Traditional and Non-Traditional Lipid Parameters in Relation to Parenchymal Hemorrhage Following Endovascular Treatment for Acute Ischemic Stroke in Anterior Circulation.

Purpose: Lipid-lowering therapy is integral in acute ischemic stroke (AIS), yet the connection between lipid parameters and parenchymal hemorrhage (PH) after endovascular treatment (EVT) for AIS is not well-defined. This research aims to assess the association between various lipid parameters and the PH risk following EVT. Patients and Methods: We examined a database of patients who underwent EVT for AIS between September 2021 and May 2023 retrospectively. Traditional and non-traditional lipid parameters were documented. PH was identified on dual energy computed tomography images within 48 h. We employed logistic regression analysis and restricted cubic splines to examine the association between various lipid parameters and the risk of PH. The predictive capacity of the lipid parameters for PH was evaluated by comparing the area under the curve. Results: The study included 384 patients, 65 of whom (17.7%) developed PH. After adjusting for potential confounders, only triglyceride was associated with PH among the traditional lipid parameters, while all non-traditional lipid parameters were related to PH. Based on ROC curve, the ratio of remnant cholesterol to high-density lipoprotein cholesterol (RC/HDL-C) exhibited the highest predictive capability for PH. Furthermore, our analysis revealed a significant nonlinear correlation between triglyceride, non-high-density lipoprotein cholesterol, RC, RC/HDL-C and PH risk. Conclusion: In assessing the risk of PH after EVT, non-traditional lipid parameters are often superior to traditional lipid parameters. It is recommended that routine evaluation of non-traditional lipid parameters could also be conducted in clinical practice as well.

Effectiveness and safety of bridging therapy and endovascular therapy in patients with large cerebral infarctions: from ANGEL-ASPECT.

BACKGROUND AND PURPOSE: The benefits of thrombolytic therapy before endovascular thrombectomy in cases of acute ischaemic stroke, with a large infarction volume, remain unclear. This analysis aims to evaluate the effectiveness and safety of bridging therapy and endovascular therapy among patients with large cerebral infarctions. METHODS: In this post-hoc analysis of the multicentre prospective study of ANGEL-ASPECT (Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core), participants were divided into two groups: an endovascular therapy group and a bridging therapy group. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. The primary safety outcome was symptomatic intracranial haemorrhage. Ordinal logistic regression was performed to compare the primary endpoint between the two groups. Subgroup analyses were conducted to further explore potential risk factors associated with the outcomes. RESULTS: 122 patients were included, of whom 77 (63%) underwent endovascular therapy and 45 (37%) underwent bridging therapy. The median scores on mRS at 90 days of the bridging therapy group and the endovascular therapy group were 3 (2-5) and 4 (2-6), with no significant differences (common OR 1.36; 95% CI 0.71 to 2.61). Symptomatic intracranial haemorrhage was reported in three patients who were in the endovascular and bridging therapy groups (relative risk (RR) 1.71; 95% CI 0.36 to 8.12). The mortality between two groups did not differ (RR 0.75; 95% CI 0.37 to 1.54). CONCLUSIONS: Our study indicated that endovascular therapy alone might be a viable option for patients with large cerebral infarctions, displaying no noticeable disparity in outcomes compared with bridging therapy.

NaHCO3 loading causes increased arterial pressure and kidney damage in rats with chronic kidney disease.

