1.Liuwei Dihuang Wan inhibits oxidative stress in premature ovarian failure mice by regulating intestinal microbiota
Jiawen ZHONG ; Bo JIANG ; Wenyan ZHANG ; Xiaorong LI ; Ling QIN ; Ting GAO
Chinese Journal of Tissue Engineering Research 2025;29(11):2285-2293
BACKGROUND:Studies have shown that patients with premature ovarian failure have changes in the structure of intestinal flora and that imbalance of intestinal microbiota may be one of the important mechanisms in the development of premature ovarian failure. OBJECTIVE:To investigate the effect of Liuwei Dihuang Wan on oxidative stress and intestinal microbiota in premature ovarian failure mice induced by cyclophosphamide. METHODS:Forty-five female ICR mice were randomized into three groups:blank group(normal mice),model group(premature ovarian failure mice),and Liuwei Dihuang Wan group.A mouse model of premature ovarian failure was prepared by one-time intraperitoneal injection of cyclophosphamide(120 mg/kg)in the latter two groups.After successful modeling,the Liuwei Dihuang Wan group was intragastrically administered for 28 continuous days,and the other two groups were intragastrically administered with the same amount of normal saline for 28 days.Mouse body mass was recorded weekly and ovarian index was calculated.The development of mouse follicles was observed using hematoxylin-eosin staining.ELISA method was used to detect serum levels of anti-Mullerian hormone,estradiol,follicle stimulating hormone,superoxide dismutase,glutathione peroxidase,and malondialdehyde.Meanwhile,the gut microbiome of all mice was detected through 16S rDNA sequencing. RESULTS AND CONCLUSION:The mice in the model group had loose hair,decreased vigor and grip strength,almost no increase in body mass,and decreased ovarian index.Whereas,the mouse body mass and ovarian index were increased after treatment with Liuwei Dihuang Wan(P<0.05).The estrous cycle of mice in the model group was disorganized;Liuwei Dihuang Wan could restore the estrous cycle and reduce the number of atretic follicles in mice with premature ovarian failure.The serum levels of follicle stimulating hormone and malondialdehyde in the model group significantly increased(P<0.01),while the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase significantly decreased(P<0.01).Liuwei Dihuang Wan could significantly decrease the serum levels of follicle stimulating hormone and malondialdehyde(P<0.01),and increase the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase.According to the 16S rDNA sequencing results,Liuwei Dihuang Wan could regulate the abundance and diversity of intestinal microbiota,and increase the relative abundance of beneficial bacteria.KEGG pathway analysis showed that the intestinal microbiota and metabolic pathways,biosynthesis of secondary metabolites,microbial metabolism in different environments,and biosynthesis of amino acids were regulated by Liuwei Dihuang Wan.To conclude,the changes in the structure of intestinal microbiome may be one of the potential mechanisms of Liuwei Dihuang Wan in treating premature ovarian failure.Liuwei Dihuang Wan can regulate the structure of intestinal microbiome,increase the number of beneficial bacteria,reduce the number of harmful bacteria,and thus improve the balance of intestinal microbiota.This regulatory effect helps to reduce oxidative stress levels and further inhibit ovarian oxidative stress in mice with premature ovarian failure.
