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Background: The Old World sand fly, Phlebotomus papatasi (Scopoli), a vector of zoonotic cutaneous leishmaniasis, is usually controlled by insecticides, including anticholinesterases. Previous studies have revealed 85% amino acid sequence identity of recombinant P. papatasi acetylcholinesterase (rPpAChE1) to mosquito AChE. They identified synthetic carbamates that selectively inhibited rPpAChE1 and circumvented the G119S mutation responsible for high-level resistance to anticholinesterases. This study reports the construction, baculovirus expression, and biochemical properties of rPpAChE1 containing the F290V and F331W orthologous mutations from mosquitoes., Methods: Recombinant PpAChE1 enzymes with or without the F290V, F331W, and G119S orthologous mosquito mutations were expressed in Sf21cells utilizing the baculoviral system. Ellman assays determined changes in catalytic properties and inhibitor sensitivity resulting from wild type and mutant rPpAChE1 containing single or combinations of orthologous mosquito mutations., Results: Each of the orthologous mutations (F290V, F331W, and G119S) from mosquito AChE significantly reduced inhibition sensitivity to organophosphate or carbamate pesticides, and catalytic activity was lost when they were expressed in combination. Novel synthetic carbamates were identified that significantly inhibited the rPpAChEs expressing each of the single orthologous mosquito mutations., Conclusions: These novel carbamates could be developed as efficacious insecticides, with improved specificity and safety for use in sand fly or mosquito populations expressing the mutant AChEs., Competing Interests: Declarations. Ethics approval and consent to participate: Institutional biosafety committee approval was granted IBC no. 2022–02 for the reported recombinant DNA in vitro expression in cell culture studies. Other ethics and consent to participate is not applicable. Consent for publication: Written informed consent for publication was obtained from all authors. Competing interests: The authors declare no competing interests., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The COVID-19 pandemic has had a significant impact on the physical and mental health of human beings. Most adolescents in mainland of China have been infected with COVID-19 after the adjustment of the dynamic zero-COVID-19 policy. This study aims to analyze the relationship between the COVID-19 pandemic effect and depressive symptoms among adolescents in mainland China., Methods: This school-based repeated cross-sectional study was conducted on students aged 11-19 years from September to October 2022 and September to October 2023 in Ningbo, Zhejiang Province, China, using a stratified cluster, multistage sampling method. Data analysis occurred from January to June 2024. Depression symptoms and bullying victimization, exclusion of cyberbullying, were assessed using the 20-item Center for Epidemiological Studies Depression Scale (CES-D) and Bully/Victim Questionnaire, respectively., Results: In the first survey wave in 2022 during the dynamic zero-COVID-19 policy period in Mainland China, 10,224 participants completed the questionnaires. In wave 2 survey in 2023 which was the first year after lifting of the dynamic zero-COVID-19 policy, 11,604 participants completed the questionnaires. This resulted in a sample of 10,224 in wave 1 and 11,604 in wave 2. The mean age in wave 1 was 15.2 (SD = 1.7) and 15.1 (SD = 1.8) in wave 2. The prevalence of depression symptoms in adolescents in wave 2 was higher than in wave 1 (17.0% vs. 14.6%, P < 0.05). The prevalence of bullying victimization and types of bullying victimization in school among adolescents were higher in 2023 than in 2022. A total of 3.2% of the 2023 participants and 1.7% of the 2022 participants experienced bullying victimization in school (P < 0.05). The odds ratio of experiencing depression (CES-D Score ≧ 16) and bullying victimization in school were 1.18 (95% CI, 1.10-1.28) and 1.86 (95% CI, 1.55-2.24) times higher, respectively, in 2023 than in 2022 (P < 0.01). The mediated regression analysis revealed that after lifting of the dynamic zero-COVID-19 had a significant association with an increase in depression symptoms, which was partially mediated by bullying victimization in school (total association:β = 0.175; SE = 0.038; P < 0.001; direct association:β = 0.138; SE = 0.039; P < 0.001; indirect association: a*b = 0.037; P < 0.001; the proportion of mediation: 20.88%, P < 0.001)., Conclusions: The findings of this repeated cross-sectional study suggest that an increased risk of depression symptoms or bullying victimization has been associated with the COVID-19 pandemic in mainland China after lifting the dynamic zero-COVID-19 policy. In addition, bullying victimization may play a mediating role in the associations between the pandemic and depression symptoms. These findings indicated that additional support should be offered to Chinese adolescents in the period of post-pandemic COVID-19., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: The protocol for the research project had been approved by the Ningbo CDC Institutional Review Board (No. 202201) and had therefore been performed following the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Both the participant and his/her parents or guardian have signed written informed consent forms, and all information related to participants and schools is confidential. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: There are mixed findings in the literature regarding the association between HIV status and the risk of COVID-19 infection. Thus, we aimed to estimate the association between characteristics of HIV infection and the risk of COVID-19 Infection in a Chinese sample., Methods: We conducted a cross-sectional survey of 1995 people living with HIV (PLWH) and 3503 HIV-negative adults in Ningbo, China. We compared the prevalence rates of the SARS-CoV-2 infection and the long nucleic acid conversion time (more than 2 weeks) among PLWH and HIV-negative participants, respectively. In addition, we explored the risk factors associated with SARS-CoV-2 infection and the long nucleic acid conversion time among the two groups., Results: Overall, 1485/1995 (74.4%) PLWH and 2864/3503 (81.8%) HIV-negative people were infected with SARS-CoV-2. Among the SARS-CoV-2-infected participants, 437/1485 (29.4%) PLWH and 649/2864 (22.7%) HIV-negative people had the long nucleic acid conversion time. After controlling for the potential confounders, the rate of the SARS-CoV-2 infection was lower among the PLWH than the HIV-negative group (adjusted OR = 0.836, 95% CI = 0.706-0.990). However, PLWH had a significantly higher risk of the long nucleic acid conversion time after the SARS-CoV-2 infection (adjusted OR = 1.417, 95% CI = 1.176-1.707) than the HIV negative participants. Compared with those who did not receive ART, PLWH adults who received ART significantly had the increased risk of SARS-CoV-2 infection. Furthermore, HIV-negative participants receiving COVID-19 vaccines significantly displayed the decreased likelihood of the long nucleic acid conversion time after the SARS-CoV-2 infection., Conclusions: Our study indicates that different HIV Infection status was significantly and differently associated with the SARS-CoV-2 infection and the long nucleic acid conversion time. However, the further studies are needed to confirm the effect of ART and COVID-19 vaccines on SARS-CoV-2 infection in PLWH., Competing Interests: Declarations. Ethics approval and consent to participate: The studies involving participants provided informed consent forms when they were enrolled. The study was approved by the Human Research Ethics Committee of Ningbo CDC in Ningbo, China (No. 201913). The study was conducted in accordance with the Declaration of Helsinki.2.2 Data collection. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: This study sought to evaluate the value of a CO 2 field-flooding device in cardiopulmonary bypass (CPB) surgical procedures for congenital heart disease (CHD) performed via a right-side small incision approach., Methods: Between April 2022 and December 2023, 234 children with simple CHD who underwent CPB via a right-side small incision approach were separated into a control group (n = 93) without the use of a CO 2 field-flooding device and a treatment group (n = 141) in which this device was added to the traditional surgical manual exhaust. Demographic, perioperative, arterial blood gas (ABG), and laboratory test data were then compared between these groups of patients., Results: There was a significant difference in abnormal electrocardiogram (ECG) after aorta de-clamping during CPB, and interventions for abnormal ECG after aorta de-clamping during CPB between the control and treatment groups (17(18.3%) vs.14(9.9%), P = 0.048;12(85.7%) vs.7(50%),P = 0.013). The treatment group exhibited a lower pH (7.34 ± 0.07 vs. 7.36 ± 0.06, P = 0.039) and a higher PaCO 2 (43.08 ± 7.36 vs. 38.86 ± 5.65 mmHg, P = 0.042) at the time of 30 min after initiation of CPB. A significant reduction in postoperative CK-MB was observed in treatment group (41.20 ± 17.88 vs. 56.57 ± 22.99 U/L, P = 0.002). Lower 3-day postoperative CRP levels were also observed in the treatment group relative to control (5.77 ± 0.48 vs. 9.45 ± 0.98 mg/L, P < 0.001). The S100ß concentration in the relevant patient cohort increased significantly from the time just after induction, intubation, and installation of the right central venous line to the time of admission to CCU (71.61 ± 11.83 vs. 124.04 ± 38.80, P = 0.01) and at the time of 24 h after operation (71.61 ± 11.83 vs. 101.97 ± 30.31, P = 0.01). No differences on S100β serum concentration level were found at the time of installation of the right central venous line between two groups. But there were statistically significant differences in S100β serum concentration level at the time of admission to CCU between control group and treatment group. (161.19 ± 6.62 vs. 86.89 ± 9.69 pg/ml, P = 0.01). Similar results were observed at the time of 24 h after operation. (127.62 ± 19.44 vs. 76.33 ± 10.40, P = 0.01)., Conclusion: These data suggest that the CO 2 field-flooding device can safely be used when performing CPB surgical procedures via a right-side small incision approach to treat CHD without hypercapnia. The use of such a CO2 field-flooding device at a flow rate of 5 L/min may help protect against cardiac and nervous system damage in children undergoing CHD surgery., Competing Interests: Declarations. Ethics approval and consent to participate: This statement confirming the approval of the study by the ethical committee of Beijing Children’s Hospital, Capital Medical University in Beijing, China. ID number [2022]-E-083-Y. All patients were consented for the participation in the study. The ethics declaration: In accordance with the Declaration of Helsinki. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Berry syndrome is a group of rare congenital cardiac malformations including aortopulmonary window (APW), aortic origin of the right pulmonary artery (AORPA), interruption of the aortic arch (IAA), patent ductus arteriosus (PDA) (supplying the descending aorta) and intact ventricular septum. This paper will analyze the clinical data of 7 patients with Berry syndrome who underwent surgical treatment in our institution and discuss the one-stage surgical correction of Berry syndrome in combination with the literature., Methods: From January 2013 to July 2024, a total of 7 children with Berry syndrome were admitted to the Cardiac Surgery Department of Beijing Children's Hospital. The median age was 3 months (range, 1-36 months). All patients' IAA morphology were type A. The APW morphology was type IIA in 2, type IIB in 4, and type III in 1 patient. Three different surgical correction techniques were used to repair the APW and AORPA, including intra-aortic patch in 2, RPA angioplasty with aortic cuff in 2, RPA detachment and reimplant in 3 patients., Results: Among the 7 patients, one died in the early postoperative period, (1/7, 14.3%). The remaining 6 surviving patients, mechanical ventilation was lasted for 51 to 166 h postoperatively, with an average of (113.3 ± 50.8) hours; the CCU stay was 6 to 23 days, with an average of (11.8 ± 6.5) days. Two cases (2/7, 28.6%) of patients adopted the strategy of delayed sternal closure. The 6 surviving children were followed up for a period ranging from 3 to 132 months, with a median follow-up duration of 36 months. During the follow-up, 2 patients underwent a second operations (2/6, 33.3%). The remaining 4 patients showed no obvious RPA stenosis, descending aorta (DAO) stenosis, aortic valve stenosis or aortic valve regurgitation (AR) during the follow-up period. In the latest follow-up, the average velocity of the RPA of the 4 patients was 1.68 ± 0.36 m/s, and the average pressure gradient was 11.9 ± 4.8 mmHg; the average velocity of the DAO was 2.1 ± 1.7 m/s, and the average pressure gradient was 17.9 ± 2.6 mmHg. All the AR were less than mild., Conclusion: Most children can achieve one-stage surgical correction. For children with APW type IIA, the intra-aortic patch method can be attempted, but its therapeutic effect still requires medium to long-term follow-up. The surgical approach of RPA detachment and reimplant can be applied to all types of patients with Berry syndrome, and the medium to long-term follow-up result is favorable. For the treatment of IAA, it is recommended that end-to-side anastomosis be performed between the DAO and the aortic arch, and the anterior wall be augmented by using bovine pericardial tissue patches. For the residual obstruction at the postoperative anastomosis site, balloon dilation angioplasty can be considered. Compression of the left main bronchus can be supported by intratracheal stents., Perspective Statement: In the English literature accessed thus far, there are less than 50 cases associated with the surgical treatment of Berry syndrome. In this work, we analyzed the clinical data of 7 patients from January 2013 to July 2024 with Berry syndrome who underwent surgical treatment in our institution and showed one-stage surgical correction can achieved acceptable outcomes., Competing Interests: Declarations. Ethics approval and consent to participate: The hospital ethics committee approved this study (ID number [2024]-E-124-R) and waived the need for individual consent. Data were collected retrospectively from hospital records and outpatient clinics. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Breast cancer (BC) is the leading cause of cancer-related mortality among women globally, affecting approximately one-quarter of all female cancer patients and accounting for one-sixth of cancer-related deaths in women. Despite significant advancements in diagnostic and therapeutic approaches, breast cancer treatment remains challenging due to issues such as recurrence and metastasis. Recently, a novel form of regulated cell death, termed cuproptosis, has been identified. This process disrupts mitochondrial respiration by targeting the copper-dependent cellular pathways. The role of cuproptosis has been extensively investigated in various therapeutic contexts, including chemotherapy, immunotherapy, radiotherapy, and nanotherapy, with the development of novel drugs significantly improving clinical outcomes. This article aims to further elucidate the connection between cuproptosis and breast cancer, focusing on its therapeutic targets, signaling pathways, and potential biomarkers that could enhance treatment strategies. These insights may offer new opportunities for improved patient care and outcomes in breast cancer therapy., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors are in agreement with the content for publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Tuberculous meningitis (TBM) is a severe central nervous system (CNS) infection with a challenging diagnosis due to inadequate detection methods. This study evaluated current clinical detection methods and their applicability., Methods: A cohort of 514 CNS infection patients from 2018 to 2020 was studied. Data on general demographics, Cerebrospinal Fluid (CSF) analysis, epidemiology, and clinical outcomes were collected. TBM patients were identified, and the sensitivities of mmetagenomic next-generation sequencing (NGS), GeneXpert, and microbial culture were compared. Kappa statistic assessed the consistency between methods., Results: Among the patients involved, TBM (29%) and neurosyphilis (25%) were the two most prevalent CNS infections. CSF analysis indicated that 76% of patients had leukocytosis, suggesting a potential CNS inflammation. In TBM cases, 92.5% had elevated CSF protein and leukocyte counts. Moreover, the percentage of positive mNGS results was 55.6%. GeneXpert and MTB cultures alone had lower sensitivity, but combined use resulted in a 53.4% positive rate., Conclusions: This study highlights the high sensitivity of mNGS, comparable to GeneXpert and MTB culture. The combined methods are cost-effective and straightforward, and can partially substitute for mNGS, offering valuable alternatives for TBM diagnosis and providing insights into multiple diagnostic strategies in clinical practice., (© 2024. The Author(s).)

