The pursuit of healthy aging has long rendered aging and senescence captivating. Age-related ailments, such as cardiovascular diseases, diabetes, and neurodegenerative disorders, pose significant threats to individuals. Recent studies have shed light on the intricate mechanisms encompassing genetics, epigenetics, transcriptomics, and metabolomics in the processes of senescence and aging, as well as the establishment of age-related pathologies. Amidst these underlying mechanisms governing aging and related pathology metabolism assumes a pivotal role that holds promise for intervention and therapeutics. The advancements in metabolomics techniques and analysis methods have significantly propelled the study of senescence and aging, particularly with the aid of multiscale metabolomics which has facilitated the discovery of metabolic markers and therapeutic potentials. This review provides an overview of senescence and aging, emphasizing the crucial role metabolism plays in the aging process as well as age-related diseases.
Humans ; Aging/metabolism* ; Metabolomics/methods* ; Neurodegenerative Diseases/metabolism* ; Cardiovascular Diseases/metabolism*

OBJECTIVE: To investigate the current status of early pain and agitation management in critically ill patients in Guizhou Province. METHODS: A retrospective study was performed using data collected from a quality control activity conducted between April and June 2021 in non-provincial public hospitals with general intensive care unit (ICU) in Guizhou Province. Hospital-level data included hospital name and grade, ICU staffing, and number of ICU beds. Patient-level data included characteristics of patients treated in the general ICU on the day of the survey (e.g., age, sex, primary diagnosis), as well as pain and agitation assessments and the types of analgesic and sedative medications administered within 24 hours of ICU admission. RESULTS: A total of 947 critically ill ICU patients from 145 hospitals were included, among which 104 were secondary-level hospitals and 41 were tertiary-level hospitals. Within 24 hours of ICU admission, 312 (32.9%) critically ill patients received pain assessments, and 277 (29.3%) received agitation assessments. Among the pain assessment tools, the critical care pain observation tool (CPOT) was used in 44.2% (138/312) of critically ill ICU patients, with a significantly higher usage rate in tertiary hospitals compared to secondary hospitals [52.3% (69/132) vs. 38.3% (69/180), P < 0.05]. The Richmond agitation-sedation scale (RASS) was used in 93.8% (260/277) of critically ill ICU patients for agitation assessment, with no significant difference between hospital levels. Among the 947 critically ill patients, 592 (62.5%) received intravenous analgesics within 24 hours, with remifentanil being the most commonly used [42.9% (254/592)]; 510 (53.9%) received intravenous sedatives, with midazolam being the most frequently used [60.8% (310/510)]. Mechanical ventilation data were available for 932 critically ill patients, of whom 579 (62.1%) received mechanical ventilation and 353 (37.9%) did not. Compared with non-ventilated patients, ventilated patients had significantly higher rates of analgesic and sedative use [analgesics: 77.9% (451/579) vs. 38.8% (137/353); sedatives: 71.8% (416/579) vs. 25.8% (91/353); both P < 0.05]. In terms of analgesic selection, ventilated patients were more likely to receive strong opioids than non-ventilated patients [85.8% (95/137) vs. 69.3% (387/451), P < 0.05]. For sedatives, ventilated patients preferred midazolam [66.6% (277/416)], whereas non-ventilated patients more often received dexmedetomidine [45.1 (41/91)]. Blood pressure within 24 hours of ICU admission were available for 822 critically ill patients, of whom 245 (29.8%) had hypotension and 577 (70.2%) did not. Compared with non-hypotensive patients, hypotensive patients had significantly higher rates of analgesic and sedative use [analgesics: 74.7% (183/245) vs. 59.8% (345/577); sedatives: 65.7% (161/245) vs. 51.3% (296/577); both P < 0.05], but there was no significant difference in the choice of analgesic or sedative agents between the two groups. CONCLUSIONS The proportion of critically ill ICU patients in Guizhou Province who received standardized pain and agitation assessments was relatively low. The most commonly used assessment tools were CPOT and RASS, while remifentanil and midazolam were the most frequently used analgesic and sedative agents, respectively. Secondary-level hospitals had a lower rate of using standardized pain assessment tools compared to tertiary-level hospitals. Mechanical ventilation and hypotension were associated with the use of analgesic and sedative medications.
Humans ; Critical Illness ; Intensive Care Units ; Analgesics/therapeutic use* ; Hypnotics and Sedatives/therapeutic use* ; Retrospective Studies ; China ; Pain Measurement ; Pain Management ; Female ; Male ; Critical Care ; Middle Aged

