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To test whether targeting left and right posterior parietal cortex (PPC) with continuous theta-burst stimulation (cTBS) in healthy adults would strengthen associative memory (AM) performance. This study consisted of two experiments (a behavioral experiment and a formal experiment during each of the two experimental sessions). In Experiment 1, 18 adults (one male, age = 22.83 ± 3.92 years) were included in the behavioral phase and 18 adults (seven males, age = 40.11 ± 12.27 years) in the stimulation phase. There were 120 neutral facial images paired with 120 two-character nouns and then divided into six test versions (10 male faces and 10 female faces paired with 20 different nouns were considered as one version). In the behavioral experiment, participants were tested by six-version tests to assess memory materials, and in the formal experiment, participants' face-word AM performance was measured by certified tests based on a cued recall paradigm. Furthermore, 30 adults (seven males, age = 20.97 ± 1.85 years) and 15 adults (five males, age = 22.27 ± 1.29 years) participated in Experiment 2, respectively. Stimuli and procedure were the same as in Experiment 1, but the AM test was based on a forced-choice paradigm. Experiment 1 did not yield anticipated outcomes; Experiment 2 showed that cTBS of left and right PPC strengthened the AM performance compared with the control condition. In conclusion, cTBS to left and right PPC improved AM in healthy adults, which provided further experimental evidence for strengthening AM by cTBS., (© 2024 Massachusetts Institute of Technology.)

Background: Alcohol use contributes considerably to the global impact of disease. However, limited research has been conducted recently to explore the changes in the prevalence of alcohol use, especially in urban Shanghai, China., Objectives: To estimate the prevalence changes of alcohol use and explore related sociodemographic factors among urban residents of Xuhui district, Shanghai, China., Methods: Using a multistage probability proportionate-to-size sampling method, three waves of household investigations via a structured questionnaire were conducted in Xuhui district, Shanghai, China, between 2010 and 2021. Data were collected by face-to-face interviews among residents aged 15 or older who responded to the 2010, 2015, and 2021 Health Status and Health Service Utilization Survey. Age and sex standardized prevalence of alcohol use was calculated, and the linear trend was tested using logistic regression models. Multilevel mixed-effects logistic regression models with robust covariance matrix estimators were used to estimate related factors of alcohol use., Results: A total of 24 552 participants aged 15-109 years were included. The standardized overall prevalence of current regular alcohol use statistically declined from 8.8 % in 2010 to 5.5 % in 2021. This decreasing trend was statistically significant, especially among men aged 30-59 and ≥ 75 years old. However, the prevalence of overall alcohol use, regardless of frequency, increased from 19.6 % in 2015 to 24.0 % in 2021. Multivariate regression analysis showed that men had a significantly higher likelihood of regular alcohol use than women. Also, age was positively related to regular alcohol use, while education level was negatively related to this behavior., Conclusions: Alcohol use was still common, although a significant decreasing trend in the prevalence of regular alcohol use was observed overall, in this study population. The findings call for strengthened health education and alcohol control in the context of the harmful effects of alcohol use at any level., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To investigate the relationship between the expression of PD-L1 in OSCC and the clinicopathological features and prognosis of patients., Methods: We retrospectively analyzed the clinicopathological data and prognosis of 381 OSCC patients. Immunohistochemical staining was performed on OSCC tumor specimens, and the expression level of PD-L1 was evaluated according to the combined positive score (CPS). Kaplan-Meier analysis was used to identify the effect of PD-L1 expression and clinicopathological features on the prognosis of patients. Univariate and multivariate Cox regression analyses were conducted to determine the hazard factors affecting the prognosis of patients., Results: PD-L1 overexpression was significantly associated with cervical lymph node metastasis (p = 0.018), worse clinical stage (p = 0.022), worse tumor differentiation (p = 0.046), and worse depth of invasion (DOI) (p = 0.003). Poorer clinical stage and degree of tumor differentiation were significantly associated with poorer OS and DSS in patients. PD-L1 expression was not associated with prognosis in patients with OSCC., Conclusions: High PD-L1 expression was significantly associated with higher tumor malignancy in OSCC patients. Poorer clinical stage and degree of tumor differentiation were associated with poor prognosis in OSCC patients. Our results may help clinicians develop more appropriate individualized treatment strategies for their patients, thus improving their outcomes., (© 2024 John Wiley & Sons Ltd.)

The purpose of this study is to systematically analyze the development trend, research hotspots, and future development direction on the treatment of neuropathic pain (NP) with spinal cord stimulation through bibliometric method. We extracted the literature related to the treatment of NP with spinal cord stimulation from January 2004 to December 2023 from the Web of Science database. As a result, a total of 264 articles were retrieved. By analyzing the annual published articles, authors, countries, institutions, journals, co-cited literature, and keywords, we found that the count of publication in this field has been experiencing an overall growth, and the publications within the past 5 years accounted for 42% of the total output. Experts from the United States and the UK have made significant contributions in this field and established a stable collaborative team, initially establishing an international cooperation network. Pain is the frequently cited journal in this field. The study on spinal cord stimulation therapy for NP especially the study on spinal cord stimulation therapy for back surgery failure syndrome (FBSS) and its potential mechanisms are the research hotspots in this field, while the study on novel paradigms such as high-frequency spinal cord stimulation and spinal cord burst stimulation represents the future development directions. In short, spinal cord stimulation has been an effective treatment method for NP. The novel paradigms of spinal cord stimulation are the key point of future research in this field., (© 2024. The Author(s).)

The aim of this study is to describe the general information, disease and treatment of venous thromboembolism (VTE) in critically ill patients, to explore the characteristics of severe patients with deep venous VTE and provide clinical reference data for the prevention and treatment of VTE in critically ill patients. This study carried out a retrospective study on the medical records of patients who were treated in the intensive care unit of Affiliated Hospital of Jining Medical College from 2020 to 2022. The general data, general conditions, drug use, past history, VTE prevention measures, post-VTE conditions, and Padua risk score of 297 patients with VTE during the period of hospitalization in intensive care unit (ICU) were classified and statistically analyzed. A total of 297 including 171 male and 126 male patient medical records were included in the analysis, we compared multiple clinical indicators between male and female patients. Compared to women, male patients have a higher acute physiology and chronic health evaluation II score(APACHE-II score) (P = .027), a higher state of consciousness (P = .003), a higher rate of smoking and drinking history (P < .001), a lower rate of heart failure (P = .003) and chronic depression (P = .013), and a higher rate of recommended operations for male patients after VTE (P = .031). The prothrombin time (PT) (P = .041) and activated partial thromboplastin time (APTT) (P = .040) of male patients were significantly higher than those of female patients, while triglyceride (P = .009) and total cholesterol (TC) (P = .001) were significantly lower than those of female patients. The difference in D-dimer (P = .739) was not significant. This study shows that male and female patients with VTE in the ICU have significant differences in general characteristics, general clinical conditions, history of past illness, thrombosis character, and examination items, this may be the reason for the different rates of VTE between male and female patients in the ICU., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Jinlida granule (JLD) is a Traditional Chinese Medicine (TCM) formula used for the treatment of type 2 diabetes mellitus (T2DM). However, the mechanism of JLD treatment for T2DM is not fully revealed. In this study, we explored the mechanism of JLD against T2DM by an integrative pharmacology strategy. Active components and corresponding targets were retrieved from Traditional Chinese Medicine System Pharmacology (TCMSP), SwissADME and Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine Database (BATMAN-TCM) database. T2DM-related targets were obtained from Drugbank and Genecards databases. The protein-protein interaction (PPI) network was constructed and analyzed with STRING (Search Toll for the Retrieval of Interacting Genes/proteins) and Cytoscape to get the key targets. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed with the Database for Annotation, Visualization and Integrated Discovery (DAVID). Lastly, the binding capacities and reliability between potential active components and the targets were verified with molecular docking and molecular dynamics simulation. In total, 185 active components and 337 targets of JLD were obtained. 317 targets overlapped with T2DM-related targets. RAC-alpha serine/threonine-protein kinase (AKT1), tumor necrosis factor (TNF), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), prostaglandin G/H synthase 2 (PTGS2), Caspase-3 (CASP3) and signal transducer and activator of transcription 3 (STAT3) were identified as seven key targets by the topological analysis of the PPI network. GO and KEGG enrichment analyses showed that the effects were primarily associated with gene expression, signal transduction, apoptosis and inflammation. The pathways were mainly enriched in PI3K-AKT signaling pathway and AGE-RAGE signaling pathway in diabetic complications. Molecular docking and molecular dynamics simulation verified the good binding affinity between the key components and targets. The predicted results may provide a theoretical basis for drug screening of JLD and a new insight for the therapeutic effect of JLD on T2DM., (© 2024. The Author(s).)

