[A quality improvement project on reducing antibiotic use duration in very low birth weight preterm infants in the neonatal intensive care unit]. / é™ä½Žæ–°ç”Ÿå„¿é‡ç—‡ç›‘æŠ¤å®¤æžä½Žå‡ºç”Ÿä½“é‡æ—©äº§å„¿æŠ—ç”Ÿç´ ä½¿ç”¨æ—¶é—´çš„è´¨é‡æ”¹è¿›ç ”ç©¶.

OBJECTIVES: To develop effective measures to reduce antibiotic use duration in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit through quality improvement methods. METHODS: The study population consisted of hospitalized VLBW preterm infants, with the percentage of hospitalization time during which antibiotics were used from November 2020 to June 2021 serving as the baseline. The specific quality improvement goal was to reduce the duration of antibiotic use. Factors affecting antibiotic use duration in preterm infants were analyzed using Pareto charts. Key drivers were identified, and specific interventions were formulated based on the stages of antibiotic use. Changes in the percentage of antibiotic use duration were monitored with run charts until the quality improvement target was achieved. RESULTS: From November 2020 to June 2021, the baseline antibiotic use duration percentage was 49%, with a quality improvement target to reduce this by 10% within 12 months. The Pareto analysis indicated that major factors influencing antibiotic duration included non-standard antibiotic use; delayed cessation of antibiotics when no infection evidence was present; prolonged central venous catheter placement; insufficient application of kangaroo care; and delayed progress in enteral nutrition. The interventions implemented included: (1) establishing sepsis evaluation and management standards; (2) educating medical staff on the rational use of antibiotics for preterm infants; (3) supervising the enforcement of antibiotic use standards during ward rounds; (4) for those without clear signs of infection and with negative blood cultures, discontinued the use of antibiotics 36 hours after initiation; (5) reducing the duration of central venous catheterization and parenteral nutrition to lower the risk of infection in preterm infants. The control chart showed that with continuous implementation of interventions, the percentage of antibiotic use duration was reduced from 49% to 32%, a statistically significant decrease. CONCLUSIONS: The application of quality improvement tools based on statistical principles and process control may significantly reduce the antibiotic use duration in VLBW preterm infants. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 736-742.

Metformin alleviates benzo[a]pyrene-induced alveolar injury by inhibiting necroptosis and protecting AT2 cells.

Exposure to benzo[a]pyrene (B[a]P) has been linked to lung injury and carcinogenesis. Airway epithelial cells express the B[a]P receptor AHR, so B[a]P is considered to mainly target airway epithelial cells, whereas its potential impact on alveolar cells remains inadequately explored. Metformin, a first-line drug for diabetes, has been shown to exert anti-inflammatory and tissue repair-promoting effects under various injurious conditions. Here, we explored the effect of chronic B[a]P exposure on alveolar cells and the impact of metformin on B[a]P-induced lung injury by examining the various parameters including lung histopathology, inflammation, fibrosis, and related signal pathway activation. MLKL knockout (Mlkl-/-) and AT2-lineage tracing mice (SftpcCre-ERT2;LSL-tdTomatoflox+/-) were used to delineate the role of necroptosis in B[a]P-induced alveolar epithelial injury and repair. Mice receiving weekly administration of B[a]P for 6 weeks developed a significant alveolar damaging phenotype associated with pulmonary inflammation, fibrosis, and activation of the necroptotic cell death pathway. These effects were significantly relieved in MLKL null mice. Furthermore, metformin treatment, which were found to promote AMPK phosphorylation and inhibit RIPK3, as well as MLKL phosphorylation, also significantly alleviated B[a]P-induced necroptosis and lung injury phenotype. However, the protective efficacy of metformin was rendered much less effective in Mlkl null mice or by blocking the necroptotic pathway with RIPK3 inhibitor. Our findings unravel a potential protective efficacy of metformin in mitigating the detrimental effects of B[a]P exposure on lung health by inhibiting necroptosis and protecting AT2 cells.

SPAUTIN-1 alleviates LPS-induced acute lung injury by inhibiting NF-κB pathway in neutrophils.

