Analysis of the Relationship Between the Changes of Serum SAA, LP-PLA2, sCD40L and Carotid Atherosclerosis Plaque in Patients with Acute Cerebral Infarction.

Objective: To explore the relationship between Serum amyloid protein A(SAA), lipoprotein-associated Phospholipase A2 (Lp-PLA2) and soluble CD40 ligand (sCD40L) in detecting the stability of carotid Atherosclerosis plaque. Methods: We examined 90 patients admitted to our hospital with acute cerebral infarction from July 2020 to December 2022. Carotid artery ultrasounds were performed for all of them. These patients were then divided into two groups: the stable plaque group (45 cases) and the unstable plaque group (45 cases), based on the ultrasound results. Additionally, we included a control group of 30 healthy individuals from our hospital. We collected fasting blood samples from the patients upon admission and used enzyme-linked immunosorbent assays to measure the mass concentrations of sCD40L, Lp-PLA2, and SAA in their serum. The results of these biomarkers were compared and analyzed to assess potential associations with plaque stability in patients with cerebral infarction. Results: Comparison of general clinical data and laboratory data: except for High-density lipoprotein, there was a statistical difference between the control group and the cerebral infarction group (P < .05), there was no statistical difference in gender, smoking history, drinking history and age (P > .05). Compared with the control group, the mass concentrations of sCD40L, Lp-PLA2, and SAA in patients with stable and unstable plaques increased significantly (P < .05); Compared with the stable plaque group, the mass concentrations of sCD40L, Lp-PLA2, and SAA in unstable plaque patients increased with statistical significance (P < .05). Correlation analysis shows that the mass concentrations of sCD40L, Lp-PLA2, and SAA are positively correlated with the stability of carotid artery plaques. SCD40L, Lp-PLA2 and SAA have certain diagnostic significance in the subject's working characteristic curve (Receiver operating characteristic) as a marker molecule for the diagnosis of unstable plaque. sCD40L (AUC=0.883) has more diagnostic value than SAA (AUC=0.756) and Lp-PLA2 (AUC=0.826). A binary logistic regression analysis was conducted using the stability of carotid artery plaques as the dependent variable and sCD40L, Lp-PLA2, and SAA as independent variables. The results showed that elevated serum sCD40L, Lp-PLA2, and SAA were independent risk factors for unstable carotid artery plaques (P < .05). Conclusion: The concentrations of sCD40L, Lp-PLA2 and SAA are closely related to the formation and type of carotid Atherosclerosis plaque in patients with acute cerebral infarction. This has potentially important clinical implications for the management and prevention of cardiovascular disease.

Utility of isolated-check visual evoked potential technique in dysthyroid optic neuropathy.

PURPOSE: To analyze the utility of isolated-check visual evoked potential (icVEP) for discriminating between eyes with dysthyroid optic neuropathy (DON) and eyes with thyroid-associated ophthalmopathy (TAO) but not DON. METHODS: Forty-three eyes with TAO but not DON (as non-DON), fifty-three eyes with DON, and sixty healthy eyes (as controls) were included. Comprehensive ophthalmic examinations, including best-corrected visual acuity, refraction, color vision test, intraocular pressure measurement, slit-lamp biomicroscopy, ophthalmoscopy, RAPD, exophthalmometry measurements, pVEP test, icVEP test, standard automated perimetry, and clinical activity score classification of TAO, as well as demographic information, were collected and analyzed. RESULTS: In the DON group, the signal-to-noise ratio (SNR) value of icVEPs decreased significantly compared with that of the non-DON group as well as control (p < 0.05). The SNR values under 8%, 16% and 32% depth of modulation (DOM) were significantly negatively correlated with BCVA (p < 0.05, r = - 0.9 ~ - 0.6), papilledema (Y/N) (p < 0.05, r = - 0.8 ~ 0.4) and DON (Y/N) (p < 0.001, r = - 0.7 ~ - 0.5). The 8% DOM of icVEP had the largest area under the receiver operating characteristic curve (AUC) (0.842) for discriminating DON from non-DONs. Meanwhile, decision curve analysis (DCA) showed that patients clinically benefit most from 8% DOM of icVEP. Furthermore, the 8% DOM of icVEP combing with papilledema (Y/N) and BCVA (Model 1) has significantly larger AUC than the 8% DOM of icVEP (p = 0.0364), and has better clinical benefit in DCA analysis. CONCLUSIONS: The SNR of 8% DOM from icVEP may represent a significant ancillary diagnostic method for DON detection. Furthermore, icVEP combined with papilledema (Y/N) and BCVA should be considered as a diagnostic model in future clinical practice.

