Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

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 explore the characteristics of portal vein thrombosis (PVT) formation in patients with hepatitis B cirrhosis and its effect on long-term prognosis.Methods:The clinical data of a cohort of patients with hepatitis B cirrhosis who visited Beijing Youan Hospital from May 2009 to August 2020 were retrospectively analyzed. Enhanced CT examination was used as the standard for diagnosing PVT and its classification. Patients with hepatitis B cirrhosis without PVT at baseline were selected as the research subjects. According to whether PVT was formed during the follow-up period, they were divided into the PVT and control groups including 99 and 168 patients in the PVT and control groups with a follow-up time of 52.0 (46.7, 57.3) months. The changes in baseline and endpoint clinical indicators of the two groups were compared. Kaplan-Meier survival curve, log-rank test, and Cox regression were used to analyze the effect of PVT on prognosis.Results:In the PVT group, 28.28% (28/99) of patients underwent splenectomy, and 74.75% (74/99) did not receive anticoagulation therapy. The main portal vein thrombosis, portal vein branch thrombosis, and thrombosis in both groups accounted for 34.34% (34/99), 23.23% (23/99), and 15.15% (15/99), respectively. The splenic vein or superior mesenteric vein accounted for 27.27% (27/99). PVT was stable in 63.27% (63/99), progressed in 31.31% (31/99), and relieved in 5.05% (5/99) during the follow-up period. The white blood cell, hemoglobin, and platelet counts were all decreased in the PVT group compared with the baseline ( P<0.05). The international normalized ratio (INR) [1.28 (1.14, 1.39) vs. 1.33 (1.19, 1.46), P=0.041] and spleen length [(163.84±30.68) mm vs. (177.26±32.61) mm, P<0.001] was increased compared with the baseline. The proportion of gastroesophageal variceal bleeding was higher in the PVT group than in the control group (57.0% vs. 28.7%, P<0.001), and the constituent ratio of hepatic encephalopathy was not statistically significantly different ( P>0.05). The proportion of patients with ascites in the control group decreased (63.1% vs. 41.7%, P<0.001), while the proportion of patients with ascites in the PVT group was not statistically significantly different ( P>0.05). The incidence of composite clinical endpoint events in the PVT and the control group was 21.21% (21/99) and 4.17% (7/168), respectively ( P＜0.05). The incidence of composite clinical endpoint events in PVT patients without anticoagulation and anticoagulation treatment was 25.68% (19/74) and 8.00% (2/25), respectively ( P=0.062). Cox regression analysis found that PVT formation was an independent risk factor for liver-related adverse events in patients with hepatitis B cirrhosis ( HR=9.36, 95% CI: 3.65～24.02, P=0.001). Conclusions:The presence of PVT in patients with hepatitis B cirrhosis is assoliated with worse prognosis. The formation of PVT is closely related to the increased risk of liver-related adverse prognosis in patients with hepatitis B cirrhosis.

Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

Objective:To explore the characteristics of portal vein thrombosis (PVT) formation in patients with hepatitis B cirrhosis and its effect on long-term prognosis.Methods:The clinical data of a cohort of patients with hepatitis B cirrhosis who visited Beijing Youan Hospital from May 2009 to August 2020 were retrospectively analyzed. Enhanced CT examination was used as the standard for diagnosing PVT and its classification. Patients with hepatitis B cirrhosis without PVT at baseline were selected as the research subjects. According to whether PVT was formed during the follow-up period, they were divided into the PVT and control groups including 99 and 168 patients in the PVT and control groups with a follow-up time of 52.0 (46.7, 57.3) months. The changes in baseline and endpoint clinical indicators of the two groups were compared. Kaplan-Meier survival curve, log-rank test, and Cox regression were used to analyze the effect of PVT on prognosis.Results:In the PVT group, 28.28% (28/99) of patients underwent splenectomy, and 74.75% (74/99) did not receive anticoagulation therapy. The main portal vein thrombosis, portal vein branch thrombosis, and thrombosis in both groups accounted for 34.34% (34/99), 23.23% (23/99), and 15.15% (15/99), respectively. The splenic vein or superior mesenteric vein accounted for 27.27% (27/99). PVT was stable in 63.27% (63/99), progressed in 31.31% (31/99), and relieved in 5.05% (5/99) during the follow-up period. The white blood cell, hemoglobin, and platelet counts were all decreased in the PVT group compared with the baseline ( P<0.05). The international normalized ratio (INR) [1.28 (1.14, 1.39) vs. 1.33 (1.19, 1.46), P=0.041] and spleen length [(163.84±30.68) mm vs. (177.26±32.61) mm, P<0.001] was increased compared with the baseline. The proportion of gastroesophageal variceal bleeding was higher in the PVT group than in the control group (57.0% vs. 28.7%, P<0.001), and the constituent ratio of hepatic encephalopathy was not statistically significantly different ( P>0.05). The proportion of patients with ascites in the control group decreased (63.1% vs. 41.7%, P<0.001), while the proportion of patients with ascites in the PVT group was not statistically significantly different ( P>0.05). The incidence of composite clinical endpoint events in the PVT and the control group was 21.21% (21/99) and 4.17% (7/168), respectively ( P＜0.05). The incidence of composite clinical endpoint events in PVT patients without anticoagulation and anticoagulation treatment was 25.68% (19/74) and 8.00% (2/25), respectively ( P=0.062). Cox regression analysis found that PVT formation was an independent risk factor for liver-related adverse events in patients with hepatitis B cirrhosis ( HR=9.36, 95% CI: 3.65～24.02, P=0.001). Conclusions:The presence of PVT in patients with hepatitis B cirrhosis is assoliated with worse prognosis. The formation of PVT is closely related to the increased risk of liver-related adverse prognosis in patients with hepatitis B cirrhosis.