Induced pluripotent stem cells (iPSCs) have wide applications in disease modeling, personalized medicine, and tissue engineering. The generation of iPSCs from somatic cells via transcriptional-factor- or chemical molecule-based approaches are time-consuming and inefficient. Here, a cell-reprogramming-inspired dynamically responsive hydrogel is fabricated via a synthetic-biology-based strategy. Human and mouse somatic cells (including senescent cells) are efficiently reprogrammed into iPSCs that exhibit key features of embryonic stem cells. The cell-reprogramming-responsive hydrogel possesses dynamic bioresponsiveness, and it faithfully senses metabolic remodeling and extracellular acidification during cell reprogramming, responding by changing its mechanical properties accordingly. Mechanistic study demonstrates that the autonomous change of the mechanical properties of the cell-reprogramming-responsive hydrogel elicits the formation of Yes-associated protein (YAP) biomolecular condensates with the appropriate timing during cell reprogramming, ensuring a faster and more efficient generation of iPSCs than conventional cell reprogramming approach. Taken together, this study reveals the robust induction of pluripotency by coordination of cell-reprogramming-inspired dynamically responsive hydrogel and phase-separated biomolecular condensates., (© 2023 Wiley‐VCH GmbH.)

Anaplastic thyroid carcinoma (ATC) is the most advanced and aggressive thyroid cancer, and poorly differentiated thyroid carcinoma (PDTC) lacks anaplastic histology but has lost architectural and cytologic differentiation. Only a few studies have focused on the genetic relationship between the two advanced carcinomas and coexisting differentiated thyroid carcinomas (DTCs). In the present study, we investigated clinicopathologic features and genetic profiles in 57 ATC and PDTC samples, among which 33 cases had concomitant DTC components or DTC history. We performed immunohistochemistry for BRAF V600E, p53, and PD-L1 expression, Sanger sequencing for TERT promoter and RAS mutations, and fluorescence in situ hybridization for ALK and RET rearrangements. We found that ATCs and PDTCs shared similar gene alterations to their coexisting DTCs, and most DTCs were aggressive subtypes harboring frequent TERT promoter mutations. A significantly higher proportion of ATCs expressed p53 and PD-L1, and a lower proportion expressed PAX-8 and TTF-1, than the coexisting DTCs. Our findings provide more reliable evidence that ATCs and PDTCs are derived from DTCs., (© 2024 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Background: Stroke stands as the second leading cause of death worldwide. Currently, extensive research has been conducted on stroke risk factors. However, when stroke patients contend with multiple risk factors, the impact on clinical indicators remains uncertain., Objectives: This study seeks to investigate potential significant variations among distinct ranges of clinical indicators in instances where stroke patients experience multiple risk factors and various ischemic stroke subtypes., Material and Methods: The research encompassed 440 stroke patients admitted to the First People's Hospital of Wenling City, Zhejiang Province, China. These patients were classified based on the type and quantity of risk factors and subtypes of ischemic stroke they presented. The χ 2 test was employed to assess the relationship between the risk of comorbid diseases and clinical indicators in stroke patients., Results: The results of our study have underscored a significant correlation between various comorbid risk factors in stroke patients and the patients' age (P < 0.010). Furthermore, we observed noteworthy disparities in the plasma levels of IL-2, IL-4, IL-6, IL-10, TNF-α, and INF-γ between patients devoid of risk factors and those presenting with comorbid risk factors associated with stroke. Significant differences in INF-γ were observed between the two subtypes of ischemic stroke, namely lacunar infarction and cardioembolic stroke., Conclusion: Age is correlated with an elevated risk of stroke. Individuals exhibiting multiple stroke risk factors and diverse ischemic stroke subtypes commonly present with abnormal lipid levels and imbalances in Th1/Th2 cytokines. These factors significantly contribute to the onset and progression of stroke. Furthermore, inflammatory responses, particularly those induced by atherosclerosis, play a pivotal role in the genesis of stroke and exert a substantial influence on its prognosis., (© 2024. The Author(s).)

Background: This study aimed to investigate the interactions among three core elements of respiratory infection-pathogen, lung microbiome, and host response-and their avocation with the severity and outcomes of Mycoplasma pneumoniae pneumonia (MPP) in children., Methods: We prospectively collected bronchoalveolar lavage fluid from a cohort of 41 children with MPP, including general MPP (GMPP) and complicated MPP (CMPP), followed by microbiome and transcriptomic analyses to characterize the association among pathogen, lung microbiome, and host response and correlate it with the clinical features and outcomes., Results: The lung microbiome of patients with CMPP had an increased relative abundance of Mycoplasma pneumoniae (MP) and reduced alpha diversity, with 76 differentially expressed species. Host gene analysis revealed a key module associated with neutrophil function and several inflammatory response pathways. Patients with a high relative abundance of MP, manifested by a specific lung microbiome and host response type, were more prone to CMPP and had a long imaging recovery time., Conclusion: Patients with CMPP have a more disrupted lung microbiome than those with GMPP. MP, lung microbiome, and host response interacts with each other and are closely related to disease severity and outcomes in children with MPP., (© 2024. The Author(s).)

Background: The imaging findings of Mycoplasma pneumoniae pneumonia (MPP) vary; however, few studies have focused on the relationship of imaging classification with clinical manifestations and outcomes., Objective: To prospectively investigate whether chest imaging classification in Mycoplasma pneumoniae pneumonia (MPP) is associated with its clinical features and outcomes., Methods: A total of 1,401 hospitalized children with MPP were enrolled from January 2019 to December 2021. Imaging findings were categorized as bronchopneumonia and consolidation/atelectasis according to X-ray, and bronchopneumonia, consolidation/atelectasis, bronchiolitis, and mosaic pattern according to computed tomography (CT). Clinical characteristics and outcomes of patients with different imaging classifications were prospectively analyzed based on electronic medical records., Results: Bronchopneumonia was the most common finding (59.6%), while consolidation/atelectasis was the most severe group. Clinical manifestations and laboratory indicators for the consolidation/atelectasis group included serious abnormalities. Further, outcomes of the patients were worse, including having longer total durations of fever and hospitalization, greater hospitalization expenses, and a higher likelihood of developing refractory MPP, necrotizing pneumonia, and bronchiolitis obliterans (BO) in this group. The incidence of bronchiolitis, a disease characterized by a high prevalence of fever, moist rales, and an atopic constitution, tended to increase after the coronavirus disease pandemic and predisposed patients to BO. A mosaic pattern occurred in allergic and young individuals, with wheezing as the main manifestation, with patients having relatively mild symptoms and good outcomes., Conclusion: Different imaging classifications have different clinical features and clinical outcomes; thus, formulating an imaging-based classification system is of great clinical value., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Mycoplasma pneumoniae pneumonia (MPP) may lead to various significant outcomes, such as necrotizing pneumonia(NP) and refractory MPP (RMPP). We investigated the potential of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) to predict outcomes in patients with MPP., Methods and Materials: This was a prospective study of patients with MPP who were admitted to our hospital from 2019 to 2021. Demographic and clinical data were collected from patient records and associated with the development of NP and RMPP and other outcome measures., Results: Of the 1,401 patients with MPP included in the study, 30 (2.1%) developed NP. The NLR was an independent predictor of NP (odds ratio 1.153, 95% confidence interval 1.022-1.300, P =0.021). The probability of NP was greater in patients with a high NLR (≥1.9) than in those with a low NLR (<1.9) ( P <0.001). The NLR was also an independent predictor of RMPP (odds ratio 1.246, 95% confidence interval 1.102-1.408, P <0.005). Patients with a high NLR were more likely to develop NP and RMPP and require intensive care, and had longer total fever duration, longer hospital stays, and higher hospitalization expenses than those with a low NLR (all P <0.005)., Discussion: The NLR can serve as a predictor of poor prognosis in patients with MPP. It can predict the occurrence of NP, RMPP, and other poor outcomes. The use of this indicator would allow the simple and rapid prediction of prognosis in the early stages of MPP, enabling the implementation of appropriate treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Gu, Chen, Wu, Jiang, Huang, Zhao and Liu.)