Changes in the gut microbiota of patients with Graves' orbitopathy according to severity grade.

BACKGROUND: To explore the changes of gut microbiota in Graves' orbitopathy (GO) patients of different severity grades and to identify the pathogenic bacteria of GO and the associated mechanism. METHODS: A total of 18 healthy controls and 62 GO patients were recruited. The baseline information and faecal samples of all subjects were collected for gut microbiota analysis and metabolic function prediction analysis. 16SrDNA sequencing was used for microbial diversity detection. The operational taxonomic unit (OTU) was divided using the Mothur software, and the dominant microbiota was analysed. OTU number, Chao1 index, ACE index, and Shannon index of microbiota in faecal samples were analysed using the QIIME1.9.0 software. The relative abundance of microbiota in faecal samples was analysed through principal component analysis (PCA) using the Canoco Software 5.0. The metabolic function of microbiota in faecal samples was predicted using PICRUSt 2.0. RESULTS: There was no remarkable difference in gut microbiota diversity between groups; however, the gut microbial community and dominant microbiota significantly differed among groups. Klebsiella_pneumoniae was deemed the potentially pathogenic bacteria of GO, and its abundance was positively correlated with disease severity. The metabolic prediction results revealed that inorganic nutrition metabolism, fatty acid and lipid degradation, electron transfer, aromatic compound degradation, and alcohol degradation were notably different between groups with high and low abundance of Klebsiella_pneumoniae and among groups with different GO severity grades, thereby showing a positive correlation with GO clinical risks. CONCLUSIONS: Klebsiella_pneumoniae was a potential GO-related pathogen, which may regulate the metabolic pathways to affect GO progression.

Subacute exposure to dechlorane 602 dysregulates gene expression and immunity in the gut of mice.

Dechlorane 602 (Dec 602) has biomagnification potential. Our previous studies suggested that exposure to Dec 602 for 7 days induced colonic inflammation even after 7 days of recovery. To shed some light on the underlying mechanisms, disturbances of gut immunity and gene expression were further studied. Adult C57BL/6 mice were administered orally with Dec 602 for 7 days, then allowed to recover for another 7 days. Colonic type 3 innate lymphoid cells (ILC3s) in lamina propria lymphocytes (LPLs) and lymphocytes in mesenteric lymph nodes (MLNs) were examined by flow cytometry. Expressions of genes in the gut were determined by RNA-Seq. It was found that Dec 602 exposure up-regulated the percentage of CD4+ T cells in MLNs. The mean fluorescent intensity (MFI) of interleukin (IL)- 22 in LPLs was decreased, while the MFI of IL-17a as well as the percentage of IL-17a+ ILC3s in LPLs were increased after exposure to Dec 602. Genes involved in the formation of blood vessels and epithelial-mesenchymal transition were up-regulated by Dec 602. Ingenuity pathway analysis of differentially expressed genes predicted that exposure to Dec 602 resulted in the activation of liver X receptor/retinoid X receptor (LXR/RXR) and suppression of muscle contractility. Our results, on one hand, verified that the toxic effects of Dec 602 on gut immunity could last for at least 14 days, and on the other hand, these results predicted other adverse effects of Dec 602, such as muscle dysfunction. Overall, our studies provided insights for the further investigation of Dec 602 and other emerging environmental pollutants.