On a global note, oral health plays a critical role in improving the overall human health. In this vein, dental-related issues with dentin exposure often facilitate the risk of developing various oral-related diseases in gums and teeth. Several oral-based ailments include gums-associated (gingivitis or periodontitis), tooth-based (dental caries, root infection, enamel erosion, and edentulous or total tooth loss), as well as miscellaneous diseases in the buccal or oral cavity (bad breath, mouth sores, and oral cancer). Although established conventional treatment modalities have been available to improve oral health, these therapeutic options suffer from several limitations, such as fail to eradicate bacterial biofilms, deprived regeneration of dental pulp cells, and poor remineralization of teeth, resulting in dental emergencies. To this end, the advent of nanotechnology has resulted in the development of various innovative nanoarchitectured composites from diverse sources. This review presents a comprehensive overview of different nanoarchitectured composites for improving overall oral health. Initially, we emphasize various oral-related diseases, providing detailed pathological circumstances and their effects on human health along with deficiencies of the conventional therapeutic modalities. Further, the importance of various nanostructured components is emphasized, highlighting their predominant actions in solving crucial dental issues, such as anti-bacterial, remineralization, and tissue regeneration abilities. In addition to an emphasis on the synthesis of different nanostructures, various nano-therapeutic solutions from diverse sources are discussed, including natural (plant, animal, and marine)-based components and other synthetic (organic- and inorganic-) architectures, as well as their composites for improving oral health. Finally, we summarize the article with an interesting outlook on overcoming the challenges of translating these innovative platforms to clinics., (© 2024. The Author(s).)

