Objective:To investigate the effect of deubiquitinating enzymes(DUBs) USP2 on depressive-like behavior and hippocampal NF-κB expression in mice.Methods:(1) USP2 silencing experiment: Two USP2 silencing interference sequences with the highest knockdown efficiency were screened and cloned into a lentivirus vector. Mice were microinjected with lentivirus vector into both sides of hippocampus to silence the USP2 gene, and depressive behavior and USP2 protein expression in hippocampal tissue were observed. (2) Venlafaxine intervention experiment: total 32 healthy male C57BL/6 mice were randomly divided into virus control group, Venlafaxine group, USP2 silencing group, and USP2 silencing+ Venlafaxine group according to the random number table method, with 8 mice in each group. Mice were injected with lentivirus into both side of the hippocampus, and 7 days later, they were given intraperitoneal injection of Venlafaxine (5 mg/kg, once a day, for a total of 14 days). After the administration, the depressive behavior of mice was detected by forced swimming test(FST) and tail suspension test(TST), and the expression levels of USP2, p-IκBα, IκBα, p-NF-κB p65, and NF-κB p65 in the hippocampus of mice were detected by Western blot.SPSS 25.0 and GraphPad Prism 8.0 were used for data processing and chart drawing.The t-test was used for comparison between two groups, One-way ANOVA was used for comparison among multiple groups, and Tukey HSD or LSD- t was used for post hoc pairwise comparison when there was homogeneity of variance. Results:(1)The results of the USP2 silencing experiment showed that both screened USP2 silencing sequences had good gene knockout effects. The expression levels of USP2 protein in the hippocampus of mice injected with USP2 silencing virus were lower than those of the negative control virus groups (both P<0.05). The immobility time of mice in the FST and TST was higher than that of the negative control virus group (both P<0.05). (2)Venlafaxine intervention experiment: There were statistically significant differences in immobility time among the four groups of mice in the FST and TST ( F=8.90, 4.41, both P<0.05). The immobility time of FST and the immobility time of TST in the USP2 silencing+ Venlafaxine group ((48.13±12.76) s, (77.38±12.35) s) were lower than those in the USP2 silencing group((129.88±11.67)s, (148.29±15.31)s) (both P<0.05). There were statistically significant differences in the expression levels of USP2, p-IκBα, and p-NF-κB p65 proteins in the hippocampal tissues of the four groups of mice ( F=8.39, 5.78, 21.32, all P<0.05).The expression level of USP2 protein in the USP2 silencing group(0.49±0.07) was lower than that in the USP2 silencing+ Venlafaxine group(0.79±0.08) and virus control group(1.00±0.07)(both P<0.05), while the expression levels of p-IκBα, p-NF-κB p65 protein (1.63±0.18, 2.14±0.24) were higher than those in the virus control group (1.00±0.06, 1.00±0.04) and the USP2 silencing+ Venlafaxine group (0.70±0.23, 0.68±0.09) (both P<0.05). Conclusion:USP2 scilencing can induce depressive-like behaviors in mice. Venlafaxine ameliorates USP2 silencing-induced depressive-like behaviors, which may be associated with the hippocampal NF-κB signaling pathway.