BACKGROUND: Acute lung injury (ALI) is an inflammatory condition characterized by acute damage to lung tissue. SPAUTIN-1, recognized as a small molecule drug targeting autophagy and USP10/13, has been reported for its potential to inhibit oxidative stress damage in various tissue injuries. However, the role and mechanism of SPAUTIN-1 in ALI remain unclear. This study aims to elucidate the protective effects of SPAUTIN-1 on ALI, with a particular focus on its role and mechanism in pulmonary inflammatory responses. METHODS: Lipopolysaccharides (LPS) were employed to induce inflammation-mediated ALI. Bleomycin was used to induce non-inflammation-mediated ALI. The mechanism of SPAUTIN-1 action was identified through RNA-Sequencing and subsequently validated in mouse primary cells. Tert-butyl hydroperoxide (TBHP) was utilized to create an in vitro model of lung epithelial cell oxidative stress with MLE-12 cells. RESULTS: SPAUTIN-1 significantly mitigated LPS-induced lung injury and inflammatory responses, attenuated necroptosis and apoptosis in lung epithelial cells, and inhibited autophagy in leukocytes and epithelial cells. However, SPAUTIN-1 exhibited no significant effect on bleomycin-induced lung injury. RNA-sequencing results demonstrated that SPAUTIN-1 significantly inhibited the NF-κB signaling pathway in leukocytes, a finding consistently confirmed by mouse primary cell assays. In vitro experiments further revealed that SPAUTIN-1 effectively mitigated oxidative stress injury in MLE-12 cells induced by TBHP. CONCLUSION: SPAUTIN-1 alleviated LPS-induced inflammatory injury by inhibiting the NF-κB pathway in leukocytes and protected epithelial cells from oxidative damage, positioning it as a potential therapeutic candidate for ALI.

[Analysis of acupoints selection rules and efficacy evaluation of acupuncture and moxibustion for allergic rhinitis].

OBJECTIVE: To explore the rules of acupoints selection of acupuncture and moxibustion in the treatment of allergic rhinitis (AR) by using data mining technology, as well as to compare the efficacy of different acupoints selection methods. METHODS: Papers about acupuncture and moxibustion for treating AR published from January 2002 to August 2022 was retrieved from Chinese and English databases including CNKI, Wanfang, VIP, SinoMed and PubMed by using keywords of "acupuncture", "moxibustion" and "allergic rhinitis". According to the inclusion and exclusion criteria, the collected literature was screened to establish the AR database. Frequency statistic analysis was conducted for detecting high-frequency acupoints and specific acupoints frequency, and the curative effects of different acupoints selection methods were compared. SPSS26.0 software was used for factor analysis, cluster analysis and QUEST decision tree model identification. RESULTS: A total of 289 papers were included, with 384 acupuncture prescriptions extracted. A total of 99 acupoints were involved with the application frequency of 2 430 times. Among them, the application frequency of Yingxiang (LI20) is the highest (296 times, 12.18%), followed by Yintang (GV24+) and Hegu (LI4), etc. The main invloved meridians are the Bladder Meridian of Foot-Taiyang, the Large Intestine Meridian of Hand-Yangming and the Governor Vessel. The involved specific acupoints with the highest frequency of application is the crossing acupoints. Nine common factors of acupoints combinations units were extracted by factor analysis, and two cluster prescriptions of acupoints combinations correlation were obtained by cluster analysis. Three decision paths of simplified acupoints selection were simulated by the decision tree, with LI20 as the dependent variable. CONCLUSION: In the treatment of AR with acupuncture and moxibustion, the regularities and characteristics of acupoints selection are as follows: 1) often selecting local acupoints and acupoint combinations along meridians, 2) focusing on combination of dispelling pathogenic factors with strengthening vital energy, 3) advocating diversification of acupoint matching methods. The combination of factor analysis, cluster analysis and QUEST decision tree application provides three directions for clinical acupoints selection of AR.

Upregulation of Wnt2b exerts neuroprotective effect by alleviating mitochondrial dysfunction in Alzheimer's disease.