Background: Brain metastasis is one of the main causes of recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy is the main local therapy for brain metastasis, it is inevitable that some cancer cells become resistant to radiation. Microglia, as macrophages colonized in the brain, play an important role in the tumor microenvironment. Radiotherapy could activate microglia to polarize into both the M1 and M2 phenotypes. Therefore, searching for crosstalk molecules within the microenvironment that can specifically regulate the polarization of microglia is a potential strategy for improving radiation resistance., Methods: We used databases to detect the expression of MIF in NSCLC and its relationship with prognosis. We analyzed the effects of targeted blockade of the MIF/CD74 axis on the polarization and function of microglia during radiotherapy using flow cytometry. The mouse model of brain metastasis was used to assess the effect of targeted blockade of MIF/CD74 axis on the growth of brain metastasis., Result: Our findings reveals that the macrophage migration inhibitory factor (MIF) was highly expressed in NSCLC and is associated with the prognosis of NSCLC. Mechanistically, we demonstrated CD74 inhibition reversed radiation-induced AKT phosphorylation in microglia and promoted the M1 polarization in combination of radiation. Additionally, blocking the MIF-CD74 interaction between NSCLC and microglia promoted microglia M1 polarization. Furthermore, radiation improved tumor hypoxia to decrease HIF-1α dependent MIF secretion by NSCLC. MIF inhibition enhanced radiosensitivity for brain metastasis via synergistically promoting microglia M1 polarization in vivo., Conclusions: Our study revealed that targeting the MIF-CD74 axis promoted microglia M1 polarization and synergized with radiotherapy for brain metastasis in NSCLC., (© 2024. The Author(s).)

Background: Automatic and accurate extraction of diverse biomedical relations from literature is a crucial component of bio-medical text mining. Currently, stacking various classification networks on pre-trained language models to perform fine-tuning is a common framework to end-to-end solve the biomedical relation extraction (BioRE) problem. However, the sequence-based pre-trained language models underutilize the graphical topology of language to some extent. In addition, sequence-oriented deep neural networks have limitations in processing graphical features., Results: In this paper, we propose a novel method for sentence-level BioRE task, BioEGRE (BioELECTRA and Graph pointer neural net-work for Relation Extraction), aimed at leveraging the linguistic topological features. First, the biomedical literature is preprocessed to retain sentences involving pre-defined entity pairs. Secondly, SciSpaCy is employed to conduct dependency parsing; sentences are modeled as graphs based on the parsing results; BioELECTRA is utilized to generate token-level representations, which are modeled as attributes of nodes in the sentence graphs; a graph pointer neural network layer is employed to select the most relevant multi-hop neighbors to optimize representations; a fully-connected neural network layer is employed to generate the sentence-level representation. Finally, the Softmax function is employed to calculate the probabilities. Our proposed method is evaluated on three BioRE tasks: a multi-class (CHEMPROT) and two binary tasks (GAD and EU-ADR). The results show that our method achieves F1-scores of 79.97% (CHEMPROT), 83.31% (GAD), and 83.51% (EU-ADR), surpassing the performance of existing state-of-the-art models., Conclusion: The experimental results on 3 biomedical benchmark datasets demonstrate the effectiveness and generalization of BioEGRE, which indicates that linguistic topology and a graph pointer neural network layer explicitly improve performance for BioRE tasks., (© 2023. The Author(s).)

Background: Sepsis is a high mortality disease which seriously threatens human life and health, for which the pathogenetic mechanism still unclear. There is increasing evidence showed that immune and inflammation responses are key players in the development of sepsis pathology. LncRNAs, which act as ceRNAs, have critical roles in various diseases. However, the regulatory roles of ceRNA in the immunopathogenesis of sepsis have not yet been elucidated., Results: In this study, we aimed to identify immune biomarkers associated with sepsis. We first generated a global immune-associated ceRNA (IMCE) network based on data describing interactions pairs of gene-miRNA and miRNA-lncRNA. Afterward, we excavated a dysregulated sepsis immune-associated ceRNA (SPIMC) network from the global IMCE network by means of a multi-step computational approach. Functional enrichment indicated that lncRNAs in SPIMC network have pivotal roles in the immune mechanism underlying sepsis. Subsequently, we identified module and hub genes (CD4 and STAT4) via construction of a sepsis immune-related PPI network. Then, we identified hub genes based on the modular structure of PPI network and generated a ceRNA subnetwork to analyze key lncRNAs associated with sepsis. Finally, 6 lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) that identified as immune biomarkers of sepsis. Moreover, the CIBERSORT algorithm and the infiltration of circulating immune cells types were performed to identify the inflammatory state of sepsis. Correlation analyses between immune cells and sepsis immune biomarkers showed that the LINC00265 was strongly positive correlated with the macrophages M2 (r = 0.77)., Conclusion: Collectively, these results may suggest that these lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) played important roles in the immune pathogenesis of sepsis and provide potential therapeutic targets for further researches on immune therapy treatment in patients with sepsis., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Breast cancer bone metastasis has become a common cancer type that still lacks an effective treatment method. Although epigenetic drugs have demonstrated promise in cancer therapy, their nontargeted accumulation and drug resistance remain nonnegligible limiting factors. Herein, we first found that icaritin had a strong synergistic effect with an epigenetic drug (JQ1) in the suppression of breast cancer, which could help to relieve drug resistance to JQ1. To improve tumor-targeted efficacy, we developed a hypoxia-cleavable, RGD peptide-modified poly(D,L-lactide-co-glycolide) (PLGA) nanoparticle (termed ARNP) for the targeted delivery of JQ1 and icaritin. The decoration of long cleavable PEG chains can shield RGD peptides during blood circulation and reduce cellular uptake at nonspecific sites. ARNP actively targets breast cancer cells via an RGD-αvβ3 integrin interaction after PEG chain cleavage by responding to hypoxic tumor microenvironment. In vitro and in vivo assays revealed that ARNP exhibited good biodistribution and effectively suppressed primary tumor and bone metastasis. Meanwhile, ARNP could alleviate bone erosion to a certain extent. Furthermore, ARNP significantly inhibited pulmonary metastasis secondary to bone metastasis. The present study suggests that ARNP has great promise in the treatment of breast cancer and bone metastasis due to its simple and practical potential., (© 2023. The Author(s).)

