Objective:To identify factors associated with depressive symptoms in maintenance hemodialysis patients and to examine the relationship between these symptoms and mortality.Methods:Between January and December 2019, patients who received maintenance hemodialysis in the Blood Purification Center of the Second Affiliated Hospital of Nanjing Medical University were enrolled in a prospective cohort study. Depressive symptoms were assessed using the internationally validated patient health questionnaire-8 (PHQ-8). Sleep quality and anxiety were measured with the Pittsburgh sleep quality index (PSQI) and the generalized anxiety disorder-7 (GAD-7) scale, respectively. Follow-up continued until December 31, 2022, with all-cause mortality as the primary outcome. Ordinal logistic regression was used to identify independent predictors of depression severity. Cox proportional hazards models evaluated the association between depressive symptoms and mortality.Results:A total of 532 maintenance hemodialysis (MHD) patients completed the study. Among them, 177 (33.3%) exhibited depressive symptoms. Compared with patients without depression, those with mild or moderate-to-severe depression were older [median age: 58 (50, 66) vs. 60 (55, 65) vs. 55 (46, 64)], more likely to smoke [35.9% (51/142) vs. 40.0% (14/35) vs.26.2% (93/355)], had poorer sleep quality [PSQI: 9 (6, 13) vs. 12 (9, 17) vs. 5 (3, 9)], and higher anxiety levels [GAD-7: 1 (0, 3) vs. 3 (1, 6) vs. 0 (0, 1)], the differences among the three groups were statistically significant (all P<0.05). Ordinal logistic regression identified smoking status, history of diabetes or cardiovascular disease, hemoglobin level, PSQI score, and GAD-7 score as independent predictors of depression severity ( OR=1.60, 1.80, 1.81, 0.98, 3.67, 8.67; all P<0.05). After a median follow-up of 40 (35, 44) months, 109 patients died, including 66 (60.6%) from cardio-cerebrovascular causes and 24 (22.0%) from infections. Kaplan-Meier analysis revealed significantly lower cumulative survival in the depression group compared to the non-depression group ( P<0.001). Cox regression analysis demonstrated that depressive symptoms remained independently associated with all-cause mortality after adjusting for confounders ( HR=1.06, 95% CI 1.00-1.13, P=0.048), with an even stronger association observed for patients with PHQ-8 scores≥2.9 ( HR=1.10, 95% CI 1.03-1.16, P=0.005). However, the associations between depression and cardio-cerebrovascular mortality ( P=0.111) or infection-related mortality ( P=0.509) were not statistically significant. Conclusions:Depressive symptoms are prevalent among maintenance hemodialysis patients and are independently associated with increased all-cause mortality. Smoking, comorbid diabetes or cardiovascular disease, low hemoglobin level, poor sleep quality, and anxiety are risk factors contributing to depression. Maintenance hemodialysis patients with PHQ-8 scores≥3 should be considered at heightened risk for mortality.

Acute kidney injury (AKI) is a common clinical acute and critical condition. There is a lack of clinical interventions or therapeutic drugs that can significantly improve AKI outcomes. Lipids, including fatty acids, triglycerides, sphingolipids, phospholipids and cholesterol play crucial roles in energy metabolism, cell membrane composition, cell signaling, and cell homeostasis and survival. Recent lipidomics studies have revealed significant alterations in the content and composition of renal lipids during AKI, highlighting their important roles in the onset, progression, and outcomes of the disease. A common feature of AKI across multiple etiologies is altered lipid metabolism, characterized by insufficient energy generation due to mitochondrial damage and deposition of excess lipids in the kidney. The article summarizes the characteristics of renal lipid metabolism in physiological state, alterations of renal lipid metabolism in AKI and molecular mechanisms related to lipid metabolism disorders that aggravate AKI through mitochondrial damage, oxidative stress, autophagy dysfunction, activation of inflammatory and immune responses and regulated cell death, to provide new ideas and therapeutic targets for the clinical treatment of AKI.

Acute kidney injury (AKI) is a common clinical acute and critical condition. There is a lack of clinical interventions or therapeutic drugs that can significantly improve AKI outcomes. Lipids, including fatty acids, triglycerides, sphingolipids, phospholipids and cholesterol play crucial roles in energy metabolism, cell membrane composition, cell signaling, and cell homeostasis and survival. Recent lipidomics studies have revealed significant alterations in the content and composition of renal lipids during AKI, highlighting their important roles in the onset, progression, and outcomes of the disease. A common feature of AKI across multiple etiologies is altered lipid metabolism, characterized by insufficient energy generation due to mitochondrial damage and deposition of excess lipids in the kidney. The article summarizes the characteristics of renal lipid metabolism in physiological state, alterations of renal lipid metabolism in AKI and molecular mechanisms related to lipid metabolism disorders that aggravate AKI through mitochondrial damage, oxidative stress, autophagy dysfunction, activation of inflammatory and immune responses and regulated cell death, to provide new ideas and therapeutic targets for the clinical treatment of AKI.