Sodium bicarbonate (NaHCO3) is commonly utilized as a therapeutic to treat metabolic acidosis in people with chronic kidney disease (CKD). While increased dietary sodium chloride (NaCl) is known to promote volume retention and increase blood pressure, the effects of NaHCO3 loading on blood pressure and volume retention in CKD remain unclear. In the present study, we compared the effects of NaCl and NaHCO3 loading on volume retention, blood pressure, and kidney injury in both 2/3 and 5/6 nephrectomy remnant kidney rats, a well-established rodent model of CKD. We tested the hypothesis that NaCl loading promotes greater volume retention and increases in blood pressure than equimolar NaHCO3. Blood pressure was measured 24 h daily using radio telemetry. NaCl and NaHCO3 were administered in drinking water ad libitum or infused via indwelling catheters. Rats were housed in metabolic cages to determine volume retention. Our data indicate that both NaHCO3 and NaCl promote hypertension and volume retention in remnant kidney rats, with salt-sensitivity increasing with greater renal mass reduction. Importantly, while NaHCO3 intake was less pro-hypertensive than equimolar NaCl intake, NaHCO3 was not benign. NaHCO3 loading significantly elevated blood pressure and promoted volume retention in rats with CKD when compared with control rats receiving tap water. Our findings provide important insight into the effects of sodium loading with NaHCO3 in CKD and indicate that NaHCO3 loading in patients with CKD is unlikely to be benign.

Extravasation of Blood and Blood Toxicity Drives Tubular Injury from RBC Trapping in Ischemic AKI.

Red blood cell (RBC) trapping is common in ischemic acute kidney injury (AKI) and presents as densely packed RBCs that accumulate within and engorge the kidney medullary circulation. In this study, we tested the hypothesis that "RBC trapping directly promotes tubular injury independent of extending ischemia time." Studies were performed on rats. Red blood cell congestion and tubular injury were compared between renal arterial clamping, venous clamping, and venous clamping of blood-free kidneys. Vessels were occluded for either 15 or 45 min with and without reperfusion. We found that RBC trapping in the medullary capillaries occurred rapidly following reperfusion from renal arterial clamping and that this was associated with extravasation of blood from congested vessels, uptake of blood proteins by the tubules, and marked tubular injury. To determine if this injury was due to blood toxicity or an extension of ischemia time, we compared renal venous and arterial clamping without reperfusion. Venous clamping resulted in RBC trapping and marked tubular injury within 45 min of ischemia. Conversely, despite the same ischemia time, RBC trapping and tubular injury were minimal following arterial clamping without reperfusion. Confirming the role of blood toward tubular injury, injury was markedly reduced in blood-free kidneys with venous clamping. Our data demonstrate that RBC trapping results in the rapid extravasation and uptake of blood components by tubular cells, causing toxic tubular injury. Tubular toxicity from extravasation of blood following RBC trapping appears to be a major component of tubular injury in ischemic AKI, which has not previously been recognized.

Association of insulin resistance with intra- and extra-cranial atherosclerotic burden in the nondiabetic community population.

AIMS: Few population-based studies have investigated the association between insulin resistance and atherosclerotic burden in intra- and extra-cranial arteries. The purpose of this study is to explore the relationship between insulin resistance and intra- and extra-cranial atherosclerotic burden in community-based nondiabetic participants. METHODS: This is a cross-sectional analysis from a population-based prospective cohort-PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in China. The homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity indices (ISI0-120) were stratified by the quartiles, respectively. The atherosclerotic presence of plaques and burden was evaluated by high-resolution MRI. Binary or ordinal logistic regression was performed to assess the association between HOMA-IR or ISI0-120 and the presence and burden of atherosclerosis. RESULTS: Among the 2754 participants, the mean age was 60.9 ± 6.6 years, and 1296 (47.1%) were males. Compared with the lowest quartile of HOMR-IR, the highest quartile of HOMA-IR (indicating a higher level of insulin resistance) was associated with an increased presence of plaques (OR:1.54, 95% CI:1.14-2.08), and atherosclerotic burden (OR:1.53, 95%CI:1.14-2.07) in intracranial arteries. Meanwhile, we observed a similar relationship between HOMA-IR and the presence or burden in extracranial atherosclerosis. The first (indicating a higher level of insulin resistance) quartiles of ISI0-120 were associated with the intracranial plaques (Q1, OR:1.56, 95%CI:1.16-2.11) and atherosclerotic burden (Q1, OR:1.57, 95%CI:1.17-2.12), but not extracranial plaques or atherosclerotic burden, compared with the fourth quartile of ISI0-120. CONCLUSIONS: Insulin resistance was associated with an increased intra-and extra-cranial atherosclerotic burden in the nondiabetic elderly Chinese population.