2.Analysis of the relationship between intestinal segmented filamentous bacteria and rotavirus infection in children
Ting YANG ; Bo CHEN ; Gao LONG ; Xiaoli SHU ; Mizu JIANG
Chinese Journal of Pediatrics 2024;62(7):643-648
Objective:To investigate the association between intestinal colonization of segmented filamentous bacteria (SFB) and the risk of rotavirus infection, and the possible mechanisms by which SFB resist rotavirus infection.Methods:This case-control study enrolled 50 children aged 0 to 5 years who present to the outpatient Department of Children′s Hospital, Zhejiang University School of Medicine with diarrhea and positive stool tests for rotavirus. The children were divided into rotavirus enteritis group and control group consisting of 55 children with non-gastrointestinal and non-infectious surgical diseases.The age and sex composition of the two groups was matched. The DNA of the fecal flora was extracted and SFB was detected by real-time fluorescence quantitative PCR analysis. The children in the rotavirus enteritis group and the control group were subgrouped by age and sex to analyze the differences in SFB positivity rates between different groups, and further compare and analyze the differences in SFB positivity rates between these two groups of children in the ≤2 years old subgroup and the >2-5 years old subgroup. Neutralization test was performed with p3340 protein and rotavirus to determine the relationship between rotavirus infection rate and p3340 concentration in Vero cells. χ2 test or Fisher′s exact probability method was used for comparison between the two groups. Results:There were 50 children in the rotavirus enteritis group with an age of (1.7±0.9) years, and 55 children in the control group with an age of (1.8±1.1) years. The positive rate of SFB in children with rotavirus enteritis showed a declining trend across ages groups, with the highest rate of 10/14 in the ≤1 year old group, followed by 67% (14/21) in the >1-2 years old group, 9/15 in the >2-5 years old group, and there was no statistically significant difference ( P=0.867). The positive rate of SFB in the control group was 12/15 in the ≤1 year old group, 95% (19/20) in the >1-2 years old group, 50% (10/20) in the >2-5 years old group, with statistical significance ( P=0.004). The positive rate of SFB in children with rotavirus enteritis was 74% (20/27) in males and 56% (13/23) in females ( χ2=1.71, P=0.192). In the control group, it was 79% (22/28) in males and 70% (19/27) in females ( χ2=0.49, P=0.485). The positive rate of SFB was 66% (33/50) in the rotavirus enteritis group and 75% (41/55) in the control group, with no statistically significant ( χ2=0.56, P=0.454). In the children ≤2 years old, the SFB positivity rate was 69% (24/35) in the rotavirus enteritis group and 89% (31/35) in the control group, with a statistically significant difference ( χ2=4.16, P=0.041). However, in the children >2-5 years old, no statistically significant difference was observed, with the positive rate of SFB being 9/15 in the rotavirus enteritis group and 50% (10/20) in the control group ( P=0.734). Pearson correlation analysis revealed a negative correlation between rotavirus infection and SFB positivity ( r=-0.87, P<0.001). As the concentration of the p3340 specific protein increased, the luminescence intensity of the luciferase in the Vero cells, which were suitable for cultivating rotavirus, exhibited a decreasing trend ( F=4.17, P=0.001). Conclusions:SFB colonization in infants less than 2 years old is associated with a reduced risk of rotavirus infection. Cloning of specific SFB functional protein p3340 neutralizes rotavirus infection of Vero cells, and this mechanism of targeting rotavirus infection differs from the common antiviral mechanism.
3.Cholesterol paradox in the community-living old adults: is higher better?
Sheng-Shu WANG ; Shan-Shan YANG ; Chun-Jiang PAN ; Jian-Hua WANG ; Hao-Wei LI ; Shi-Min CHEN ; Jun-Kai HAO ; Xue-Hang LI ; Rong-Rong LI ; Bo-Yan LI ; Jun-Han YANG ; Yue-Ting SHI ; Huai-Hao LI ; Ying-Hui BAO ; Wen-Chang WANG ; Sheng-Yan DU ; Yao HE ; Chun-Lin LI ; Miao LIU
Journal of Geriatric Cardiology 2023;20(12):837-844
OBJECTIVE:
To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.
METHODS:
A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators.
RESULTS:
A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death.
CONCLUSIONS
In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.
4.Expert consensus on late stage of critical care management.
Bo TANG ; Wen Jin CHEN ; Li Dan JIANG ; Shi Hong ZHU ; Bin SONG ; Yan Gong CHAO ; Tian Jiao SONG ; Wei HE ; Yang LIU ; Hong Min ZHANG ; Wen Zhao CHAI ; Man hong YIN ; Ran ZHU ; Li Xia LIU ; Jun WU ; Xin DING ; Xiu Ling SHANG ; Jun DUAN ; Qiang Hong XU ; Heng ZHANG ; Xiao Meng WANG ; Qi Bing HUANG ; Rui Chen GONG ; Zun Zhu LI ; Mei Shan LU ; Xiao Ting WANG
Chinese Journal of Internal Medicine 2023;62(5):480-493
We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans
;
Consensus
;
Critical Care/methods*
;
Intensive Care Units
;
Pain/drug therapy*
;
Analgesics/therapeutic use*
;
Delirium/therapy*
;
Critical Illness
5.Measuring and analysis of the shoulder circumferences of 840 adults' permanent teeth crown preparations.