Myeloid-derived suppressor cells improve corneal graft survival through suppressing angiogenesis and lymphangiogenesis.

Myeloid-derived suppressor cells (MDSC) are one of the major negative regulators of immune responses during many pathological conditions such as cancer and transplantation. Emerging evidence indicates that MDSC also contribute to tumor progression through their pro-angiogenic activity in addition to immunosuppressive function. However, virtually nothing is known about the role of MDSC in the regulation of neovascularization after transplantation. Here we showed that antibody-mediated depletion of MDSC in mice led to robust growth of blood and lymphatic neovessels and rapid allograft rejection after corneal penetrating keratoplasty. In contrast, adoptive transfer of ex vivo generated MDSC from cytokine-treated bone marrow cells (evMDSC) suppressed neovascularization and prolonged corneal allograft survival in an inducible nitric oxide synthase (iNOS)-dependent manner. Mechanistically, compared to naïve MDSC control, evMDSC have increased expression of an anti-angiogenic factor thrombospondin 1 (Tsp-1) and decreased expression of two critical pro-angiogenic factors, vascular endothelial growth factor A (VEGF-A), and VEGF-C. These findings demonstrate MDSC as a critical anti-angiogenic regulator during transplantation. Our study also indicates that evMDSC are a valuable candidate agent for development of novel cell therapy to improve allograft survival after transplantation.

CircCDC45 promotes the malignant progression of glioblastoma by modulating the miR-485-5p/CSF-1 axis.

BACKGROUND: Glioblastoma (GBM) is characterized by progressive growth and metastasis. Numerous studies claim that the deregulation of circular RNAs (circRNAs) is associated with cancer progression. However, the role of circRNAs in GBM is largely limited. The purpose of this study was to investigate the functions of circCDC45 in GBM and provide a feasible functional mechanism to support its role. METHODS: The expression of circCDC45, miR-485-5p and colony-stimulating factor 1 (CSF-1) mRNA was examined using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed using cell counting kit - 8 (CCK-8) assay and colony formation assay. Cell migration and cell invasion were monitored using transwell assay. The protein levels of proliferation-related markers and CSF-1 were determined using western blot. The target relationship was predicted using bioinformatics tools and validated using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Animal models were constructed to verify the role of circCDC45 in vivo. RESULTS: The expression of circCDC45 and CSF-1 was elevated in GBM tissues and cells, while the expression of miR-485-5p was declined. Downregulation of circCDC45 or CSF-1 blocked GBM cell proliferation, invasion and migration as well as tumor growth in vivo. In mechanism, circCDC45 positively regulated the expression of CSF-1 by targeting miR-485-5p. Inhibition of miR-485-5p reversed the biological effects caused by circCDC45 downregulation in GBM cells. CONCLUSION: CircCDC45 promoted the progression of GBM by mediating the miR-485-5p/CSF-1 axis, and circCDC45 might be a promising plasmatic biomarker for GBM diagnosis and treatment.

Predictive Value of Insulin Resistance as Determined by Homeostasis Model Assessment in Acute Ischemic Stroke Patients: A Systematic Review and Meta-Analysis.

Studies on association between homeostasis model assessment of insulin resistance (HOMA-IR) and adverse outcomes have yielded conflicting results in patients with acute ischemic stroke (AIS). This meta-analysis aimed to assess the predictive value of HOMA-IR in AIS patients. Two authors comprehensively searched PubMed and Embase databases until February 28, 2021. All observational studies investigating the association between HOMA-IR and adverse outcomes in AIS patients were included. Outcome measures were poor functional outcome (Modified Rankin Scale≥3), all-cause mortality, stroke recurrence, and neurologic worsening. Seven studies (eight articles) involving 8330 AIS patients were identified. For the highest versus lowest HOMA-IR, the pooled risk ratio (RR) of poor functional outcome was 2.55 (95% CI 1.76-3.70) after adjustment of conventional confounding factors. In addition, elevated HOMA-IR was associated with higher risk of neurologic worsening (RR 1.93; 95% CI 1.15-3.26). However, there were conflicting findings on the association of HOMA-IR with stroke recurrence and all-cause mortality. This meta-analysis confirms that HOMA-IR is significantly associated with an increased risk of poor functional outcome in patients with AIS. However, interpretation of the results of mortality, stroke recurrence, and neurologic worsening should be done with caution due to small number of studies available.

