Dynamic A-to-I RNA editing during acute neuroinflammation in sepsis-associated encephalopathy.

Introduction: The activation of cerebral endothelial cells (CECs) has recently been reported to be the earliest acute neuroinflammation event in the CNS during sepsis-associated encephalopathy (SAE). Importantly, adenosine-to-inosine (A-to-I) RNA editing mediated by ADARs has been associated with SAE, yet its role in acute neuroinflammation in SAE remains unclear. Methods: Our current study systematically analyzed A-to-I RNA editing in cerebral vessels, cerebral endothelial cells (CECs), and microglia sampled during acute neuroinflammation after treatment in a lipopolysaccharide (LPS)-induced SAE mouse model. Results: Our results showed dynamic A-to-I RNA editing activity changes in cerebral vessels during acute neuroinflammation. Differential A-to-I RNA editing (DRE) associated with acute neuroinflammation were identified in these tissue or cells, especially missense editing events such as S367G in antizyme inhibitor 1 (Azin1) and editing events in lincRNAs such as maternally expressed gene 3 (Meg3), AW112010, and macrophage M2 polarization regulator (Mm2pr). Importantly, geranylgeranyl diphosphate synthase 1 (Ggps1) and another three genes were differentially edited across cerebral vessels, CECs, and microglia. Notably, Spearman correlation analysis also revealed dramatic time-dependent DRE during acute neuroinflammation, especially in GTP cyclohydrolase1 (Gch1) and non-coding RNA activated by DNA damage (Norad), both with the editing level positively correlated with both post-LPS treatment time and edited gene expression in cerebral vessels and CECs. Discussion: The findings in our current study demonstrate substantial A-to-I RNA editing changes during acute neuroinflammation in SAE, underlining its potential role in the disease.

Efficacy of Nurse-led Telepsychological Intervention for Patients with Postpartum Depression: A Systematic Review and Meta-analysis.

Objective: The aim of the study was to systematically evaluate the therapeutic effect of nurse-led telepsychological intervention on patients with postpartum depression. Methods: PubMed, Embase, CINAHL, Web of Science, the Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Database, and China VIP database were searched for articles on the effectiveness of remote psychological intervention in improving postpartum depression. The search time was limited from the establishment of the database to December 2023. The literature was screened, and data were extracted. The Cochrane risk of bias assessment tool was used to evaluate the quality of randomized controlled trials that met standards, and RevMan5.4 was used for meta-analysis. Results: A total of 14 studies involving 1765 patients from 9 countries were included. Meta-analysis results showed that compared with routine care, telepsychological intervention can alleviate maternal depression (Standard Mean Difference [SMD] = -0.60, 95% CI [-0.91, -0.29], I 2 = 88%, P < .01). Sensitivity and subgroup analyses revealed that 3 studies using the Edinburgh Postpartum Depression Scale evaluation tool were the source of heterogeneity in the meta-analysis. Conclusion: Telepsychological postpartum depression intervention can effectively improve postpartum depression, indicating that it has a certain clinical application value.

The Role of m6A-Mediated DNA Damage Repair in Tumor Development and Chemoradiotherapy Resistance.

Among the post-transcriptional modifications, m6A RNA methylation has gained significant research interest due to its critical role in regulating transcriptional expression. This modification affects RNA metabolism in several ways, including processing, nuclear export, translation, and decay, making it one of the most abundant transcriptional modifications and a crucial regulator of gene expression. The dysregulation of m6A RNA methylation-related proteins in many tumors has been shown to lead to the upregulation of oncoprotein expression, tumor initiation, proliferation, cancer cell progression, and metastasis.Although the impact of m6A RNA methylation on cancer cell growth and proliferation has been extensively studied, its role in DNA repair processes, which are crucial to the pathogenesis of various diseases, including cancer, remains unclear. However, recent studies have shown accumulating evidence that m6A RNA methylation significantly affects DNA repair processes and may play a role in cancer drug resistance. Therefore, a comprehensive literature review is necessary to explore the potential biological role of m6A-modified DNA repair processes in human cancer and cancer drug resistance.In conclusion, m6A RNA methylation is a crucial regulator of gene expression and a potential player in cancer development and drug resistance. Its dysregulation in many tumors leads to the upregulation of oncoprotein expression and tumor progression. Furthermore, the impact of m6A RNA methylation on DNA repair processes, although unclear, may play a crucial role in cancer drug resistance. Therefore, further studies are warranted to better understand the potential biological role of m6A-modified DNA repair processes in human cancer and cancer drug resistance.

