Vascular aging (VA) is a common etiology of various chronic diseases and represents a major public health concern. Intermittent hypoxia (IH) associated with obstructive sleep apnea-hypopnea syndrome (OSAHS) is a primary pathological and physiological driver of OSAHS-induced systemic complications. A substantial proportion of OSAHS patients, estimated to be between 40% and 80%, have comorbidities such as hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, aneurysm, and stroke, all of which are closely associated with VA. This review examines the molecular and cellular features common to both OSAHS and VA, highlighting decreased melatonin secretion, impaired autophagy, increased apoptosis, increased inflammation and pyroptosis, increased oxidative stress, accelerated telomere shortening, accelerated stem cell depletion, metabolic disorders, imbalanced protein homeostasis, epigenetic alterations, and dysregulated neurohormonal signaling. The accumulation and combination of these features may underlie the pathophysiological link between OSAHS and VA, but the exact mechanisms by which OSAHS affects VA may require further investigation. Taken together, these findings suggest that OSAHS may serve as a novel risk factor for VA and related vascular disorders, and that targeting these features may offer therapeutic potential to mitigate the vascular risks associated with OSAHS.
Humans ; Sleep Apnea, Obstructive/pathology* ; Aging/physiology* ; Oxidative Stress/physiology* ; Animals

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

Objective To investigate the virological features of patients with chronic hepatitis B(CHB)and metabolic associated fatty liver disease(MAFLD)through a stratified analysis.Methods A retrospective analysis was performed for 131 patients with CHB and MAFLD and 168 patients with CHB alone who underwent percutaneous liver biopsy and did not receive antiviral therapy or withdrew from drugs for more than 6 months in Beijing YouAn Hospital,Capital Medical University,from January 1,2013 to December 31,2019.The two groups were compared in terms of general data,biochemical parameters,and virological parameters.The patients in the two groups were stratified according to liver inflammation grade(G)and liver fibrosis stage(S),and the patients with CHB and MAFLD were further analyzed based on the degree of hepatic steatosis and NAFLD activity score(NAS).Virological features(the serum levels of HBV DNA and HBV HBsAg)were compared between groups.The Wilcoxon test was used for comparison of continuous data between two groups,and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups;the chi-square test was used for comparison of categorical data between two groups.Results Compared with the CHB group,the CHB+MAFLD group had a significantly higher proportion of male patients,a significantly higher proportion of patients with hypertension or type 2 diabetes mellitus,and significantly higher levels of the blood biochemical parameters of triglyceride,low-density lipoprotein cholesterol,apolipoprotein B,alanine aminotransferase,gamma-glutamyl transpeptidase,uric acid,and fasting blood glucose(all P<0.05),as well as significantly lower levels of high-density lipoprotein cholesterol,apolipoprotein A1,and HBV DNA(all P<0.05).The stratified analysis based on liver fibrosis stage showed that for both the patients with CHB alone and those with CHB and MAFLD,the significant fibrosis(S2—4)group had a significantly lower level of HBV DNA than the non-significant fibrosis(S0—1)group(P<0.05),and for the patients with CHB alone,the significant fibrosis(S2—4)group had a significantly lower level of HBsAg than the non-significant fibrosis(S0—1)group(P<0.05).The stratified analysis based on inflammation grade showed that for the patients with CHB and MAFLD,the high inflammation grade(G3)group had a significantly higher level of HBV DNA than the low inflammation grade(G1—2)group(P<0.05),and in the low inflammation grade(G1—2)group,the patients with CHB and MAFLD had a significantly lower level of HBsAg than the patients with CHB alone(P<0.05).The stratified analysis based on the degree of hepatic steatosis showed that the level of HBV DNA gradually decreased with the increase in the degree of steatosis,and the severe steatosis group had a significantly lower level of HBV DNA than the mild group(P<0.05),while there was no significant difference in HBsAg level between the groups with different degrees of hepatic steatosis(P>0.05).The stratified analysis based on NAS score showed that the NAS≥4 group had significantly higher levels of HBV DNA and HBsAg than the NAS<4 group(both P<0.05).Conclusion Patients with CHB and MAFLD have significant abnormalities in metabolic markers and aminotransferases,while virological indicators show different features in stratified analyses based on various indicators.

Objective:intrahepatic portocaval shunt (TIPS) in the treatment of hepatic sinusoidal obstruction syndrome (HSOS).Methods:A retrospective analysis was performed on 27 patients with HSOS who were treated with TIPS in our center from July 2018 to July 2020. The changes of portal vein pressure (PVP), portal vein pressure gradient (PPG) and liver function were observed, so as to evaluate the efficacy. Paired t test was adopted to evaluate the quantitative parameters, while χ2 test was used to analyze qualitative parameters, with P < 0.05 as statistical difference. Results:PVP decreased from (4.41 ± 0.18) kPa before shunt to (2.69 ± 0.11) kPa after shunt ( t = 82.41, P < 0.001), PPG decreased from (3.23 ± 0.18) kPa before shunt to (1.46 ± 0.23) kPa after shunt ( t = 32.41, P < 0.001). The liver function improved significantly after operation. After 24 months of follow-up, 3 patients developed stent restenosis and recanalized after balloon dilation. Three patients developed hepatic encephalopathy, which was improved after drug treatment. One patient underwent liver transplantation due to liver failure. Conclusion:TIPS is effective in the treatment of HSOS in the short and medium term, and can provide time for liver transplantation patients to wait for liver source.