Chlorinated Flame-Retardant Dechlorane 602 Potentiates Type 2 Innate Lymphoid Cells and Exacerbates Airway Inflammation.

Chlorinated flame-retardant dechloranes are emerging substitutes for restricted flame retardants. Recent studies have demonstrated that they are accumulated in wildlife and detectable in humans; however, their effects on human health are poorly understood. Here, for the first time, we revealed that widely used chlorinated flame-retardant dechlorane 602 (Dec 602) exacerbated airway inflammation in two mouse models induced by house dust mite (HDM) or IL-33, respectively. Deteriorated airway inflammation by Dec 602 was associated with a higher production of type 2 cytokines including IL-4, IL-5, and IL-13, and IgE, accompanied by enhanced mRNA expression of proinflammatory cytokines such as TNF-α and IL-6. Mechanistically, we found that Dec 602 directly potentiated mouse and human group 2 innate lymphoid cells and, as such, promoted airway inflammation even in the absence of conventional T cells in Rag -/- mice. These findings provide novel immunological insights necessary for further studies of the health impact of emerging flame-retardant dechloranes including Dec 602.

Adaptation of an Obstetric Anesthesia Service for the Severe Acute Respiratory Syndrome Coronavirus-2 Pandemic: Description of Checklists, Workflows, and Development Tools.

BACKGROUND: Care of the pregnant patient during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic presents many challenges, including creating parallel workflows for infected and noninfected patients, minimizing waste of materials, and ensuring that clinicians can seamlessly transition between types of anesthesia. The exponential community spread of disease limited the time for development and training. METHODS: The goals of our workflow and process development were to maximize safety for staff and patients, minimize the risk of contamination, and reduce the waste of unused supplies and materials. We used a cyclical improvement system and the plus/delta debriefing method to rapidly develop workflows consisting of sequential checklists and procedure-specific packs. RESULTS: We designed independent workflows for labor analgesia, neuraxial anesthesia for cesarean delivery, conversion of labor analgesia to cesarean anesthesia, and general anesthesia. In addition, we created procedure-specific material packs to optimize supplies and prevent wastage. Finally, we generated sequential checklists to allow staff to perform standard operating procedures without extensive training. CONCLUSIONS: Collectively, these workflows and tools allowed our staff to urgently care for patients in high-risk situations without prior experience. Over time, we refined the workflows using a cyclical improvement system. We present our checklists and workflows as well as the system we used for their development, so that others may use them to their benefit.

Rapid Cycle Implementation and Retrospective Evaluation of a SARS-CoV-2 Checklist in Labor and Delivery.

BACKGROUND: Preparedness efforts for a COVID-19 outbreak required redesign and implementation of a perioperative workflow for the management of obstetric patients. In this report we describe factors which influenced rapid cycle implementation of a novel comprehensive checklist for the perioperative care of the COVID-19 parturient. METHODS: Within our labour and delivery unit, implementation of a novel checklist for the COVID-19 parturient requiring perioperative care was accomplished through rapid cycling, debriefing and on-site walkthroughs. Post-implementation, consistent use of the checklist was reported for all obstetric COVID-19 perioperative cases (100% workflow checklist utilization). Retrospective analysis of the factors influencing implementation was performed using a group deliberation approach, mapped against the Consolidated Framework for Implementation Research (CFIR). RESULTS: Analysis of factors influencing implementation using CFIR revealed domains of process implementation and innovation characteristics as overwhelming facilitators for success. Constructs within the outer setting, inner setting, and characteristic of individuals (external pressures, baseline culture, and personal attributes) were perceived to act as early barriers. Constructs such as communication culture and learning climate, shifted in influence over time. CONCLUSION: We describe the influential factors of implementing a novel comprehensive obstetric workflow for care of the COVID-19 perioperative parturient during the first surge of the pandemic using the CFIR framework. Early workflow adoption was facilitated primarily by two domains, namely thoughtful innovation design and careful implementation planning in the setting of a long-standing culture of improvement. Factors initially assessed as barriers such as communication, culture and learning climate, transitioned into facilitators once a perceived benefit was experienced by healthcare teams. These results provide important information for the implementation of rapid change during a time of crisis.