Metabolic disorders in prediabetes: From mechanisms to therapeutic management.

Diabetes, one of the world's top ten diseases, is known for its high mortality and complication rates and low cure rate. Prediabetes precedes the onset of diabetes, during which effective treatment can reduce diabetes risk. Prediabetes risk factors include high-calorie and high-fat diets, sedentary lifestyles, and stress. Consequences may include considerable damage to vital organs, including the retina, liver, and kidneys. Interventions for treating prediabetes include a healthy lifestyle diet and pharmacological treatments. However, while these options are effective in the short term, they may fail due to the difficulty of long-term implementation. Medications may also be used to treat prediabetes. This review examines prediabetic treatments, particularly metformin, glucagon-like peptide-1 receptor agonists, sodium glucose cotransporter 2 inhibitors, vitamin D, and herbal medicines. Given the remarkable impact of prediabetes on the progression of diabetes mellitus, it is crucial to intervene promptly and effectively to regulate prediabetes. However, the current body of research on prediabetes is limited, and there is considerable confusion surrounding clinically relevant medications. This paper aims to provide a comprehensive summary of the pathogenesis of pre-diabetes mellitus and its associated therapeutic drugs. The ultimate goal is to facilitate the clinical utilization of medications and achieve efficient and timely control of diabetes mellitus.

Study on the Anti-Mycobacterium marinum Activity of a Series of Marine-Derived 14-Membered Resorcylic Acid Lactone Derivatives.

With the emergence of drug-resistant strains, the treatment of tuberculosis (TB) is becoming more difficult and there is an urgent need to find new anti-TB drugs. Mycobacterium marinum, as a model organism of Mycobacterium tuberculosis, can be used for the rapid and efficient screening of bioactive compounds. The 14-membered resorcylic acid lactones (RALs) have a wide range of bioactivities such as antibacterial, antifouling and antimalarial activity. In order to further study their bioactivities, we initially constructed a 14-membered RALs library, which contains 16 new derivatives. The anti-M. marinum activity was evaluated in vitro. Derivatives 12, 19, 20 and 22 exhibited promising activity with MIC90 values of 80, 90, 80 and 80 µM, respectively. The preliminary structure-activity relationships showed that the presence of a chlorine atom at C-5 was a key factor to improve activity. Further studies showed that 12 markedly inhibited the survival of M. marinum and significantly reduced the dosage of positive drugs isoniazid and rifampicin when combined with them. These results suggest that 12 is a bioactive compound capable of enhancing the potency of existing positive drugs, and its effective properties make it a very useful leads for future drug development in combating TB resistance.

Comparative Analysis of Molecular Landscape in Mouse Models and Patients Reveals Conserved Inflammation Pathways in Age-Related Macular Degeneration.

Purpose: The purpose of this study was to identify key genes and their regulatory networks that are conserved in mouse models of age-related macular degeneration (AMD) and human AMD. Methods: Retinal RNA-Seq was performed in laser-induced choroidal neovascularization (CNV) mice at day 3 and day 7 after photocoagulation. Mass spectrometry-based proteomic analysis was performed with retinas collected at day 3. Retinal RNA-Seq data was further compared among mouse models of laser-induced CNV and NaIO3-induced retinal degeneration (RD) and a large AMD cohort. Results: Retinal RNA-Seq revealed upregulated genes and pathways related to innate immunity and inflammation in mice with CNV, with more profound changes at the early stage (day 3). Proteomic analysis further validated these differentially expressed genes and their networks in retinal inflammation during CNV. Notably, the most evident overlap in the retina of mice with laser-induced CNV and NaIO3-induced RD was the upregulation of inflammation-related genes, pointing to a common vital role of retinal inflammation in the early stage for both mouse AMD models. Further comparative transcriptomic analysis of the mouse AMD models and human AMD identified 48 conserved genes mainly involved in inflammation response. Among them, B2M, C3, and SERPING1 were upregulated in all stages of human AMD and the mouse AMD models compared to controls. Conclusions: Our study demonstrates conserved molecular changes related to retinal inflammation in mouse AMD models and human AMD and provides new insight into the translational application of these mouse models in studying AMD mechanisms and treatments.