Wei Liang WU ; Xun Tao GAN ; Bo Chao LI ; Yan Hua ZHANG ; Yue Mei LIAO ; Wan Ting LIN ; Xiao Qiang LIU ; Jiang CHEN
Chinese Journal of Stomatology 2023;58(5):422-426
Objective: To measure and analyze the shoulder circumferences of adults' permanent teeth crown preparations based on data collected through the intraoral scanning, so as to provide dental anatomy data for clinical diagnosis and analysis. Methods: Intraoral scanning data of 840 complete crown preparations were collected, and were entrusted to the World Dental Laboratory Co., Ltd. in Fuzhou between March 2021 and June 2022. Except the data of the third molar, the rest data were categorized in terms of 14 tooth positions in the upper and lower jaw (each category involved 30 samples from male group and 30 samples from female group). Image measurement software was used to measure the shoulder circumferences of permanent teeth crown preparations. And analysis was conducted to reveal the difference of shoulder circumference diameters between male and female groups. And then they were grouped according to the mean value at each tooth position, on the premise that the difference between the maximum and minimum values and the mean value of the entire group was≤±1.00 mm. Analysis were further conducted to determine the differences of shoulder circumference diameters between each dental position and the differences between male and female in the same groups. Results: Bivariate analysis of variance showed that gender had no effect on the shoulder circumference of full crown preparations (F=0.55, P=1.457), while tooth position had a significant impact on the shoulder circumference of full crown preparations (F=273.15, P<0.001). The samples were classified into 5 groups according to the mean values of shoulder circumference diameters relating to each tooth position. Statistical analysis showed that Group 1, covering maxillary lateral incisor, mandibular central incisor and mandibular lateral incisor, had shoulder circumference with diameters of (16.62±2.21) mm; Group 2, consisting of maxillary central incisor, maxillary cusp, mandibular cusp, mandibular first premolar and mandibular second premolar, had diameters of (20.78±2.48) mm; Group 3, consisting of maxillary first premolar and maxillary second premolar, had diamerters of (22.09±2.72) mm; Group 4, covering maxillary first molar, maxillary second molar and mandibular first molar, had diamerters of (30.21±2.67) mm; while group 5, with mandibular second molar alone its member, had diamerters of (31.34±3.18) mm. The difference among the 5 groups was statistically significant (P<0.05). Conclusions: Significant differences of shoulder circumference diameters could be found between different tooth positions, while at the same tooth position, the differences between male and female are not significant. The 14 tooth positions could be grouped into 5 groups according to their shoulder circumference diameters. Future research could take the grouping as reference.
6.Correlation between heart rate index, SBPpeak-to-SBPrest ratio and peak oxygen consumption in patients with chronic heart failure.
Qian LUO ; Yu Qin SHEN ; Bo ZHUANG ; Ting SHEN ; Xiao Ling LIU ; Guang He LI ; Yu Mei JIANG ; De Jie LI ; Meng Yi ZHAN ; Hao Ming SONG ; Le Min WANG
Chinese Journal of Cardiology 2022;50(8):785-790
Objective: To investigate the correlation between heart rate index (HRI), systolic blood pressure(SBP) peak-to-SBPrest ratio (SBPR) and peak oxygen consumption (peakVO2) in patients with chronic heart failure (CHF), and discuss the possibility of using HRI and SBPR collected during exercise to assess the exercise tolerance of CHF patients in the absence of gas analysis. Methods: In this cross-sectional study, a total of 547 patients with CHF who underwent cardiopulmonary exercise test(CPET) in Tongji Hospital Heart Rehabilitation Center Affiliated to Tongji University from March 2007 to December 2018 were collected retrospectively, focusing on their clinical data including age, gender, type of heart failure,BMI as well as data collected during their CPETs, such as peakVO2, HRI and SBPR. Spearman univariate correlation analysis was used for statistical analysis, to unveil the correlations between peakVO2 and those parameters, and multiple linear regression analysis was also conducted. Results: A total of 547 CHF patients conducting CPET were included in this research, of which 447 were male, at age of 63(56, 69). Univariate analysis indicates that HRI, SBPR and peakVO2 showed significant positive correlation (r=0.323, 0.263, respectively, all P<0.001); Age and peak VO2 showed significant negative correlation(r=-0.207, P<0.001); Male patients showed peakVO2 higher than female(r=-0.229, P<0.001); PeakVO2 of heart failure with reduced ejection fraction(HFrEF) was lower than heart failure with mid-range ejection fraction(HFmrEF)and heart failure with preserved ejection fraction(HFpEF) (r=0.181, P<0.001). Body mass index (BMI) had no significant correlation with peakVO2 (P>0.05). Multivariate linear regression analysis showed that the HRI, SBPR were positively correlated with peakVO2(t=7.68, 5.08, respectively, all P<0.05), while age and BMI showed negative correlation with peakVO2(t=-5.43, -0.31, respectively, all P<0.05). PeakVO2 of male was higher than female(t=-6.03, P<0.05), and peakVO2 of HFrEF was lower than those of HFmrEF and HFpEF(t=3.17, 4.48, respectively, all P<0.05). A linear equation (F=33.52, adjusted R2=0.29) could be constructed: peakVO2=10.65(male) or 8.53(female)+4.26HRI+3.31SBPR-0.07age-0.13BMI+0(HFrEF) or 1.05 (HFmrEF) or 1.62(HFpEF). Conclusion: HRI and SBPR are positively correlated with peakVO2. In the absence of gas analysis, it is possible to apply HRI and SBPR during exercise to predict exercise tolerance in patients with CHF.
