BackgroundAdolescents with depressive disorder often engage in non-suicidal self-injury （NSSI） behaviors， which severely impacts their physical and mental health. Impulsivity and emotional regulation are key factors influencing NSSI behaviors. However， research on the mechanisms through which impulsivity and emotional regulation affect NSSI behaviors in adolescent depressive disorder patients with NSSI remains insufficient， limiting the development of effective intervention strategies. ObjectiveTo explore the differences in impulsivity and emotion regulation abilities between adolescent patients with depressive disorder accompanied by and without NSSI behaviors， and to analyze the association between NSSI behaviors and impulsivity and emotion regulation abilities in adolescent patients with depressive disorder accompanied by NSSI behaviors. MethodsA total of 184 adolescents hospitalized in the child and adolescent psychiatry department of Wuxi Mental Health Center from October 2023 to August 2024， who met the diagnostic criteria for depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， were consecutively enrolled as study subjects. Based on the diagnostic criteria for NSSI in DSM-5， patients were divided into NSSI group （n=108） and non-NSSI group （n=76）. The Barratt Impulsiveness Scale-11 （BIS-11）， the Emotion Regulation Questionnaire （ERQ）， the Adolescent Self-Harm Questionnaire， and the Positive and Negative Suicide Ideation （PANSI） were used for assessment. Spearman correlation analysis was employed to explore the correlation between the scores of the Adolescent Self-Harm Questionnaire and the scores of BIS-11 and ERQ in the NSSI group. Multiple regression analysis was conducted to examine the effects of impulsivity and emotion regulation on NSSI behaviors in the NSSI group. ResultsCompared to the non-NSSI group， the NSSI group showed significantly higher scores in BIS-11 non-planned impulsivity （Z=-4.181， P<0.05）， action impulsivity （t=4.944， P<0.05）， cognitive impulsivity （Z=-3.392， P<0.05）， and total score （t=4.763， P<0.05）， and lower scores in the cognitive reappraisal of ERQ （t=-4.094， P<0.05） and total score （Z=-2.299， P<0.05）， and higher scores in the expression inhibition of ERQ （Z=-3.019， P<0.05）. The correlation analysis results showed that the score of the adolescent self-harm questionnaire in the NSSI group was positively correlated with the behavioral impulsivity factor score in the BIS-11 （r=0.434， P<0.05）. Multiple regression analysis indicated that action impulsivity factor was a significant correlate of self-injury behaviors in the NSSI group （B=0.855， P<0.05）， explaining 22.30% of the total variance. ConclusionAdolescent patients with depressive disorder accompanied by NSSI behaviors exhibit higher levels of impulsivity and poorer emotional regulation abilities. Action impulsivity may play a significant role in the mechanism of NSSI behaviors. ［Funded by Wuxi Municipal Health Commission Research Project （number， Q202320）］

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Palliative and hospice care is an emerging medical care model for the development of modern medicine,and its emergence is not only a sign of social demand and the development of human civilization,but also an important manifestation of the change in the modern medical model.Hospice care is the final stage of palliative care,which is of great significance for the end-of-life treatment of incurable diseases.Palliative and hospice care has become an independent discipline in many countries,and its development has been rapid.However,the develop-ment of hospice and palliative care in China is not satisfactory,and the lack of money and human resources are the main reasons limiting its development.Many scholars have carried out a lot of useful practices in this regard.How to explore a road of hospice and palliative care development suitable for China′s national conditions is an urgent problem to be solved.By reviewing domestic and foreign literature,this paper summarizes the development mode and payment method of palliative and hospice care abroad,identifies the challenges encountered in the practice of hospice care in China,and draws on the development experience of palliative and hospice care in foreign countries.We aimed to identify pain points and difficulties faced in developing palliative and hospice care in China,so as to better serve patients at the end of life,gradually promote the concept of palliative and hospice care,and contribute to the sustainable development of palliative and hospice care in China.

【Objective】 To investigate the association between genetic variations in the glucagon-like peptide-1 receptor (GLP-1R) gene and BP responses to sodium and potassium intake. 【Methods】 A total of 514 subjects from 124 families were recruited in Meixian County, Shaanxi Province, in 2004, resulting in the establishment of a "salt-sensitive hypertension study cohort" . The subjects followed a dietary regimen which involved a normal diet for 3 days, a low-salt diet for 7 days, a high-salt diet for 7 days, and a high-salt potassium-supplemented diet for 7 days. BP measurement was conducted at different intervention periods, and peripheral blood samples were collected. Additionally, eight single nucleotide polymorphisms (SNPs) of the GLP-1R gene were genotyped using the MassARRAY detection platform. 【Results】 The GLP-1R gene SNP rs9462472 exhibited a significant association with systolic BP, diastolic BP, and mean arterial pressure response to high-salt intervention. Similarly, SNP rs2268637 showed a significant association with systolic BP response to high-salt intervention. Furthermore, SNP rs2268637 was significantly associated with systolic BP and mean arterial pressure responses to high-salt plus potassium supplementation intervention. 【Conclusion】 Our findings indicate a significant association of genetic variations in the GLP-1R gene with BP responses to sodium and potassium intake. This suggests that the GLP-1R gene plays a role in the regulation of BP salt sensitivity and potassium sensitivity.