Transcatheter closure of perimembranous ventricular septal defect using a novel fully bioabsorbable occluder: multicenter randomized controlled trial.

Although the use of bioabsorbable occluder is expected to reduce the risk of metal occluder-related complications, it has not been approved due to incomplete degradation and new complications. Novel fully bioabsorbable occluders were designed to overcome such limitations. The aim of this study was to investigate the efficacy and safety of a fully biodegradable occluder in patients with ventricular septal defects. 125 patients with perimembranous ventricular septal defect (VSD) larger than 3 mm were screened from April 2019 to January 2020 in seven centers. 108 patients were enrolled and randomized into the bioabsorbable occluder group (n = 54 patients) and nitinol occluder group (n = 54). A non-inferiority design was utilized and all patients underwent transcatheter device occlusion. Outcomes were analyzed with a 24-month follow-up. All patients were successfully implanted and completed the trial. No residual shunt >2 mm was observed during follow-up. Transthoracic echocardiography showed a hyperechoic area corresponding to the bioabsorbable occluder which decreased primarily during the first year after implantation and disappeared within 24 months. Postprocedural arrhythmia was the only occluder-related complication with an incidence of 5.56% and 14.81% for the bioabsorbable and nitinol groups, respectively (P = 0.112). The incidence of sustained conduction block was lower in the bioabsorbable occluder group (0/54 vs. 6/54, P = 0.036) at 24-month follow-up. In conclusion, the novel fully bioabsorbable occluder can be successfully and safely implanted under echocardiography guidance and reduce the incidence of sustained postprocedural arrythmia. The efficacy and safety of this fully biodegradable occluder are non-inferior to that of a traditional nitinol one.

Self-Assembly-Based Nanoprobes for the Simultaneous Detection and Downregulation of HSP90α mRNA to Enhance Photothermal Therapy.

Although photothermal therapy (PTT) has been widely applied for tumor treatment, tumor cells thermotolerance still limits PTT efficiency. Since the overexpressed HSP90α in tumor cells further enhances thermotolerance and protects them from PTT damage, a new nanoprobe that can specifically detect and downregulate HSP90α mRNA was developed to enhance the PTT effect. Based on the HSP90α mRNA sequence, the nanoprobe Au-DNA1/DNA2 can specifically bind to HSP90α mRNA for recovering its fluorescence and further inhibit the synthesis of HSP90α to reduce tumor heat tolerance. Moreover, another nanoprobe, Au-DNA3, can self-assemble with the Au-DNA1 nanoprobe after the detection to form Au aggregations to enhance PTT afterward for better efficiency. Simultaneously, such a design improves tissue penetration and tumor retention, thereby reducing the damage to the surrounding normal tissues. Both in vitro and in vivo experiments showed that the nanoprobes have excellent tumor diagnosis and cancer treatment capabilities, which is of great significance for clinical translational applications.

Higher visceral adiposity index and lipid accumulation product in relation to increased risk of atherosclerotic burden in community-dwelling older adults.