AIMS: This study investigated the relationship between plasma Wnt2b levels and Alzheimer's disease (AD), and explored the effect of Wnt2b on mitochondrial dysfunction in AD. METHODS: Healthy and AD subjects, AD transgenic mice, and in vitro models were used to investigate the roles of Wnt2b in abnormalities in canonical Wnt signaling and mitochondria in AD. RT-qPCR, immunoblotting, and immunofluorescence analysis were performed to assay canonical Wnt signaling. Mitochondrial structure was analyzed by electron microscopy. Flow cytometry was used to examine the intracellular calcium and neuronal apoptosis. RESULTS: Plasma Wnt2b levels were lower in AD patients and positively correlated with cognitive performance. Similarly, Wnt2b was reduced in the hippocampus of AD mice and in vitro models. Next, Wnt2b overexpression and recombinant Wnt2b were used to endogenously and exogenously upregulate Wnt2b levels. Upregulation of Wnt2b could effectively prevent downregulation of canonical Wnt signaling, mitochondrial dysfunction in in vitro AD models. Subsequently, intracellular calcium overload and neuronal damage were ameliorated. CONCLUSIONS: Our study highlights that Wnt2b decline is associated with cognitive impairment in AD, and upregulation of Wnt2b can exert neuroprotective effects in AD, particularly in ameliorating mitochondrial dysfunction.

ESE1/AGR2 axis antagonizes TGF-ß-induced epithelial-mesenchymal transition in low-grade pancreatic cancer.

Epithelium-specific ETS transcription factor 1 (ESE1) has been implicated in epithelial homeostasis, inflammation, as well as tumorigenesis, and cancer progression. However, numerous studies have reported contradictory roles-as an oncogene or a tumor suppressor of ESE1 in different cancers, and its function in the development and progression of pancreatic ductal adenocarcinoma (PDAC) has remained largely unexplored. Herein, we report that ESE1 was found upregulated in primary PDAC compared to normal pancreatic tissue, but high expression of ESE1 correlated to better relapse-free survival in patients with PDAC. Interestingly, ESE1 was found to exhibit dual roles in regulation of malignant properties of PDAC cells in that its overexpression promoted cell proliferation, whereas its downregulation enhanced epithelial-mesenchymal transition (EMT) phenotype. In the context of TGF-ß-induced EMT, ESE1 is markedly downregulated at post-transcriptional level, and reconstituted ESE1 expression partially reversed TGF-ß-induced EMT marker expression. Furthermore, we identify AGR2 as a novel transcriptional target of ESE1 that participates in TGF-ß-induced EMT in PDAC. Collectively, our findings reveal an ESE1/AGR2 axis that interacts with TGF-ß signaling to modulate EMT phenotype in PDAC.

[Analysis on combination regularities of Houxi (SI3) in ancient times of China based on latent structure model].

OBJECTIVE: To explore the feasibility and application value of combination regularities of acupoint Houxi (SI3) in Chinese ancient times based on latent structure model. METHODS: Relevant articles about SI3 for treating various diseases with acupuncture, moxibustion, acupoint application, etc. were mainly searched from book Chinese Medical Classics (5th edition), followed by establishment of a Database of Houxi Acupoint Recipes. The Lantern 5.0 software was used to construct and analyze the latent structure model of high-frequently-used acupoints. RESULTS: A total of 46 high frequently-used acupoints contained in 240 articles of 26 medical books were collected. The top 7 acupoints are Shenmai (BL62), Hegu (LI4), Qiangu (SI2), Fengchi (GB20), Jianshi (PC5), Wangu (SI4) and Quchi (LI11) in sequence. After modeling the 46 high-frequently used adjunct acupoints, 12 latent variables (Y0-Y11) and 24 latent classes were obtained by setting the cumulative coverage threshold ratio to be 95%. According to the Bayesian information criterion (BIC) measure, the model score was -2 170.68 points. Seven comprehensive clustering models were summarized up according to the latent structure. Compared with the yin meridians, the yang meridians played a more significant role. The multiple combinations of SI3 with specific acupoints provided a reference for clinical practice. The supplementary acupoints mainly distribute in the upper and lower limbs, head, face, neck, etc. and the SI3 acupoint recipes function mainly in dredging and activating meridians and collaterals, clearing away pathologic heat and wind, improving eyesight, and relieving swelling and pain. CONCLUSION: The latent structure model is applicable in analysis of the regularities of SI3 acupoint combination for treating some diseases. Comprehensive clustering is employed to determine the primary acupoint SI3 and adjunct acupoint matching, revealing the common regularity and logical progressive relationship between the primary and secondary points, which may be helpful for teaching, clinical and scientific research.

