AIM:This study aims to investigate the role of cathelicidin-related antimicrobial peptide(Camp)gene in lung tumors in mice and to elucidate its molecular mechanisms in regulating epithelial-mesenchymal transition(EMT)and the TGF-β/Smad signaling pathway.METHODS:We conducted histological examinations and survival anal-yses using a KrasG12D spontaneous lung cancer mouse model with Camp gene knockout.This model was utilized to assess the impact of Camp on tumor nodule count,volume,and survival rate in mice.At the cellular level,we constructed A549-Camp and H1975-Camp cell lines to evaluate the effects of Camp on the proliferation,migration,and invasion of lung ade-nocarcinoma cells through soft agar colony formation assays,Scratch assays for cell migration rates,and Transwell assays.Additionally,we performed angiogenesis experiments to assess vascular development.At the molecular level,qRT-PCR was employed to detect the expression of angiogenic factors VEGF,bFGF,and TGF-β.Western blot analysis was utilized to examine the effects of Camp on the expression of EMT-related proteins(E-cadherin,N-cadherin,and Snail)and pro-teins associated with the TGF-β/Smad signaling pathway(TGF-β,p-TGF-β,Smad3,and Smad7).RESULTS:Camp gene knockout significantly suppressed lung tumorigenesis in mice,resulting in a decrease in tumor nodule count and vol-ume,as well as an enhancement in survival rates.In vitro,overexpression of Camp stimulated the proliferation,migra-tion,and invasion of lung adenocarcinoma cells.CONCLUSION:Molecular mechanism studies indicated that Camp modulated the expression of EMT-related proteins by influencing the TGF-β/Smad signaling pathway.

Objective To observe the clinical effect of Huangqi Yixin Decoction combined with sacubitril/valsartan in treatment of patients with heart failure with preserved ejection fraction(HFpEF)of Qi deficiency and blood stasis type.Methods A total of 86 patients with HFpEF of Qi deficiency and blood stasis type were randomly divided into western medicine group and combination group using the random number table method,with 43 cases in each group.The western medicine group was trea-ted with sacubitril/valsartan sodium tablets on the basis of conventional anti-heart failure therapy,while the combination group was additionally treated with Huangqi Yixin Decoction on the basis of the western medicine group's treatment.The therapeutic efficacy,traditional Chinese medicine(TCM)syndrome scores,cardiac function indicators[Tei index,N-terminal pro-brain natriuretic peptide(NT-proBNP)],exercise tolerance[6-minute walk distance(6MWD),maximum exercise heart rate,metabolic equivalent(MET)],and the occurrence of adverse reactions were compared between the two groups.Results The overall clinical effective rate in the combination group was 93.02％,which was higher than that in the western medicine group(76.74％),and the difference was statistically significant(P＜0.05).After treatment,the TCM syndrome scores in both groups were lower than those before treatment,and the scores in the combination group were lower than those in the western medicine group,with a statistically significant difference(P＜0.05).After treatment,the levels of Tei index and NT-proBNP in both groups were lower than those before treatment,and the levels in the combination group were lower than those in the western medicine group,with a statistically sig-nificant difference(P＜0.05).After treatment,the 6MWD,maximum exercise heart rate,and MET in both groups were higher than those before treatment,and the values in the combination group were higher than those in the western medicine group,with a statistically significant difference(P＜0.05).The incidence of adverse reactions in the western medicine group was 18.60％,which was higher than that in the combination group(4.65％),and the difference was statistically signifi-cant(P＜0.05).Conclusion Huangqi Yixin Decoction combined with sacubitril/valsartan has a good therapeutic effect on HFpEF of Qi deficiency and blood stasis type.It can reduce the TCM syn-drome scores of patients,improve exercise tolerance,and has good safety.

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.