BACKGROUND AND AIMS: Visceral adiposity index (VAI) and lipid accumulation product (LAP), as anthropometric indices, have been applied to predict the risk of cardiovascular diseases (CVD). However, few studies investigated the correlation between these two indicators and cardio-cerebro-vascular atherosclerosis in community populations. Our study was to explore the association of VAI and LAP with coronary, intracranial and extracranial atherosclerosis in a community-based asymptomatic middle-aged and older population. METHODS: Participants without a history of CVD in the study of PRECISE (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) were included. The sex-special indicators of VAI and LAP were calculated and stratified by the tertiles. The presence of plaque and coronary segmental stenosis score (SSS) were assessed by coronary computed tomography (CTA), as well as intracranial and extracranial atherosclerotic burden were evaluated by high-resolution magnetic resonance imaging (HR-MRI), respectively. Binary or ordinal logistic regression was conducted to assess the association between each of the indexes and the presence and burden of atherosclerosis. RESULTS: A total of 2875 subjects were included in the final analysis. The mean age was 60.9 ± 6.6 years and 1329 (46.2 %) participants were males. Compared with the first tertile of VAI, the higher tertile was associated with the presence of plaques (T3 vs T1, OR, 1.49, 95%CI, 1.12-1.98, for males; OR, 1.64, 95%CI, 1.24-2.17, for females) and atherosclerotic burden (T3 vs T1, adjusted cOR, 1.63, 95%CI, 1.24-2.14, for males; adjusted cOR, 1.70, 95%CI, 1.29-2.24, for females) in major coronary arteries. A similar association was found for LAP. VAI level has presented an association with the extracranial atherosclerotic plaques (T3 vs T1, OR, 1.34, 95%CI, 1.02-1.77) and burden (T3 vs T1, adjusted cOR 1.32, 95 % CI 1.00-1.73) only in females. Whereas, for intracranial atherosclerosis, the results failed to show any statistically significant association. CONCLUSIONS: Among community-dwelling asymptomatic older adults, VAI and LAP were associated with the presence and burden of coronary atherosclerotic plaques, while VAI presented a weaker significant association with extracranial atherosclerosis in females.

Tumor-derived endomucin promotes colorectal cancer proliferation and metastasis.

BACKGROUND: Endomucin (EMCN) is a type I transmembrane glycoprotein and a mucin-like component of the endothelial cell glycocalyx. The mechanism of EMCN action in colorectal cancer (CRC) remains unclear. AIMS: Our aim was to explore the role of EMCN in the progression of CRC. MATERIALS & METHODS: We examined EMCN expression in CRC tissues and normal para-carcinoma tissues. The function and mechanisms of EMCN were checked in CRC cell lines and in mouse xenograft. Additionally, we used co-immunoprecipitation and mass spectrometry to identify the potential EMCN-binding proteins. Functional annotation analysis showed where these genes were enriched. RESULTS: We found that EMCN was overexpressed in tumor tissues compared with that in normal para-carcinoma tissues. We also found that overexpression of EMCN induced CRC proliferation and metastasis both in vitro and in vivo. EMCN knockdown prevents epithelial-mesenchymal transition in vitro. We identified 178 potential EMCN-binding partners. Furthermore, functional annotation analysis indicated that these genes were considerably enriched in carcinogenic-related functions and pathways. Collectively, the identification of EMCN-binding partners enhanced our understanding of the mechanism of EMCN-mediated malignant phenotypes, and this research may provide valuable insights into the molecular mechanisms underlying CRC. CONCLUSION: Tumor-derived endomucin promotes colorectal cancer proliferation and metastasis. We identified 178 EMCN-binding proteins and initially screened three potential EMCN-interacting proteins: NALCN, and TPM2, ANKK1. Our study provides valuable insights into the molecular mechanisms underlying CRC development.

Discordance of apolipoprotein B with low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol and coronary atherosclerosis.

AIMS: High level of apolipoprotein B (Apo B) is associated with incident subclinical atherosclerosis. The present study evaluated the associations between discordant Apo B with low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and coronary atherosclerotic burden. METHODS AND RESULTS: This study enrolled 3043 participants aged 50-75 years from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study that was conducted in the community in Lishui City, China. Discordant Apo B with LDL-C and non-HDL-C were defined by residuals and medians. Coronary atherosclerotic burden was evaluated by segment involvement score (SIS) and segment stenosis score (SSS) which were determined by computed tomography angiography. We performed discordance analyses examining associations of discordant Apo B with LDL-C or non-HDL-C with the coronary atherosclerotic burden. The mean age of participants was 61.2 ± 6.7 years, 53.6% were females. Participants with discordant high Apo B relative to non-HDL-C were at higher odds of plaques [odds ratio (OR), 1.30; 95% confidence interval (CI), 1.08-1.57], SIS [common odds ratio (cOR), 1.35; 95% CI, 1.14-1.60], and SSS (cOR, 1.40; 95% CI, 1.18-1.67) compared with concordant group. However, discordantly low Apo B with non-HDL-C was associated with decreased odds of the coronary atherosclerotic plaques and its burden. Similar results were shown for discordant analyses for Apo B with LDL-C. CONCLUSION: Discordantly high Apo B with LDL-C and non-HDL-C were associated with an increased odds of the coronary atherosclerotic plaques and its burden. These findings highlighted the importance of Apo B for primary prevention of coronary atherosclerosis.

Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized PADN-CFDA Trial.

BACKGROUND: World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) is a progressive, debilitating disease. Previous observational studies have demonstrated that pulmonary artery denervation (PADN) reduces pulmonary artery pressures in PAH. However, the safety and effectiveness of PADN have not been established in a randomized trial. OBJECTIVES: The aim of this study was to determine the treatment effects of PADN in patients with group 1 PAH. METHODS: Patients with WHO group 1 PAH not taking PAH-specific drugs for at least 30 days were enrolled in a multicenter, sham-controlled, single-blind, randomized trial. Patients were assigned to receive PADN plus a phosphodiesterase-5 inhibitor or a sham procedure plus a phosphodiesterase-5 inhibitor. The primary endpoint was the between-group difference in the change in 6-minute walk distance from baseline to 6 months. RESULTS: Among 128 randomized patients, those treated with PADN compared with sham had a greater improvement in 6-minute walk distance from baseline to 6 months (mean adjusted between-group difference 33.8 m; 95% CI: 16.7-50.9 m; P < 0.001). From baseline to 6 months, pulmonary vascular resistance was reduced by -3.0 ± 0.3 WU after PADN and -1.9 ± 0.3 WU after sham (adjusted difference -1.4; 95% CI: -2.6 to -0.2). PADN also improved right ventricular function, reduced tricuspid regurgitation, and decreased N-terminal pro-brain natriuretic peptide. Clinical worsening was less (1.6% vs 13.8%; OR: 0.11; 95% CI: 0.01-0.87), and a satisfactory clinical response was greater (57.1% vs 32.3%; OR: 2.79; 95% CI: 1.37-5.82) with PADN treatment during 6-month follow-up. CONCLUSIONS: In patients with WHO group 1 PAH, PADN improved exercise capacity, hemodynamic status, and clinical outcomes during 6-month follow-up. (Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension [PADN-CFDA]; NCT03282266).

Late-Onset Hereditary Transthyretin Amyloidosis Val30Met in an Elderly Person in a Non-Endemic Area.

Introduction: Patients with late-onset transthyretin Val30Met-associated hereditary transthyretin amyloidosis (hATTR) in non-endemic areas still remain undiagnosed because of diverse clinical presentations and various non-specific symptoms. Case Presentation: A 76-year-old male patient presented with progressive numbness, pain and weakness in his limbs, sweating, constipation and unexplained weight loss over the past seven years. He has shortness of breath, edema and hypotension for one month. The low QRS voltage on limb leads was not consistent with left ventricular hypertrophy, which is an important clue of cardiac amyloidosis (CA). The results of echocardiography speckle tracking imaging were consistent with CA. Serum immunofixation electrophoresis was negative, and serum-free light chain Fκ/Fλ ratio is normal or close to normal (0.26-1.65) for the patient, so AL amyloidosis can be excluded. A missense mutation c. 148 G-A Val30Met (p.Val50Met) was detected in TTR gene sequencing. The genetic finding confirmed hATTR Val30Met, familial amyloid polyneuropathy (FAP) and CA for the patient. The treatment effect was poor, and he died of cardiac involvement. Conclusion: It is challenge to make early diagnosis in patients with hATTR, due to the diversity of symptoms. Echocardiography is a vital tool in initial diagnosis. Genetic testing played vital roles in the definitive diagnosis of this disease. Raising awareness is critical for early diagnosis and provides opportunities for early treatment.