Objective:To identify factors associated with depressive symptoms in maintenance hemodialysis patients and to examine the relationship between these symptoms and mortality.Methods:Between January and December 2019, patients who received maintenance hemodialysis in the Blood Purification Center of the Second Affiliated Hospital of Nanjing Medical University were enrolled in a prospective cohort study. Depressive symptoms were assessed using the internationally validated patient health questionnaire-8 (PHQ-8). Sleep quality and anxiety were measured with the Pittsburgh sleep quality index (PSQI) and the generalized anxiety disorder-7 (GAD-7) scale, respectively. Follow-up continued until December 31, 2022, with all-cause mortality as the primary outcome. Ordinal logistic regression was used to identify independent predictors of depression severity. Cox proportional hazards models evaluated the association between depressive symptoms and mortality.Results:A total of 532 maintenance hemodialysis (MHD) patients completed the study. Among them, 177 (33.3%) exhibited depressive symptoms. Compared with patients without depression, those with mild or moderate-to-severe depression were older [median age: 58 (50, 66) vs. 60 (55, 65) vs. 55 (46, 64)], more likely to smoke [35.9% (51/142) vs. 40.0% (14/35) vs.26.2% (93/355)], had poorer sleep quality [PSQI: 9 (6, 13) vs. 12 (9, 17) vs. 5 (3, 9)], and higher anxiety levels [GAD-7: 1 (0, 3) vs. 3 (1, 6) vs. 0 (0, 1)], the differences among the three groups were statistically significant (all P<0.05). Ordinal logistic regression identified smoking status, history of diabetes or cardiovascular disease, hemoglobin level, PSQI score, and GAD-7 score as independent predictors of depression severity ( OR=1.60, 1.80, 1.81, 0.98, 3.67, 8.67; all P<0.05). After a median follow-up of 40 (35, 44) months, 109 patients died, including 66 (60.6%) from cardio-cerebrovascular causes and 24 (22.0%) from infections. Kaplan-Meier analysis revealed significantly lower cumulative survival in the depression group compared to the non-depression group ( P<0.001). Cox regression analysis demonstrated that depressive symptoms remained independently associated with all-cause mortality after adjusting for confounders ( HR=1.06, 95% CI 1.00-1.13, P=0.048), with an even stronger association observed for patients with PHQ-8 scores≥2.9 ( HR=1.10, 95% CI 1.03-1.16, P=0.005). However, the associations between depression and cardio-cerebrovascular mortality ( P=0.111) or infection-related mortality ( P=0.509) were not statistically significant. Conclusions:Depressive symptoms are prevalent among maintenance hemodialysis patients and are independently associated with increased all-cause mortality. Smoking, comorbid diabetes or cardiovascular disease, low hemoglobin level, poor sleep quality, and anxiety are risk factors contributing to depression. Maintenance hemodialysis patients with PHQ-8 scores≥3 should be considered at heightened risk for mortality.

Objective:To analyze the correlation between serum lipid levels and diabetic nephropathy in patients with type 2 di-abetic mellitus.Methods:A total of 240 patients with type 2 diabetic mellitus from Jun 2011 to Jul 2013 were enrolled.There were 100 patients with diabetic nephropathy and 140 patients without any complication.Gender,age,duration of diabetes, baseline fasting glucose,glycosylated hemoglobin and serum lipid were compared between the two groups.The odds ratio(OR) and 95% confidence interval(CI)of correlation between these factors and diabetic nephropathy were calculated and analyzed with Logistic regression model.Results:The differences of age,duration of diabetes,systolic pressure between the two groups were statistically significant(P <0.01).Adjusted Logistic regression model showed that age> 70(OR= 2.92,95% CI:1.31-6.51),duration of diabetes>10 years(OR=3.33,95%CI:1.79-6.16),diastolic pressure>90 mmHg(OR=2.23,95%CI:1.06-4.69),and low density lipoprotein>3.64 mmol/L(OR=2.85,95%CI:1.16-7.03)were independent risk factors for type 2 Dia-betic Mellitus complicated by diabetic nephropathy(P <0.01 and 0.05).Conclusions:Low density lipoprotein has the potential to be a predictive,prophylactic and therapeutic target for diabetic nephropathy.