Background: Many gaps remain in our understanding of the immune and molecular characteristics that underlie activated phosphoinositide 3-kinase delta syndrome (APDS)., Methods: We performed RNA sequencing of peripheral blood leukocytes obtained from a child with APDS and his healthy parents and deconvoluted bulk transcriptional data to assess immune cell status., Results: Pathway enrichment analysis suggested signaling pathways enriched in virus infection as well as the PI3K, mitogen-activated protein kinase (MAPK), natural killer cell-mediated cytotoxicity, and nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathways. The proportion of B cells memory, T cells CD4 memory resting and dendritic cells activated were reduced, whereas B cells naïve, T cells CD8, NK cells resting, monocytes and macrophages M2 were increased in the child. Top 10 hub genes were screened and showed moderate to strong relatedness with immune cell proportions., Conclusion: Deconvolution of bulk RNA sequencing to assess immune cells status can provide further insight into the alterations in immunological features underlying APDS and other rare diseases., (© 2023 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Background: Transitioning from marriage to widowhood presents inevitable and significant challenges for many older adults. This study explored the impact of widowhood on a range of mental health outcomes, including pulse pressure and fasting blood glucose levels, among older adults in nursing homes., Methods: This cross-sectional study utilized cluster random sampling to recruit participants, with data analyzed from 388 older Chinese adults. Psychosocial traits were assessed using the Perceived Social Support from Family scale (PSS-Fa) for family support, the Generalized Anxiety Disorder 7-item scale (GAD-7) for anxiety symptoms, and the 9-item Patient Health Questionnaire (PHQ-9) for depressive symptoms and suicidal ideation. Propensity score matching (PSM) was employed to control for confounding factors. A multivariate linear regression analysis was performed to explore the relationship between widowhood, mental health outcomes, pulse pressure, and fasting blood glucose levels., Results: After applying PSM, the sample size was refined to 268 ( N  = 134 for both married and widowed groups) from the initial 388, excluding 120 unmatched cases. Widowed older adults were found to have notably lower family support ( β  = -0.81, p  = 0.002), increased depressive symptoms ( β  = 1.04, p  = 0.043), elevated pulse pressure ( β  = 8.90, p  < 0.001), and higher fasting blood glucose levels ( β  = 3.22, p  = 0.027). These associations exhibited greater beta values compared to pre-matching analysis., Conclusion: Our findings revealed that widowed participants had reduced family support, an increased risk of depressive symptoms, heightened pulse pressure, and elevated fasting blood glucose in comparison to their married counterparts. Interventions focusing on social support, mental health, and cardiovascular well-being could be advantageous for this at-risk group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Chen, Sun, Feng, Wang, Gu, Jia, Zhang, Ding, Lu and Zhang.)

Triple-negative breast cancer (TNBC) remains the most challenging breast cancer subtype due to its lack of targeted therapies and poor prognosis. In order to treat patients with these tumors, efforts have been made to explore feasible targets. Epidermal growth factor receptor (EGFR)-targeted therapy is currently in clinical trials and regarded to be a promising treatment strategy. In this study, an EGFR-targeting nanoliposome (LTL@Rh2@Lipo-GE11) using ginsenoside Rh2 as a wall material was developed, in which GE11 was used as the EGFR-binding peptide to deliver more ginsenoside Rh2 and luteolin into TNBC. In comparison to non-targeted liposomes (Rh2@Lipo and LTL@Rh2@Lipo), the nanoliposomes LTL@Rh2@Lipo-GE11 demonstrated a high specificity to MDA-MB-231 cells that expressed a high level of EGFR both in vitro and in vivo, contributing to the strong inhibitory effects on the growth and migration of TNBC. These results suggest that LTL@Rh2@Lipo-GE11 is a prospective candidate for targeted therapy of TNBC, with a remarkable capability to inhibit tumor development and metastasis.

Poststroke aphasia is an acquired language disorder and has been proven to have adverse effects on patients' social skills and quality of life. However, there are some inconsistencies in the neuroimaging studies investigating poststroke aphasia from the perspective of regional alterations. A meta-analysis has been employed to examine the common pattern of abnormal regional spontaneous brain activity in poststroke aphasia in the current study. Specifically, the Anisotropic effect-size version of seed-based d mapping was utilized, and 237 poststroke aphasia patients and 242 healthy controls (HCs) from 12 resting-state functional magnetic resonance imaging studies using amplitude of low-frequency fluctuations (ALFF), fractional ALFF, or regional homogeneity were included. The results showed that compared with HCs, patients with poststroke aphasia demonstrated increased regional spontaneous brain activity in the right insula, right postcentral gyrus, left cerebellar lobule IX, left angular gyrus, right caudate nucleus, left parahippocampal gyrus, and right supplementary motor area, and decreased regional spontaneous brain activity in the left cerebellar lobule VI, left median cingulate and paracingulate gyri, right cerebellar crus I, and left supplementary motor area. The study could provide further evidence for pathophysiological mechanism of poststroke aphasia and help find targets for treatment., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Mycoplasma pneumoniae (MP) is a major pathogen of community-acquired pneumonia in children. However, the specific pathogenesis of the progression of Mycoplasma pneumoniae pneumonia (MPP) is unclear. We aimed to reveal the landscape of microbiota and the host immune response in MPP., Methods: This self-controlled study analyzed the microbiome and transcriptome of bronchoalveolar lavage fluid (BALF) from the severe side (SD) and opposite side (OD) of 41 children with MPP from January to December 2021 and revealed the differences of the peripheral blood neutrophil function among children with mild MPP, severe MPP, and healthy children through transcriptome sequencing., Results: The MP load or the pulmonary microbiota had no significant difference between the SD group and OD group, and the deterioration of MPP was related to the immune response, especially the intrinsic immune response., Discussion: The immune response plays a role in MPP, which may inform treatment strategies for MPP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Luo, Li, Jiang, Du, Wang, Li, Gu, Li, Tang, Qin, Xu, Liu, Zhao, Guo and Liu.)