Objective To investigate the changes of serum cathepsin L(CTSL)in patients with acute exacerbation of chronic heart failure(CHF)and its relationship with lipid metabolism and severity of the disease.Methods A prospective study was conducted on 186 elderly patients with acute exacerbation of CHF admitted to our hospital from February 2021 to October 2024.Their serum levels of CTSL and lipid metabolism indicators were measured at admission.According to the quartile of CTSL,they were divided into groups A(CTSL≤3.31 μg/L,47 cases),B(3.31μg/L＜CTSL≤3.70 μg/L,46 cases),C(3.70 μg/L＜CTSL＜4.41 μg/L,47 cases),and D(CTSL≥4.41 μg/L,46 cases).The general clinical data,blood lipid metabolism and severity of disease were compared among the four groups.Pearson correlation analysis was used to analyze the correlation between CTSL and blood lipid metabolism indicators,and ordinal regression model and restricted cubic spline analysis was employed to examine the relationship between serum CTSL and the se-verity of acute exacerbation of CHF.Results There were significant differences in total cholester-ol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C)and low density lipopro-tein cholesterol(LDL-C)among the four groups of patients(P＜0.05,P＜0.01).Pearson correla-tion analysis showed that serum CTSL level was positively correlated with TC,TG and LDL-C levels(r=0.203,P=0.005;r=0.178,P=0.015;r=0.184,P=0.012),and negatively with HDLC(r=—0.344,P=0.000).Ordinal regression analysis indicated that serum CTSL level was an inde-pendent risk factor affecting the severity of CHF in patients with acute exacerbation(P＜0.05).Restricted cubic spline analysis revealed that serum CTSL level was in a linear relationship with the severity of acute exacerbation of CHF(x2=3.140,P=0.371).When serum CTSL＞3.73μg/L,the severity of the condition was increased significantly.Conclusion Serum CTSL level is closely associated with lipid metabolism in elderly patients with acute exacerbation of CHF,and is an independent risk factor for the severity of disease.

Objective To investigate the relationship between the expression of absent in melanoma 2(AIM2)gene in peripheral blood peripheral blood mononuclear cell(PBMC)of patients with advanced gastric cancer(GC)and the intestinal flora and the efficacy of targeted therapy.Methods 83 patients with advanced GC who were treated from January to December 2023 were all given Trastuzumab/Nebuliumab combined with conventional chemotherapy for 4 weeks/course and 3 continuous courses of treatment to evaluate the efficacy of targeted therapy.The abundance of intestinal flora was analyzed using 16S rDNA sequencing technologies.Quantitative real-time PCR(qRT-PCR)was used to detect AIM2 mRNA expression levels in PBMC,which were divided into a high expression group and a low expression group according to the median digit.Pearson correlation analysis was used to investigate the relationship between AIM2 expression and the relative abundance of intestinal flora,the efficacy of targeted therapy and clinical features.Results At the phylum level,the relative abundance of Bacteroidetes(0.70±0.15)and Proteobacteria(0.71±0.21)in the high expression group of AIM2 was significantly lower than that in the low expression group(0.81±0.17,0.80±0.16),and the relative abundance of Firmicutes(0.73±0.12)was significantly higher than that in the low expression group(0.64±0.08),and the differences were statistically significant(t=3.108,2.210,4.061,all P＜0.05).At the genus level,the relative abundance of Bacteroides(0.13±0.02)in the high expression group of AIM2 was significantly lower than that in the low expression group(0.19±0.04),and the relative abundance of Enterococcus(0.31±0.08 vs 0.12±0.05)and Escherichia coli(0.18±0.04 vs 0.10±0.02)was significantly higher than that in the low expression group(0.12±0.05,0.10±0.02),and the differences were statistically significant(t=8.472,153.462,11.722,all P<0.05).Pearson correlation showed that at phylum level,AIM2 expression was positively correlated with the relative abundance of Firmicutes(r=0.598,P<0.05),and negatively correlated with the relative abundance of Bacteroides and Proteobacteria(r=-0.641,-0.520,all P<0.05).At the genus level,AIM2 expression was positively correlated with the relative abundance of Enterococcus and Escherichia coli(r=0.529,0.577,all P<0.05),and negatively correlated with the relative abundance of Bacteroides(r=-0.574,P<0.05).Among the 83 patients with advanced GC,17 cases were effective and 66 cases were ineffective,and the Overall response rate(ORR)was 20.48%.The lesion diameter(5.73±0.74cm)and the proportion of cTNM stage IV(53.85%)in AIM2 high expression group were significantly lower than those in low expression group(6.08±0.51cm,75.00%),and the targeted therapy ORR(30.77%)was higher than that in low expression group(11.36%),with statistical significance(t/χ2/Z=2.477,6.558,4.780,all P<0.05).Conclusion The expression of AIM2 in PBMC of advanced GC patients is closely related to the imbalance of intestinal flora and the effect of targeted therapy.Detection of AIM2 expression is conducive to guiding clinical screening of patients who benefit from targeted therapy.

