The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

Objective To explore the relationship between serum levels of glycoprotein fibroglycan(SRGN)and secretory CD146(sCD146)and clinicopathological characteristics and prognosis in elderly pa-tients with breast cancer(BC).Methods A total of 128 elderly BC patients treated in the hospital from April 2019 to April 2021 were retrospectively selected as the BC group,and another 70 healthy elderly women were selected as the control group.The serum SRGN and sCD146 levels in BC group and control group,and patients with different clinical and pathological characteristics in BC group were compared.Kaplan-Meier curve and COX regression were used to analyze the effect of serum levels of SRGN and sCD146 on the prognosis of eld-erly BC patients.Receiver operating characteristic curve was used to analyze the predictive value of serum lev-els of SRGN and sCD146 for the prognosis of elderly BC patients.Results The levels of serum SRGN and sCD146 were(13.17±3.35)μg/L,(118.23±20.51)ng/L in the BC group,which were higher than(2.52±0.41)μg/L,(20.03±4.16)ng/L in the control group(t=26.460,39.572,both P<0.001).Compared with elderly BC patients with TNM stage Ⅰ-Ⅱ and histological grade Ⅰ-Ⅱ,serum SRGN and sCD146 levels in elderly BC patients with TNM stage Ⅲ and histological grade Ⅲ were higher(P<0.05).The 3-year progres-sion free survival rates in SRGN high and low expression groups were 66.13%(41/62)and 92.42%(61/66),respectively,and the 3-year progression free survival rate in SRGN high expression group was lower than that in SRGN low expression group(Log Rank χ2=14.180,P<0.001).The 3-year progression free survival rates in sCD146 high and low expression groups were 68.85%(42/61)and 89.55%(60/67),respectively,and the 3-year progression free survival rate in sCD146 high expression group was lower than that in sCD146 low ex-pression group(Log Rank χ2=8.614,P=0.003).TNM stage Ⅲ,histological grade Ⅲ,serum SRGN and sCD146 were risk factors for the poor prognosis of elderly BC patients.The area under the curve(AUC)of the combination of serum SRGN and sCD146 for predicting the prognosis of elderly BC patients was 0.850,which was larger than that of SRGN(AUC=0.798)and sCD146(AUC=0.771)alone(Z=2.057,2.217,P=0.042,0.029).Conclusion Serum levels of SRGN and sCD146 are elevated in elderly BC patients,and both are in-volved in the disease progression of BC.The combination of the two factors has high predictive value for the prognosis of elderly BC patients.

Objective To investigate the association between gastroesophageal reflux disease(GERD)and the risk of incident chronic obstructive pulmonary disease(COPD)and explore potential effect modifiers influencing this association.Methods Clinical data from 476 175 participants in the UK Biobank(2006-2010)were collected.A Cox proportional hazards model was used to assess the relationship between GERD and the risk of incident COPD.Subgroup analyses were conducted to examine potential modifiers of the primary findings.Results A total of 11 587(2.43%)new COPD cases were diagnosed.The Cox proportional hazards model revealed that GERD was associated with an increased risk of incident COPD(HR=1.59,95%CI=1.46-1.74,P<0.001).GERD was linked to a higher risk of incident COPD in individuals aged<60 years(P<0.001)and non-smokers(P=0.011).No association was observed between GERD and the risk of incident COPD in current smokers with a daily cigarette consumption<10 cigarettes(P=0.261).Conclusion GERD may increase the risk of incident COPD.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Gastroesophageal Reflux/epidemiology* ; Middle Aged ; Proportional Hazards Models ; Incidence ; Male ; Risk Factors ; Female ; Aged

Objective:To establish tumor specific protein (SP70) targeted tumor cell enrichment technology and to assess applicational value of next-generation sequencing (NGS) analysis for enriched circulating tumor cell (CTC) in precision medicines of non-small cell lung cancer (NSCLC).Methods:The monoclonal antibody NJ001 was covalently coupled to the surface of magnetic beads to build targeted magnetic bead enrichment technology based on SP70. The limit of detection, coincidence rate, interference experiment, recovery test and clinical performance were evaluated. From March 2016 to August 2017, NGS analysis with or without pre-treatment of targeted enrichment for serous fluids of 43 NSCLC in the First Affiliated Hospital with Nanjing Medical University were compared (Kappa or Fisher exact test).Results:The CTC enrichment technology based on SP70 targeted immunomagnetic beads can specifically enrich tumor cells. The limit of detection was 10 4 SPC-A1 cells/L, and the coincidence rate, sensitivity and specificity were 100% (3/3). The endogenous interfering substances such as red blood cells, hemoglobin, white blood cells, epithelial cells and triglycerides had no interfering effects, as well as the exogenous interfering substances such as EDTA-K2, cefoxitin, carboplatin and paclitaxel. The recovery rate was 56.0% (56 000/100 000). A total of 30 gene mutations including 65 loci were found in 43 NSCLC under SP70 targeted enrichment, with a higher detection rate compared with unenrichment method [95.0% (19/20) vs 65.0% (13/20), χ 2=5.625, P=0.044]. Conclusion:In this study, SP70-targeted enriched CTC liquid biopsy method was established, with higher sensitivity and specificity of NGS detection than unenrichment method.