OBJECTIVE To screen for GJB2,mitochondrial DNA12S rRNA 1555A>G and SLC26A4 gene mutations in 27 non syndromic hereditary hearing loss families,clarify the genetic causes.METHODS 125 members from 27 deaf families were for questionnaire surveys,audiological examinations,and peripheral blood DNA extraction.The GJB2,SLC26A4,and mitochondrial DNA A1555G coding regions were amplified and directly sequenced.RESULTS Twelve families and 52 individuals were screened for deafness gene mutations,the detection rate in 27 families was 44%(12/27),and the detection rate in all the members was 42%(52/125).The detection rate of gene mutation for GJB2 is 31%(39/125),for SLC26A4 is 6%(8/125),and for mitochondrial DNA1555A>G mutation is 4%(5/125).CONCLUSION GJB2,SLC26A4 and mitochondrial A1555G have a high detection rate in families with hereditary deafness.Mutation screening of these three genes can clarify the genetic causes of most deafness families and can be used as genetic screening targets for hereditary deaf families.

AIM:This study aims to investigate the role of cathelicidin-related antimicrobial peptide(Camp)gene in lung tumors in mice and to elucidate its molecular mechanisms in regulating epithelial-mesenchymal transition(EMT)and the TGF-β/Smad signaling pathway.METHODS:We conducted histological examinations and survival anal-yses using a KrasG12D spontaneous lung cancer mouse model with Camp gene knockout.This model was utilized to assess the impact of Camp on tumor nodule count,volume,and survival rate in mice.At the cellular level,we constructed A549-Camp and H1975-Camp cell lines to evaluate the effects of Camp on the proliferation,migration,and invasion of lung ade-nocarcinoma cells through soft agar colony formation assays,Scratch assays for cell migration rates,and Transwell assays.Additionally,we performed angiogenesis experiments to assess vascular development.At the molecular level,qRT-PCR was employed to detect the expression of angiogenic factors VEGF,bFGF,and TGF-β.Western blot analysis was utilized to examine the effects of Camp on the expression of EMT-related proteins(E-cadherin,N-cadherin,and Snail)and pro-teins associated with the TGF-β/Smad signaling pathway(TGF-β,p-TGF-β,Smad3,and Smad7).RESULTS:Camp gene knockout significantly suppressed lung tumorigenesis in mice,resulting in a decrease in tumor nodule count and vol-ume,as well as an enhancement in survival rates.In vitro,overexpression of Camp stimulated the proliferation,migra-tion,and invasion of lung adenocarcinoma cells.CONCLUSION:Molecular mechanism studies indicated that Camp modulated the expression of EMT-related proteins by influencing the TGF-β/Smad signaling pathway.

Genome miniaturization drives key evolutionary innovations of adaptive traits in verte-brates,such as the flight evolution of birds.However,whether similar evolutionary processes exist in invertebrates remains poorly understood.Derived from the second-largest animal phylum,scallops are a special group of bivalve molluscs and acquire the evolutionary novelty of the swimming lifestyle,providing excellent models for investigating the coordinated genome and lifestyle evolution.Here,we show for the first time that genome sizes of scallops exhibit a generally negative correlation with loco-motion activity.To elucidate the co-evolution of genome size and swimming lifestyle,we focus on the Asian moon scallop(Amusium pleuronectes)that possesses the smallest known scallop genome while being among scallops with the highest swimming activity.Whole-genome sequencing of A.pleuronectes reveals highly conserved chromosomal macrosynteny and microsynteny,suggestive of a highly con-tracted but not degenerated genome.Genome reduction of A.pleuronectes is facilitated by significant inactivation of transposable elements,leading to reduced gene length,elevated expression of genes involved in energy-producing pathways,and decreased copy numbers and expression levels of biomineralization-related genes.Similar evolutionary changes of relevant pathways are also observed for bird genome reduction with flight evolution.The striking mimicry of genome miniaturization underlying the evolution of bird flight and scallop swimming unveils the potentially common,pivotal role of genome size fluctuation in the evolution of novel lifestyles in the animal kingdom.