Objectives: To compare clinical outcomes in patients with severe pneumonia according to the diagnostic strategy used., Methods: In this retrospective, nested, case-control study, patients with severe pneumonia who had undergone endotracheal aspirate (ETA) metagenomic next-generation sequencing of (mNGS) testing (n = 53) were matched at a ratio of 1 to 2 (n = 106) by sex, age, underlying diseases, immune status, disease severity scores, and type of pneumonia with patients who had undergone bronchoalveolar lavage fluid (BALF) mNGS. The microbiological characteristics and patient's prognosis of the two groups were compared., Results: An overall comparison between the two groups showed no significant differences in bacterial, fungal, viral, or mixed infections. However, subgroup analysis of 18 patients who received paired ETA and BALF mNGS showed a complete agreement rate for the two specimens of 33.3%. There were more cases for whom targeted treatment was initiated (36.79% vs. 22.64%; P = 0.043) and fewer cases who received no clinical benefit after mNGS (5.66% vs. 15.09%; P = 0.048) in the BALF group. The pneumonia improvement rate in the BALF group was significantly higher than in the ETA group (73.58% vs. 87.74%, P = 0.024). However, there were no significant differences in ICU mortality or 28-day mortality., Conclusions: We do not recommend using ETA mNGS as the first-choice method for analyzing airway pathogenic specimens from severe pneumonia patients., (© 2023. The Author(s).)

Background: Thyroid-associated ophthalmopathy (TAO) is an autoimmune disorder. It has discriminable appearance. This study was conducted to dig the clinical significance of demographic characteristics and ophthalmologic diagram features in TAO diagnosis and stage/severity evaluation., Results: We included 320 males and 633 females, with an average age of 41.75 ± 13.75. A majority of TAO patients had hyperthyroidism, and most of them were in the inactive stage and at the moderate level. The thyroid function type, stage and severity were closely associated with hypopsia, eyelid congestion, conjunctival congestion, corneal ulcer, ocular motility disorder, best corrected visual acuity, and extraocular muscle thickening. Using these features, we established different logistic regression models to predict thyroid function subtypes, abnormal thyroid function, stage, and severity, in which the AUC of the ROC curve and accuracies were satisfactory., Conclusion: Together, TAO subtype, stage and severity can be diagnosed by auxiliary references including demographic factors, symptoms from complains, and image features. These non-invasive indices can be applied in a timely manner in clinical estimating TAO status., (© 2023. The Author(s).)

Background: The double-lumen tube (DLT) is an essential equipment for thoracic anesthesia and the precise position of DLT placement is particularly important for anesthesia and surgery. However, the incidence of DLT malposition remains high and it leads to lung isolation failure and hypoxemia during one-lung ventilation. This trial aims to explore the clinical application and efficacy of intubation in the lateral position under general anesthesia induction to reduce the incidence of DLT malposition in patients undergoing unilateral video-assisted thoracic surgery (VATS)., Methods: In this prospective, single-center, parallel group, randomized, controlled trial, we will recruit 108 patients, aged 18-80 years, scheduled for elective unilateral VATS with DLT intubation under general anesthesia, and they will be randomly assigned to two groups: a lateral DLT intubation group (group L) and a conventional supine DLT intubation group (group C). The left-sided DLT will be used to intubate in patients of both groups. The position of DLT will be confirmed and adjusted by using the fiberoptic bronchoscopy (FOB). The primary outcome is the incidence of DLT malposition observed via the FOB, and the secondary outcomes include the time of intubation, the frequency and duration of re-adjustments of DLT placement under FOB, whether to re-intubate, intraoperative vital signs, and postoperative recovery., Discussion: Accurate DLT positioning is crucially important for thoracic surgery, but the incidence of DLT malposition is still high in the present clinical practice of thoracic anesthesia. This trial aims to investigate whether lateral DLT intubation can reduce the incidence of DLT malposition, with more stable intraoperative vital signs and less postoperative complications., Trial Registration: The study protocol was registered at Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) with registration number: ChiCTR2200060794 on June 11, 2022., (© 2023. The Author(s).)

Purpose: The combination of taxanes and anthracyclines is still the mainstay of chemotherapy for early breast cancer. Capecitabine is an active drug with a favorable toxicity profile, showing strong anti-tumor activity against metastatic breast cancer. This trial assessed the efficacy and safety of the TX regimen (docetaxel and capecitabine) and compared it with the TE (docetaxel and epirubicin) regimen in locally advanced or high risk early HER2-negative breast cancer., Patients and Methods: This randomized clinical trial was conducted at five academic centers in China. Eligible female patients were randomly assigned (1:1) to the TX (docetaxel 75 mg/m 2 d1 plus capecitabine 1000 mg/m 2 twice d1-14, q3w) or TE (docetaxel 75 mg/m 2 d1 plus epirubicin 75 mg/m 2 d1, q3w) groups for four cycles. The primary endpoint was a pathological complete response in the breast (pCR). Secondary endpoints included pCR in the breast and axilla, invasive disease-free survival (iDFS), overall survival (OS), and safety., Results: Between September 1, 2012, and December 31, 2018, 113 HER2-negative patients were randomly assigned to the study groups (TX: n = 54; TE: n = 59). In the primary endpoint analysis, 14 patients in the TX group achieved a pCR, and nine patients in the TE group achieved a pCR (25.9% vs. 15.3%), with a not significant difference of 10.6% (95% CI -6.0-27.3%; P = 0.241). In a subgroup with high Ki-67 score, TX increased the pCR rate by 24.2% (95% CI 2.2-46.1%; P = 0.029). At the end of the 69-month median follow-up period, both groups had equivalent iDFS and OS rates. TX was associated with a higher incidence of hand-foot syndrome and less alopecia, with a manageable toxicity profile., Conclusion: The anthracycline-free TX regimen yielded comparable pCR and long-term survival rates to the TE regimen. Thus, this anthracycline-free regimen could be considered in selected patients., Trial Registration: ACTRN12613000206729 on 21/02/2013, retrospectively registered., (© 2022. The Author(s).)