Best evidences for postpartum follow-up in patients with gestational diabetes / 现代临床护理

Objective To summarise the best evidence for postpartum follow-up acquired from patients with gestational diabetes mellitus so as to provide an evidence-based reference for establishment of a postpartum follow-up program.Methods Literature on postpartum blood glucose follow-up in patients with gestational diabetes mellitus was retrieved from 17 major databases including BMJ Best Practice,UpToDate,Joanna Briggs Institute(JBI),International Guide Collaboration Network,National Institute for Health and Care Excellence(NICE),American Diabetes Association website,Medlive,Cochrane Library,Embase,OVID,PubMed,Web of Science,Quanfang local PubMed,CNKI,Wanfang Data,VIP,and Sinomed from the inception of databases to July 2023.The literature to be retrieved included guidelines,expert consensus,evidence summaries,systematic reviews,clinical decisions,and the original studies.Results A total of 9 articles,five practice guidelines,a systematic review,an evidence summaries,an expert consensus and a clinical decisions,were included.Totally,17 pieces of best evidence were summarised from the five aspects:postpartum blood glucose,lifestyle guidance,breastfeeding,drug treatment and health education.Conclusions The summarised best evidences can provide evidence-based references for postpartum follow-up of patients with gestational diabetes.Nursing staff in hospitals and community health centres should formulate relevant follow-up plans according to the actual postpartum conditions of patients in order to prevent the incidence of postpartum Type Ⅱ diabetes.

The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A" / 中华危重病急救医学

The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.

From disinfectants to antibiotics: Enhanced biosafety of quaternary ammonium compounds by chemical modification.

The excessive use of quaternary ammonium compounds (QACs) following the COVID-19 pandemic has raised substantial concerns regarding their biosafety. Overuse of QACs has been associated with chronic biological adverse effects, including genotoxicity or carcinogenicity. In particular, inadvertent intravascular administration or oral ingestion of QACs can lead to fatal acute toxicity. To enhance the biosafety and antimicrobial efficacy of QACs, this study reports a new series of QACs, termed as PACs, with the alkyl chain of benzalkonium substituted by a phthalocyanine moiety. Firstly, the rigid phthalocyanine moiety enhances the selectivity of QACs to bacteria over human cells and reduces alkyl chain's entropic penalty of binding to bacterial membranes. Furthermore, phthalocyanine neutralizes hemolysis and cytotoxicity of QACs by binding with albumin in plasma. Our experimental results demonstrate that PACs inherit the optical properties of phthalocyanine and validate the broad-spectrum antibacterial activity of PACs in vitro. Moreover, the intravascular administration of the most potent PAC, PAC1a, significantly reduced bacterial burden and ameliorated inflammation level in a bacteria-induced septic mouse model. This study presents a new strategy to improve the antimicrobial efficacy and biosafety of QACs, thus expanding their range of applications to the treatment of systemic infections.

Analysis of research status and trends on marine benthic dinoflagellate toxins: A bibliometric study based on web of science database and VOSviewer.

Marine benthic dinoflagellate toxins, potent bioactive compounds with wide-ranging presence in marine ecosystems, have surged in response to global climate change and human activities, prompting an urgent and imperative inquiry. This study conducts an in-depth review of contemporary research concerning these toxins, employing meticulous bibliometric analysis. Leveraging a dataset of 736 relevant literatures sourced from the Web of Science (spanning from 2000 to May 2023), our analysis delves comprehensively into the scientific discourse surrounding these toxic compounds. Employing tools such as VOSviewer, co-citation analysis, co-occurrence analysis, and cluster analysis, our study yields nuanced insights into the intricate characteristics and trajectories of the field. The co-citation analysis underscores the pivotal role played by benthic and epiphytic dinoflagellates like Ostreopsis and Gambierdiscus in shaping prevailing research trends. Our study identifies four distinct research directions, encompassing the domains of ecology, toxicology, toxin production, and taxonomy. Moreover, it traces the evolutionary journey of research stages, marking the transition from a focus on taxonomy to an emphasis on unraveling molecular mechanisms. The culmination of our comprehensive analysis yields three pertinent research recommendations: a call for widescale global studies, the advancement of rapid toxin monitoring techniques, and a deeper exploration of the factors influencing toxin synthesis and toxicity. These findings provide invaluable insights to researchers grappling with the complex realm of harmful algal blooms and substantially enrich the understanding of this pivotal and pressing field.