Objective: To explore the influencing factors of happiness of nurses in Beijing Emergency Department and analyze their correlation with job burnout and mindfulness. Methods: From February 2018 to February 2019, 184 nurses in Emergency Departments of five 3A hospitals in Beijing were investigated by convenient sampling method. General data of nurses were collected by using self-made sociodemographic characteristics data. Mindfulness awareness questionnaire was used to evaluate nurses′ mindfulness thoughts. Nurses′ job burnout was evaluated by nurses′ job burnout questionnaire. The occupational well-being scale was used to evaluate nurses′ well-being, and then single-factor and multi-factor Logistic regression was used to analyze the influencing factors of nurses′ well-being in Beijing Emergency Department, and the mediating effect of mindfulness on job burnout and well-being. Results: The mindfulness scores of 184 nurses were (65.23±5.48), of which 54 (29.35%) had low mindfulness level, 80 (43.48%) had medium mindfulness level, and 50 (27.17%) had high mindfulness level. The emotional exhaustion (EE) score of job burnout was (29.76±4.32), depersonalization (DP) score was (9.66±1.30) and dimindished personal accomplishmen (tPA) score was (30.15±3.28), of which 63 (33.70%) were mild burnout, 70 (38.04%) were moderate burnout and 52 (28.26%) were severe burnout. The score of occupational well-being was (64.68±7.38). Univariate results showed that the factors affecting the happiness of nurses in Emergency Department included age, education level, professional title, working years, overtime work, monthly income and nature of employment. The scores of occupational well-being of Emergency Department nurses with mild, moderate and severe job burnout were (69.97±8.21), (61.72±9.21) and (56.41±7.02) respectively, with statistically significant difference (F=32.176, P<0.01). The occupational well-being scores of Emergency Department nurses with low mindfulness level, medium mindfulness level and high mindfulness level were (59.43±8.11), (63.72±9.51) and (76.41±6.98) respectively, the difference was statistically significant (F=40.291, P<0.01). Logistic regression analysis showed that working years, overtime work and job burnout were independent risk factors affecting the happiness of nurses in Emergency Department, while mindfulness was the protective factor. Occupational well-being of nurses in Emergency Department was proportional to mindfulness (r=0.812, P< 0.01), proportional to dimindished personal accomplishmen score in job burnout (r=0.713, P=0.008), and inversely proportional to EE score (r=-0503, P<0.01) and DP score (r=-0.614, P=0.012) in job burnout. The mediating effect of mindfulness was -0.179 4, accounting for 27.63% of the total effect. Conclusions Job burnout affects job burnout and well-being of nurses in emergency department, and mindfulness was the protective factor of well-being of nurses in emergency department.

Myeloid leukemias are highly diverse diseases and have been shown to be associated with microRNA (miRNA) expression aberrations. The present study involved an in-depth miRNome analysis of two human acute myeloid leukemia (AML) cell lines, HL-60 and THP-1, and one human chronic myeloid leukemia (CML) cell line, K562, via massively parallel signature sequenc-ing. mRNA expression profiles of these cell lines that were established previously in our lab facil-itated an integrative analysis of miRNA and mRNA expression patterns. miRNA expression profiling followed by differential expression analysis and target prediction suggested numerous miRNA signatures in AML and CML cell lines. Some miRNAs may act as either tumor suppres-sors or oncomiRs in AML and CML by targeting key genes in AML and CML pathways. Expres-sion patterns of cell type-specific miRNAs could partially reflect the characteristics of K562, HL-60 and THP-1 cell lines, such as actin filament-based processes, responsiveness to stimulus and phag-ocytic activity. miRNAs may also regulate myeloid differentiation, since they usually suppress dif-ferentiation regulators. Our study provides a resource to further investigate the employment of miRNAs in human leukemia subtyping, leukemogenesis and myeloid development. In addition, the distinctive miRNA signatures may be potential candidates for the clinical diagnosis, prognosis and treatment of myeloid leukemias.