AIMS:Hypertension is a major global health burden, and the central nervous system (CNS) plays a pivotal role in regulating blood pressure. However, the underlying cellular and molecular mechanisms remain incompletely understood. This study aimed to characterize the spatial and single-cell transcriptomic profiles of CNS regions implicated in hypertension. MATERIALS AND METHODS:Spatial transcriptomic sequencing and single-cell RNA sequencing were performed on the hypothalamus and medulla oblongata of spontaneously hypertensive rats and normotensive Wistar-Kyoto controls at 4 and 10 weeks of age. Transcriptomic findings were integrated with histological analyses and validated using human brain tissues. KEY FINDINGS:Spatial mapping identified previously unrecognized brain regions within the hypothalamus and medulla oblongata that may contribute to the initiation and progression of hypertension. Distinct neuronal subsets, including Ano5+, Oxt+, and Zeb2+ neurons, were characterized, exhibiting potential crosstalk with microglia, astrocytes, and oligodendrocytes. Further integrated analyses revealed a significant upregulation of Eno1 in hypertensive brains, implicating it in neural regulation of blood pressure. Findings in human samples were consistent with the results obtained from rats. SIGNIFICANCE:This study provides a comprehensive spatial transcriptomic atlas of the hypertensive brain, uncovering multidimensional molecular mechanisms underlying CNS-mediated blood pressure regulation. These results advance our understanding of neurogenic hypertension and may inform future diagnostic and therapeutic strategies.

Background The STEP (Strategy of Blood Pressure Intervention in the older Hypertensive Patients) trial showed that intensive systolic blood pressure (SBP) control resulted in a lower incidence of cardiovascular events than standard treatment. This study analyzed the effects of intensive SBP lowering on cognitive function. Methods STEP was a multicenter, randomized controlled trial of hypertensive patients aged 60–80 years. Participants were randomly assigned (1:1) to SBP goals of 110–130 mmHg (intensive treatment) or 130–150 mmHg (standard treatment). Each individual was asked to complete a cognitive function test (Mini-Mental State Examination; MMSE) at baseline and during follow-up. The primary outcome for this study was the annual change in MMSE score. Subjects with a score less than education-specific cutoff point were categorized as cognitive decline. Results The analysis enrolled 6,501 participants (3,270 participants in the intensive-treatment and 3,231 participants in the standard-treatment groups). Median follow-up was 3.34 years. There was a minor change in MMSE score, with an annual change of −0.001 [95% confidence interval [CI] −0.020, 0.018] and 0.030 (95% CI 0.011, 0.049) in the intensive- and standard-treatment groups, respectively (p = 0.052). Cognitive decline occurred in 46/3,270 patients (1.4%) in the intensive-treatment group and 42/3,231 (1.3%) in the standard-treatment group (hazard ratio 0.005, 95% CI 0.654, 1.543, p = 0.983). Conclusions Compared with standard treatment, intensive SBP treatment did not result in a significant change in cognitive function test score. The impact of intensive blood pressure lowering was not evident using this global cognitive function test. Trial registration ClinicalTrials.gov. Unique identifier: NCT03015311.

ObjectiveMounting evidence has linked microbiome and metabolome to systemic autoimmunity and cardiovascular diseases (CVDs). Takayasu arteritis (TAK) is a rare disease that shares features of immune‐related inflammatory diseases and CVDs, about which there is relatively limited information. This study was undertaken to characterize gut microbial dysbiosis and its crosstalk with phenotypes in TAK.MethodsTo address the discriminatory signatures, we performed shotgun sequencing of fecal metagenome across a discovery cohort (n = 97) and an independent validation cohort (n = 75) including TAK patients, healthy controls, and controls with Behçet's disease (BD). Interrogation of untargeted metabolomics and lipidomics profiling of plasma and fecal samples were also used to refine features mediating associations between microorganisms and TAK phenotypes.ResultsA combined model of bacterial species, including unclassified Escherichia, Veillonella parvula, Streptococcus parasanguinis, Dorea formicigenerans, Bifidobacterium adolescentis, Lachnospiraceae bacterium 7 1 58FAA, Escherichia coli, Streptococcus salivarius, Klebsiella pneumoniae, Bifidobacterium longum, and Lachnospiraceae Bacterium 5 1 63FAA, distinguished TAK patients from controls with areas under the curve (AUCs) of 87.8%, 85.9%, 81.1%, and 71.1% in training, test, and validation sets including healthy or BD controls, respectively. Diagnostic species were directly or indirectly (via metabolites or lipids) correlated with TAK phenotypes of vascular involvement, inflammation, discharge medication, and prognosis. External validation against publicly metagenomic studies (n = 184) on hypertension, atrial fibrillation, and healthy controls, confirmed the diagnostic accuracy of the model for TAK.ConclusionThis study first identifies the discriminatory gut microbes in TAK. Dysbiotic microbes are also linked to TAK phenotypes directly or indirectly via metabolic and lipid modules. Further explorations of the microbiome–metagenome interface in TAK subtype prediction and pathogenesis are suggested.