Background: Automatic and accurate recognition of various biomedical named entities from literature is an important task of biomedical text mining, which is the foundation of extracting biomedical knowledge from unstructured texts into structured formats. Using the sequence labeling framework and deep neural networks to implement biomedical named entity recognition (BioNER) is a common method at present. However, the above method often underutilizes syntactic features such as dependencies and topology of sentences. Therefore, it is an urgent problem to be solved to integrate semantic and syntactic features into the BioNER model., Results: In this paper, we propose a novel biomedical named entity recognition model, named BioByGANS (BioBERT/SpaCy-Graph Attention Network-Softmax), which uses a graph to model the dependencies and topology of a sentence and formulate the BioNER task as a node classification problem. This formulation can introduce more topological features of language and no longer be only concerned about the distance between words in the sequence. First, we use periods to segment sentences and spaces and symbols to segment words. Second, contextual features are encoded by BioBERT, and syntactic features such as part of speeches, dependencies and topology are preprocessed by SpaCy respectively. A graph attention network is then used to generate a fusing representation considering both the contextual features and syntactic features. Last, a softmax function is used to calculate the probabilities and get the results. We conduct experiments on 8 benchmark datasets, and our proposed model outperforms existing BioNER state-of-the-art methods on the BC2GM, JNLPBA, BC4CHEMD, BC5CDR-chem, BC5CDR-disease, NCBI-disease, Species-800, and LINNAEUS datasets, and achieves F1-scores of 85.15%, 78.16%, 92.97%, 94.74%, 87.74%, 91.57%, 75.01%, 90.99%, respectively., Conclusion: The experimental results on 8 biomedical benchmark datasets demonstrate the effectiveness of our model, and indicate that formulating the BioNER task into a node classification problem and combining syntactic features into the graph attention networks can significantly improve model performance., (© 2022. The Author(s).)

Background: Apoptosis signal-regulating kinase 1 (ASK1) not only causes neuronal programmed cell death via the mitochondrial pathway but also is an essential component of the signalling cascade during microglial activation. We hypothesize that ASK1 selective deletion modulates inflammatory responses in microglia/macrophages(Mi/Mϕ) and attenuates seizure severity and long-term cognitive impairments in an epileptic mouse model., Methods: Mi/Mϕ-specific ASK1 conditional knockout (ASK1 cKO) mice were obtained for experiments by mating ASK1 flox/flox mice with CX3CR1 creER mice with tamoxifen induction. Epileptic seizures were induced by intrahippocampal injection of kainic acid (KA). ASK1 expression and distribution were detected by western blotting and immunofluorescence staining. Seizures were monitored for 24 h per day with video recordings. Cognition, social and stress related activities were assessed with the Y maze test and the three-chamber social novelty preference test. The heterogeneous Mi/Mϕ status and inflammatory profiles were assessed with immunofluorescence staining and real-time polymerase chain reaction (q-PCR). Immunofluorescence staining was used to detect the proportion of Mi/Mϕ in contact with apoptotic neurons, as well as neuronal damage., Results: ASK1 was highly expressed in Mi/Mϕ during the acute phase of epilepsy. Conditional knockout of ASK1 in Mi/Mϕ markedly reduced the frequency of seizures in the acute phase and the frequency of spontaneous recurrent seizures (SRSs) in the chronic phase. In addition, ASK1 conditional knockout mice displayed long-term neurobehavioral improvements during the Y maze test and the three-chamber social novelty preference test. ASK1 selective knockout mitigated neuroinflammation, as evidenced by lower levels of Iba1 + /CD16 + proinflammatory Mi/Mϕ. Conditional knockout of ASK1 increased Mi/Mϕ proportion in contact with apoptotic neurons. Neuronal loss was partially restored by ASK1 selective knockout., Conclusion: Conditional knockout of ASK1 in Mi/Mϕ reduced seizure severity, neurobehavioral impairments, and histological damage, at least via inhibiting proinflammatory microglia/macrophages responses. ASK1 in microglia/macrophages is a potential therapeutic target for inflammatory responses in epilepsy., (© 2022. The Author(s).)

Background: It is estimated that breast cancer (BC) incidence, especially that of early-stage breast cancer cases continues to rise due to increased universal screening. Breast-conserving surgery (BCS) is the main intervention for early-stage BC. Lympho-vascular invasion (LVI) is reported to influence breast cancer prognosis but its prognostic value in breast-conserving treatment is controversial., Methods: A search was conducted on the Cochrane library, PubMed, Web of Science, and EMBASE from inception to December 1 st , 2021, without language restrictions, to identify studies that explored the prognosis of lympho-vascular invasion in breast-conserving surgery. Reviews of each study were conducted, and data extracted. The meta-analysis was performed with StataSE 16. Study quality assessment was evaluated using the Newcastle-Ottawa Scale., Results: Overall, 15 studies with 21,704 patients deemed eligible for this study. Event-free survival (EFS), disease-free survival (DFS), overall survival (OS), distant metastases (DM), loco-regional recurrence (LRR), local recurrence (LR), breast recurrence (BR), disease specific survival (DSS), and breast cancer specific survival (BCSS), were extracted from each study. We found that LVI leads to poor OS (HR = 1.46, 95% CI: 1.17-1.83), DM (HR = 2.08, 95% CI: 1.66-2.60) and LR (HR = 2.00, 95% CI: 1.54-2.61)., Conclusions: We confirmed that early-stage BC patients with LVI-positive have poorer OS, DFS, LRR, BCSS, DM and LR following receiving BCS than those LVI-negative patients. Mastectomy, in combination with radical systemic therapies could be considered, especially in those requiring second surgery. How to change the impact of LVI on the local recurrence rate and long-term survival in patients who undergo BCS may be a valuable research direction in the future., (© 2022. The Author(s).)

Background: Isobutyryl-CoA dehydrogenase deficiency (IBDD) is a rare autosomal recessive metabolic disorder resulting from variants in ACAD8, and is poorly understood, as only dozens of cases have been reported previously. Based on a newborn screening program, we evaluated the incidence, phenotype and genotype of IBDD as well as the prognosis. Moreover, we reviewed the variant spectrum in ACAD8 associated with IBDD., Methods: Forty unrelated patients with IBDD were retrospectively screened for newborns between Jan 2012 and Dec 2020. Tandem mass spectrometry (MS/MS) was used to determine the concentrations of C4-acylcarnitine, C4/C2 (acetylcarnitine), and C4/C3 (propionylcarnitine). All suspected cases were genetically tested by metabolic genes panel., Results: The incidence of IBDD here was 1: 62,599. All patients presented continuously elevated C4-acylcarnitine levels with higher ratios of C4/C2 and C4/C3. Isobutyrylglycine occurred in only 8 patients. During follow-up, four patients had a transient motor delay, and two patients had growth delay. Notably, one case harbored both ACAD8 compound heterozygous variants and a KMT2A de novo variant (c.2739del, p.E914Rfs*35), with IBDD and Wiedemann-Steiner syndrome together, had exact severe global developmental delay. All patients were regularly monitored once they were diagnosed, and each patient gradually had a normal diet after 6 months of age. After 3-108 months of follow-up, most individuals were healthy except the case harboring the KMT2A variant. A total of 16 novel variants in ACAD8, c.4&#95;5delCT, c.109C > T, c.110-2A > T, c.236G > A, c.259G > A, c.381-14G > A, c.413delA, c.473A > G, c.500delG, c.758 T > G, c.842-1G > A, c.911A > T, c.989G > A, c.1150G > C, c.1157A > G and c.1165C > T, were identified. Along with a literature review on 51 ACAD8 variants in 81 IBDD patients, we found that the most common variant was c.286G > A (27.2%), which has been observed solely in the Chinese population to date, followed by c.1000C > T (8.6%), c.1176G > T (3.7%) and c.455 T > C (3.1%)., Conclusion: The concentration of C4-acylcarnitine in NBS plus subsequent genetic testing is necessary for IBDD diagnosis. Both the genotypes and ACAD8 variants in IBDD are highly heterogeneous, and no significant correlations between genotype and phenotype are present here in patients with IBDD. Our IBDD cohort with detaied clinical characteristics, genotypes and long-term prognosis will be helpful for the diagnosis and management of patients with IBDD in the future., (© 2021. The Author(s).)