Background: Chondroblastoma is a primary bone tumor typically arising from the intramedullary space of the epiphysis or epimetaphysis. A non-epiphyseal chondroblastoma is uncommon. Case report: An 11-year-old girl presented with an eccentric cortical osteolytic lesion in the distal femur metaphysis. The typical morphology, diffuse H3.3 K36M immunohistochemical expression and H3F3B point mutation ( c. 110A > T ) unequivocally supported the diagnosis of chondroblastoma. Discussion: We described a non-epiphyseal cortical-based chondroblastoma involving the distal femur harboring the typical H3F3B mutation. Non-epiphyseal chondroblastoma may harbor the H3F3B mutation.

Although metastasis is the major cause of death in cervical cancer, the mechanism of metastasis is still unclear. The mRNA expression and protein level of latent transforming growth factor beta binding protein 1 (LTBP1) were detected in tumor tissues and paracancerous tissues from in-house samples. Cell proliferation, cell cycle, migration, and in vivo metastasis were determined after LTBP1 was knocked down. Then, 13 drugs were screened, and the changes in cell apoptosis and proliferation and tumor metastasis were detected after drug treatment in shRNA cells. In our in-house samples, LTBP1 was lowly expressed in cervical cancer tissues. After LTBP1 knockdown, cell proliferation was increased, and the ability of in vitro migration and in vivo metastasis was enhanced. At the same time, the proportion of myeloid derived suppressor cells (MDSC) in situ increased, the proportion of T cells decreased, and transforming growth factor beta-1 (TGFβ1) signaling was activated. After carboplatin treatment, LTBP1 shRNA cell line apoptosis increased, metastasis in vivo was limited, and the proportion of MDSC in situ decreased. LTBP1 was lowly expressed in cervical cancer, and the inhibition of LTBP1 can improve the malignant degree of the tumor, and this process can be blocked by carboplatin.

Background: Symptom networks can provide empirical evidence for the development of personalized and precise symptom management strategies. However, few studies have explored the symptom networks of multidimensional symptom experiences in cancer survivors. The objectives of this study were to generate symptom networks of multidimensional symptom experiences in cancer survivors and explore the centrality indices and density in these symptom networks METHODS: Data from 1065 cancer survivors were obtained from the Shanghai CANcer Survivor (SCANS) Report. The MD Anderson Symptom Inventory was used to assess the prevalence and severity of 13 cancer-related symptoms. We constructed contemporaneous networks with all 13 symptoms after controlling for covariates., Results: Distress (r s  = 9.18, r c  = 0.06), sadness (r s  = 9.05, r c  = 0.06), and lack of appetite (r s  = 9.04, r c  = 0.06) had the largest values for strength and closeness. The density of the "less than 5 years" network was significantly different from that of the "5-10 years" and "over 10 years" networks (p < 0.001). We found that while fatigue was the most severe symptom in cancer survivorship, the centrality of fatigue was lower than that of the majority of other symptoms., Conclusion: Our study demonstrates the need for the assessment of centrality indices and network density as an essential component of cancer care, especially for survivors with <5 years of survivorship. Future studies are warranted to develop dynamic symptom networks and trajectories of centrality indices in longitudinal data to explore causality among symptoms and markers of interventions., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: X-linked cone-rod dystrophy (CORDX) is one form of inherited retinal disorders (IRDs) characterized by progressive dysfunction of photoreceptor. Three types of CORDX were reported and CACNA1F gene defect can cause CORDX3. The aim of this study was to investigate the pathogenic variant in a Chinese family with IRD., Methods: The two affected subjects including the proband and his elder sister underwent ophthalmic examinations. Whole exome sequencing (WES) was performed in the proband at first, then co-segregation analysis was performed in the family by Sanger sequencing. Minigene approach was used to verify the effect of the mutation on the splicing of CACNA1F. X-chromosomal inactivation assay was performed to evaluate the inactivation patterns of the female carriers., Results: The ophthalmic examination results of the proband fit the clinical description of CORDX3, and the female patient presented with only mild symptoms due to mildly skewed X-chromosomal inactivation (ratio 67: 33). Molecular genetic testing identified a novel splice-site mutation c.3847-2A > G in CACNA1F (NM&#95;005183.4) gene in the patients, which inherited from their asymptomatic mother. Minigene approach confirmed that c.3847-2A > G could affect the splicing of CACNA1F., Conclusion: Our study identified a novel splice-site mutation in the CACNA1F gene, which expanded the mutational spectrum of CACNA1F-releated diseases and demonstrated the importance of combining clinical and genetic testing in the diagnosis of IRDs., (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background: Ovarian cancer (OC) is a highly heterogeneous disease, of which the mesenchymal subtype has the worst prognosis, is the most aggressive, and has the highest drug resistance. The cell cycle pathway plays a vital role in ovarian cancer development and progression. We aimed to screen the key cell cycle genes that regulated the mesenchymal subtype and construct a robust signature for ovarian cancer risk stratification. Methods: Network inference was conducted by integrating the differentially expressed cell cycle signature genes and target genes between the mesenchymal and non-mesenchymal subtypes of ovarian cancer and identifying the dominant cell cycle signature genes. Results: Network analysis revealed that two cell cycle signature genes ( POLA2 and KIF20B ) predominantly regulated the mesenchymal modalities of OC and used to construct a prognostic model, termed the Cell Cycle Prognostic Signature of Ovarian Cancer (CCPOC). The CCPOC-high patients showed an unfavorable prognosis in the GSE26712 cohort, consistent with the results in the seven public validation cohorts and one independent internal cohort (BL-OC cohort, qRT-PCR, n = 51). Functional analysis, drug-sensitive analysis, and survival analysis showed that CCPOC-low patients were related to strengthened tumor immunogenicity and sensitive to the anti-PD-1/PD-L1 response rate in pan-cancer ( r = -0.47, OC excluded), which indicated that CCPOC-low patients may be more sensitive to anti-PD-1/PD-L1. Conclusion: We constructed and validated a subtype-specific, cell cycle-based prognostic signature for ovarian cancer, which has great potential for predicting the response of anti-PD-1/PD-L1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Gu, Zhou, Wu, Sun and Han.)

Cyclic GMP-AMP synthase (cGAS) plays a major role in detecting pathogenic DNA. It produces cyclic dinucleotide cGAMP, which subsequently binds to the adaptor protein STING and further triggers antiviral innate immune responses. However, the molecular mechanisms regulating cGAS enzyme activity remain largely unknown. Here, we characterize the cGAS-interacting protein Poly(rC)-binding protein 2 (PCBP2), which plays an important role in controlling cGAS enzyme activity, thereby mediating appropriate cGAS-STING signaling transduction. We find that PCBP2 overexpression reduces cGAS-STING antiviral signaling, whereas loss of PCBP2 significantly increases cGAS activity. Mechanistically, we show that PCBP2 negatively regulates anti-DNA viral signaling by specifically interacting with cGAS but not other components. Moreover, PCBP2 decreases cGAS enzyme activity by antagonizing cGAS condensation, thus ensuring the appropriate production of cGAMP and balancing cGAS-STING signal transduction. Collectively, our findings provide insight into how the cGAS-mediated antiviral signaling is regulated., (© 2022. The Author(s).)