Chronic Disease
;
Cross-Sectional Studies
;
Female
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Heart Failure
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Heart Rate
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Humans
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Male
;
Oxygen Consumption/physiology*
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Prognosis
;
Retrospective Studies
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Stroke Volume/physiology*
7.Management and short-term outcomes of neonates born to mothers infected with SARS-CoV-2 Omicron variant.
Shu Juan LI ; Lan ZHANG ; Hao YUAN ; Xiao Bo ZHANG ; Chuan Qing WANG ; Gong Bao LIU ; Ying GU ; Tong Ling YANG ; Xiao Ting ZHU ; Xiao Wen ZHAI ; Yu SHI ; Si Yuan JIANG ; Ke ZHANG ; Kai YAN ; Peng ZHANG ; Xiao Jing HU ; Qing LIU ; Rui Wei GAO ; Juan ZHAO ; Jian Guo ZHOU ; Yun CAO ; Zhi Hua LI
Chinese Journal of Pediatrics 2022;60(11):1163-1167
Objective: To summarize the management and short-term outcomes of neonates delivered by mothers infected with SARS-CoV-2 Omicron variant. Methods: A retrospective study was performed on 158 neonates born to mothers infected with SARS-CoV-2 Omicron variant admitted to the isolation ward of Children's Hospital of Fudan University from March 15th, 2022 to May 30th, 2022. The postnatal infection control measures for these neonates, and their clinical characteristics and short-term outcomes were analyzed. They were divided into maternal symptomatic group and maternal asymptomatic group according to whether their mothers had SARS-CoV-2 symptoms. The clinical outcomes were compared between the 2 groups using Rank sum test and Chi-square test. Results: All neonates were under strict infection control measures at birth and after birth. Of the 158 neonates, 75 (47.5%) were male. The gestational age was (38+3±1+3) weeks and the birth weight was (3 201±463)g. Of the neonates included, ten were preterm (6.3%) and the minimum gestational age was 30+1 weeks. Six neonates (3.8%) had respiratory difficulty and 4 of them were premature and required mechanical ventilation. All 158 neonates were tested negative for SARS-COV-2 nucleic acid by daily nasal swabs for the first 7 days. A total of 156 mothers (2 cases of twin pregnancy) infected with SARS-CoV-2 Omicron variant, the time from confirmed SARS-CoV-2 infection to delivery was 7 (3, 12) days. Among them, 88 cases (56.4%) showed clinical symptoms, but none needed intensive care treatment. The peripheral white blood cell count of the neonates in maternal symptomatic group was significantly higher than that in maternal symptomatic group (23.0 (18.7, 28.0) × 109 vs. 19.6 (15.4, 36.6) × 109/L, Z=2.44, P<0.05). Conclusions: Neonates of mothers infected with SARS-CoV-2 Omicron variant during third trimester have benign short-term outcomes, without intrauterine infection through vertical transmission. Strict infection control measures at birth and after birth can effectively protect these neonates from SARS-CoV-2 infection.
Female
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Humans
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Infant
;
Infant, Newborn
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Male
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Pregnancy
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COVID-19
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Mothers
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Pregnancy Complications, Infectious/prevention & control*
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Retrospective Studies
;
SARS-CoV-2
8.Prognosis of adenoid cystic carcinoma of head and neck and risk factors for lung metastasis.