CaMKIIα Signaling Is Required for the Neuroprotective Effects of Dl-3-n-Butylphthalide in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of neurodegenerative disease and most anti-AD drugs have failed in clinical trials; hence, it is urgent to find potentially effective drugs against AD. DL-3-n-butylphthalide (NBP) is a compound extracted from celery seed and is a multiple-target drug. Several studies have demonstrated the neuroprotective effects of NBP on cognitive impairment, but the mechanisms of NBP remains relatively unexplored. In this study, we found that NBP could alleviated the increase of intracellular Ca2+ and reversed down-regulation of Ca2+/calmodulin-dependent protein kinase alpha (CaMKIIα) signaling and rescued neuronal apoptosis in SH-SY5Y cells treated by Aß oligomers. However, these neuroprotective effects of NBP on neuronal damage and CaMKIIα signaling were abolished when CaMKIIα expression was knocked down or its activity was inhibited. Thus, our findings suggested that CaMKIIα signaling was required for the neuroprotective effects of NBP in AD and provided an improved basis for elucidating the mechanism and treatment of NBP in AD.

Efficacy and Safety of Transcutaneous Electrical Acupoint Stimulation (TEAS) for Postoperative Pain in Laparoscopy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: This meta-analysis aimed to assess the efficacy and safety of transcutaneous acupoint electrical stimulation (TEAS) for postoperative pain in laparoscopy. The review has been registered on the "INPLASY" website and the registration number is INPLASY202150101. METHODS: Relevant randomized controlled trials are selected from seven electronic databases (PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure, Chongqing VIP Information, WanFang Data, and Chinese Biomedical Database) from their inception up to November 30, 2020. Twenty-eight studies were included in this meta-analysis, and the statistical analyses and the exploration of heterogeneity sources were conducted by Stata 15.0 software. Besides, the bias assessment of the included studies was evaluated using the Cochrane risk of bias tool. RESULTS: In total, 28 RCTs covering 2787 participants were included. The meta-analysis suggested that TEAS can effectively relieve pain in the short term after laparoscopy, reduce the postoperative consumption of rescue analgesics, improve the quality of life of patients, and shorten the length of hospitalization. And no serious adverse events are related to TEAS. Therefore, TEAS is relatively safe and efficacy for clinical application. The most used acupoints were Hegu (LI14), Neiguan (PC6), and Zusanli (ST36). CONCLUSIONS: TEAS can be recommended as a complementary and alternative therapy for the treatment of postoperative pain after laparoscopy. However, the included RCTs had some methodological limitations. Therefore, larger-size, more rigorous, and higher-quality RCTs are needed in the future to further explore the efficacy and safety of TEAS for postoperative pain after laparoscopy.

Enhanced nuclear localization of YAP1-2 contributes to EGF-induced EMT in NSCLC.

YAP1, a key mediator of the Hippo pathway, plays an important role in tumorigenesis. Alternative splicing of human YAP1 mRNA results in two major isoforms: YAP1-1, which contains a single WW domain, and YAP1-2, which contains two WW domains, respectively. We here investigated the functions and the underlying regulatory mechanisms of the two YAP1 isoforms in the context of EGF-induced epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). Human NSCLC cell lines express both YAP1-1 and YAP1-2 isoforms-although when compared to YAP1-1, YAP1-2 mRNA levels are higher while its protein expression levels are lower. EGF treatment significantly promoted YAP1 expression as well as EMT process in NSCLCs, whereas EGF-induced EMT phenotype was significantly alleviated upon YAP1 knockdown. Under normal culture condition, YAP1-1 stable expression cells exhibited a stronger migration ability than YAP1-2 expressing cells. However, upon EGF treatment, YAP1-2 stable cells showed more robust migration than YAP1-1 expressing cells. The protein stability and nuclear localization of YAP1-2 were preferentially enhanced with EGF treatment. Moreover, EGF-induced EMT and YAP1-2 activity were suppressed by inhibitor of AKT. Our results suggest that YAP1-2 is the main isoform that is functionally relevant in promoting EGF-induced EMT and ultimately NSCLC progression.