Objectives: To investigate the roles that Toll-like receptors (TLRs) play in lung inflammation mediated by Mycoplasma pneumoniae (MP)., Methods: The changes in TLRs and tumor necrosis factor alpha (TNF-α) in peripheral blood of children with M. pneumoniae pneumonia (MPP) were monitored, and the interactions of signaling molecules regulating TNF-α release in A549 cells and neutrophils after M. pneumoniae stimulation were investigated. In TLR2 knockout (TLR2-/-) mice, the levels of TNF-α in bronchial alveolar lavage fluid (BALF) and peripheral blood after mycoplasma infection and the pathological changes in the lung tissue of mice were detected., Results: TNF-α levels in peripheral blood of children with MPP were higher than those in non-infected children, and children with refractory MPP had the highest levels of TNF-α and TLR2. TNF-α secretion and TLR2, myeloid differentiation primary response 88 (MyD88) and phospho-p65(p-p65) levels were increased in stimulated cells. TNF-α secretion was suppressed upon siRNA-mediated TLR2 silencing. Pharmacological inhibition of nuclear factor-kappa B (NF-κB) and MyD88 effectively reduced TNF-α expression. Compared with wild-type mice, the TNF-α in serum and BALF decreased, and lung pro-inflammatory response was partially suppressed in TLR2-/- mice., Conclusion: We concluded that TLR2 regulates M. pneumoniae -mediated lung inflammation and TNF-α release through the TLR2-MyD88-NF-κB signaling pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Deng, Zhao, Miao, Gu, Bi, Zhu, Guo, Shi, Xu, Zhao and Liu.)

Bioorganic fertilizers can alleviate (a) biotic stresses and sustainably increase crop yields. The effect of bioorganic fertilizers on the rhizosphere bacterial community of Panax notoginseng and soil metabolism remains unknown. Here, we tracked the changes in the soil physicochemical properties, bacterial microbiota responses, and soil metabolic functions after the addition of a bioorganic fertilizer in a P. notoginseng field. The application of a bioorganic fertilizer reduced the soil acidification, improved the organic matter, and increased the contents of the total/available soil nutrients. Soil amendment with a bioorganic fertilizer significantly affected the structure of the rhizosphere bacterial community, leading to the enrichment of specific bacterial consortia such as Rhodanobacter , Arthrobacter , Sphingomonas , Devosia , Pseudolabrys , Luteimonas , Lysobacter , Nitrosospira, and Nakamurella . Previously, many of these genera have been associated with nutrient cycling, plant productivity, and disease suppression. Metabolome analysis further highlighted that the bioorganic fertilizer treatment significantly reduced phenolic acids and flavonoids and enhanced organic acids, saccharides and alcohols, and amino acids. This result indicates a high survival of bacterial microbiota in the rhizosphere and an availability of nutrients for P. notoginseng growth. This work showed that the application of bioorganic fertilizers significantly improves soil health status, alters soil metabolic functions, and stimulates a specific subset of rhizosphere microbiota for nutrient cycling and disease protection in P. notoginseng .

Objective: This study aimed to investigate the role of p50-associated cyclooxygenase- (COX-2) extragenic RNA (PACER) on the inflammation of airway epithelium caused by Mycoplasma pneumoniae (MP) infection., Methods: A549 cells and MP strain were cultured respectively. The expressions of PACER, IL-8, TNF-α and COX-2 in MP-infected cells were detected by qRT-PCR, the concentration of IL-8 and TNF-α in the supernatant of the cells were detected by ELISA, and the expression of COX-2 protein in the cells was detected by western-blot. After knockdown of PACER, the expression of IL-8, TNF-α and COX-2 in MP infected cells were observed. The activity of NF-κB in cells was detected by fluorescence reporter assay, and the interaction between PACER and NF-κB was verified by RNA immunoprecipitation., Results: First, we observed that PACER was upregulated in MP infected A549 cells. Knockdown of PACER suppressed the production of inflammatory cytokines as well as the expression of COX-2 in A549 cells after MP infection. By performing luciferase reporter assay, we found PACER knockdown inhibited NF-κB activation induced by MP. Furthermore, RNA immunoprecipitation showed that PACER could physically bind to NF-κB p50 in MP-treated A549 cells., Conclusion: Collectively, our data demonstrated that attenuation of PACER reduces the inflammatory response of MP-infected epithelial cells via regulating NF-κB., (© 2022 by the Association of Clinical Scientists, Inc.)

This survey aimed to describe the health-related quality of life (HRQoL) and to explore the relationship between chronic diseases and HRQoL among urban residents in Shanghai, China. A cross-sectional study of 9 426 adults was conducted in Xuhui District of Shanghai, China in 2015. The EuroQol five-dimension three-level (EQ-5D-3 L) was used to measure HRQoL. The average age of subjects was 55.6 ± 17.4 years and 53% were female. Their mean values of utility and visual analogue scale (VAS) were 0.974 ± 0.099 and 80.00 ± 12.36, respectively, which were above the Chinese norm values. Women had lower scores compared with men. The utility value decreased with age, which accelerated after the age of 55 years. Chronic conditions including diabetes, tumor, cardiovascular disease, and respiratory disease, were significantly related to HRQoL, and the reported proportions of problems in the five dimensions increased with the number of chronic diseases (p < 0.05). Chronic diseases except for respiratory disease had a negative effect on HRQoL utility value and VAS score after the adjustment for covariates (p < 0.05). Chronic diseases had a negative impact on both EQ-5D-3 L utility and VAS scores, although the health-related quality of life for the study was above the national average.

The secretory function of airway epithelial cells is important in the pathogenesis of Mycoplasma pneumoniae pneumonia (MPP). To investigate the regulatory function of NKILA (nuclear factor- κ B (NF- κ B) interacting long noncoding RNA (lncRNA)) in MPP, we first detected NKILA as well as the concentration of interleukin 8 (IL-8) and tumor necrosis factor- α (TNF- α ) in bronchoalveolar lavage fluid of children with MPP. Then, NKILA was knocked down in epithelial cells to investigate its effect on their secretory function. The results suggested that NKILA was downregulated in children with MPP, while IL-8 and TNF- α levels increased. Knockdown of NKILA in vitro promoted the inflammatory effects of Mycoplasma pneumoniae (MP) in epithelial A549 and BEAS-2B cells. Knockdown of NKILA promoted inhibitor of κ B α (I κ B α ) phosphorylation and degradation, and NF- κ B p65 nuclear translocation. Furthermore, RNA immunoprecipitation showed that NKILA could physically bind to I κ B α in MP-treated A549 cells. Collectively, our data demonstrated that attenuation of NKILA enhances the effects of MP-stimulated secretory functions of epithelial cells via regulation of NF- κ B signaling., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2021 Fengxia Zhang et al.)

Background: Recurring outbreaks of infectious diseases highlight the importance of population vaccination strategies. We aimed to assess the impact of national vaccination strategies on vaccine-preventable infectious diseases (VPDs) in Shanghai, China and to identify vulnerable groups that may benefit from future vaccination policies., Methods: Infectious disease data from 1953 to 2018 was obtained from Xuhui District Center for Disease Control and Prevention, Shanghai China. We used joinpoint regression to show incidence, mortality and fatality trends and to determine annual percent change in incidence of 12 VPDs among three eras of national immunization strategies: (1)1953-1977, (2)1978-2007, and(3)2008-2018., Findings: Incidence, mortality, and fatality from VPDs have decreased drastically over the three eras, despite the inclusion of more diseases over time. Strikingly, the overall yearly incidence of VPDs shows an increasing trend from 2000 to 2018 in Shanghai (annual percentage changes, APC:7.7, p  = 0.025). In the third era (2008-2018), the three VPDs with the highest incidence were varicella (80.2 cases/100,000), hand, foot, and mouth disease (HFMD) (73.6 cases/100,000), and hepatitis (43.5 cases/100,000). A significant upward trend was also observed in hepatitis (APC:24.9, p <0.001), varicella (APC:5.9, p  = 0.006), and HFMD (APC:11.8, p  = 0.003) from 2008-2018. Hepatitis and tuberculosis are the only VPDs with fatality cases in this period., Interpretation: Focus is needed in controlling adult hepatitis and tuberculosis, either by introducing adult booster vaccines or by research into more effective vaccines. Varicella and HFMD are on the rise, but vaccines for these are not included in national programs. Strategies funded by government agencies or encouraged by research incentives are needed for varicella and HFMD, such as two-dose and novel multi-valent vaccines, respectively., Funding: Chinese Ministry of Education, Shanghai Municipal Government., Competing Interests: We declare no competing interests., (© 2021 The Authors. Published by Elsevier Ltd.)