Xue Lian WANG ; Meng Jiao ZHOU ; Ting Yao MA ; Ling Yan JIANG ; Qi Dong ZHAO ; Hong Bo XU ; Jing ZHOU ; Li Feng LI ; Lu KONG ; Xiaohong CHEN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(8):963-968
Objective: To analyze the prognosis and risk factors of lung metastasis of patients with adenoid cystic carcinoma(ACC) of head and neck. Methods: A retrospective study was conducted. The data of 157 patients with ACC of head and neck treated in Beijing Tongren Hospital, Capital Medical University from January 2014 to October 2020 were collected, including 72 males and 85 females, with onset age between 14 and 72 years old. According to whether lung metastasis occurred, the patients were divided into lung metastasis group (88 cases) and non-pulmonary metastasis group (69 cases). Kaplan-Meier method was used to calculate the overall survival rate and progression-free survival rate using SPSS 26.0 software. Log-rank test was used to evaluate statistically relevant clinicopathological factors. Cox proportional risk model was used in multivariate analysis for the factors affecting the lung metastasis-free survival using R Studio 1.2.5042. Results: The 3-year and 5-year overall survival rates were 91.5% and 85.2%, respectively. The 3-year and 5-year progression-free survival rates were 57.7% and 34.3%, respectively. Univariate analysis showed that primary site, histological grade, high-grade transformation, Ki-67, T stage, and lymph node status were the risk factors for lung metastasis (χ2=11.78, 10.41, 4.06, 4.71, 5.37, 16.20, respectively, all P<0.05). Multivariate analysis showed independent risk factors for lung metastasis, including submandibular gland and sublingual gland (HR=3.53, 95%CI: 1.19-10.46, P<0.05), T3-4 stage (HR=3.09, 95%CI: 1.54-6.23, P<0.05), and Grade Ⅱ-Ⅲ grade (HR=2.47, 95%CI: 1.26-4.86,P<0.05). Conclusion: Distant metastasis, mainly pulmonary metastasis, affects the long-term prognosis of patients with ACC significantly. Primary site, T stage and histopathological grade can be used as the predictors for the risk of lung metastasis.
Adolescent
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Adult
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Aged
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Carcinoma, Adenoid Cystic
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Female
;
Humans
;
Lung/pathology*
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Lung Neoplasms/secondary*
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Male
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Middle Aged
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Prognosis
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Retrospective Studies
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Risk Factors
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Young Adult
9.Combining ventilation efficiency and peak systolic blood pressure in prognostic assessment of patients with chronic heart failure
Qian LUO ; Yuqin SHEN ; Bo ZHUANG ; Ting SHEN ; Xiaoling LIU ; Guanghe LI ; Yumei JIANG ; Dejie LI ; Mengyi ZHAN ; Lemin WANG
Chinese Journal of General Practitioners 2022;21(4):331-336
Objective:To analyze the value of minute ventilation to carbon dioxide production slope (VE/VCO 2 slope) combined with peak systolic blood pressure (SBP) in predicting prognosis for patients with chronic heart failure (CHF). Methods:A total of 170 patients with CHF who visited the Cardiac Rehabilitation Center of Tongji Hospital Affiliated to Tongji University and completed cardiopulmonary exercise test from March 2007 to December 2018 were enrolled in the study. The clinical data, cardiopulmonary exercise testing results and follow-up information of patients were collected to explore the predictors of all-cause mortality in patients with CHF.Results:The median follow-up time was 647 (182-1 764) days. All-cause death occurred in 34 patients. Compared with surviving patients, the proportion of diabetes and angiotensin-converting enzyme inhibitor/angiotensin Ⅱ receptor blocker (ACEI/ARB) use in fatal patients was significantly higher ( P<0.01). The VE/VCO 2 slope and peak SBP*VE/VCO 2 in the fatal patients were significantly higher, and the peak oxygen consumption (peak VO 2) was lower than those in the surviving patients ( P<0.01). The areas under the receiver operating characteristic curve (AUC) of VE/VCO 2 slope and peak SBP*VE/VCO 2 in predicting all-cause mortality in patients with CHF were 0.648 ( P=0.008) and 0.681 ( P=0.001), respectively; the optimal thresholds were >40.95 ( P=0.008) and > 5 423.50 mmHg (1 mmHg=0.133 kPa, P=0.006), the sensitivity was 0.559 and 0.588, and the specificity was 0.728 and 0.735, respectively. Multivariate Cox regression analysis showed that after adjusting for age, gender, diabetes and ACEI/ARB use, VE/VCO 2 slope ( HR=2.12, P=0.036) and peak SBP*VE/VCO 2 ( HR=2.42, P=0.016) were independent risk factors for all-cause mortality in patients with CHF. Conclusion:Compared to the traditional index VE/VCO 2 slope, a novel index peak SBP* VE/VCO 2 provides a relatively better predictive value for all-cause death of CHF patients.