Serum Calcium Levels and in-Hospital Infection Risk in Patients with Acute Ischemic Stroke.

Purpose: Stroke-associated infection (SAI) is one of the most common post-stroke complications, which may lead to a relatively poor prognosis. This study aims to explore the potential relationship between serum calcium levels and SAI. Patients and Methods: This is a cross-sectional study involving 395 participants. SAI is a term that covers stroke-associated pneumonia (SAP), urinary tract infection (UTI), as well as other infections diagnosed during the first week after a stroke. Serum calcium levels were measured within 24 hrs of admission. To determine the association of serum calcium levels with the SAI, logistic regression models were calculated. An adjusted spline regression model was used to further confirm the relationship between the two. Results: Among the total patients, SAI occurred in 107 (27.1%) patients. Serum calcium was associated with SAI and was independent of the SAI risk factors for age, admission NIHSS score, and intravascular therapy [adjusted OR 0.040 (95% CI = 0.005-0.291), p = 0.002]. Remarkably, this trend applies predominantly to serum calcium levels less than 2.25mmol/L (p= 0.005 for linearity). Conclusion: Serum calcium levels are associated with the risk of SAI, when serum calcium is below normal (2.25mmol/L), the risk of SAI increases as serum calcium levels decrease.

Succession of the Gut Microbiome in the Tibetan Population of Minjiang River Basin.

Tibetans are one of the oldest ethnic groups in China and South Asia. Based on the analysis of 1,059 Tibetans in the Minjiang River basin at an altitude of 500-4,001 m, we found that the dominant phyla of the Tibetan population were Bacteroidota and Firmicutes, and the main genera were Prevotella and Bacteroides, which were mostly in consistent with other nationalities. We further evaluated in total 115 parameters of seven categories, and results showed that altitude was the most important factor affecting the variation in the microbial community. In the process of emigration from high altitudes to the plain, the gut microbial composition of late emigrants was similar to that of plateau aborigines. In addition, regarding immigration from low altitude to high altitude, the microbial community became more similar to that of high altitude population with the increase of immigration time. Changes in these microbes are related to the metabolism, disease incidence and cell functions of the Tibetan population. The results of other two cohorts (AGP and Z208) also showed the impact of altitude on the microbial community. Our study demonstrated that altitude of habitation is an important factor affecting the enterotype of the microflora in the Tibetan population and the study also provided a basis to explore the interaction of impact parameters with gut microbiome for host health and diseases.

Effect of Imaging Markers on Reperfusion Therapy in Basilar Artery Occlusion.

OBJECTIVE: We aimed to investigate the effectiveness of endovascular therapy (EVT) versus intravenous thrombolysis (IVT) in patients with basilar artery occlusion (BAO), based on the information of advanced imaging. METHODS: We analyzed data of stroke patients with radiologically confirmed BAO within 24 hours. BAO subjects were categorized into "top-of-the-basilar" syndrome (TOBS) and other types. An initial infarct size of <70ml and a ratio of ischemic tissue to infarct volume of ≥1.8 was defined as "target mismatch." The primary outcome was a good outcome, defined as a modified Rankin Scale score of 0 to 3 at 3 months. Propensity score adjustment and inverse probability of treatment weighting (IPTW) propensity score methods were used. RESULTS: Among 474 BAO patients, 93 (19.6%) were treated with IVT prior to EVT, 91 (19.2%) were treated with IVT alone, 95 (20.0%) were treated with EVT alone, and 195 (41.1%) were treated with antithrombotic therapy. In IPTW analyses, we found no benefit of EVT over IVT for good outcome in either TOBS patients (odds ratio = 1.08, 95% confidence interval [CI] = 0.88-1.31) or those with other types (odds ratio = 1.13, 95% CI = 0.94-1.36). However, in patients with other types, if there existed a target mismatch, EVT was independently related to good outcome (odds ratio = 1.46, 95% CI = 1.17-1.81). INTERPRETATION: The "target mismatch profile" seems to be a possible candidate selection standard of EVT for those with other types of BAO. Future studies should separate TOBS from other types of BAO, and try to use advanced imaging. ANN NEUROL 2022;92:97-106.