Tumor necrosis factor-alpha (TNF-α) plays an important pathogenic role in cardiac hypertrophy and heart failure (HF); however, anti-TNF is paradoxically negative in clinical trials and even worsens HF, indicating a possible protective role of TNF-α in HF. TNF-α exists in transmembrane (tmTNF-α) and soluble (sTNF-α) forms. Herein, we found that TNF receptor 1 (TNFR1) knockout (KO) or knockdown (KD) by short hairpin RNA or small interfering RNA (siRNA) significantly alleviated cardiac hypertrophy, heart dysfunction, fibrosis, and inflammation with increased tmTNF-α expression, whereas TNFR2 KO or KD exacerbated the pathological phenomena with increased sTNF-α secretion in transverse aortic constriction (TAC)- and isoproterenol (ISO)-induced cardiac hypertrophy in vivo and in vitro, respectively, indicating the beneficial effects of TNFR2 associated with tmTNF-α. Suppressing TNF-α converting enzyme by TNF-α Protease Inhibitor-1 (TAPI-1) to increase endogenous tmTNF-α expression significantly alleviated TAC-induced cardiac hypertrophy. Importantly, direct addition of exogenous tmTNF-α into cardiomyocytes in vitro significantly reduced ISO-induced cardiac hypertrophy and transcription of the pro-inflammatory cytokines and induced proliferation. The beneficial effects of tmTNF-α were completely blocked by TNFR2 KD in H9C2 cells and TNFR2 KO in primary myocardial cells. Furthermore, we demonstrated that tmTNF-α displayed antihypertrophic and anti-inflammatory effects by activating the AKT pathway and inhibiting the nuclear factor (NF)-κB pathway via TNFR2. Our data suggest that tmTNF-α exerts cardioprotective effects via TNFR2. Specific targeting of tmTNF-α processing, rather than anti-TNF therapy, may be more useful for the treatment of hypertrophy and HF., Competing Interests: The authors have declared that no competing interests exist.

Our aim was to determine whether the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in Mycoplasma pneumoniae pneumonia (MPP), and its possible mechanism of action. MALAT1 expression in the bronchoalveolar lavage fluid of 50 hospitalized children with MPP was compared to its expression in 30 children with intrabronchial foreign bodies. MALAT1 expression was higher in children with MPP, accompanied by increased inflammatory mediators interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-α), compared to the controls. In human airway epithelial cells infected with wild-type Mycoplasma pneumoniae (strain M129), MALAT1, IL-8, and TNF-α expression significantly increased, and increased expression of IL-8 and TNF-α could be suppressed by MALAT1 knockdown. Luciferase reporter gene assay and western blot showed that knockdown of MALAT1 reduced nuclear factor-κB (NF-κB) activation. In vivo , RNAi packaged with adenovirus (Adv) was nasally transfected into BALB/c mice to silence MALAT1, and an MP-infected mouse pneumonia model was prepared. The results demonstrated that the degree of pulmonary inflammatory injury, vascular permeability, secretion of inflammatory factors, and expression of phosphorylated p65 (pp65) in MP-infected mice were partly reversed after MALAT1 knockdown compared to those in the controls. In conclusion, MALAT1 is involved in the regulation of airway and pulmonary inflammation caused by MP infection via NF-κB regulation., (Copyright © 2020 Gu, Zhu, Zhou, Huang, Zhang, Zhao and Liu.)

Asthma is defined as a heterogeneous disease, usually characterized by chronic airway inflammation. Long noncoding RNAs (lncRNAs) play important roles in various biological processes. To know more about the relationships between lncRNAs and asthma, gene microarray analysis was performed to screen differentially expressed lncRNAs between the lung tissue of ovalbumin (OVA) mice and control mice. Further studies showed that downregulating differentially expressed lncRNA-AK149641 by adeno-associated virus 6 (AAV6) in OVA mice inhibited airway inflammation, with improved airway compliance and resistance, diminished infiltration of inflammatory cells, as well as less secretions of mucus, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Moreover, the activity of nuclear factor-kappa B (NF-κB) in the lung tissue was reduced after downregulating lncRNA-AK149641. In conclusion, we proposed that downregulation of lncRNA-AK149641 attenuated the airway inflammatory response in an OVA-induced asthma mouse model, probably in association with modulation of the NF-κB signaling pathway.

Anaplastic thyroid carcinoma (ATC) is an aggressive malignant tumor composed of undifferentiated thyroid follicular cells. Pathological diagnosis of ATC can be challenging as the tumor may show morphological overlap with other neoplasms with anaplastic morphology. Immunohistochemical demonstration of thyroid origin facilitates the diagnosis of ATC. Previous studies using the polyclonal anti-PAX8 antibody 10336-1-AP suggested that PAX8 was the most sensitive marker, expressed in up to 80% of ATC. According to a 2018 NordiQC report, the monoclonal anti-PAX8 antibody MRQ-50 has become the most commonly used anti-PAX8 antibody worldwide. However, validation of this antibody in ATC is lacking. In this study, we recruited 182 ATC cases from seven institutions. Pathology slides were subjected to histology review. PAX8 immunohistochemistry using the MRQ-50 antibody was performed in whole tissue slides (n = 147) or tissue microarray sections (n = 35). We found PAX8 expression in 54.4% of the cases, which was significantly lower than those reported in prior studies with the polyclonal antibody. PAX8 expression was positively correlated with the presence of an epithelial pattern (63.6% vs 37.5%, p = 0.0008) and a coexisting differentiated thyroid carcinoma component (71.6% vs 44.3%, p = 0.0004), but was not associated with age, gender, specimen type, or presence of giant cell and sarcomatoid patterns. In conclusion, we demonstrated PAX8 expression using the monoclonal antibody MRQ-50 in only half of the cases in a large ATC series. Pathologists should be aware that PAX8 expression in ATC is less than those reported in early studies to avoid misdiagnosis.

Transmembrane TNF-α (tmTNF-α) and secretory TNF-α (sTNF-α) display opposite effects in septic shock. Reducing tmTNF-α shedding can offset the detrimental effects of sTNF-α and increase the beneficial effect of tmTNF-α. We previously developed a monoclonal antibody that is specific for tmTNF-α and does not cross-react with sTNF-α. In this study, we show that this antibody can specifically suppress tmTNF-α shedding by competing with a TNF-α converting enzyme that cleaves the tmTNF-α ectodomain to release sTNF-α. This tmTNF-α antibody significantly inhibited LPS-induced secretion of interleukin (IL)-1β, IL-6, interferon-β, and nitric oxide by monocytes/macrophages, and protected mice from septic shock induced by lipopolysaccharide (LPS) or cecal ligation and puncture, while reducing the bacterial load. The mechanism associated with the protective effect of this tmTNF-α antibody involved promotion of LPS-induced toll-like receptor 4 (TLR4) internalization and degradation by recruiting Triad3A to TLR4. Moreover, the tmTNF-α antibody inhibited LPS-induced activation of nuclear factor-κB and interferon regulatory factor 3 pathways by upregulating expression of A20 and monocyte chemotactic protein-induced protein 1. Similarly, treatment of macrophages with exogenous tmTNF-α suppressed LPS/TLR4 signaling and release of proinflammatory cytokines, indicating that increased levels of tmTNF-α promoted by the antibody contributed to its inhibitory effect. Thus, use of this tmTNF-α antibody for specific suppression of tmTNF-α shedding may be a promising strategy to treat septic shock.