Objective To investigate the relationship between the expression of absent in melanoma 2(AIM2)gene in peripheral blood peripheral blood mononuclear cell(PBMC)of patients with advanced gastric cancer(GC)and the intestinal flora and the efficacy of targeted therapy.Methods 83 patients with advanced GC who were treated from January to December 2023 were all given Trastuzumab/Nebuliumab combined with conventional chemotherapy for 4 weeks/course and 3 continuous courses of treatment to evaluate the efficacy of targeted therapy.The abundance of intestinal flora was analyzed using 16S rDNA sequencing technologies.Quantitative real-time PCR(qRT-PCR)was used to detect AIM2 mRNA expression levels in PBMC,which were divided into a high expression group and a low expression group according to the median digit.Pearson correlation analysis was used to investigate the relationship between AIM2 expression and the relative abundance of intestinal flora,the efficacy of targeted therapy and clinical features.Results At the phylum level,the relative abundance of Bacteroidetes(0.70±0.15)and Proteobacteria(0.71±0.21)in the high expression group of AIM2 was significantly lower than that in the low expression group(0.81±0.17,0.80±0.16),and the relative abundance of Firmicutes(0.73±0.12)was significantly higher than that in the low expression group(0.64±0.08),and the differences were statistically significant(t=3.108,2.210,4.061,all P＜0.05).At the genus level,the relative abundance of Bacteroides(0.13±0.02)in the high expression group of AIM2 was significantly lower than that in the low expression group(0.19±0.04),and the relative abundance of Enterococcus(0.31±0.08 vs 0.12±0.05)and Escherichia coli(0.18±0.04 vs 0.10±0.02)was significantly higher than that in the low expression group(0.12±0.05,0.10±0.02),and the differences were statistically significant(t=8.472,153.462,11.722,all P<0.05).Pearson correlation showed that at phylum level,AIM2 expression was positively correlated with the relative abundance of Firmicutes(r=0.598,P<0.05),and negatively correlated with the relative abundance of Bacteroides and Proteobacteria(r=-0.641,-0.520,all P<0.05).At the genus level,AIM2 expression was positively correlated with the relative abundance of Enterococcus and Escherichia coli(r=0.529,0.577,all P<0.05),and negatively correlated with the relative abundance of Bacteroides(r=-0.574,P<0.05).Among the 83 patients with advanced GC,17 cases were effective and 66 cases were ineffective,and the Overall response rate(ORR)was 20.48%.The lesion diameter(5.73±0.74cm)and the proportion of cTNM stage IV(53.85%)in AIM2 high expression group were significantly lower than those in low expression group(6.08±0.51cm,75.00%),and the targeted therapy ORR(30.77%)was higher than that in low expression group(11.36%),with statistical significance(t/χ2/Z=2.477,6.558,4.780,all P<0.05).Conclusion The expression of AIM2 in PBMC of advanced GC patients is closely related to the imbalance of intestinal flora and the effect of targeted therapy.Detection of AIM2 expression is conducive to guiding clinical screening of patients who benefit from targeted therapy.

Objective To investigate the changes of serum cathepsin L(CTSL)in patients with acute exacerbation of chronic heart failure(CHF)and its relationship with lipid metabolism and severity of the disease.Methods A prospective study was conducted on 186 elderly patients with acute exacerbation of CHF admitted to our hospital from February 2021 to October 2024.Their serum levels of CTSL and lipid metabolism indicators were measured at admission.According to the quartile of CTSL,they were divided into groups A(CTSL≤3.31 μg/L,47 cases),B(3.31μg/L＜CTSL≤3.70 μg/L,46 cases),C(3.70 μg/L＜CTSL＜4.41 μg/L,47 cases),and D(CTSL≥4.41 μg/L,46 cases).The general clinical data,blood lipid metabolism and severity of disease were compared among the four groups.Pearson correlation analysis was used to analyze the correlation between CTSL and blood lipid metabolism indicators,and ordinal regression model and restricted cubic spline analysis was employed to examine the relationship between serum CTSL and the se-verity of acute exacerbation of CHF.Results There were significant differences in total cholester-ol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C)and low density lipopro-tein cholesterol(LDL-C)among the four groups of patients(P＜0.05,P＜0.01).Pearson correla-tion analysis showed that serum CTSL level was positively correlated with TC,TG and LDL-C levels(r=0.203,P=0.005;r=0.178,P=0.015;r=0.184,P=0.012),and negatively with HDLC(r=—0.344,P=0.000).Ordinal regression analysis indicated that serum CTSL level was an inde-pendent risk factor affecting the severity of CHF in patients with acute exacerbation(P＜0.05).Restricted cubic spline analysis revealed that serum CTSL level was in a linear relationship with the severity of acute exacerbation of CHF(x2=3.140,P=0.371).When serum CTSL＞3.73μg/L,the severity of the condition was increased significantly.Conclusion Serum CTSL level is closely associated with lipid metabolism in elderly patients with acute exacerbation of CHF,and is an independent risk factor for the severity of disease.