Lipopolysaccharide Pretreatment Prevents Medullary Vascular Congestion following Renal Ischemia by Limiting Early Reperfusion of the Medullary Circulation.

BACKGROUND: Vascular congestion of the renal medulla-trapped red blood cells in the medullary microvasculature-is a hallmark finding at autopsy in patients with ischemic acute tubular necrosis. Despite this, the pathogenesis of vascular congestion is not well defined. METHODS: In this study, to investigate the pathogenesis of vascular congestion and its role in promoting renal injury, we assessed renal vascular congestion and tubular injury after ischemia reperfusion in rats pretreated with low-dose LPS or saline (control). We used laser Doppler flowmetry to determine whether pretreatment with low-dose LPS prevented vascular congestion by altering renal hemodynamics during reperfusion. RESULTS: We found that vascular congestion originated during the ischemic period in the renal venous circulation. In control animals, the return of blood flow was followed by the development of congestion in the capillary plexus of the outer medulla and severe tubular injury early in reperfusion. Laser Doppler flowmetry indicated that blood flow returned rapidly to the medulla, several minutes before recovery of full cortical perfusion. In contrast, LPS pretreatment prevented both the formation of medullary congestion and its associated tubular injury. Laser Doppler flowmetry in LPS-pretreated rats suggested that limiting early reperfusion of the medulla facilitated this protective effect, because it allowed cortical perfusion to recover and clear congestion from the large cortical veins, which also drain the medulla. CONCLUSIONS: Blockage of the renal venous vessels and a mismatch in the timing of cortical and medullary reperfusion results in congestion of the outer medulla's capillary plexus and promotes early tubular injury after renal ischemia. These findings indicate that hemodynamics during reperfusion contribute to the renal medulla's susceptibility to ischemic injury.

Application of fecal microbial transplantation in hepatic encephalopathy after transjugular intrahepatic portosystemic shunt.

RATIONALE: Transjugular intrahepatic portosystemic shunt (TIPS) is mainly used to treat acute and chronic esophageal, gastric, and intestinal variceal bleeding and refractory ascites caused by portal hypertension. The most common complication of TIPS is the development of hepatic encephalopathy (HE). Fecal microbiota transplantation (FMT) is an emerging method for treating diseases by altering the intestinal flora. We present 2 cases of FMT that ameliorated liver function and HE after TIPS. PATIENT CONCERNS: In this report, 2 patients with liver cirrhosis secondary to hepatitis B had recurrent Grade 2-3 HE after TIPS. DIAGNOSIS: Two patients were diagnosed as having HE. INTERVENTIONS: The 2 patients separately received 3 times of FMT. OUTCOMES: The liver function of both patients improved, the clinical symptoms were relieved, and the number of HE attacks decreased significantly after FMT. LESSONS: FMT may be another effective way to treat HE, and is worthy of further research.

Balloon-Assisted Angioplasty for the Treatment of In-Stent Restenosis After Vertebral Artery Ostium Stenting: Experiences From One Single Center.

BACKGROUND: Stenting appears to be a safe means of treatment for vertebral artery ostium stenosis with low complication rates and positive long-term effects, but the incidence of in-stent restenosis (ISR) after stenting is high. Different treatment strategies are applied for the revascularization of ISR; however, currently the optional approach is not recommended. The study was designed to investigate the feasibility, safety, and effectiveness of balloon-assisted angioplasty for the treatment of ISR after vertebral artery ostium stenosis. METHODS: In this study, we included patients from the Department of Neurology, Lishui Hospital of Zhejiang University, who were treated with balloon-assisted angioplasty as a result of suffering from ISR after previously undergoing vertebral artery ostium stenting. We retrospectively analyzed the clinical and functional outcomes of the patients. RESULTS: From January 2015 to December 2019, 11 patients were included in the study. The technical success rate reached 100% and the average operation time was 73 minutes. The Thrombolysis in Cerebral Infarction Score 2b-3 was acquired in all patients except 1 patient, who was presented with symptoms of hypoperfusion syndrome. The remaining 10 patients did not experience any intraoperative or postoperative complications. No restenosis, new cerebral infarction or transient ischemic attack were reported within 6 months of follow-up. CONCLUSION: Balloon-assisted angioplasty could be feasible for the treatment of ISR after vertebral artery ostium stenting, however, more research is needed to confirm this.