Background: Epithelial ovarian cancer (EOC) is a heterogeneous disease, which has been recently classified into four molecular subtypes, of which the mesenchymal subtype exhibited the worst prognosis. We aimed to identify a microRNA- (miRNA-) based signature by incorporating the molecular modalities involved in the mesenchymal subtype for risk stratification, which would allow the identification of patients who might benefit from more rigorous treatments., Method: We characterized the regulatory mechanisms underlying the mesenchymal subtype using network analyses integrating gene and miRNA expression profiles from The Cancer Genome Atlas (TCGA) cohort to identify a miRNA signature for prognosis prediction., Results: We identified four miRNAs as the master regulators of the mesenchymal subtype and developed a risk score model. The 4-miRNA signature significantly predicted overall survival (OS) and progression-free survival (PFS) in discovery ( p =0.004 and p =0.04) and two independent public datasets (GSE73582: OS, HR: 2.26 (1.26-4.05), p =0.005, PFS, HR: 2.03 (1.34-3.09), p <0.001; GSE25204: OS, HR: 3.07 (1.73-5.46), p <0.001, PFS, HR: 2.59 (1.72-3.88), p <0.001). Moreover, in multivariate analyses, the miRNA signature maintained as an independent prognostic predictor and achieved superior efficiency compared to the currently used clinical factors., Conclusions: In conclusion, our network analysis identified a 4-miRNA signature which has prognostic value superior to currently reported clinical covariates. This signature warrants further testing and validation for use in clinical practice.

Objectives: LDCT screening for lung cancer has been widely used in China since the release of the NLST trial data in 2011, but little is known about its impact on the incidence and mortality rates of lung cancer in China., Methods: Official cancer registry data of lung cancer incidence and mortality were collected by Shanghai Municipal Center for Disease Control and Prevention from 2005 to 2014. Two districts (Xuhui and Songjiang Districts) were selected to represent populations with different levels of accessibility to LDCT. Incidence and mortality age-standardized rates (ASRs) were calculated using the Segi/Doll 1960 world standard population. Trends in lung cancer incidence and mortality rate over time, the average annual percent change (APC) and the corresponding 95% confidence interval (CI) were calculated using Joinpoint., Results: In Shanghai, lung cancer incidence rate in men did not change significantly between 2005 and 2014 (APC = 0.76%; 95% CI: -0.27%, 1.80%; P = 0.127); while lung cancer incidence in women increased significantly (APC: 5.50%; 95% CI: 2.94%, 8.13%; P = 0.001). In Xuhui district, where eight tertiary hospitals was located, including Shanghai Cancer Center and Shanghai Chest Hospital, both of which provided LDCT lung cancer screening for eligible patients, the incidence rate of lung cancer increased significantly in women only since 2011(APC: 19.84%, P < 0.001). Overall mortality rate of lung cancer showed a significantly decreasing trend from 2005 to 2014 in men (APC = -2.68%, P = 0.009) but not in women (APC = -0.91%, P = 0.305). In Songjiang district, where limited access to LDCT was provided, lung cancer incidence in women increased significantly between 2005 and 2014 (APC: 5.42%, P = 0.001). Lung cancer incidence rates did not change significantly in men in either district from 2005 to 2014. Mortality rate of lung cancer did not change significantly from 2005 to 2014 in both men (APC = -0.51%, P = 0.259) and women (APC = -1.46%, P = 0.186)., Conclusion: There is a steady increase in the incidence of lung cancer in women, especially after the wide use of LDCT screening, but without a clear mortality reduction., (Copyright © 2019. Published by Elsevier B.V.)

Chronic neuroinflammation is a characteristic of Parkinson's disease (PD). Previous investigations have shown that Parkin gene mutations are related to the early-onset recessive form of PD and isolated juvenile-onset PD. Further, Parkin plays important roles in mitochondrial quality control and cytokine-induced cell death. However, whether Parkin regulates other cellular events is still largely unknown. In this study, we performed overexpression and knockout experiments and found that Parkin negatively regulates antiviral immune responses against RNA and DNA viruses. Mechanistically, we show that Parkin interacts with tumor necrosis factor receptor-associated factor 3 (TRAF3) to regulate stability of TRAF3 protein by promoting Lys 48 -linked ubiquitination. Our findings suggest that Parkin plays a novel role in innate immune signaling by targeting TRAF3 for degradation and maintaining the balance of innate antiviral immunity., (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)

E3 ubiquitin ligase c-Caritas B cell lymphoma (c-cbl) is associated with negative regulation of receptor tyrosine kinases, signal transduction of antigens and cytokine receptors, and immune response. However, the expression and function of c-cbl in the regulation of neuropathic pain after chronic constriction injury (CCI) are unknown. In rat CCI model, c-cbl inhibited the activation of spinal cord microglia and the release of pro-inflammatory factors including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), which alleviated mechanical and heat pain through down-regulating extracellular signal-regulated kinase (ERK) pathway. Additionally, exogenous TNF-α inhibited c-cbl protein level vice versa. In the primary microglia transfected with c-cbl siRNA, when treated with TNF-α or TNF-α inhibitor, the corresponding secretion of IL-1β and IL-6 did not change. In summary, CCI down-regulated c-cbl expression and induced the activation of microglia, then activated microglia released inflammatory factors via ERK signaling to cause pain. Our data might supply a novel molecular target for the therapy of CCI-induced neuropathic pain.

Introduction: The Smoking Control Regulation in Public Places (hereafter, the 'regulations') has been implemented in Shanghai since 2010. This study explores the changes in smoking prevalence and its influencing factors among urban Shanghai residents., Methods: Two rounds of household investigations (the Health Status and Health Service Utilization Survey) were carried out using a multistage probability proportionate-to-size sampling method in an urbanized district in 2010 and 2015. Descriptive and logistic regression analyses were applied to the statistics., Results: From 2010 to 2015, the standardized current smoking rate fell from 24.8% to 19.1% (38.3% to 32.0% among men, and 1.9% to 1.4% among women). Meanwhile, the standardized smoking cessation rate increased from 18.1% to 23.3%. Smoking prevalence in respondents aged 45 to 59 years was still higher than that of other age groups. Changes in smoking prevalence and cessation rates were more obvious in respondents aged 30-44 and over 75 years. Sex, age, education, marital status, and alcohol use were influencing factors of current smoking, while sex, age and alcohol use were influencing factors of smoking cessation., Conclusions: The implementation of smoking control regulations may be beneficial for reducing smoking and increasing smoking cessation, especially among middle-aged and older men. Nevertheless, tobacco control in urban Shanghai still faces huge challenges. Therefore, more targeted and comprehensive measures should be taken., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported.

Columnar cell variant of papillary thyroid carcinoma (CCV-PTC) is an unusual neoplasm, the clinical behavior of which mainly depends on the encapsulation or infiltration. Patients with extensive extrathyroidal extension usually have an aggressive biological behavior. This study confirmed that beta-human chorionic gonadotropin (β-hCG) secreting invasive CCV-PTC has good prognosis comparing with a cohort of follicular cell differentiated thyroid carcinoma. On the contrary, positive immunoreaction with β-hCG was proved in three anaplastic thyroid carcinoma patients showing aggressive clinical courses. The clinicopathologic characteristics of CCV-PTC and the paraneoplastic syndromes in follicular cell differentiated thyroid carcinoma were further summarized using literature review., (© 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Vimentin, among the family of the intermediate filament, plays as the organizer of some critical proteins involved in migration, attachment, and cell signaling. In this study, the role of vimentin in chronic constriction injury (CCI) was investigated. Western blot revealed increased protein level of vimentin following CCI, peaking at 7 days. Double immunofluorescent staining showed that vimentin was mostly co-localized with astrocytes, not with neurons or microglia. In vitro, sensory neuronal injury stimulated astrocytes to produce more pro-inflammation cytokines, p-ERK (phosphorylated extracellular signal-regulated protein kinase), and vimentin. However, vimentin knockdown by siRNA (small interfering RNA) reversed the upregulation of p-ERK and vimentin expression and reduced the release of pro-inflammatory cytokines. Overall, stimulated astrocytes might release pro-inflammatory cytokines to promote the development of neuropathic pain via vimentin/ERK signaling.