Background: In the STEP trial (Strategy of Blood Pressure Intervention in older Hypertensive Patients), the risk of cardiovascular events is significantly lower in patients who received intensive systolic blood psressure (BP) treatment than in those who received standard treatment. This study compared the lifetime health benefits and medical costs of intensive BP treatment with those of standard BP treatment. Methods: A microsimulation model included 10 000 hypothetical samples of Chinese adults aged 60 to 80 years old with baseline systolic BP higher than 140 mm Hg. Primary outcome was the incremental cost-effectiveness ratio from a payer’s perspective. Secondary outcome was cardiovascular events, including acute coronary syndrome, stroke, acute decompensated heart failure, atrial fibrillation, and death from cardiovascular causes. Results: The model simulated that cardiovascular events occurred in 36.88% of the patients in the intensive treatment group, as compared to 41.28% of the patients in the standard treatment group over the lifetime horizon. The mean number of quality-adjusted life-years would be 0.16 higher in patients who received intensive treatment than in those who received standard treatment and would cost Chinese yuan 12 614 (International dollars 3018) more per quality-adjusted life-year gained. Most simulation results indicated that intensive treatment would be cost-effective (82%–95% below the willingness-to-pay threshold of Chinese yuan 72 000 [1× the gross domestic product per capita in China in 2020]). Sensitivity analyses showed that these conclusions were robust. Conclusions: In this study, intensive BP treatment prevented cardiovascular events among older patients with hypertension in China and was cost-effective in most scenarios. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03015311

1 病例资料 患者,女,60岁,以"胸背部疼痛5年,加重4个月"入院.患者5年前逐渐出现持重物或重体力劳动后胸骨后、背部疼痛,每次持续数小时至数天不等,自行缓解,当地医院检查未见异常.4个月前疼痛症状加重,呈撕裂样,不能耐受.

1病例资料 患者,女性,21岁,因"发现血压升高10年,加重3个月"入院.患者10年前体检时发现血压偏高140/90mmHg(1mmHg=0.133kPa),无特殊不适,未在意.入院前3个月(2016-09)患者体检发现血压升高达170/1 10mmHg,就诊于当地医院,腹部超声示:肾动脉狭窄(具体不详),建议手术治疗,患者拒绝,予马来酸左旋氨氯地平片(2.5mgqd)、比索洛尔片(2.5mgqd)治疗高血压,血压降至140/90mmHg.

OBJECTIVE:The present study aimed to evaluate the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) aiding in diagnosing and evaluating disease activity in Takayasu arteritis (TA) patients with atypical clinical manifestations.METHODS:A retrospective study of 22 TA patients was conducted. All the participants were classified into two groups. Group one including 12 patients, who did not fulfill American College of Rheumatology (ACR) criteria, were diagnosed by modified Ishikawa criteria. Group two involving ten patients, who did not satisfy the modified Ishikawa criteria or ACR criteria, were clinically diagnosed as TA after panel discussion by a combination of clinical data, excluding other diagnoses. PET/CT results were analyzed using quantitative and qualitative metrics. Disease activity was evaluated using the US National Institutes of Health (NIH) criteria.RESULTS:In group one, nine patients in active stage and two patients in inactive stage had active FDG uptake. One patient in inactive stage had inactive PET/CT results. In group two, five patients in active stage had active FDG uptake and five patients in inactive stage had inactive FDG uptake with SUVmax values of several vascular lesions slightly lower than livermean in each person. The sensitivity of PET/CT scans for evaluating disease activity was 100.0%, specificity was 75.0%, positive predictive value was 87.5%, and negative predictive value was 100.0% compared to NIH criteria.CONCLUSIONS:PET/CT plays a unique role in diagnosing these TA with atypical manifestation and assisting in evaluating disease activity. Key Points • Diagnosis of these TA patients with atypical manifestations may be difficult. • PET/CT plays a unique role in diagnosing these TA patients and assisting in evaluating disease activity.