Characterized by multiple complex mutations, including activation by oncogenes and inhibition by tumor suppressors, cancer is one of the leading causes of death. Application of CRISPR-Cas9 gene-editing technology in cancer research has aroused great interest, promoting the exploration of the molecular mechanism of cancer progression and development of precise therapy. CRISPR-Cas9 gene-editing technology provides a solid basis for identifying driver and passenger mutations in cancer genomes, which is of great value in genetic screening and for developing cancer models and treatments. This article reviews the current applications of CRISPR-Cas9 gene-editing technology in various cancer studies, the challenges faced, and the existing solutions, highlighting the potential of this technology for cancer treatment., (© 2021. The Author(s).)

Background: Although the ACOSOG Z0011 study showed that axillary lymph node dissection (ALND) could be avoided in a specific population of sentinel lymph node-positive patients, it is not widely accepted by Chinese surgeons. We conducted a prospective single-arm study to confirm whether or not the results of Z0011 are applicable to Chinese patients., Methods: Patients conforming to the Z0011 criteria were prospectively enrolled at the Peking University People's Hospital Breast Center from November 2014 to June 2019. The clinicopathological features of the study group were compared with those of the Z0011 study group. Lymphedema after surgery, the incidence of local-regional recurrence, and survival were analyzed., Results: One hundred forty-two patients who met the Z0011 eligibility criteria were enrolled in this study; 115 underwent sentinel lymph node biopsy (SLNB) alone. Compared with the Z0011 trial, younger patients were included (median age, 52 [26-82] years vs 54 [25-90] years; P = 0.03). For clinical T stage, tumor histology, hormone status, lymphovascular invasion, and the number of positive sentinel lymph nodes (SLNs), no statistically significant differences were observed. More patients received adjuvant chemotherapy and endocrine therapy in this study (90.85% vs 58.0% and 80.99% vs 46.6% respectively, P <0.001). A similar percentage of patients received radiotherapy, but more nodal radiotherapy procedures were carried out in our study (54.5% vs 16.9%). After a median follow-up of 29 months, only 1 patient (0.9%) had ipsilateral breast tumor recurrence, and no regional recurrence occurred., Conclusion: Our study showed that it is achievable to avoid ALND in patients eligible for Z0011 in China., Trial Registration: ClinicalTrials.gov. Registration number NCT03606616 . Retrospectively registered on 31 July 2018.

Background: The increasing availability of high-throughput sequencing data provides researchers with unprecedented opportunities to investigate viral genetic elements in host genomes that contribute to virus-linked cancers. Almost all of the available computational tools for secondary analysis of sequencing data detect viral infection or genome integration events. However, viral oncogenes expression is likely of importance in carcinoma. We therefore developed a new software, DisV-HPV16, for the evaluation of HPV16 oncogenes expression., Results: HPV16 virus and viral oncogenes expression was detected more rapidly using DisV-HPV16 compared to other software. DisV-HPV16 was proved highly convenient for detecting candidate virus after modification of the reference file. The accuracy of DisV-HPV16 was empirically confirmed in laboratory experiments. DisV-HPV16 exhibited greater reliability than other software., Conclusions: DisV-HPV16 is a new, dependable software to detect virus and viral oncogenes expression through analysis of RNA sequencing data. Use of DisV-HPV16 can yield deeper, more comprehensive insights into virus infection status and viral and host cell gene expression.

Background: Brain metastasis (BM) is associated with poor prognosis, recurrence, and death in patients with non-small cell lung cancer (NSCLC). Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been reported to be involved in the progression, metastasis and recurrence of malignancies. However, the potential role of LPCAT1 in NSCLC remains poorly understood. This study was aimed to identify genes involved in lung adenocarcinoma (LUAD) brain metastasis, and look into the role of LPCAT1 in LUAD progression., Methods: We used integrative genomic analysis to identify genes involved in lung adenocarcinomas. LPCAT1 expression was evaluated in tumor tissues from LUAD patients and LUAD cell lines. The role of LPCAT1 was subsequently investigated both in vitro and in vivo. The mechanism underlying the involvement of LPCAT1 in LUAD progression was explored with the activator of PI3K/AKT pathway. RNA sequencing was performed to confirm the involvement of LPCAT1 and associated pathway in LUAD brain metastasis., Results: LPCAT1 was up-regulated in LUAD tissues and cell lines. shRNA-mediated depletion of LPCAT1 not only abrogated cell proliferation, migration and invasion in vitro, but also arrested tumor growth and brain metastases in vivo. Notably, LPCAT1 at least partially influenced LUAD progression through PI3K/AKT signal pathway by targeting MYC transcription. Moreover, expression of LPCAT1 was higher in tissues of LUAD patients with BM than those without BM as revealed by IHC staining, RNA-Sequencing and qPCR analysis. Finally, elevated LPCAT1 expression in patients with lung adenocarcinomas was associated with a poor clinical outcome., Conclusions: This study showed that LPCAT1 works as a regulator of cell metastasis and may serve as a novel therapeutic target for BM in lung adenocarcinoma.

