indicated by Weighted Adverse Outcome Score (WAOS) ≥ 20. Multivariable logistic regression was used to examine the association of PASD with WAOS. We also calculated and compared the prevalence of PASD in different regions of China. RESULTS: The weighted prevalence of PASD was 2.20% (95% CI 0.76 to 4.95) in our population，and there was a substantial difference in the prevalence of PASD by geographic regions in China. Two or more previous CS (adjusted OR 2.34, 95%CI 1.41 to 3.88) and repeated surgical abortion (twice: 2.16, 1.20 to 3.92; 3 times: 4.31, 1.70 to 10.96; ≥4 times: 4.76, 3.12 to 7.26) were significant risk factors for PASD. PASD (adjusted OR 3.77, 95% CI 2.80 to 5.06) was a significant risk factor for severe adverse perinatal outcomes indicated by WAOS score. DISCUSSION: The prevalence of PASD in China appeared higher than that in other countries, and varied substantially by geographic regions. Two or more previous CS and repeated surgical abortion were major risk factors for PASD. Pregnant women with PASD had more severe adverse pregnancy outcomes. Reducing primary cesarean section and repeated surgical abortion are the key to decreasing PASD.

[The RHD zygosity in Dong ethnic population in the southeast area of Guizhou province].

OBJECTIVE: To investigate the RHD zygosity distribution and the genetic characteristics of RHD gene in the Dong ethnic population in southeast area of Guizhou province. METHODS: Based on the characteristics of Chinese RHD and the RHD specific deletion, two pairs of primers specific for hybrid Rhesus box and exon 1 of RHD respectively, were designed, combined with a pair of internal control primers. Polymerase chain reaction was performed to genotype the samples. RESULTS: In the 292 RhD positive samples, 58 (19.86%) were RHD+/RHD- heterozygotes, and the others (80.14%) were RHD+/RHD+ homozygotes. In the 9 D negative samples, 5 were RHD+/RHD- heterozygotes (2 weak D, 3 Del), 3 were RHD+/RHD+ homozygotes (1weak D, 2 Del), and 1 was RHD-/RHD- homozygote. CONCLUSION: RHD+/RHD- heterozygosity is higher (19.86%) in D positive individuals of Dong ethnic group in Guizhou province than that in other areas; RHD gene heterozygosity is also high in the D negative individuals in this ethnic group.

Potentiated antimicrobial blue light killing of methicillin resistant Staphylococcus aureus by pyocyanin.

As antimicrobial resistance continues to threaten the efficacy of conventional antibiotic therapy, it is paramount that we investigate innovative approaches to treat infectious diseases. In this study, we investigated the antimicrobial capabilities of the innovative combination of antimicrobial blue light (aBL; 405 nm wavelength) with the Pseudomonas aeruginosa pigment pyocyanin against methicillin resistant Staphylococcus aureus (MSRA. We explored the effects of different radiant exposures of aBL and increasing concentrations of pyocyanin against planktonic cells and those within biofilms. In addition, we investigated the effect of the aBL/pyocyanin on the endogenous staphyloxanthin pigment, as well as the role of hydrogen peroxide and singlet oxygen scavenging in the efficacy of this combination. Lastly, we investigated the potential for the aBL/pyocyanin to reduce the MRSA burden within a proof-of-principle mouse abrasion infection model. We found pyocyanin to be a powerful potentiator of aBL activity under all in vitro conditions tested. In addition, we serendipitously discovered the capability of the aBL/pyocyanin combination to bleach staphyloxanthin within colonies of MRSA. Furthermore, we established that singlet oxygen is an important mediator during combined aBL/pyocyanin exposure. Moreover, we found that the combination of aBL and pyocyanin could significantly reduce the viability of MRSA within a proof-of-principle early onset MRSA skin abrasion infection. Exposure to the treatment did not have deleterious effects on skin tissue. In conclusion, the combination of aBL and pyocyanin represents a potentially powerful therapeutic modality for the treatment of infections caused by MRSA.