Paternal fenvalerate exposure transgenerationally impairs cognition and hippocampus in female offspring.

The impairments of maternal fenvalerate exposure have been well documented in previous study, but little was known about the effects of paternal fenvalerate exposure. The current study aimed to assess the effects of paternal fenvalerate exposure on spatial cognition and hippocampus across generations. Adult male mice (F0) were orally administered with fenvalerate (0, 2 or 20 mg/kg) for 5 weeks. F0 males were mated with untreated-females to generate F1 generation. F1 males were mated with F1 control females to generate F2 generation. For F1 and F2 adult offspring, spatial learning and memory were detected by Morris water maze. Results showed that spatial learning and memory were impaired in F1 females but not F1 males derived from F0 males exposed to 20 mg/kg FEN. Furthermore, significant impairment of spatial learning and memory were found in F2 females but not F2 males derived from F0 males exposed to 20 mg/kg FEN. As expected, histopathology showed that neural density in hippocampal CA3 region was reduced in F1 and F2 females but not F1 and F2 males derived from F0 males exposed to 20 mg/kg FEN. Mechanistically, hippocampal thyroid hormone receptor alpha1 (TRα1) was down-regulated in F1 and F2 females derived from F0 males exposed to 20 mg/kg FEN. Correspondingly, hippocampal brain-derived neurotrophic factor, tropomyosin receptor kinase B and p75 neurotrophin receptor, three downstream genes of TR signaling, were down-regulated in F1 and F2 females. Taken together, the present study firstly found that paternal fenvalerate exposure transgenerationally impaired spatial cognition in a gender-dependent manner. Hippocampal TR signaling may, at least partially, contribute to the process of cognitive impairment induced by paternal fenvalerate exposure. Further exploration in the mode of action of fenvalerate is critically important to promote human health and environmental safety.

The Complementary Relationship Between Echocardiography and Multi-Slice Spiral CT Coronary Angiography in the Diagnosis of Coronary Artery Thrombosis in Children With Kawasaki Disease.

Aim: To compare the diagnostic values by using transthoracic echocardiography (ECHO) and multi-slice spiral CT coronary angiography (CTCA) for identifying coronary artery thrombosis in children with Kawasaki disease (KD). Methods: Total 97 KD children with coronary artery dilation complications in our hospital from June 2012 to December 2020 were included in the study. CTCA and ECHO were performed after over 1 month of illness. Results: Coronary artery thrombosis was found in 14 out of 97 patients. Among them, 10 were identified as positive by CTCA, 9 were identified as positive by ECHO, and 5 were identified as positive by both CTCA and ECHO. Conclusion: Both CTCA and ECHO can be used to diagnose coronary artery thrombosis. ECHO has advantage in identifying low-density thrombus, and CTCA is better for the clot in distal coronary artery. They can complement each other.

Yap1-2 Isoform Is the Primary Mediator in TGF-ß1 Induced EMT in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive human malignancy and intrinsically resistant to conventional therapies. YAP1, as a key downstream effector of the Hippo pathway, plays an important role in tumorigenesis including PDAC. Alternative mRNA splicing of YAP1 results in at least 8 protein isoforms, which are divided into two subgroups (YAP1-1 and YAP1-2) based on the presence of either a single or double WW domains. We investigated the functions and regulatory mechanisms of YAP1-1 and YAP1-2 in PDAC cells induced by TGF-ß to undergo epithelial-to-mesenchymal transition (EMT). CRISPR-Cas9 and shRNA were used to silence YAP1 expression in pancreatic cancer cells. Re-constituted lentivirus mediated overexpression of each single YAP1 isoform was generated in the parental knockout L3.6 cells. EMT was induced by treatment with TGF-ß, EGF and bFGF in parental and the constructed stable cell lines. Western blot and qPCR were used to detect the expression of EMT markers. Scratch wound healing and transwell assays were used to detect cell migration. The stability and subcellular localization of YAP1 proteins were determined by Western blot analysis, immunofluorescence, as well as ubiquitination assays. We showed that TGF-ß, EGF and bFGF all significantly promoted EMT in PDAC cells, which was inhibited by knockdown of YAP1 expression. Interestingly, YAP1-1 stable cells exhibited a stronger migratory ability than YAP1-2 cells under normal culture condition. However, upon TGF-ß treatment, L3.6-YAP1-2 cells exhibited a stronger migratory ability than L3.6-YAP1-1 cells. Mechanistically, TGF-ß treatment preferentially stabilizes YAP1-2 and enhances its nuclear localization. Furthermore, TGF-ß-induced EMT and YAP1-2 activity were both blocked by inhibition of AKT signaling. Our results showed that both YAP1-1 and YAP1-2 isoforms are important mediators in the EMT process of pancreatic cancer. However, YAP1-2 is more important in mediating TGF-ß-induced EMT, which requires AKT signaling.