TSLP Induces Epithelial-Mesenchymal Transition in Nasal Epithelial Cells From Allergic Rhinitis Patients Through TGF-ß1/Smad2/3 Signaling.

BACKGROUND: Airway remodeling is demonstrated in Asian patients with allergic rhinitis (AR). The epithelial-mesenchymal transition (EMT) is one of the key mechanisms underlying airway remodeling. Thymic stromal lymphopoietin (TSLP) is an important contributor to airway remodeling. Although increased TSLP is found in AR, little is known about whether TSLP is involved in airway remodeling through induction of the EMT. OBJECTIVE: We investigated the effect of TSLP on the EMT in human nasal epithelial cells (HNECs) from AR patients. METHODS: Human nasal epithelial cells from AR patients were stimulated with TSLP in the absence or presence of the preincubation with a selective inhibitor of transforming growth factor beta 1 (TGF-ß1) receptor (SB431542). The expression of TGF-ß1 in the cells was evaluated by using real-time polymerase chain reaction, Western blotting, and immunocytochemistry. Western blotting and immunocytochemistry were used to assay EMT markers including vimentin, fibroblast-specific protein 1 (FSP1) and E-cadherin, small mothers against decapentaplegic homolog2/3 (Smad2/3), and phosphorylated Smad2/3 in the cells. The levels of extracellular matrix components such as collagens I and III in supernatants were measured by enzyme-linked immunoassay. Morphological changes of the cells were observed under inverted phase-contrast microscope. RESULTS: A concentration-dependent increase of TGF-ß1 mRNA and protein was observed following stimulation with TSLP. Furthermore, TSLP decreased the expression of E-cadherin protein, but upregulated the production of FSP1 and vimentin proteins along with increased levels of collagens I and III, and the morphology of the cells was transformed into fibroblast-like shape. Additionally, a significant increase was found in phosphorylation of Smad2/3 protein. However, these effects were reversed by SB431542 preincubation. CONCLUSION: TSLP-induced HNECs to undergo the EMT process via TGF-ß1-mediated Smad2/3 activation. TSLP is an activator of the EMT in HNECs and might be a potential target for inhibiting EMT and reducing airway remodeling in AR.

RNA modification: mechanisms and therapeutic targets.

RNA modifications are dynamic and reversible chemical modifications on substrate RNA that are regulated by specific modifying enzymes. They play important roles in the regulation of many biological processes in various diseases, such as the development of cancer and other diseases. With the help of advanced sequencing technologies, the role of RNA modifications has caught increasing attention in human diseases in scientific research. In this review, we briefly summarized the basic mechanisms of several common RNA modifications, including m6A, m5C, m1A, m7G, Ψ, A-to-I editing and ac4C. Importantly, we discussed their potential functions in human diseases, including cancer, neurological disorders, cardiovascular diseases, metabolic diseases, genetic and developmental diseases, as well as immune disorders. Through the "writing-erasing-reading" mechanisms, RNA modifications regulate the stability, translation, and localization of pivotal disease-related mRNAs to manipulate disease development. Moreover, we also highlighted in this review all currently available RNA-modifier-targeting small molecular inhibitors or activators, most of which are designed against m6A-related enzymes, such as METTL3, FTO and ALKBH5. This review provides clues for potential clinical therapy as well as future study directions in the RNA modification field. More in-depth studies on RNA modifications, their roles in human diseases and further development of their inhibitors or activators are needed for a thorough understanding of epitranscriptomics as well as diagnosis, treatment, and prognosis of human diseases.

Identification of Necroptosis-related Subtypes and Characterization of Tumor Microenvironment Infiltration in Non-small Cell Lung Cancer.