Objective:To establish tumor specific protein (SP70) targeted tumor cell enrichment technology and to assess applicational value of next-generation sequencing (NGS) analysis for enriched circulating tumor cell (CTC) in precision medicines of non-small cell lung cancer (NSCLC).Methods:The monoclonal antibody NJ001 was covalently coupled to the surface of magnetic beads to build targeted magnetic bead enrichment technology based on SP70. The limit of detection, coincidence rate, interference experiment, recovery test and clinical performance were evaluated. From March 2016 to August 2017, NGS analysis with or without pre-treatment of targeted enrichment for serous fluids of 43 NSCLC in the First Affiliated Hospital with Nanjing Medical University were compared (Kappa or Fisher exact test).Results:The CTC enrichment technology based on SP70 targeted immunomagnetic beads can specifically enrich tumor cells. The limit of detection was 10 4 SPC-A1 cells/L, and the coincidence rate, sensitivity and specificity were 100% (3/3). The endogenous interfering substances such as red blood cells, hemoglobin, white blood cells, epithelial cells and triglycerides had no interfering effects, as well as the exogenous interfering substances such as EDTA-K2, cefoxitin, carboplatin and paclitaxel. The recovery rate was 56.0% (56 000/100 000). A total of 30 gene mutations including 65 loci were found in 43 NSCLC under SP70 targeted enrichment, with a higher detection rate compared with unenrichment method [95.0% (19/20) vs 65.0% (13/20), χ 2=5.625, P=0.044]. Conclusion:In this study, SP70-targeted enriched CTC liquid biopsy method was established, with higher sensitivity and specificity of NGS detection than unenrichment method.

Objective:To explore the role of arginine metabolism in the inflammatory response to influenza A virus (FluA) infection.Methods:Eighteen-month-old mice were infected with FluA via nasal drip, with samples collected on the 6th day post-infection. The concentration of cytokines was determined by the Luminex multifactor assay, while the metabolites in bronchoalveolar lavage fluid (BALF) were analyzed using targeted metabolomic method. Correlation analysis was employed to examine the correlation between cytokines and metabolites. Macrophages were infected with FluA at a multiplicity of infection (MOI) of 1 and cultured with different concentrations of arginine for 24 h. The mRNA and protein expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α) and IL-10 were detected by real time fluorescence quantitative RT-PCR (qRT-PCR) and Cytometric Bead Array (CBA).Results:In comparison to the control group, the levels of surfactant protein D (SP-D), TNF-α, monocyte chemotactic protein-1 (MCP-1), IL-1α, IL-6, IL-10, recombinant S100 calcium binding protein (S100) A9, interferon inducible protein 10 (IP-10), macrophage inflammatory protein-1α (MIP-1α), matrix metalloprotein-9 (MMP-9), and Complement Factor D in BALF of FluA infection exhibited a significant elevation. The concentrations of arginine, aspartate, citrulline, glutamic acid, ornithine, proline, creatine, and sarcosine in arginine metabolism were up-regulated, which was correlated with most of elevated cytokine levels. The supplementation of arginine after FluA infection significantly decreased the levels of IL-1β, IL-6, and TNF-α, but increased the level of IL-10 in macrophages.Conclusions:Arginine reduces the inflammatory response induced by FluA infection in macrophages, suggesting that it may be a potential intervention target for severe pulmonary inflammation following FluA infection.