Corrigendum: An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness.

[This corrects the article DOI: 10.3389/fcell.2020.00287.].

An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness.

Cancer stemness is associated with high malignancy and low differentiation, as well as therapeutic resistance of tumors including pancreatic ductal adenocarcinoma (PDAC). Fibroblast growth factors (FGFs) exert pleiotropic effects on a variety of cellular processes and functions including embryonic stem cell pluripotency and cancer cell stemness via the activation of four tyrosine kinase FGF receptors (FGFRs). FGF ligands have been a major component of the cocktail of growth factors contained in the cancer stemness-inducing (CSI) and organoid culture medium. Although FGF/FGFR signaling has been hypothesized to maintain cancer stemness, its function in this process is still unclear. We report that inhibition of FGF/FGFR signaling impairs sphere-forming ability of PDAC in vitro, and knocking down FGFR1 and FGFR2 decreased their tumorigenesis abilities in vivo. Mechanistically, we demonstrated that SOX2 is down-regulated upon loss of FGFR signaling. The overexpression of SOX2 in SOX2-negative cells, which normally do not display stemness capabilities, is sufficient to induce spheroid formation. Additionally, we found that AKT phosphorylation was reduced upon FGFR signaling inhibition. The inhibition of AKT using specific pharmacological inhibitors in the context of CSI medium leads to the loss of spheroid formation associated with loss of SOX2 nuclear expression and increased degradation. We demonstrate that an FGFR/AKT/SOX2 axis controls cancer stemness in PDAC and therefore may represent an important therapeutic target in the fight against this very aggressive form of cancer.

Depression and myocardial injury in ST-segment elevation myocardial infarction: A cardiac magnetic resonance imaging study.

BACKGROUND: Depression is common in patients with myocardial infarction and has been independently associated with adverse outcomes. However, the association between depression and myocardial injury on cardiac magnetic resonance (CMR) in patients with ST-segment elevation myocardial infarction (STEMI) has still not been assessed. AIM: To assess the association between depression and myocardial injury on CMR in patients with STEMI. METHODS: A total of 107 STEMI patients undergoing primary percutaneous coronary intervention (P-PCI) were analyzed in this prospectivecohort study. Each subject completed the Patient Health Questionnaire-9 (PHQ-9) to assess the presence and severity of depressive symptoms. CMR was performed at a median of 3 d after P-PCI for quantifying post-MI myocardial injury. Correlations between depression identified by the PHQ-9 and myocardial injury measured on CMR were assessed. RESULTS: In this study, 19 patients (17.8%) were diagnosed with major depression identified by the PHQ-9 ≥ 10. PHQ-9 was analyzed both as a continuous variable and dichotomous variable. After multivariable adjustment, the proportion of patients with large infarction size was significantly higher in the major depression group (PHQ-9 ≥ 10) (OR: 4.840, 95%CI: 1.122-20.868, P =0.034). When the PHQ-9 was evaluated as a continuous variable, after multivariable adjustment, an increased PHQ-9 score was associated with an increased risk of large infarction size (OR: 1.226, 95%CI: 1.073-1.401, P =0.003). CONCLUSION: In patients with STEMI undergoing PCI, depression was independently associated with a large infarction size.

A phylogenomics approach to characterizing sensory neuron membrane proteins (SNMPs) in Lepidoptera.