BACKGROUND: Necroptosis is correlated with the development, prognosis, and treatment of tumors. However, the function of necroptosis-associated genes (NRGs) in the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC) remains unclear. METHODS: In this study, 1210 NSCLC samples were classified into different subtypes based on the expression of 66 NRGs by unsupervised clustering analysis, and further analyzed the TME characteristics of these subtypes. In addition, we identified common differentially expressed genes (co-DEGs) in NRG subtypes and constructed the NRG score using principal component analysis (PCA) to assess the NRG-mediated TME characteristics of patients with NSCLC. RESULTS: Using unsupervised cluster analysis, 1210 NSCLC samples were divided into NRGcluster A and B subtypes. The NRGcluster B survived significantly better than the NRGcluster A. TME characterization revealed that NRGcluster B was upregulated in immune and stromal signaling activation, whereas NRGcluster A was upregulated in oncogenic signaling. The NRG score constructed based on co-DEGs of the two NRG-related subtypes was positively correlated with immune cell infiltration and negatively correlated with the number of cancer stem cells (CSCs) and tumor mutational burden (TMB). In addition, survival was significantly worse in the low-NRG-score group compared to the high-NRG-score group. Finally, the assessment of immunotherapeutic efficacy showed that immunotherapeutic response was significantly worse in the low-NRG-score group compared to the high- NRG-score group. CONCLUSION: This research reveals that NRGs are associated with the complexity and diversity of TME in NSCLC. Adopting the NRG score to quantitatively assess NRG-mediated TME in individual patients with NSCLC may help in planning clinical treatment strategies.

Toxic effects and bioaccumulation of pinacolyl methylphosphonate acid in zebrafish following soman exposure to a water environment.

Soman has been shown to be highly neurotoxic and can be easily degraded to produce pinacolyl methylphosphonate acid (PMPA). Thus, the perniciousness of PMPA deserved serious attention after soman was exposed to the environment. However, the toxicity of PMPA was not clearly elucidated to date. In this regard, the objective of this study was to determine if PMPA could pose an environmental risk after soman exposure to a water environment. In this study, the toxicity and bioaccumulation assessments of PMPA were carried out on zebrafish. Histological examination was used to assess the toxicity of PMPA in zebrafish and revealed that PMPA has chronic toxicity in view of tissue injury. The contents of PMPA in whole zebrafish and tissues were determined after soman exposure. The result showed that PMPA bioaccumulated in the whole zebrafish and tissue, especially the liver and intestinal tissues. This is the first report showing that the hydrolyzate of a G-series chemical nerve agent could accumulate in organisms. This study offers novel insights into the environmental risk assessments associated with soman exposure to a water environment.

Radiation-induced liver disease: beyond DNA damage.

Radiation-induced liver disease (RILD), also known as radiation hepatitis, is a serious side effect of radiotherapy (RT) for hepatocellular carcinoma. The therapeutic dose of RT can damage normal liver tissue, and the toxicity that accumulates around the irradiated liver tissue is related to numerous physiological and pathological processes. RILD may restrict treatment use or eventually deteriorate into liver fibrosis. However, the research on the mechanism of radiation-induced liver injury has seen little progress compared with that on radiation injury in other tissues, and no targeted clinical pharmacological treatment for RILD exists. The DNA damage response caused by ionizing radiation plays an important role in the pathogenesis and development of RILD. Therefore, in this review, we systematically summarize the molecular and cellular mechanisms involved in RILD. Such an analysis is essential for preventing the occurrence and development of RILD and further exploring the potential treatment of this disease.

The efficacy and safety of intravenous sucrose iron therapy for recurrent iron deficiency anemia / 中华血液学杂志

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.

Analysis of multiline therapy for small cell lung cancer transformed from lung adenocarcinoma and review of the literature / 中国综合临床

Objective:To investigate the effect of multi line therapy for lung adenocarcinoma transformed into small cell lung cancer (SCLC), and review and discuss the related literature.Methods:Combined with the clinical examples of lung adenocarcinoma transformed SCLC after treatment with anti epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), the diagnostic process and multi line treatment plan of transformed SCLC were analyzed, and the therapeutic effect was evaluated by imaging. At the same time, it was reviewed and discussed in combination with relevant literature.Results:Serological tumor markers were significant for the diagnosis of transformed SCLC after EGFR-TKI treatment of lung adenocarcinoma, and pathology was still the gold standard for its diagnosis. The multiline therapy of SCLC has certain effect on transformed small cell lung cancer.Conclusion:The overall prognosis of lung adenocarcinoma transformed into SCLC after EGFR TKIs treatment is poor, so it is necessary to diagnose and treat it as early as possible, evaluate the effect of imaging in time, and make treatment adjustment quickly.