Spinal cord injury (SCI) is one of the most common and severe complications in spine injury. It is difficult to prevent cell necroptosis and promote the survival of residual neurons after SCI. Proteasome beta-4 subunit (PSMB4) is the first proteasomal subunit with oncogenic properties promoting cancer cell survival and tumor growth in vivo, and our previous study showed that PSMB4 is significantly associated with neuronal apoptosis in neuroinflammation. However, PSMB4 function in the necroptosis after SCI is unkown. RIP3, a key regulatory factor of necroptosis, correlates with the induction of necroptosis in various types of cells and signaling pathway. Upregulation of the RIP3 expression may play a role as a novel molecular mechanism in secondary neural tissue damage following SCI. In this study, we established an acute spinal cord contusion injury model in adult rats to investigate the potential role of PSMB4 during the pathological process of SCI. We found PSMB4 expression was significantly up-regulated 3 days after injury by western blot and immunohistochemical staining. Double immunofluorescent staining indicated obvious changes of PSMB4 expression occurred in neurons. Significant up-regulation of PSMB4 expression was observed in Rip3 positive neurons at 3 days after SCI, which indicated that PSMB4 might play a vital role in the regulation of Rip3. Overexpress and knockdown PSMB4 could intervene the RIP3 and Mixed lineage kinase domain-like protein (MLKL) pathway in Tumor necrosis factor-α (TNF-α) induced necroptosis cell model. Based on our experimental data, we boldly conclude that PSMB4 is associated with RIP3 involved necroptosis after SCI.

Myelin and lymphocyte protein (MAL) was identified as a tetraspan proteolipid that is highly expressed by oligodendrocytes and Schwann cells as a component of compact myelin. It has also been reported to be a tumour suppressor and induces apoptosis through the Fas pathway. However, its expression and function in spinal cord injury are still unclear, especially in gray matter. In this study, we performed a spinal cord contusion injury (SCI) model in adult rats and detected the dynamic changes of MAL expression in spinal cord. Western blot and immunohistochemistry analysis revealed that MAL was present in gray and white matter of normal spinal cord. It gradually increased, got a peak at 1 day, and then declined to basal levels after spinal cord injury. Double immunofluorescence staining showed that MAL immunoreactivity was found in neurons and oligodendrocytes. Interestingly, MAL expression was increased predominantly in neurons rather than oligodendrocytes. We also examined the expression profiles of active caspase-3, whose changes were correlated with the expression profiles of MAL. Moreover, co-localization of MAL with active caspase-3 was detected. In conclusion, this is the first description of MAL expression changes in gray matter after spinal cord injury. Our results prompted that MAL might participate in CNS pathophysiology after SCI.

Some microbial pathogens utilize human complement regulatory proteins, such as factor H (FH) and factor H-like protein 1 (FHL-1), for immune evasion. FbaA is an FHL-1 and FH binding protein expressed on the surface of group A streptococcus (GAS), a common agent of pharyngeal, skin, and soft tissue infections. In this study, we prepared monoclonal antibodies (MAbs) against FbaA, assayed them for specificity, and located their binding domains in FbaA. We found an MAb called FbaA MAb2, which demonstrated the highest affinity to GAS among all of the MAbs. Based on the binding with component peptides, the detected epitope, which was specific for FbaA MAb2, was the amino acid residues 95 to 118 of FbaA; on the other hand, it did not bind with the truncated protein of the internally deleted residues of the segment from 95 to 118 of FbaA. Furthermore, the predominant amino acids specific for FbaA MAb2 screened by phage display epitope library were I, T, P, D, and L, corresponding to the amino acid residues 101, 103, 105, 106, and 110 of FbaA, respectively. The binding location of FbaA with FH and FHL-1 was a 16-amino-acid region corresponding to amino acid residues 97 to 112 of FbaA, which overlapped the FbaA MAb2 binding domain, as confirmed by competitive inhibition enzyme-linked immunosorbent assay and immunofluorescence microscopy. Based on the results of the invasion assay, FbaA MAb2 can inhibit the binding of FH to GAS.

Rats exposed to repeated restraint stress (3 h of restraint on each of 3 days) lose weight during stress and do not return to the weight of nonstressed controls once stress ends. Others have reported that chronic stress raises the daily nadir of corticosterone release and increases the adrenal response to subsequent stress; therefore, we examined glucocorticoid release in rats that had been exposed to repeated restraint. Repeated restraint had no effect on the diurnal pattern of corticosterone or insulin release, measured 12 days after restraint had ended, indicating that the reduced weight of the rats is not associated with an elevated corticosterone-insulin ratio. In contrast, rats that had been exposed to repeated restraint, 12 days previously, showed a blunted corticosterone release during a second restraint stress, a normal response to the novel physiological stress of 2-deoxy glucose (2-DG) injection, but an exaggerated corticosterone response to the novel mild stress (MS) of either placement in a unfamiliar environment or an intraperitoneal injection of saline. Mice exposed to repeated restraint showed a similar hyperresponsiveness to novel MS, suggesting that repeated restraint lowers the threshold for stress-induced activation of the adrenal gland. MS caused a small, but significant, degree of hypophagia in rats that had been exposed to repeated restraint stress. Therefore, multiple aspects of the stress response may be exaggerated in these animals and contribute to the chronic reduction in body weight.

The population distribution patterns of fig wasps associated with Ficus racemosa in Xishuangbanna were studied by using several indexes. The results indicated that the distribution patterns of 6 fig wasp species were all clump. The aggregative intensity of pollinating wasp (Ceratosolen fusciceps) population at primeval rain forest was nearly equal to that at seriously disturbed site, whereas they were both much higher than that at moderately disturbed site. In the meanwhile, the population aggregative intensity for the same wasp species was higher in rainy season than in dry-hot season, and the lowest was occurred in foggy-cool season. Non-pollinating wasp (Platyneura testacea, Platyneura mayri, Platyneura agraensis, Apocrypta westwoodi, Apocrypta sp.) population and each of their sex group were varied significantly in aggregative intensity, responding to the habitat change and seasonal alteration. The protection of original habitat should be focused on the protection of the mutualism of Ficus racemosa and fig wasps.

Ficus racemosa is a keystone plant in tropical rainforest of Xishuangbanna, Yunnan. The structure, dynamic and biodiversity of insect community on its syconia fruits were investigated in different plots located in Menglun nature reserve, ravine rainforest in the botanical garden, and secondary forest by Luosuo River. The results showed that the total number of collected insects were 184 264, belonging to 5 order, 19 families, 36 genera, and 51 species. Hymenoptera was the most dominant group, accounted for 37.3% of the total collected species. The pollinator of Ceratosolen fusciceps had huge individual quantities among Hymenoptera, and its successful pollination influenced the stability and development of F. racemosa population. In addition, the proportion of Lepidopter inspects was 31.4%, and the other 31.3% species belonged to Coleoptera, Homopter and Diptera. Through calculating diversity index, evenness index and richness of three plots, it showed that these three indexes were the highest in Menglun nature reserve, secondary in ravine rainforest, and low species diversity and richness in secondary forest by Luosuo River. The experimental results reported here showed that the insect species decreased, the individual number of common species increased, and special species reduced.