Objective To investigate the relationship of miRNA gene polymorphisms with blood pressure(BP)responses to the sodium and potassium diet intervention.Methods In 2004,we recruited 514 participants from 124 families in seven villages of Baoji,Shaanxi Province,China.All subjects were given a three-day normal diet,followed by a seven-day low-salt diet,a seven-day high-salt diet,and finally a seven-day high-salt and potassium supplementation.A total of 19 miRNA single nucleotide polymorphisms(SNPs)were selected for analysis.Results Throughout the sodium-potassium dietary intervention,the BP of the subjects fluctuated across all phases,showing a decrease during the low-salt period and an increase during the high-salt period,followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet.MiR-210-3p SNP rs 12364149 was significantly associated with systolic BP(SBP),diastolic BP(DBP)and mean arterial pressure(MAP)responses to low-salt diet.MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention.In addition,miR-26b-3p SNP rs115254818 was significantly correlated with SBP,DBP and MAP responses to high-salt intervention.MiR-1307-5p SNPs rs1 1191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet.MiR-4638-3p SNP rs6601178,miR-210-3p SNP rs12364149,miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet.In addition,miR-26b-3p SNP rs115254818 was significantly associated with SBP,DBP and MAP responses to potassium supplementation.MiR-1307-5p SNPs rs11191676,rs2292807,and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation.Conclusion miRNA gene polymorphisms are associated with BP response to sodium and potassium,suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.

Objective To investigate the mechanism by which EFHD2 affects the occurrence and progression of breast cancer based on the NOX4/ROS signaling pathway.Methods Cells were divided into an NC-shRNA group and EFHD2-shRNA group.A lentiviral vector for EFHD2 silencing and a control vector were constructed and used to transfect MDA-MB-23 and MCF-7 breast cancer cells.The transfection efficiency was verified by qRT-PCR.A CCK8 assay was used to detect cell proliferation activity.A plate cloning assay was employed to measure cell colony formation ability.A scratch test was used to detect cell migration,and a Transwell assay used to assess cell invasion.Flow cytometry was applied to detect apoptosis and ROS levels.qRT-PCR was used to analyze the mRNA expression of GLUT1,PDK1,PFK1,PKM2,PDH,and LDH,while Western blot was applied to detect the expression of Cleaved caspase-3,MMP-2,and NOX4 proteins.Results Compared with the NC-shRNA group,the EFHD2-shRNA group's EFHD2 expression was significantly decreased and its cell survival and colony formation ability were weakened.The apoptosis rate and the expression of the pro-apoptotic protein Cleaved caspase-3 increased.The cell migration distance was shortened,while the number of invading cells and the expression of MMP-2,which promotes migration and invasion,were decreased.The levels of lactic acid and GLUT1,PDK1,PFK1,PKM2,and LDH decreased,while the levels of ATP and PDH increased.Streaming result showed that ROS levels were reduced and NOX4 protein was down-regulated after silencing EFHD2.Conclusions EFHD2 inhibits ROS production by regulating the NOX4/ROS signaling pathway,causing lactic acid and glucose accumulation,promoting the apoptosis of breast cancer cells,and inhibiting cell proliferation,migration,and invasion.

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.

【Objective】 Corin, a transmembrane serine protease that can cleave atrial natriuretic peptide precursor (pro-ANP) into atrial natriuretic peptide with smaller bioactive molecules, participates in the pathophysiological process of hypertension and cardiac hypertrophy. The purpose of this study was to explore the relationship of Corin gene variation with blood pressure responses to sodium and potassium dietary interventions. 【Methods】 In 2004, we recruited 514 participants from 124 families in 7 villages of Baoji, Shaanxi Province, China. All the subjects received a 3-day normal diet, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Fifteen single nucleotide polymorphisms (SNPs) of Corin gene were selected for final analysis. 【Results】 SNPs rs12509275 were significantly associated with diastolic blood pressure (DBP) response to low-salt diet, while rs3749584 was associated with pulse pressure (PP) response to low-salt diet.SNP rs3749584 and rs10517195 were significantly associated with PP response to high-salt diet. In addition,rs17654278 were significantly associated with systolic blood pressure (SBP) response to high-salt and potassium supplementation, rs2271037 was significantly correlated with DBP responses to high-salt and potassium supplementation, and rs4695253, rs12509275, rs2351783, rs36090894 were significantly associated with PP response to high-salt and potassium supplementation. 【Conclusion】 Corin gene polymorphisms were associated with blood pressure response to sodium and potassium, suggesting that Corin gene may be involved in pathophysiological process of salt sensitivity and potassium sensitivity.

【Objective】 4-like protein with down-regulated expression and development in neural precursor cells (NEDD4L) plays an important role in blood pressure (BP) regulation and sodium homeostasis by regulating epithelial sodium channel protein. In this study, we aimed to explore the relationship of NEDD4L gene polymorphisms with BP responses to sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Meixian County, Shaanxi Province, were recruited to establish a salt-sensitive hypertension study cohort. All the subjects received a 3-day baseline survey, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Their BP was measured and peripheral blood samples were collected at different intervention periods. The 14 gene polymorphisms of NEDD4L gene were genotyped and analyzed by MassARRAY platform. 【Results】 BP decreased on a low-salt diet, and significantly increased on a high-salt diet, and decreased again after potassium supplementation. NEDD4L SNPs rs74408486 were significantly associated with systolic BP, diastolic BP and mean arterial pressure responses to the low-salt diet. SNPs rs292449 and rs2288775 were significantly associated with pulse pressure response to the high-salt diet. In addition, SNPs rs563283 and rs292449 were significantly associated with diastolic BP, mean arterial pressure, and pulse pressure responses to high-salt and potassium supplementation diet. 【Conclusion】 NEDD4L gene polymorphisms were significantly associated with BP responses to sodium and potassium intake, suggesting that NEDD4L gene may be involved in the development of salt sensitivity and potassium sensitivity.