Extensive serum biomarker analysis before and after treatment in healing of diabetic foot ulcers using a cytokine antibody array.

Diabetic foot ulcers (DFU) remain a serious public health problem. However, the current evaluation and confirmation of the efficacy of DFU is unclear. The present study aimed to measure the alterations of circulating proteins in patients after DFU healing for the exploration of the prognostic biomarkers. The serum cytokine profiles of DFU patients before and after treatment were analyzed by a human antibody microarray technology using diabetic patients and healthy population as control groups. The results showed that ten differential cytokines were associated with DFU healing. Among these ten cytokines, comparing to DFU group, nine ones (Jagged-1, CD14, Cathepsin S, Syndecan 4, MDC, TARC, Angiopoietin-4, Clusterin and HGFR) were significantly up-regulated in DFU-treated group and Follistatin-like 1 was significantly down-regulated, while their levels in DFU-treated group showed no significant differences from those in control groups. Furthermore, ELISA validation also showed that compares to DFU group four of ten (MDC, TARC, Clusterin, and Syndecan 4) were increased in DFU-treated group equal to the levels in control groups, consistent with the array results. Our finding shows that these four cytokines may have great potential for prognostic evaluation of DFU healing.

Ventilatory frequency during intraoperative mechanical ventilation and postoperative pulmonary complications: a hospital registry study.

BACKGROUND: High ventilatory frequencies increase static lung strain and possibly lung stress by shortening expiratory time, increasing intrathoracic pressure, and causing dynamic hyperinflation. We hypothesised that high intraoperative ventilatory frequencies were associated with postoperative respiratory complications. METHODS: In this retrospective hospital registry study, we analysed data from adult non-cardiothoracic surgical cases performed under general anaesthesia with mechanical ventilation at a single centre between 2005 and 2017. We assessed the association between intraoperative ventilatory frequency (categorised into four groups) and postoperative respiratory complications, defined as composite of invasive mechanical ventilation within 7 days after surgery or peripheral oxygen desaturation after extubation, using multivariable logistic regression. In a subgroup, we adjusted analyses for arterial blood gas parameters. RESULTS: A total of 102 632 cases were analysed. Intraoperative ventilatory frequencies ranged from a median (inter-quartile range [IQR]) of 8 (8-9) breaths min-1 (Group 1) to 15 (14-18) breaths min-1 (Group 4). High ventilatory frequencies were associated with higher odds of postoperative respiratory complications (adjusted odds ratio=1.26; 95% confidence interval, 1.14-1.38; P<0.001), which was confirmed in a subgroup after adjusting for arterial partial pressure of carbon dioxide and the ratio of arterial oxygen partial pressure to fractional inspired oxygen. We identified considerable variability in the use of high ventilatory frequencies attributable to individual provider preference (ranging from 22% to 88%) and temporal change; however, the association with postoperative respiratory complications remained unaffected. CONCLUSIONS: High intraoperative ventilatory frequency was associated with increased risk of postoperative respiratory complications, and increased postoperative healthcare utilisation.

Characterization of the Aryl Hydrocarbon Receptor (AhR) Pathway in Anabas testudineus and Mechanistic Exploration of the Reduced Sensitivity of AhR2a.