Liver stiffness measurement (LSM) has been widely used in predicting portal hypertension in clinical practice, and in recent years, spleen stiffness measurement (SSM) has also become a diagnostic tool. Studies have shown that SSM can predict portal hypertension and its complications such as esophagogastric variceal bleeding in patients with chronic liver diseases and assist in the risk stratification management of portal hypertension and esophagogastric variceal bleeding. It can accurately predict clinically significant portal hypertension, high-risk esophageal and gastric varices, decompensation rate, and mortality rate in patients with chronic liver diseases. At present, SSM data in most studies are obtained by detection using the liver equipment FibroScan Ⓡ (SSM@50 Hz). FibroScan Ⓡ 630 is a new scanner dedicated for SSM with a special mode for SSM (SSM@100 Hz). This article elaborates on the significance of SSM in predicting portal hypertension and briefly introduces the advantages and disadvantages of the new equipment for SSM.

BACKGROUND: Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients. METHODS: Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes. RESULTS: Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53-3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32-2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24-1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs, except for invasive mechanical ventilation in the subgroup with CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality. CONCLUSION: Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients. CLINICAL TRIAL REGISTRATION Chinese Clinical Trail Registry, No. ChiCTR2100044625.
Humans ; Blood Pressure ; Pulmonary Disease, Chronic Obstructive/therapy* ; Cohort Studies ; Respiration, Artificial ; Inpatients ; Hospital Mortality

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To explore the correlation between portal vein pressure gradient (PPG) and hepatic vein pressure gradient (HVPG) in patients with portal hypertension (PHT).Methods:752 cases with portal hypertension (PHT) who underwent transjugular intrahepatic portosystemic shunt (TIPS) and met the enrollment criteria between January 2016 to December 2019 were analyzed for hepatic vein, inferior vena cava and portal vein pressure. Paired t-test was used for analysis. Pearson correlation test was used to estimate correlation coefficient and coefficient of determination. P<0.05 were considered statistically significant. Results:Wedged hepatic vein pressure (WHVP), portal vein pressure (PVP), correlation coefficient, and coefficient of determination were 27.98±8.95 mmHg, 33.85±7.33 mmHg, 0.329 ( P<0.001), and 0.108, respectively. HVPG, PPG,correlation coefficient, and coefficient of determination were 16.84±7.97 mmHg, 25.11±6.95 mmHg ( P<0.001), 0.145, and 0.021 ( P<0.001), respectively. The difference between HVPG and PPG was greater than 5 mmHg in 524 cases, accounting for 69.7%. The difference between HVPG and PPG was within 5 mmHg or basically equal in 228 cases, accounting for 30.3%. The correlation coefficient between free hepatic venous pressure (FHVP) and inferior vena cava pressure (IVCP) was 0.568 ( P<0.001), and the coefficient of determination was 0.323. According to the presence or absence of hepatic venous collaterals after balloon occluded hepatic angiography, they were divided into two groups: 157 (20.9%) cases in the group with hepatic venous collaterals, and 595 (79.1%) cases in the group without hepatic venous collaterals. The parameters of the two groups were compared: WHVP (15.73±3.63) mmHg vs. (31.22±6.90) mmHg, P<0.001; PVP (31.69±8.70) mmHg vs. (34.42±6.81) mmHg, P<0.001; HVPG (7.18±4.40) mmHg vs. (19.40±6.62) mmHg, P<0.001; PPG (24.24±8.11) mmHg vs. (25.34±6.60) mmHg, P<0.001; free hepatic venous pressure (FHVP) (8.58±3.37) mmHg vs. (11.82±5.07) mmHg , P<0.001; inferior vena cava pressure (IVCP) (7.45±3.29) mmHg vs. (9.09±4.14) mmHg, P<0.001. Conclusion:The overall correlation is poor between HVPG and PPG. HVPG of most patients is not an accurate representation of PPG, and the former is lower than the latter. Hepatic venous collateral formation is one of the important reasons for the serious underestimation of HVPG values.