Sensory neuron membrane proteins (SNMPs) play a critical role in the insect olfactory system but there is a deficit of functional studies beyond Drosophila. Here, we use a combination of available genome sequences, manual curation, genome and transcriptome data, phylogenetics, expression profiling and gene knockdown to investigate SNMP superfamily in various insect species with a focus on Lepidoptera. We curated 81 genes from 36 insect species and identified a novel lepidopteran SNMP gene family, SNMP3. Phylogenetic analysis shows that lepidopteran SNMP3, but not the previously annotated lepidopteran SNMP2, is the true homologue of the dipteran SNMP2. Digital expression, microarray and qPCR analyses show that the lepidopteran SNMP1 is specifically expressed in adult antennae. SNMP2 is widely expressed in multiple tissues while SNMP3 is specifically expressed in the larval midgut. Microarray analysis suggest SNMP3 may be involved in the silkworm immunity response to virus and bacterial infections. We functionally characterized SNMP1 in the silkworm using RNA interference (RNAi) and behavioral assays. Our results suggested that Bombyx mori SNMP1 is a functional orthologue of the Drosophila melanogaster SNMP1 and plays a critical role in pheromone detection. Split-ubiquitin yeast hybridization study shows that BmorSNMP1 has a protein-protein interaction with the pheromone receptor (BmorOR1), and the co-receptor (BmorOrco). Concluding, we propose a novel molecular model in which BmorOrco, BmorSNMP1 and BmorOR1 form a heteromer in the detection of the silkworm sex pheromone bombykol.

[Clinical features and TTC21B genotype of a child with nephronophthisis type 12].

Nephronophthisis (NPHP) is a group of autosomal recessive tubulointerstitial cystic kidney disorders. This article reports a case of NPHP type 12 caused by TTC21B mutations. The girl had an insidious onset, with moderate proteinuria, renal dysfunction, stage 2 hypertension, situs inversus, and short phalanges when she visited the hospital for the first time at the age of 3 years and 6 months. The renal lesions progressed to end-stage renal disease (ESRD) before she was 4 years old. Urine protein electrophoresis showed glomerular proteinuria. There were significant increases in urinary ß2-microglobulin and α1-microglobulin. Gene detection revealed two compound heterozygous mutations, c.1552T>C (p.C518R) and c.752T>G (p.M251R), in the TTC21B gene, which came from her father and mother respectively. The c.752T>G mutation was a novel mutation. It is concluded that besides typical tubular changes of NPHP, marked glomerular damage is also observed in patients with TTC21B gene mutations.

Clinical features and prognosis of patients with thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus: a review of 25 cases.

OBJECTIVE: To report the clinical features of patients with systemic lupus erythematosus (SLE) associated with thrombotic thrombocytopenic purpura (TTP). Their diagnosis, treatment, and prognosis were also discussed. METHODS: A total of 25 TTP-SLE pediatric patients were included in this study. Their clinical symptoms, laboratory findings, disease activity, and renal biopsy were retrospectively reviewed. RESULTS: The median age of the patient cohort was 14 years old. Nine patients were first diagnosed with SLE, followed by the diagnosis of TTP-SLE, whereas 15 patients were diagnosed with TTP and SLE concurrently. All the 25 TTP-SLE patients had decreased platelet count and microangiopathic hemolytic anemia. Fever, rash, edema and neurological symptoms were the main clinical symptoms. Fragmentation of erythrocytes on blood smear and increased LDH were found in all patients. Nineteen patients (76%) had impaired renal function. Renal biopsy showed that most of the patients had lupus nephritis class IV (20%) and TMA (20%). 13 patients (52%) were treated with glucocorticoids in combination with immunosuppressive agent, and 10 patients (40%) were treated with plasma exchange combined with glucocorticoids plus immunosuppressive agent. One patient died due to lung infection; others had disease remission. Fifteen patients had follow-up regularly, and their conditions were stable. CONCLUSION: Patients with TTP-SLE often had moderate to severe lupus disease activity. Testing of LDH level and blood smear should be performed when kidney and neurological symptoms arise in children with SLE. The use of combination therapy, glucocorticoids plus immunosuppressive agent, provided satisfactory clinical outcome. Patients with refractory TTP-SLE will also need plasma exchange therapy.