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:To evaluate the short-term antiviral efficacy and safety profile of tenofovir amibufenamide (TMF) in patients with hepatitis B cirrhosis.Methods:The biochemical indexes, renal function, and complication status in patients with hepatitis B cirrhosis who were treated with tenofovir amibufenamide (TMF) in Beijing You'an Hospital Affiliated to Capital Medical University from March 2022 to June 2024 were retrospectively analyzed.Results:A total of 98 cases with hepatitis B cirrhosis were included. Among them, 62 and 36 cases with hepatitis B cirrhosis had previously undergone partial resection for hepatocellular carcinoma. 66.7% (62/93) of the treated patients were HBV DNA negative before treatment. The longest follow-up time for medication was 24 months, with an average follow-up of (14.1±4.7) months. There were no statistically significant differences in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBil) levels at 18 months of treatment compared with those before treatment ( P>0.05). The ALT return to normal rate was 91.3%. The HBV DNA negativity rate was 90.6% and 93.5% at 18 and 12 months of follow-up, respectively. There were no significant changes in the estimated glomerular filtration rate (eGFR) and low-density lipoprotein cholesterol (LDL-C) compared with those before treatment ( P>0.05). 36 cases were still HBV DNA positive (including 31 treated and 5 never treated) before treatment. A total of 29 cases were followed up for 12 months, and 24 cases (82.8%) had HBV DNA negative conversion. Conclusion:TMF antiviral therapies have an HBV DNA negative rate of over 80% at 12 months and can improve the liver function in patients with hepatitis B cirrhosis. However, there were no significant changes in renal function and blood lipids before and after treatment.

Objective:To evaluate the short-term antiviral efficacy and safety profile of tenofovir amibufenamide (TMF) in patients with hepatitis B cirrhosis.Methods:The biochemical indexes, renal function, and complication status in patients with hepatitis B cirrhosis who were treated with tenofovir amibufenamide (TMF) in Beijing You'an Hospital Affiliated to Capital Medical University from March 2022 to June 2024 were retrospectively analyzed.Results:A total of 98 cases with hepatitis B cirrhosis were included. Among them, 62 and 36 cases with hepatitis B cirrhosis had previously undergone partial resection for hepatocellular carcinoma. 66.7% (62/93) of the treated patients were HBV DNA negative before treatment. The longest follow-up time for medication was 24 months, with an average follow-up of (14.1±4.7) months. There were no statistically significant differences in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBil) levels at 18 months of treatment compared with those before treatment ( P>0.05). The ALT return to normal rate was 91.3%. The HBV DNA negativity rate was 90.6% and 93.5% at 18 and 12 months of follow-up, respectively. There were no significant changes in the estimated glomerular filtration rate (eGFR) and low-density lipoprotein cholesterol (LDL-C) compared with those before treatment ( P>0.05). 36 cases were still HBV DNA positive (including 31 treated and 5 never treated) before treatment. A total of 29 cases were followed up for 12 months, and 24 cases (82.8%) had HBV DNA negative conversion. Conclusion:TMF antiviral therapies have an HBV DNA negative rate of over 80% at 12 months and can improve the liver function in patients with hepatitis B cirrhosis. However, there were no significant changes in renal function and blood lipids before and after treatment.

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.