AIM: To evaluate the changes in corneal epithelial thickness(CET)and corneal optical density(CD)after smart pulse technology(SPT)-assisted transepithelial photorefractive keratectomy(TPRK)and analyze their correlation.METHODS: The prospective study included 60 patients(120 eyes)with myopia and myopic astigmatism who underwent SPT-TPRK in the ophthalmology department at the First Affiliated Hospital of Xinxiang Medical University between February and August 2023. Changes in CET and CD were evaluated preoperatively and at 1 wk, 1 and 3 mo postoperatively.RESULTS: A total of 14 cases(28 eyes)were lost to follow-up, and 3 patients(6 eyes)with postoperative haze were excluded from this study, resulting in a final inclusion of 43 patients(86 eyes). At 1 wk after SPT-TPRK, CET had statistically significantly thickened compared to preoperative levels(P<0.05), particularly in the CET at 0-2 mm central corneal area(P<0.05). At 1 mo after SPT-TPRK, the CET at 0-2 mm area had statistically significantly decreased(P<0.05). At 3 mo after SPT-TPRK, the CET at 0-2 mm had essentially reached preoperative levels. Postoperative CD values increased, with a positive correlation between CET in the 0-2 mm area and CD in the whole 0-2 mm area(r=0.256, P<0.05), and a positive correlation between CET in the 2-5 mm area and CD in the anterior 2-6 mm area(r=0.319, P<0.05).CONCLUSION: Corneal epithelial remodeling takes 3 mo in areas within 2 mm of the central cornea; areas with thinner CET have faster postoperative corneal epithelial remodeling and greater thickening in the early postoperative period; CD increases in the early postoperative period compared to the preoperative value, and in some areas, there is a positive correlation between CET and CD value.

Objective:To explore the status quo of hospice care attitude of nurses and analyze its influencing factors.Methods:From April to June 2021, 121 nurses from Henan Provincial Chest Hospital were selected as research subjects by convenient sampling. The nurses were investigated with the General Information Questionnaire, Chinese Version of Frommelt Attitudes Toward Care of the Dying Scale Form B (FATCOD-BC), Chinese Version of Interpersonal Response Index-C (IRI-C), Trait Coping Style Questionnaire (TCSQ) and Chinese Version of Templer-Death Anxiety Scale (CT-DAS). Pearson correlation was used to explore the relationship between the hospice care attitude of nurses and death anxiety, empathy ability and coping style. A total of 121 questionnaires were issued and 119 valid questionnaires were recovered, with a valid recovery rate of 98.35%.Results:The total FATCOD-BC score of 119 nurses was (96.23±8.34). Pearson correlation showed that the total score of FATCOD-BC of nurses was positively correlated with the total score of IRI-C and the score of positive coping dimension of TCSQ ( P<0.05), and negatively correlated with the total score of CT-DAS and the score of negative coping dimension of TCSQ ( P<0.05) . Conclusions:The attitude of nurses towards hospice care is low and needs to be improved. The hospice care attitude of nurses was related to death anxiety, empathy ability and coping style. Nursing managers should strengthen death education for nurses, and actively carry out hospice care training and empathy training to improve the enthusiasm of nurses.

Objective To research and propose the proper calcium concentration for shipboard seawater reverse osmosis remineralization.Methods Comprehensive analyses were made on the calcium nutrient intake of adults,the effects of [Ca2+] level on the desalination corrosion index,the methods of shipboard seawater reverse osmosis remineralization and related remineralization criteria.Then,the range of proper calcium concentration of soft water remineralization was recommended for shipboard seawater reverse osmosis remineralization from different angels,which was verified by municipal drinking water quality survey results.Results Food was the main source of human calcium intake.[Ca2 +] concentration elevation could significantly reduce the corrosiveness of desalinated water,however,the contribution ratio for Langelier index (LSI) was debased when [Ca2+] reached 41 mg/L.Shipboard desalination remineralization was more preferable with direct added agential.At present,for the sake of health,the minimum quality criteria for [Ca2+] in soft water was 16 mg/L.Calcium chloride was commonly used for desalinated water remineralization,with the maximum permitted concentration being 36 mg/L.Conclusions In consideration of the shipboard environment and support capability comprehensively,the applicable calcium concentration of shipboard RO desalination remineralization was 16-36 mg/L,which was within the range of drinking water calcium concentration for 57％ of the cities of our countries.

Objective To research and propose the proper calcium concentration for shipboard seawater reverse osmosis remineralization.Methods Comprehensive analyses were made on the calcium nutrient intake of adults,the effects of [Ca2+] level on the desalination corrosion index,the methods of shipboard seawater reverse osmosis remineralization and related remineralization criteria.Then,the range of proper calcium concentration of soft water remineralization was recommended for shipboard seawater reverse osmosis remineralization from different angels,which was verified by municipal drinking water quality survey results.Results Food was the main source of human calcium intake.[Ca2 +] concentration elevation could significantly reduce the corrosiveness of desalinated water,however,the contribution ratio for Langelier index (LSI) was debased when [Ca2+] reached 41 mg/L.Shipboard desalination remineralization was more preferable with direct added agential.At present,for the sake of health,the minimum quality criteria for [Ca2+] in soft water was 16 mg/L.Calcium chloride was commonly used for desalinated water remineralization,with the maximum permitted concentration being 36 mg/L.Conclusions In consideration of the shipboard environment and support capability comprehensively,the applicable calcium concentration of shipboard RO desalination remineralization was 16-36 mg/L,which was within the range of drinking water calcium concentration for 57％ of the cities of our countries.