One group of Bcl-2 protein family, which shares only the BH3 domain (BH3-only), is critically involved in the regulation of programmed cell death. Herein we demonstrated a novel human BH3-only protein (designated as Bop) which could induce apoptosis in a BH3 domain-dependent manner. Further analysis indicated that Bop mainly localized to mitochondria and used its BH3 domain to contact the loop regions of voltage dependent anion channel 1 (VDAC1) in the outer mitochondrial membrane. In addition, purified Bop protein induced the loss of mitochondrial transmembrane potential (Δψm) and the release of cytochrome c. Furthermore, Bop used its BH3 domain to contact pro-survival Bcl-2 family members (Bcl-2, Bcl-X(L), Mcl-1, A1 and Bcl-w), which could inhibit Bop-induced apoptosis. Bop would be constrained by pro-survival Bcl-2 proteins in resting cells, because Bop became released from phosphorylated Bcl-2 induced by microtubule-interfering agent like vincristine (VCR). Indeed, knockdown experiments indicated that Bop was partially required for VCR induced cell death. Finally, Bop might need to function through Bak and Bax, likely by releasing Bak from Bcl-X(L) sequestration. In conclusion, Bop may be a novel BH3-only factor that can engage with the regulatory network of Bcl-2 family members to process intrinsic apoptotic signaling.
Amino Acid Sequence ; Animals ; Apoptosis ; Cell Line ; Cell Survival ; Humans ; Mice ; Mitochondria ; metabolism ; Mitochondrial Membranes ; metabolism ; Molecular Sequence Data ; Protein Structure, Tertiary ; Protein Transport ; Proto-Oncogene Proteins c-bcl-2 ; chemistry ; metabolism ; Signal Transduction ; Time Factors ; Voltage-Dependent Anion Channel 1 ; metabolism ; bcl-2 Homologous Antagonist-Killer Protein ; metabolism ; bcl-2-Associated X Protein ; metabolism

BACKGROUND AND OBJECTIVEEpidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has been widely used as the second- and third-line therapy in patients with advanced non-small cell lung cancer (NSCLC). However, its effect in the first-line treatment is unclear. The aim of this study was to evaluate the efficacy and safety of EGFR-TKI as first-line therapy.

METHODSThe clinical characteristics, responses rate, disease control rate and overall survival were retrospectively analyzed in 77 chemonaive patients with advanced NSCLC. All of the patients received oral gefitinib (250 mg/d) or erlotinib (150 mg/d) until disease progression or unacceptable toxicity occurrence.

RESULTSThe overall response rate was 33.8% and the disease control rate was 68.8%. The median progression-free survival and the median survival time were 6.0 months and 8.9 months, respectively. One-year survival rate was 61.4%. Responses correlated significantly with histology, PS score, smoking history, skin rash, EGFR mutations and serum CEA. Histology and skin rash were the independent predictors of survival. Common toxicities were skin rash and mild diarrhea. EGFR-TKI could improve the clinical symptoms and the quality of life.

CONCLUSIONEGFR-TKI is effective and well tolerated as first-line therapy in patients with advanced NSCLC.

Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; mortality ; Erlotinib Hydrochloride ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Quinazolines ; administration & dosage ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Retrospective Studies ; Young Adult

Objective　To investigate the pattern of monocyte chemoattractant prolein-1 (MCP-1) distribution in the renal interstitium and evaluate its pathogenic role in tubulo-interstitial lesions in patients with lupus nephritis, the distribution of MCP-1 in renal tissue was observed. Methods　Eighteen female patients with biopsy-proven lupus nephritis were enrolled in this study. No intensive immunosuppresive therapy was used in these patients during the 3 months prior to renal biopsy. The distribution of MCP-1, infiltration of CD68+ (macrophage/monocyte), CD4+ and CD8+ cells in the tubulo-interstitium of patients with lupus nephritis was detected using immunohistochemical staining with specific antibodies. Renal specimens from patients with minimal change glomerulonephritis were used as controls. Results　MCP-1 protein was widely distributed in the renal tissue of patients with lupus nephritis, mainly located at the baso-lateral surface of tubular epithelial cells (16/18 biopsies), and on the wall of interstitial blood vessels (9/18 biopsies). In contrast, tubular MCP-1 staining was weak and rare in renal tissue from controls (7.4±6.2% vs 26.7±22.8%, P<0.01). Tubulo-interstitial infiltration of CD68+, CD4+ and CD8+ cells was markedly increased in patients with lupus nephritis as compared to controls. The tubular expression of MCP-1 was strongly associated with the amount of CD68+ cell infiltration in the interstitium (r=0.5420, P<0.05) and the extent of interstitial fibrosis. There was no correlation between MCP-1 production in tubules and the degree of urinary protein excretion in patients with lupus nephritis (r=0.0547, P>0.05). Conclusions　The expression of MCP-1 in the renal tubules and vascular wall was markedly increased in patients with lupus nephritis. The overproduction of MCP-1 in renal tissue may contribute to monocyte recruitment in the interstitium and thus result in tubulo-interstitial damage in lupus nephritis.