Field investigations have revealed the ability of the climbing perch Anabas testudineus to survive in highly contaminated water bodies. The aryl hydrocarbon receptor (AhR) pathway is vital in mediating the toxicity of aromatic hydrocarbon contaminants, and genotypic variation in the AhR can confer resistance to these contaminants. Thus, we characterized the AhR pathway in A. testudineus in order to understand the mechanism(s) underlying the resistance of this species to contaminants and to broaden current knowledge on teleost AhR. In A. testudineus, four AhRs, two AhR nuclear translocators (ARNTs), and one AhR repressor (AhRR) were found. Transient transfection assays revealed that AhR1a, AhR1b, and AhR2b were functional, whereas AhR2a was poorly activated by the potent agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Two ARNTs (partner of AhR) and one AhRR (repressor of AhR) all were functional with each of the active AhR. As a major form, the insensitivity of AhR2a might serve as a potential mechanism for A. testudineus' reduced sensitivity to severe contamination. We explored the key residues that may account for AhR2a's insensitivity in silico and then functionally validated them in vitro. Two sites (VCS322-324, M370) in its ligand-binding domain (LBD) were proved critical for its sensitivity to TCDD. This systematic exploration of the AhR pathway showed that most members have maintained their traditional functions as expected, whereas a nonfunctionalization event has occurred for AhR2a.

Sufentanil Alleviates Intrathecal Lidocaine Induced Prolonged Sensory and Motor Impairments but not the Spinal Histological Injury in Rats.

Spinal anesthesia has evolved into a safe and widely accepted method of anesthesia. Synergy between opioids and local anesthetics further increases the quality of analgesia and decreases the dose requirement of both local anesthetics and opioids. However, over the last decades compelling evidence suggested that lidocaine could be more neurotoxic than other commonly used local anesthetics. Whether opioids can modify the local anesthetics-induced neurotoxicity is largely unexplored. Here, we investigated the effect of sufentanil on the neurotoxicity induced by intrathecal lidocaine in a rat model. Our data showed that 5 µg/ml sufentanil didn't deteriorate nor reduce the histopathological injuries induced by intrathecal application of 10% lidocaine in a rat model. However, it did alleviate sensory and motor function impairments induced by 10% lidocaine. Repeated intrathecal injection of 5 µg/ml sufentanil also decreased the paw withdraw threshold compared to the baseline. An increase in expression of activating transcription factor 3, a stress response gene, as a marker for injured neurons, was also detected in lidocaine-induced neurotoxicity, while 5 µg/ml sufentanil inhibited lidocaine-induced the upregulation of activating transcription factor 3. These results suggest that sufentanil alleviates lidocaine induced sensory and motor impairments, and did not worsen histopathological injury induced by intrathecal lidocaine.

Dioxin induces expression of hsa-miR-146b-5p in human neuroblastoma cells.

Dioxin can cause a series of neural toxicological effects. MicroRNAs (miRs) play important roles in regulating nervous system function and mediating cellular responses to environmental pollutants, such as dioxin. Hsa-miR-146b-5p appears to be involved in neurodegenerative diseases and brain tumors. However, little is known about effects of dioxin on the expression of hsa-miR-146b-5p. We found that the hsa-miR-146b-5p expression and its promoter activity were significantly increased in dioxin treated SK-N-SH cells, a human-derived neuroblastoma cell line. Potential roles of hsa-miR-146b-5p in mediating neural toxicological effects of dioxin may be due to the regulation of certain target genes. We further confirmed that hsa-miR-146b-5p significantly suppressed acetylcholinesterase (AChE) activity and targeted the 3'-untranslated region of the AChE T subunit, which has been down-regulated in dioxin treated SK-N-SH cells. Functional bioinformatic analysis showed that the known and predicted target genes of hsa-miR-146b-5p were involved in some brain functions or cyto-toxicities related to known dioxin effects, including synapse transmission, in which AChE may serve as a responsive gene for mediating the effect.

[Study on biocompatibility of carbon-based composites].