Objective:To investigate the effect of deubiquitinating enzymes(DUBs) USP2 on depressive-like behavior and hippocampal NF-κB expression in mice.Methods:(1) USP2 silencing experiment: Two USP2 silencing interference sequences with the highest knockdown efficiency were screened and cloned into a lentivirus vector. Mice were microinjected with lentivirus vector into both sides of hippocampus to silence the USP2 gene, and depressive behavior and USP2 protein expression in hippocampal tissue were observed. (2) Venlafaxine intervention experiment: total 32 healthy male C57BL/6 mice were randomly divided into virus control group, Venlafaxine group, USP2 silencing group, and USP2 silencing+ Venlafaxine group according to the random number table method, with 8 mice in each group. Mice were injected with lentivirus into both side of the hippocampus, and 7 days later, they were given intraperitoneal injection of Venlafaxine (5 mg/kg, once a day, for a total of 14 days). After the administration, the depressive behavior of mice was detected by forced swimming test(FST) and tail suspension test(TST), and the expression levels of USP2, p-IκBα, IκBα, p-NF-κB p65, and NF-κB p65 in the hippocampus of mice were detected by Western blot.SPSS 25.0 and GraphPad Prism 8.0 were used for data processing and chart drawing.The t-test was used for comparison between two groups, One-way ANOVA was used for comparison among multiple groups, and Tukey HSD or LSD- t was used for post hoc pairwise comparison when there was homogeneity of variance. Results:(1)The results of the USP2 silencing experiment showed that both screened USP2 silencing sequences had good gene knockout effects. The expression levels of USP2 protein in the hippocampus of mice injected with USP2 silencing virus were lower than those of the negative control virus groups (both P<0.05). The immobility time of mice in the FST and TST was higher than that of the negative control virus group (both P<0.05). (2)Venlafaxine intervention experiment: There were statistically significant differences in immobility time among the four groups of mice in the FST and TST ( F=8.90, 4.41, both P<0.05). The immobility time of FST and the immobility time of TST in the USP2 silencing+ Venlafaxine group ((48.13±12.76) s, (77.38±12.35) s) were lower than those in the USP2 silencing group((129.88±11.67)s, (148.29±15.31)s) (both P<0.05). There were statistically significant differences in the expression levels of USP2, p-IκBα, and p-NF-κB p65 proteins in the hippocampal tissues of the four groups of mice ( F=8.39, 5.78, 21.32, all P<0.05).The expression level of USP2 protein in the USP2 silencing group(0.49±0.07) was lower than that in the USP2 silencing+ Venlafaxine group(0.79±0.08) and virus control group(1.00±0.07)(both P<0.05), while the expression levels of p-IκBα, p-NF-κB p65 protein (1.63±0.18, 2.14±0.24) were higher than those in the virus control group (1.00±0.06, 1.00±0.04) and the USP2 silencing+ Venlafaxine group (0.70±0.23, 0.68±0.09) (both P<0.05). Conclusion:USP2 scilencing can induce depressive-like behaviors in mice. Venlafaxine ameliorates USP2 silencing-induced depressive-like behaviors, which may be associated with the hippocampal NF-κB signaling pathway.

Objective To investigate the impact of type 2 inflammation markers blood eosinophils(EOS)and fractional exhaled nitric oxide(FeNO)on bronchodilator responsiveness(BDR)in patients with chronic obstructive pulmonary disease(COPD).Methods This study was conducted among 389 patients with an established diagnosis of COPD in our hospital from October,2019 to October,2023,who all underwent bronchial dilation test(BDT)of the large and small airways.Based on smoking history,blood EOS,and FeNO,these patients were divided group A(blood EOS<300/μL+FeNO<35 ppb+smoking history<20 pack-years),group B(blood EOS<300/μL+FeNO<35 ppb+smoking history≥20 pack-years),group C(blood EOS≥300/μL or FeNO≥35 ppb+smoking history≥20 pack-years),and group D(blood EOS≥300/μL or FeNO≥35 ppb+smoking history<20 pack-years)for analyzing the relationship between clinical indexes and BDR.Results BDR evaluation based on forced expiratory volume in 1 second(FEV1),forced vital capacity(FVC),and maximum mid-expiratory flow(MMEF)yielded consistent results,all showing a younger mean age,higher FeNO levels,and higher blood EOS counts and percentages in patients positive for BDT(P<0.05).The improvement value and improvement rate of FEV1 were significantly lower in group A than in group D.The improvement value and improvement rate of FEV1 as well as the improvement rate of MMEF were significantly lower in group B than in group D.In the overall patients,age and FeNO were significantly correlated with the improvement value and improvement rate of FEV1 and the improvement rate of MMEF(P<0.05).Conclusion Type 2 inflammation markers have different effects on BDR in the large and small airways of COPD patients,and their clinical significance needs further investigation.

Objective To investigate the impact of type 2 inflammation markers blood eosinophils(EOS)and fractional exhaled nitric oxide(FeNO)on bronchodilator responsiveness(BDR)in patients with chronic obstructive pulmonary disease(COPD).Methods This study was conducted among 389 patients with an established diagnosis of COPD in our hospital from October,2019 to October,2023,who all underwent bronchial dilation test(BDT)of the large and small airways.Based on smoking history,blood EOS,and FeNO,these patients were divided group A(blood EOS<300/μL+FeNO<35 ppb+smoking history<20 pack-years),group B(blood EOS<300/μL+FeNO<35 ppb+smoking history≥20 pack-years),group C(blood EOS≥300/μL or FeNO≥35 ppb+smoking history≥20 pack-years),and group D(blood EOS≥300/μL or FeNO≥35 ppb+smoking history<20 pack-years)for analyzing the relationship between clinical indexes and BDR.Results BDR evaluation based on forced expiratory volume in 1 second(FEV1),forced vital capacity(FVC),and maximum mid-expiratory flow(MMEF)yielded consistent results,all showing a younger mean age,higher FeNO levels,and higher blood EOS counts and percentages in patients positive for BDT(P<0.05).The improvement value and improvement rate of FEV1 were significantly lower in group A than in group D.The improvement value and improvement rate of FEV1 as well as the improvement rate of MMEF were significantly lower in group B than in group D.In the overall patients,age and FeNO were significantly correlated with the improvement value and improvement rate of FEV1 and the improvement rate of MMEF(P<0.05).Conclusion Type 2 inflammation markers have different effects on BDR in the large and small airways of COPD patients,and their clinical significance needs further investigation.