Effect of muscle mass reduction on the progression of coronary artery calcification in maintenance hemodialysis patients / 中华肾脏病杂志

Objective:To evaluate the extent and progression of coronary artery calcification in maintenance hemodialysis (MHD) patients, and to explore the risk factors of rapid progression of coronary artery calcification in MHD patients.Methods:The patients who underwent MHD in the Huashan Hospital affiliated to Fudan University from January 1, 2013 to December 31, 2017 were enrolled. This study included cross-sectional study and prospective cohort study. Multi-slice spiral computed tomography was used to measure coronary artery calcification, and coronary artery calcium score (CACS) was calculated. In the cross-sectional study, 62 MHD patients were enrolled. According to baseline CACS, the patients were divided into low calcification group (CACS < 100) and high calcification group (CACS ≥ 100). The nutritional and bone mineral metabolism indexes were compared between the two groups. Multiple linear regression analysis was used to analyze the correlation between CACS and muscle mass and laboratory indicators. Since 6 patients were lost to follow-up, 56 MHD patients who were followed-up regularly were enrolled in the prospective cohort study. According to the progression of CACS, the patients were divided into slow progression group (ΔCACS/year < 100) and rapid progression group (ΔCACS/year ≥ 100). Logistic regression equation was used to analyze the risk factors of coronary calcification progression. Hosmer-Lemeshow goodness of fit test and receiver operating characteristic curve were used to evaluate the performance of multivariate logistic regression model.Results:In the cross-sectional study, the age of 62 patients was (62.34±10.82) years old, and the median dialysis age was 78 (39,139) months. Among the 33 male patients, compared with the low calcification group ( n=7), the high calcification group ( n=26) had older age ( t=-2.281, P=0.030) and higher blood triglyceride ( Z=-1.985, P=0.047), and there was no statistically significant difference in muscle mass between the two groups; among the 29 female patients, the muscle mass/height 2 ( t=-2.600, P=0.015) and serum calcium ( t=-2.641, P=0.014) in the high calcification group ( n=15) were both higher than those in the low calcification group ( n=14), and the hemoglobin level was lower ( t=2.531, P=0.018), and the difference in muscle mass between the two groups was not statistically significant. High sensitivity C-reactive protein ( β=0.425, P=0.022) was independently correlated with CACS in male patients, and muscle mass/extracellular water ( β=-0.580, P=0.001) was independently correlated with CACS in female patients. In the prospective cohort study, the age of 56 patients was (59.82±11.14) years old, and the median dialysis age was 82 (40, 146) months. There was no significant difference in all-cause mortality between slow progression group ( n=22) and rapid progression group ( n=34), but the proportion of cardiovascular events in rapid progression group was significantly higher than that in slow progression group ( P=0.017). Compared with the slow progression group, the rapid progression group had higher proportion of males ( χ2=4.791, P=0.029), older age ( Z=-2.131, P=0.038), lower baseline muscle mass/extracellular water ( Z=2.482, P=0.016) and high-density lipoprotein cholesterol ( t=2.133, P=0.042), and faster rate of muscle mass loss (Δmuscle mass·height -2·year -1) ( Z=-2.282, P=0.023). Multivariate logistic regression analysis results showed that muscle mass loss ( OR=0.089, 95% CI 0.010-0.792, P=0.030) and baseline CACS ( OR=1.003, 95% CI 1.000-1.005, P=0.021) were influencing factors for progression of coronary artery calcification in MHD patients. Conclusion:Increasing baseline CACS and rapid reduction in muscle mass are risk factors for the progression of coronary artery calcification in MHD patients.

Primary study of heat stress inducing early expression and secretion of tissue factor in vascular endothelial cells / 解放军医学杂志