Objective:To summarize experience of managing adult Langerhans cell histiocytosis(LCH) in hypothalamic-pituitary region(HPR) from Shanghai Huashan Hospital.Methods:Adult HPR-LCH patients diagnosed at oar endocrinology department from January 2013 to February 2022 were included. Clinical characteristics and treatment response were retrospectively analyzed.Results:A total of 27 adult HPR-LCH patients were included, with 14 cases involving the hypothalamus(H group) and 13 cases without(group NH). The common radiological findings included thickening of the pituitary stalk(25/27, 92.6%). At the time of diagnosis, 14 cases(51.9%) presented with panhypopituitarism, and 19 cases(70.4%) exhibited metabolic abnormalities. The group H had higher proportions of adrenal insufficiency, central hypothyroidism, panhypopituitarism, and diabetes compared to group NH(78.6% vs 23.1%; 78.6% vs 23.1%; 92.9% vs 30.8%, 35.7% vs 0%, respectively, all P<0.05). Hypothalamus syndrome was identified in 71.4%(10/14) of group H. The inital diagnosis rate was 79.2%(19/24), with 48.1% and 51.9% through biopsy of sellar and extrasellar lesions, respectively. Repeated biopsies confirmed the diagnosis in 25.9%(7/27) of cases. The peripheral lesions included bone, thyroid, lung, lymph node, thymus and liver. Out of 20 cases treated with chemotherapy, the objective response rate was 85% at 12 weeks. Four cases received local therapy, one case received traditional Chinese medicine treatment, one case abandoned treatment, and one case was lost to follow-up. The median follow-up time was 28(range 15 to 54) months. During this period, there were 3 deaths in group H and 1 death in group NH. Conclusion:Adult HPR-LCH patients presented with diabetes insipidus and high prevalences of hypopituitarism, hypothalamus syndrome and metabolic abnormalities. Typical imaging features were pituitary stalk thickening. A solitary mass in the HPR was usually very small, posing a great challenge for early diagnosis. Systemic evaluation would help to clarify the diagnosis. Patients with hypothalamus involvement had a higher mortality rate, suggesting the hypothalamus as a risk organ with poor prognosis.

Objective:To explore the therapeutic effect of HEOS hysteroscopic surgery on patients with uterine fibroids and its effect on ovarian function and trauma response indicators.Methods:The clinical data of 104 patients with uterine fibroids admitted to Shangqiu Fifth People's Hospital from Jan 2020 to Mar 2023 were retrospectively analyzed and were divided into 2 groups according to different surgical protocols.A total of patients who underwent HEOS hysteroscopic surgery were enrolled in HEOS group and 52 patients who underwent conventional hysteroscopic electroresection(TCRPR)were enrolled in TCRPR group.The surgical and postoperative recovery indicators,surgical effects,ovarian function before and after surgery[estradiol(E2),luteinizing hormone(LH),follicle-stimulating hormone(FSH)],trauma response indicators[interleukin-6(IL-6),interleukin-17(IL-17),angiotensin Ⅱ(Ang Ⅱ)],and incidence of complications were compared between the two groups.Results:The operation time,postoperative exhaust time,time of the white blood cell count returning to normal,and hospitalization time in HEOS group were shorter than those in TCRPR group,and the intraoperative blood loss was less than that in TCRPR group(P<0.01).At 1 d after operation,serum levels of IL-6,IL-17 and Ang Ⅱ in 2 groups were higher than those before operation,and serum levels of IL-6,IL-17 and Ang Ⅱ in HEOS group were lower than those in TCRPR group(P<0.01).The excellent and good rate of operation in HEOS group was 98.08％(51/52),which was higher than that in TCRPR group[84.62％(44/52)](P<0.05).At 3 months after operation,the serum E2 level was lower and the serum LH and FSH levels of 2 groups were higher than those before operation,and the serum E2 level of HEOS group was lower than that of TCRPR group,and the serum LH and FSH levels were higher than those of TCRPR group(P<0.01).The incidence of complications in HEOS group was 1.92％(1/52),which was lower than that of TCRPR group[17.31％(9/52)](P<0.05).Conclusion:Compared with conventional TCRPR in the treatment of uterine fibroids,hysteroscopic surgery with HEOS is more helpful to improve the surgical effect,optimize the surgical and postoperative recovery indicators,improve ovarian function,reduce complications,and had less traumatic reactions.

BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
Female ; Humans ; China/epidemiology* ; Cities ; Cold Temperature ; Hot Temperature ; Mortality ; Temperature ; Time Factors ; Middle Aged ; Male