Humans ; Nitric Oxide ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms ; Lung ; Nitric Oxide Synthase ; Macrophages, Alveolar ; Pulmonary Alveoli

OBJECTIVE: To investigate the prevalence of vitamin D deficiency and its association with blood eosinophil count in healthy population and patients with chronic obstructive pulmonary disease (COPD). METHODS: We analyzed the data of a total 6163 healthy individuals undergoing routine physical examination in our hospital between October, 2017 and December, 2021, who were divided according to their serum 25(OH)D level into severe vitamin D deficiency group (< 10 ng/mL), deficiency group (< 20 ng/mL), insufficient group (< 30 ng/mL) and normal group (≥30 ng/mL). We also retrospectively collected the data of 67 COPD patients admitted in our department from April and June, 2021, with 67 healthy individuals undergoing physical examination in the same period as the control group. Routine blood test results, body mass index (BMI) and other parameters were obtained from all the subjects, and logistic regression models were used to investigate the association between 25(OH)D levels and eosinophil count. RESULTS: The overall abnormal rate of 25(OH)D level (< 30 ng/mL) in the healthy individuals was 85.31%, and the rate was significantly higher in women (89.29%) than in men. Serum 25(OH)D levels in June, July, and August were significantly higher than those in December, January, and February. In the healthy individuals, blood eosinophil counts were the lowest in severe 25(OH)D deficiency group, followed by the deficiency group and insufficient group, and were the highest in the normal group (P < 0.05). Multivariable regression analysis showed that an older age, a higher BMI, and elevated vitamin D levels were all risk factors for elevated blood eosinophils in the healthy individuals. The patients with COPD had lower serum 25(OH)D levels than the healthy individuals (19.66±7.87 vs 26.39±9.28 ng/mL) and a significantly higher abnormal rate of serum 25(OH)D (91% vs 71%; P < 0.05). A reduced serum 25(OH)D level was a risk factor for COPD. Blood eosinophils, sex and BMI were not significantly correlated with serum 25(OH)D level in patients with COPD. CONCLUSION Vitamin D deficiency is common in both healthy individuals and COPD patients, and the correlations of vitamin D level with sex, BMI and blood eosinophils differ obviously between healthy individuals and COPD patients.
Male ; Humans ; Female ; Eosinophils ; Retrospective Studies ; Leukocyte Count ; Body Mass Index ; Pulmonary Disease, Chronic Obstructive

Objective:To study the risk factors of acute kidney injury in patients with diabetic nephropathy and the prognostic value of urinary neutrophil gelatinase associated lipocalin (NGAL) .Methods:The data of 80 patients with diabetic nephropathy in the First Hospital of Shanxi Medical University from Mar. 2016 to Dec. 2020 were retrospectively studied. According to the random selection of numbers + artificial arrangement, they were divided into observation group and control group according to the presence or absence of acute kidney injury (AKI) . The observation group included patients with diabetic nephropathy complicated by acute kidney injury, and the control group included patients with diabetic nephropathy. The urinary albumin/creatinine ratio (ACR) , blood routine, left ventricular ejection fraction (LVEF) , NGAL, etc. were compared between the two groups. The correlation and influencing factors of acute kidney injury in patients with diabetic nephropathy and age, eGFR, severe infection, antibiotics, heart failure, respiratory failure, ACR, LVEF, and NGAL were studied. At the same time, the prognostic value of urinary NGAL was analyzed.Results:Single factor screening: There was no significant difference in gender or body weight between the two groups ( P>0.05) . However, there were differences in age, epidermal growth factor receptor (eGFR) , severe infection, antibiotics, heart failure, respiratory failure, ACR, LVEF, and NGAL ( P<0.05) . Correlation: Acute kidney injury in patients with diabetic nephropathy was very weakly correlated with gender, age, and body weight, moderately correlated with eGFR, heart failure, respiratory failure, ACR, and LVEF, and highly correlated with NGAL, severe infection, and antibiotics. Risk factors: The independent risk factors for acute kidney injury in patients with diabetic nephropathy included severe infection, eGFR, antibiotics, ACR, LVEF, and NGAL. The prognostic value of urinary NGAL: AUC=0.967, standard error 0.021, Youden index 0.967, sensitivity 0.967, specificity 1, and zero cutoff point 30.00. Conclusion:The main influencing factors of DN complicated with AKI are severe infection, eGFR, antibiotics, ACR, LVEF, NGAL, and urinary NGAL has prognostic value for DN complicated with AKI, and it is worthy of clinical application.