Silicon carbide (SiC) film and silicon dioxide (SiO 2) film were deposited on the surface of carbon/carbon composite (C/C) by low pressure chemical vapor deposition (LPCVD). The biocompatibility of the three carbon-based composites, e. g. C/C, C/C-SiC, C/C-SiO 2 were investigated by cytotoxicity test, cell direct contact and cell adhesion experiments. Cytotoxicity, cell direct contact and cell adhesion showed that the three materials had no toxic effect on mouse fibroblasts (L929 cells). However, the particles dropped off from the three materials had a great impact on evaluation accuracy of the thiazolyl blue (MTT) test. More the particles were lost, more growth inhibition to L929 cells. The evaluation accuracy of MTT method can be kept with the filtered extract of materials. Furthermore, the results of surface particles shedding experiment showed that the amount of surface particles shed from C/C-SiO 2 was the most, followed by C/C and C/C-SiC in 72 hours. Particles shedding curves showed there was a peak reached at eighth hour and then declined to the thirty-sixth hour. The filtrate analysis showed that there was no ion exchange between the three materials and simulated body fluid (SBF) solution. The results of this study on biocompatibility of carbon-based composites have certain guiding significance for their future application in clinical filed.

A novel NHS mutation causes Nance-Horan Syndrome in a Chinese family.

BACKGROUND: Nance-Horan Syndrome (NHS) (OMIM: 302350) is a rare X-linked developmental disorder characterized by bilateral congenital cataracts, with occasional dental anomalies, characteristic dysmorphic features, brachymetacarpia and mental retardation. Carrier females exhibit similar manifestations that are less severe than in affected males. METHODS: Here, we report a four-generation Chinese family with multiple affected individuals presenting Nance-Horan Syndrome. Whole-exome sequencing combined with RT-PCR and Sanger sequencing was used to search for a genetic cause underlying the disease phenotype. RESULTS: Whole-exome sequencing identified in all affected individuals of the family a novel donor splicing site mutation (NM_198270: c.1045 + 2T > A) in intron 4 of the gene NHS, which maps to chromosome Xp22.13. The identified mutation results in an RNA processing defect causing a 416-nucleotide addition to exon 4 of the mRNA transcript, likely producing a truncated NHS protein. CONCLUSIONS: The donor splicing site mutation NM_198270: c.1045 + 2T > A of the NHS gene is the causative mutation in this Nance-Horan Syndrome family. This research broadens the spectrum of NHS gene mutations, contributing to our understanding of the molecular genetics of NHS.

No Pain Labor & Delivery: A Global Health Initiative's Impact on Clinical Outcomes in China.

The availability of labor analgesia is highly variable in the People's Republic of China. There are widespread misconceptions, by both parturients and health care providers, that labor epidural analgesia is harmful to mother and baby. Meanwhile, China has one of the highest cesarean delivery rates in the world, exceeding 50%. The goal of the nongovernmental No Pain Labor & Delivery (NPLD) is to facilitate sustainable increases in vaginal delivery rates by increasing access to safe neuraxial labor analgesia, thereby decreasing the cesarean delivery rate. NPLD was launched in 2008 with the stated goal of improving labor outcome in China by increasing the absolute labor epidural analgesia rate by 10%. NPLD established 10 training centers over a 10-year period. We hypothesized that increased availability of labor analgesia would result in reduced requests for cesarean delivery and better labor outcomes for mother and baby. Multidisciplinary teams of Western clinicians and support staff traveled to China for 8 to 10 days once a year. The approach involved establishing 24/7 obstetric anesthesia coverage in Chinese hospitals through education and modeling multidisciplinary approaches, including problem-based learning discussions, bedside teaching, daily debriefings, simulation training drills, and weekend conferences. As of November 2015, NPLD has engaged with 31 hospitals. At 24 of these sites, 24/7 obstetric anesthesia coverage has been established and labor epidural analgesia rates have exceeded 50%. Lower rates of cesarean delivery, episiotomy, postpartum blood transfusion, and better neonatal outcomes were documented in 3 impact studies comprising approximately 55,000 deliveries. Changes in practice guidelines, medical policy, and billing codes have been implemented in conjunction with the modernization of perinatal practice that has occurred concurrently in China since the first NPLD trip in 2008.