Splenectomy increases blood pressure and abolishes sex differences in renal T-regulatory cells in spontaneously hypertensive rats.

Over the past decade there has been increasing support for a role of the immune system in the development of hypertension. Our lab has previously reported that female spontaneously hypertensive rats (SHRs) have a blood pressure (BP)-dependent increase in anti-inflammatory renal regulatory T cells (Tregs), corresponding to lower BP compared with males. However, little is known regarding the mechanism for greater renal Tregs in females. The current study was designed to test the hypothesis that the greater relative abundance of renal Tregs in female SHR is due to greater Treg production. To test this hypothesis, T cell profiles were measured in the spleen by flow cytometry in male and female SHR at 5 and 14 weeks of age. Splenic Tregs did not differ between males and females, suggesting sex differences in renal Tregs is not due to differences in production. To assess the role of the spleen in sex differences in renal Tregs and BP control, rats were randomized to receive sham surgery (CON) or splenectomy (SPLNX) at 12 weeks of age and implanted with telemeters to measure BP. After 2 weeks, kidneys were harvested for flow cytometric analysis of T cells. Splenectomy increased BP in both sexes after 2 weeks. Renal Tregs decreased in both sexes after splenectomy, abolishing the sex differences in renal Tregs. In conclusion, splenic Tregs were comparable in male and female SHRs, suggesting that sex differences in renal Tregs is due to differences in renal Treg recruitment, not Treg production.

Renal mass reduction increases the response to exogenous insulin independent of acid-base status or plasma insulin levels in rats.

Impairments in insulin sensitivity can occur in patients with chronic kidney disease (CKD). Correction of metabolic acidosis has been associated with improved insulin sensitivity in CKD, suggesting that metabolic acidosis may directly promote insulin resistance. Despite this, the effect of acid or alkali loading on insulin sensitivity in a rodent model of CKD (remnant kidney) has not been directly investigated. Such studies could better define the relationship between blood pH and insulin sensitivity. We hypothesized that in remnant kidney rats, acid or alkali loading would promote loss of pH homeostasis and consequently decrease insulin sensitivity. To test this hypothesis, we determined the impact of alkali (2 wk) or acid (5-7 days) loading on plasma electrolytes, acid-base balance, and insulin sensitivity in either sham control rats, 2/3 nephrectomized rats, or 5/6 nephrectomized rats. Rats with 5/6 nephrectomy had the greatest response to insulin followed by rats with 2/3 nephrectomy and sham control rats. We found that treatment with 0.1 M sodium bicarbonate solution in drinking water had no effect on insulin sensitivity. Acid loading with 0.1 M ammonium chloride resulted in significant reductions in pH and plasma bicarbonate. However, acidosis did not significantly impair insulin sensitivity. Similar effects were observed in Zucker obese rats with 5/6 nephrectomy. The effect of renal mass reduction on insulin sensitivity could not be explained by reduced insulin clearance or increased plasma insulin levels. We found that renal mass reduction alone increases sensitivity to exogenous insulin in rats and that this is not acutely reversed by the development of acidosis.NEW & NOTEWORTHY Impairments in insulin sensitivity can occur in patients with chronic kidney disease, and previous work has suggested that metabolic acidosis may be the underlying cause. Our study investigated the effect of acid or alkali loading on insulin sensitivity in a rodent model of chronic kidney disease. We found that renal mass reduction increases the blood glucose response to insulin and that this is not acutely reversed by the development of acidosis.