10.Effects of adenovirus-mediated shRNA down-regulates PTEN expression on fibril-binding proteins vinculin, filamin A and cortactin in activated hepatic stellate cells.
Li Sen HAO ; Jie SONG ; Ming Ting ZHANG ; Xiao Jie SONG ; Mei Yu JIANG ; Jing Xiu JI ; Yan Bo MO ; Jing WANG
Chinese Journal of Hepatology 2022;30(1):38-44
Objective: To investigate the effect of adenovirus-mediated shRNA down-regulating phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression on vinculin, filamin A, and cortactin in activated hepatic stellate cells (HSCs). Methods: Activated rats hepatic stellate cell line (HSC-T6) was cultured in vitro. Recombinant adenovirus Ad-shRNA/PTEN carrying PTEN targeted RNA interference sequence [short hairpin RNA (shRNA)] and empty control virus Ad-GFP were transfected into HSCs. The PTEN mRNA and protein expression of HSCs in each group were detected by real-time fluorescence quantitative PCR and Western blot. The expressional change of vinculin, filamin A and cortactin in HSCs of each group were detected by confocal laser scanning immunofluorescence microscope. Image-pro plus 6.0 software was used for image analysis and processing. The integrated optical density (IOD) of the fluorescence protein expression was measured. The experiment was divided into three groups: control group (DMEM instead of adenovirus solution in the adenovirus transfection step), Ad-GFP group (transfected with empty virus Ad-GFP only expressing green fluorescent protein), and Ad-shRNA/PTEN group (recombinant adenovirus Ad-shRNA/PTEN carrying shRNA targeting PTEN and expressing green fluorescent protein). One-way analysis of variance was used for comparison of mean value among the three groups, and LSD-test was used for comparison between the groups. Results: shRNA targeted PTEN was successfully transfected and the expression of PTEN mRNA and protein in HSC (P < 0.05) was significantly down-regulated. HSCs vinculin was mainly expressed in the cytoplasm. HSCs vinculin fluorescence IOD in the Ad-shRNA/PTEN group (19 758.83 ± 1 520.60) was higher than control (7 737.16 ± 279.93) and Ad-GFP group (7 725.50 ± 373.03) (P < 0.05), but there was no statistically significant difference between control group and Ad-GFP group (P > 0.05). There was no statistically significant difference in the fluorescence IOD of Filamin A among the three groups (P > 0.05), but the subcellular distribution of Filamin A among the three groups were changed. Filamin A in the Ad-shrNA /PTEN HSC group was mainly distributed in the cytoplasm. Filamin A HSC was mainly located in the nucleus.The filamin A HSC in the control group and Ad-GFP group was mainly located in the nucleus. The nucleocytoplasmic ratio of Filamin A in the AD-shrNA /PTEN group (0.60 ± 0.15) was significantly lower than control group (1.20 ± 0.15) and Ad-GFP group (1.08 ± 0.23), P < 0.05. but there was no statistically significant difference in filamin A nucleocytoplasmic ratio of HSC between the control group and the Ad-GFP group (P > 0.05). Cortactin HSCs in the three groups was mainly distributed in the cytoplasm. The cortactin fluorescence IOD of HSCs in the Ad-shRNA/PTEN group was significantly higher than control group (22 959.94 ± 1 710.42) and the Ad-GFP group (22 547.11 ± 1 588.72 ) (P < 0.05), while there was no statistically significant difference in the IOD of cortactin fluorescence in HSCs between the control group and the Ad-GFP group (P > 0.05). Conclusion: The down-regulation of PTEN expression raises the expression of microfilament-binding protein vinculin and cortactin, and changes the subcellular distribution of another microfilament binding protein filamin A, that is, translocation from nucleus to the cytoplasm in activated HSC in vitro.
Adenoviridae/metabolism*
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Animals
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Carrier Proteins
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Cell Proliferation
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Cortactin
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Filamins/genetics*
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Hepatic Stellate Cells/metabolism*
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PTEN Phosphohydrolase/metabolism*
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RNA, Small Interfering/genetics*
;
Rats
;
Vinculin/genetics*

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