目的:探讨合并高血压的多发性大动脉炎患者的临床特征及预后.方法:回顾性分析2004年1月至2014年2月就诊于中国医学科学院阜外医院的381例合并高血压的多发性大动脉炎患者的临床特征、治疗方案及随访结果.结果:381例患者中,57.5％ 因高血压首次就诊;女性占79.0％;多发性大动脉炎平均发病年龄(27.3±12.2)岁,合并高血压年龄为(28.1±12.2)岁;首次出现大动脉炎相关症状至确诊平均延误(34.5±51.8)个月.Hata分型V型最常见占59.3％.患者多伴有肾动脉狭窄占69.3％,其次为胸主动脉狭窄(25.7％)、腹主动脉狭窄(20.5％)和重度主动脉瓣反流(11.8％),25.7％的患者同时出现两种及以上上述病变.321例无锁骨下动脉受累或单侧锁骨下动脉受累患者的平均上肢血压为(176.0±29.4)/(97.2±23.0)mmHg(1 mmHg=0.133 kPa),60例双侧锁骨下动脉受累患者平均主动脉压为(192.7±30.8)/(102.4±121.1)mmHg.对305例患者平均随访(38.4±36.7)个月,血压的控制率、改善率及降压治疗失败率分别为50.8％、41.0％ 和8.2％.二分类Logistic回归分析显示,抗炎治疗有助于改善降压治疗预后(P=0.008).结论:合并高血压的多发性大动脉炎患者多伴有肾动脉狭窄,其次为主动脉狭窄和重度主动脉瓣反流.在合理应用降压药物的基础上联合充分抗炎治疗有助于改善患者预后.

Following publication of the original article [1], the authors reported an error.

1 临床资料 女性 23 岁,因"血压升高 1 年、胸闷憋气 2 个月余"就诊.患者 1 年前发现血压升高,未诊治,2个月前患者怀孕 37 周开始间断出现胸闷憋气,有时伴夜间阵发性呼吸困难.就诊于当地医院,超声心动图检查示左心室舒张末期内径 62 mm,左心室射血分数 31％,诊断为"围产期心肌病 "收当地医院治疗,抗心力衰竭治疗症状缓解不明显,故于妊娠38周行剖宫产术.

Following publication of the original article [1], the authors reported an error.

BACKGROUND To investigate the clinical features, management, and outcomes of childhood Takayasu arteritis (c-TA) initially presenting with hypertension. METHODS This study retrospectively reviewed medical charts of 96 inpatient c-TA cases from January 2002 to December 2016, with 5 additional patients being prospectively recruited from January 2017 to December 2017. Data were compared between c-TA groups initially presenting with and without hypertension. Blood pressure (BP) control, event-free survival, and associated risk factors were assessed by logistic regression, Kaplan-Meier survival curve, and COX regression models. RESULTS The hypertensive cohort (N = 71, 28.2% males) as compared with non-hypertensive cohort had significantly fewer active diseases; fewer episodes of claudication, syncope, blurred vision, and myocardial ischemia; and fewer systemic symptoms (P < 0.05). The hypertensive group presented with more localized abdominal lesions (OR = 14.4, P = 0.001) and limited supradiaphragmatic arterial involvement. Renovascular disease (P = 0.001) and revascularization (P = 0.006) were associated with hypertension. At the median 3-year follow-up, 53% of hypertensive patients achieved BP control and 39% experienced events including vascular vival were 78.7% (95% CI: 65.7%-87.2%), 63.0% (95% CI: 48.1%-74.7%), 48.9% (95% CI: 32.0%-63.8%), and 31.6% (95% CI: 13.8%-51.2%), higher than in non-hypertensive group (P = 0.014). Heart failure, stroke, and body mass index < 18.5 kg/m(2) were prognostic factors for events. Intervention and baseline systolic BP were independent factors for BP control (P < 0.05). CONCLUSIONS Majority of c-TA has hypertension, presenting with a more quiescent disease without typical systemic and/or ischemia symptoms, more localized abdominal lesions, higher proportion of revascularizations and better event-free survival. Three-year BP control is more than 50%. Intervention particularly on renal artery is beneficial for BP control and decreased events.