Background: Poly C Binding Protein 1 (PCBP1) is an RNA-binding protein that binds and regulates translational activity of subsets of cellular mRNAs. Depletion of PCBP1 is implicated in various carcinomas, but the underlying mechanism in tumorigenesis remains elusive., Methods: We performed a transcriptome-wide screen to identify novel bounding mRNA of PCBP1. The bind regions between PCBP1 with target mRNA were investigated by using point mutation and luciferase assay. Cell proliferation, cell cycle, tumorigenesis and cell apoptosis were also evaluated in ovary and colon cancer cell lines. The mechanism that PCBP1 affects p27 was analyzed by mRNA stability and ribosome profiling assays. We analyzed PCBP1 and p27 expression in ovary, colon and renal tumor samples and adjacent non-tumor tissues using RT-PCR, Western Blotting and immunohistochemistry. The prognostic significance of PCBP1 and p27 also analyzed using online databases., Results: We identified cell cycle inhibitor p27 Kip1 (p27) as a novel PCBP1-bound transcript. We then demonstrated that binding of PCBP1 to p27 3'UTR via its KH1 domain mainly stabilizes p27 mRNA, while enhances its translation to fuel p27 expression, prior to p27 protein degradation. The upregulated p27 consequently inhibits cell proliferation, cell cycle progression and tumorigenesis, whereas promotes cell apoptosis under paclitaxel treatment. Conversely, knockdown of PCBP1 in turn compromises p27 mRNA stability, leading to lower p27 level and tumorigenesis in vivo. Moreover, forced depletion of p27 counteracts the tumor suppressive ability of PCBP1 in the same PCBP1 over-expressing cells. Physiologically, we showed that decreases of both p27 mRNA and its protein expressions are well correlated to PCBP1 depletion in ovary, colon and renal tumor samples, independent of the p27 ubiquitin ligase Skp2 level. Correlation of PCBP1 with p27 is also found in the tamoxifen, doxorubincin and lapatinib resistant breast cancer cells of GEO database., Conclusion: Our results thereby indicate that loss of PCBP1 expression firstly attenuates p27 expression at post-transcriptional level, and subsequently promotes carcinogenesis. PCBP1 could be used as a diagnostic marker to cancer patients.

The original article [1] contained incorrect affiliations for the authors.

Background: Recent studies show that near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve the performance of sentinel lymph node (SLN) mapping. The current cohort study was designed to assess the value of the combination of ICG and methylene blue (MB) dye in patients undergoing SLN biopsy., Methods: A prospective self-controlled trial was designed to detect the difference in the detection efficacies of ICG, MB, and combined ICG and MB (ICG + MB) navigation methods. Between 2010 and 2013, 198 consecutive early breast cancer patients eligible for sentinel lymph node biopsy were enrolled and 200 biopsy procedures were performed by injection of both ICG and MB. SLNs were searched and removed under the guidance of fluorescence and/or blue dye. The mapping characteristics, the detection rate of SLNs and positive SLNs, and the number of SLNs of ICG, MB, and ICG + MB were compared. Injection safety of ICG and MB was evaluated., Results: Fluorescence imaging of lymphatic flow, which is helpful to locate the incision site, could be seen in 184 of 200 procedures. The nodal detection rate of ICG, MB, and ICG + MB samples was 97, 89, and 99.5% (χ 2  = 26.2, p < 0.001), respectively, with the combination method yielding a superior identification result. The addition of ICG to the MB method resulted in the identification of more lymph nodes (median 3 versus 2) and more positive axillas (22.7% involved axillas were discovered by fluorescence only) than either method alone. No acute or chronic allergic reaction was observed in this study. However, 23 patients (23/82) who received breast-conserving therapy reported temporary skin staining, and 5 patients had permanent tattooing. Palpable subcutaneous nodules at the injection sites were reported in nine patients. There were no reports of skin necrosis., Conclusions: The lymphatic navigation by ICG fluorescence detects SLNs at a high detection rate and improves the mapping performance when added to the MB method. The novel ICG + MB dual tracing modality, without involvement of radioactive isotopes, exhibits great potential as an alternative to traditional standard mapping methods., Trial Registration: ACTRN12612000109808 . Retrospectively registered on 23 January 2012.

Background: Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). Recent studies demonstrated that microRNA-330-3p (miR-330-3p) was involved in NSCLC brain metastasis (BM). However, the exact parts played by miR-330-3p in BM of NSCLC remain unknown. Discovery and development of biomarkers and elucidation of the mechanism underlying BM in NSCLC is critical for effective prophylactic interventions. Here, we evaluated the expression and biological effects of miR-330-3p in NSCLC cells and explored the underlying mechanism of miR-330-3p in promoting cell migration and invasion in NSCLC., Methods: Stable over-expression and knockdown of miR-330-3p in NSCLC cells was constructed with lentivirus. Expression levels of miR-330-3p in NSCLC cells were quantified by quantitive real-time PCR (qRT-PCR). The effects of miR-330-3p on NSCLC cells were investigated using assays of cell viability, migration, invasion, cell cycle, apoptosis, western blotting, immunohistochemical, and immunofluorescence staining. A xenograft nude mouse model and in situ brain metastasis model were used to observe tumor growth and brain metastasis. The potential target of miR-330-3p in NSCLC cells was explored using the luciferase reporter assay, qRT-PCR, and western blotting. The miR-330-3p targets were identified using bioinformatics analysis and verified by luciferase reporter assay. The correlation between GRIA3 and DNA methyltransferase (DNMT) 1 and DNMT3A was tested by RT-PCR, western blotting, and co-immunoprecipitation (IP)., Results: miR-330-3p was significantly up-regulated in NSCLC cell lines. MTT assay, transwell migration, and invasion assays showed that miR-330-3p promoted the growth, migration, and invasion of NSCLC cells in vitro and induced tumor growth and metastasis in vivo. Luciferase reporter assays showed that GRIA3 was a target of miR-330-3p. qRT-PCR and western blotting exhibited that miR-330-3p promoted the growth, invasion, and migration of NSCLC cells by activating mitogen-activated protein kinase (MAPK)/extracellular-regulated protein kinases (ERK) signaling pathway. Furthermore, miR-330-3p up-regulated the total DNA methylation in NSCLC cells, and co-IP-demonstrated GRIA3 was directly related with DNMT1 and DNMT3A., Conclusions: miR-330-3p promoted the progression of NSCLC and might be a potential target for the further research of NSCLC brain metastasis.

Background: Branchial cleft anomalies constitute a frequently encountered and commonly non-lethal disease in otolaryngology, and result from aberrant embryonic development. The third branchial cleft fistula is one of the four known specific types of branchial cleft anomalies, and always presents as recurrent neck abscess and suppurative thyroiditis. Here, we report an unexpected death due to severe neck infection following a third branchial cleft fistula., Case Presentation: A 19-year-old man was sent to the hospital with a 1-week history of recurrent left-sided neck abscess, and was scheduled for incision and drainage of the abscess. However, before the surgery was performed, the man's condition deteriorated and he died. A review of his medical history showed that he had undergone a previous incision and drainage for a neck abscess 2 years ago. Postmortem examination revealed that the fatal neck abscess was induced by a third branchial cleft fistula., Conclusions: We conclude that a histopathological examination of neck tissue combined with a detailed review of medical history and examination of ultrasonographic and CT images can provide a rapid and accurate diagnosis of third branchial cleft fistula. This common, non-lethal disease can potentially lead to death if the neck infection is not properly diagnosed and treated. In medico-legal practice, medical examiners should be aware of this condition, as this knowledge would be important in the diagnosis of the cause of death.