Objective To explore the pattern of early expression and secretion of tissue factor(TF)in vascular endothelial cells induced by heat stress.Methods Thirty SPF-rated C57BL/6 male mice were randomly divided into five groups:the control group and groups of indicated recovery time,including 0,3,6,and 9 h in room temperature after heat stress(n=6).Mice in the heat stress groups were exposed to an animal incubator to reach 42.5℃for core body temperature for heat stroke.We analyzed the histopathological changes in the liver,lung,and kidney tissues with HE staining.We measured the TF mRNA in mice tissues by RT-qPCR and the plasma concentration of TF in mice with a commercial ELISA kit.Human umbilical vein endothelial cells(HUVECs)were placed in a culture incubator to build an in vitro heat stress model.HUVECs were divided into five groups,including a control group and groups of indicated recovery time,including 0,3,6,and 9 h after heat stress.We quantified the expression of TF mRNA and protein in HUVEC cells by RT-qPCR,Western blotting,and immunofluorescence and measured the secreted TF with a commercial ELISA kit.Results No significant pathological injury was observed in the tissues of the control group.Mice treated with heat stress had various degrees of structural injuries and hemorrhagic and inflammatory changes in multiple tissues.Compared to control group,the expression of TF mRNA significantly increased in the kidney of heat stress-treated mice with 0 and 3 h recovery time(1.719±0.018,1.241±0.178 vs.1.000±0.063),the lung with 3 h recovery time(2.444±0.511 vs.1.000±0.106)and the liver with 6 h recovery time(7.312±0.618 vs.1.000±0.147)(P<0.05).The concentration of TF in plasma also sustainedly elevated in mice with 0,3,6,and 9 h recovery time after heat stress as compared to control group[(132.426±17.920)pg/ml,(119.400±10.267)pg/ml,(107.374±13.495)pg/ml,(163.767±22.810)pg/ml vs.(75.479±13.831)pg/ml,respectively,P<0.01].The expression levels of TF mRNA were higher in heat stress HUVECs with 6 h and 9 h recovery time than the control cells(1.905±0.354,2.564±0.297 vs.1.000±0.097,P<0.01).Secreted TF in the supernatant from HUVECs treated with heat stress and different recovery time also increased significantly[(36.309±4.101)pg/ml,(38.425±5.484)pg/ml,(41.655±4.380)pg/ml,(43.586±4.718)pg/ml vs.(14.996±0.254)pg/ml,P<0.01].Conclusion Heat stress increased early expression and secretion of TF in vascular endothelial cells.Vascular endothelial cells may be a main source of circulating TF in heat stroke.

Analysis on the allocation of human resources for chronic disease prevention and control in 664 district/county-level centers for disease control and prevention in China in 2020 / 中华预防医学杂志

Objective: To analyze the allocation of human resources for chronic disease prevention and control of district/county-level centers for disease control and prevention(CDC) in China in 2020. Methods: Survey subjects were from National Chronic Noncommunicable Disease and Risk Factor Surveillance Sites and National Demonstration Areas for Chronic Noncommunicable Disease Prevention and Control (demonstration areas). A survey examining the allocation of human resources for chronic disease prevention and control at district/county-level CDC was conducted in December 2021 through the National Demonstration Areas Management Information System. The number and rate of allocation of human resources for chronic disease prevention and control in district/county-level CDC were analyzed and the Wilcoxon rank sum test was used to compare the difference between demonstration and non-demonstration areas and between urban and rural areas. The Kruskal-Wallis H test was used to compare the difference in east, central and west regions. The Gini coefficient and Theil index were used to evaluate the balance of human resource for chronic disease prevention and control. Results: A total of 678 districts/counties were investigated, and 664 districts/counties responded effectively, with an effective response rate of 97.9%. The establishment rate of district/county-level CDC was 98.34% (653/664), and the establishment rate of chronic disease prevention and control departments of district/county-level CDC was 96.02% (627/653). In 627 district/county-level CDC with departments for chronic disease prevention and control, the median number of full-time technical personnel for chronic disease prevention and control was 4, the median number of full-time technical personnel in demonstration areas (4 persons) was higher than in non-demonstration areas (3 persons), highest in the east region (5 persons) than in the middle region (4 persons) and the west region (4 persons), higher in urban areas (4 persons) than in rural areas (4 persons) (all P values<0.05). The allocation rate was 0.71 people/100 000, which was higher in demonstration areas (0.73 people/100 000) than in non-demonstration areas (0.67 people/100 000), highest in the west region (0.82 people/100 000) than in the middle region (0.71 people/100 000) and east region (0.67 people/100 000), higher in rural areas (0.77 people/100 000) than in urban areas (0.68 people/100 000) (all P values<0.05). The Gini coefficient for the allocation by population size was 0.352 9. The total Theil index for demonstration and non-demonstration areas, different regions, and urban-rural areas were 0.067 8, 0.076 3, and 0.000 2, with the intra-group contribution of 97.35%, 99.52%, and 98.80%, respectively. Conclusion: In 2020, the allocation of human resources for chronic disease prevention and control in district/county-level CDC is relatively balanced. The variation in the allocation of human resources for chronic disease prevention and control exist between demonstration and non-demonstration areas, urban and rural areas, and across regions.