To examine the risk factors for developing diabetes on its 3-year outcome in an elderly population with impaired fasting glucose (IFG). We selected the 328 elderly with impaired fasting glucose in Binhai new area of Tianjin as the research object. All subjects participated in objective examinations such as physical activity ability tests, blood tests and anthropometric examinations, and completed the questionnaire survey. Between baseline and 3-year outcome, 56 of the subjects with IFG at baseline have developed diabetes. After multivariate adjustments, we found that higher incidence of diabetes was associated with higher fasting plasma glucose (OR=9.30, 95%CI 2.84-30.48, P<0.01) and reduced grip strength/weight (OR=0.88, 95%CI 0.82-0.94, P<0.01). Moreover, the combination of higher fasting plasma glucose and lower grip strength/weight would lead to higher incidence of diabetes compared with higher fasting plasma glucose or lower grip strength/weight alone (P<0.05). In this study, high fasting plasma glucose and low muscle strength were associated with blood glucose worsening in three years in IFG patients. In addition to blood glucose levels, physical activity is also a risk factor for diabetes in older adults.

OBJECTIVE: To investigate the association of the time of initial diagnosis with the severity of chronic obstructive pulmonary disease (COPD). METHODS: A total of 803 patients who were diagnosed to have COPD for the first time in our hospital between May 2015 to February 2018 were enrolled in this study.The diagnoses of COPD and asthma COPD overlap (ACO) were made according GOLD guidelines and european consensus definition.Lung function of the patients was graded according to the GOLD guidelines. RESULTS: The patients with COPD had a mean age of 61.8±9.9 years,including 726 male and 77 female patients.The course of the patients (defined as the time from symptom onset to the establishment of a diagnosis) was 3(0.5,8) years.Among these patients,85.2% had a moderate disease severity (FEV1%<80%),and 48.3% had severe or very severe conditions (FEV1%<50%);47.0% of them were positive for bronchial dilation test.In the overall patients,295(36.7%) were also diagnosed to have ACO,and the mean disease course of ACO[3(1,9) years]was similar to that of COPD[3(0.5,8) years](>0.05).A significant correlation was found between the disease course and the lung function of the patients.Multiple linear regression analysis showed that an older age and a longer disease course were associated with poorer lung functions and a greater disease severity. CONCLUSIONS The delay of the initial diagnosis is significantly related to the severity of COPD.
Age Factors ; Aged ; Asthma ; diagnosis ; Delayed Diagnosis ; adverse effects ; Disease Progression ; Female ; Humans ; Lung ; physiopathology ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; diagnosis ; physiopathology ; Severity of Illness Index ; Time Factors

Objective: The aim of this paper is to identify the basic organizational structure and the key elements of integrated healthcare model of patients with Chronic Obstructive Pulmonary Disease (COPD) and propose an appropriate development strategy.Methods: Based on the literature review of research articles about integrated care on patients with COPD, an analysis was conducted with the help of the Chronic Care Model (CCM) which is a chronic disease management model.Results: From of a total 16 articles about 13 case studies were found.An integrated healthcare of COPD was carried out in 10 hospital-based or community-based care programs.Most of the patients were the elderly and health status were moderately severe or more severe.The components of healthcare programs varied from 4 to 12 included at least two CCM dimension.A coordinator or a case manager was appointed in all healthcare programs and a follow-up plan was made as well.Decision making was supported by clinic guideline and specialist resource in 9 integrated healthcare programs which community facilities involved.All programs included self-management with health education and individualized behavioral support was in 10 programs.The action plan was applied in 8 studies.8 studies using a clinical information system connected health care provider and patients.Conclusions: COPD integrated care program can be constructed according to the management model of chronic disease, and it is suggested that we can organize the COPD integrated care program based on CCM and the program comprises 4 organizational components of at least two CCM dimensions.The key elements of COPD integrated healthcare are to appoint a coordinator, to make a follow-up plan, and the necessity of community participation to support decision making, support self-management by education and individualized behavioral management with an action plan.