Background: The clear cell/signet-ring cell variant of cutaneous squamous cell carcinoma (cSCC) is extremely rare. Its carcinogenesis has consistently been linked to ultraviolet radiation and HPV in the literature. However, there is little definite information about the contribution of diabetes mellitus (DM) to cSCC., Case Presentation: A 78-year-old Chinese woman with type 2 DM presented with a mushroom-like lump in her right thigh. Histological findings revealed that the lesion was mainly composed of clear cells and signet-ring cells. The septa of vacuoles in cytoplasm displayed positivity for periodic acid schiff (PAS) and cytokeratins such as AE1/AE3, CK5/6, CK14, and CK19. Malignant cells did not express CK7, CK8, CK18, CK20, p16, p53, or c-erbB-2, and the Ki-67 index was less than 5 %. We further explored the etiology of clear cell/signet-ring cell cSCC using human papillomavirus (HPV) type-specific PCR and genotyping and confirmed that the patient was not infected with HPV. Nucleus positivity for p63 indicated the involvement of the p53 family in the lesion. Meanwhile, the expression of fibroblast growth factor receptor-2 (FGFR2), a downstream effector of p63, was upregulated in tumor cells., Conclusions: This study provides the first report on the clear cell/signet-ring cell variant of cSCC found in the right thigh of a patient with type 2 DM. Metabolic imbalance in addition to conventional pathogens such as UV and HPV may contribute to the development of the lesion via p63/FGFR2 axis.

Background: Microbubbles and contrast-enhanced ultrasound (CEUS) is a new technique for locating sentinel lymph node (SLN). The aim of this study is to explore the feasibility of SLNs tracing by CEUS using microbubbles in breast cancer patients and the value of enhancing patterns in diagnosing lymph nodes metastases., Methods: A clinical trial was registered (trial registration: ChiCTR-DDT-13003778). One hundred and one consecutive consenting patients with breast cancer undergoing SLN biopsy were enrolled. Before the surgery, microbubble was injected periareolarly. Lymphatic drainage pathway was detected by CEUS, and guidewire was deployed to locate the SLN before the operation. Blue dye was also used to help in tracing sentinel lymph node during the operation. The identification rate and the accuracy rate were recorded. Enhancing patterns of lymph nodes were recorded and compared with the pathological diagnosis., Results: Of the 101 cases, SLNs in 99 cases were successfully identified by at least one tracer, including 98 cases identified by CEUS and 97 cases by blue dye. There was no significant difference between the two methods (P = 0.705). Guidewires were deployed successfully in all 98 cases, and the localized SLNs were all isolated successfully in the following operations. The status of SLNs isolated by CEUS was completely identical to that of the whole axillary lymph node while 7.1 % cases were misdiagnosed as negative by blue dye method. The sensitivity of predicting SLNs metastases by CEUS enhancing pattern was 81.8 %, the specificity was 86.2 %, and the positive and negative predictive values were 75.0 and 90.3 %, respectively., Conclusions: Microbubbles and CEUS are feasible approaches for SLN identification. The enhancing patterns on CEUS may be helpful to recognize the metastasizing SLNs. This novel method may be a promising technique for the clinical application.

Background: Upper arm development in children is different in different ethnic groups. There have been few reports on upper arm circumference (UAC) at different stages of development in children and adolescents in China. The purpose of this study was to provide a reference for growth with weighted assessment of the overall level of development., Methods: Using a pooled analysis, an authoritative journal database search and reports of UAC, we created a new database on developmental measures in children. In conducting a weighted analysis, we compared reference values for 0~60 months of development according to the World Health Organization (WHO) statistics considering gender and nationality and used Z values as interval values for the second sampling to obtain an exponential smooth curve to analyze the mean, standard deviation, and sites of attachment., Results: Ten articles were included in the pooled analysis, and these articles included participants from different areas of China. The point of intersection with the WHO curve was 3.5 years with higher values at earlier ages and lower values at older ages. Boys curve was steeper after puberty. The curves in the studies had a merged line compatible. The Z values of exponential smoothing showed the curves were similar for body weight and had a right normal distribution., Conclusions: The integrated index of UAC in Chinese children and adolescents indicated slightly variations with regions. Exponential curve smoothing was suitable for assessment at different developmental stages.

Background: Phlebotomus papatasi vectors zoonotic cutaneous leishmaniasis. Previous expression of recombinant P. papatasi acetylcholinesterase (PpAChE1) revealed 85% amino acid sequence identity to mosquito AChE and identified synthetic carbamates that effectively inhibited PpAChE1 with improved specificity for arthropod AChEs compared to mammalian AChEs. We hypothesized that the G119S mutation causing high level resistance to organophosphate insecticides in mosquitoes may occur in PpAChE1 and may reduce sensitivity to inhibition. We report construction, expression, and biochemical properties of rPpAChE1 containing the G119S orthologous mutation., Methods: Targeted mutagenesis introduced the G119S orthologous substitution in PpAChE1 cDNA. Recombinant PpAChE1 enzymes containing or lacking the G119S mutation were expressed in the baculoviral system. Biochemical assays were conducted to determine altered catalytic properties and inhibitor sensitivity resulting from the G119S substitution. A molecular homology model was constructed to examine the modeled structural interference with docking of inhibitors of different classes. Genetic tests were conducted to determine if the G119S orthologous codon existed in polymorphic form in a laboratory colony of P. papatasi., Results: Recombinant PpAChE1 containing the G119S substitution exhibited altered biochemical properties, and reduced inhibition by compounds that bind to the acylation site on the enzyme (with the exception of eserine). Less resistance was directed against bivalent or peripheral site inhibitors, in good agreement with modeled inhibitor docking. Eserine appeared to be a special case capable of inhibition in the absence of covalent binding at the acylation site. Genetic tests did not detect the G119S mutation in a laboratory colony of P. papatasi but did reveal that the G119S codon existed in polymorphic form (GGA + GGC)., Conclusions: The finding of G119S codon polymorphism in a laboratory colony of P. papatasi suggests that a single nucleotide transversion (GGC → AGC) may readily occur, causing rapid development of resistance to organophosphate and phenyl-substituted carbamate insecticides under strong selection. Careful management of pesticide use in IPM programs is important to prevent or mitigate development and fixation of the G119S mutation in susceptible pest populations. Availability of recombinant AChEs enables identification of novel inhibitory ligands with improved efficacy and specificity for AChEs of arthropod pests.

Background: Tandem mass spectrometry (MS/MS) has been available in China for 8 years. This technique makes it possible to screen for a wide range of previously unscreened inborn errors of metabolism (IEM) using a single test. This 3-year pilot study investigated the screening, diagnosis, treatment and outcomes of IEM in symptomatic infants and children., Methods: All children encountered in the Newborn Screening Center of Zhejiang Province during a 3-year period with symptoms suspicious for IEM were screened for metabolic diseases. Dried blood spots were collected and analyzed by tandem mass spectrometry. The diagnoses were further confirmed by clinical symptoms and biochemical analysis. Neonatal intrahepatic cholestasis caused by citrin deficiency, ornithine transcarbamylase deficiency and primary carnitine deficiency were confirmed by DNA analysis., Results: A total of 11,060 symptomatic patients (6,720 boys, 4,340 girls) with a median age of 28.8 months (range: 0.04-168.2 months) were screened. Among these, 62 were diagnosed with IEM, with a detection rate of 0.56%. Thirty-five were males and 27 females and the median age was 3.55 months (range 0.07-143.9 months). Of the 62 patients, 27 (43.5%) had aminoacidemias, 26 (41.9%) had organic acidemias and nine (14.5%) had fatty acid oxidation disorders., Conclusions: Because most symptomatic patients are diagnosed at an older age, mental retardation and motor delay are difficult to reverse. Additionally, poor medication compliance reduces the efficacy of treatment. More extensive newborn screening is thus imperative for ensuring early diagnosis and enhancing the treatment efficacy of IEM.