Objective:To verify Baveno VI criteria, Expanded-Baveno VI criteria, liver stiffness×spleen diameter-to-platelet ratio risk score (LSPS), and platelet count/spleen diameter ratio (PSR) in evaluating the severity value of esophageal varices (EV) in patients with non-cirrhotic portal hypertension (NCPH).Methods:111 cases of NCPH and 204 cases of hepatitis B cirrhosis who met the diagnostic criteria were included in the study. NCPH included 70 cases of idiopathic non-cirrhotic portal hypertension (INCPH) and 41 cases of nontumoral portal vein thrombosis (PVT). According to the severity of EV on endoscopy, they were divided into the low-bleeding-risk group (no/mild EV) and the high-bleeding-risk group (moderate/severe EV). The diagnostic value of Baveno VI and Expanded-Baveno VI criteria was verified to evaluate the value of LSPS and PSR for EV bleeding risk severity in NCPH patients. The t-test or Mann-Whitney U test was used to compare the measurement data between groups. Comparisons between counting data groups were performed using either the χ2 test or the Fisher exact probability method. Results:Considering endoscopy was the gold standard for diagnosis, the missed diagnosis rates of low/high bleeding risk EVs in INCPH/PVT patients with Baveno VI and Expanded-Baveno VI criteria were 50.0%/30.0% and 53.8%/50.0%, respectively. There were no statistically significant differences in platelet count (PLT), spleen diameter, liver stiffness (LSM), LSPS, and PSR between low-bleeding-risk and high-bleeding-risk groups in INCPH patients, and the area under the receiver operating characteristic curve (AUC) of LSPS and PSR was 0.564 and 0.592, respectively ( P=0.372 and 0.202, respectively). There were statistically significant differences in PLT, spleen diameter, LSPS, and PSR between the low and high-bleeding risk groups in PVT patients, and the AUCs of LSPS and PSR were 0.796 and 0.833 ( P=0.003 and 0.001, respectively). In patients with hepatitis B cirrhosis, the Baveno VI and Expanded-Baveno VI criteria were used to verify the low bleeding risk EV, and the missed diagnosis rates were 0 and 5.4%, respectively. There were statistically significant differences in PLT, spleen diameter, LSM, LSPS and PSR between the low-bleeding-risk and high-bleeding-risk groups ( P<0.001). LSPS and PSR AUC were 0.867 and 0.789, respectively ( P<0.05). Conclusion:Baveno VI and Expanded-Baveno VI criteria have a high missed diagnosis rate for EVs with low bleeding risk in patients with INPCH and PVT, while LSPS and PSR have certain value in evaluating EV bleeding risk in PVT patients, which requires further clinical research.

Objective To analyze the clinical characteristics and prognostic factors of chronic hepatitis B (CHB) patients complicated with metabolic associated fatty liver disease (MAFLD). Methods A total of 114 CHB patients and 101 CHB patients complicated with MAFLD who underwent liver biopsy between 2005 and 2018 were included. A long-term cohort was established with the time of liver puncture as the baseline, and decompensated cirrhosis, liver cancer, liver transplantation and death related to liver disease as the clinical endpoints. The patient's NAS score, hepatitis inflammation activity (G) and fibrosis stage (S) were scored for the liver biopsy. According to fibrosis stage, patients were divided into no significant fibrosis (S0-1) and significant fibrosis (S2-4) groups. The clinical characteristics and prognosis of the CHB patients with or without MAFLD at the same fibrosis stage were compared. CHB patients with MAFLD were divided into NAS < 4 and NAS≥4 groups according to NAS score, and the influence of NAS score on clinical outcomes of patients was analyzed. The independent samples t -test / Wilcoxin test was performed for comparison of continuous data and the chi-square test was used for comparison of categorical data between groups. Survival analysis was performed using Kaplan-Meier survival cure and compared using log-rank test. Cox multivariate regression analysis was used to identify prognostic factors. Results The BMI, blood glucose and TC in CHB patients with MAFLD group were significantly higher than those in CHB alone in each fibrosis stage ( P < 0.05). In patients without significant fibrosis, the levels of ALT ( Z =-2.249, P =0.025), AST ( Z =-2.512, P =0.012) and GGT ( Z =-5.261, P < 0.001) in the complicated group were higher than those in the CHB group. With a median follow-up time of 8.0 years, the Kaplan-Meier survival analysis revealed that the complicated MAFLD significantly reduced the liver event-free survival rate of CHB patients ( χ 2 =7.607, P =0.006). Cox multivariable analysis revealed MAFLD ( HR =5.76, 95% CI : 1.54 - 21.48, P =0.009) was an independent risk factor for liver-related outcomes. In CHB patients with MAFLD, the ALT ( Z =-3.139, P =0.002), AST ( Z =-2.898, P =0.004), and GGT ( Z =-2.260, P =0.024) of patients with NAS≥4 were higher than those of patients with NAS < 4. We found that significant fibrosis ( HR =4.83, 95% CI : 1.23 - 18.91, P =0.024) was associated with the poor prognosis of CHB patients with MAFLD. Conclusions CHB patients with MAFLD are more likely to have impaired liver function in the early stage and the disease progresses more rapidly. Complicated MAFLD will increase the risk of liver-related events in patients with CHB, and significant fibrosis is an independent risk factor for adverse outcomes in CHB patients with MAFLD.