Repressing iron overload ameliorates central poststroke pain via the Hdac2-Kv1.2 axis in a rat model of hemorrhagic stroke

Thalamic hemorrhage can lead to the development of central post-stroke pain.Changes in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic area.However,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea r.Here,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus neurons.Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central pain.However,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain symptoms.Moreover,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain rats.These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.

Hemorrhagic Stroke: About a Pediatric Case

Stroke is a rare but serious condition with high mortality and morbidity. We report the case of a 10-year-old child with no known pathological history who was transferred to the pediatric department for hemorrhagic stroke. He had been hospitalized 6 days earlier in a peripheral center for a tonic-clonic seizure accompanied by loss of consciousness and fever. Clinical examination revealed meningeal syndrome, facial paralysis, right hemiparesis, ataxia with disturbed balance, aphasia, and a peripapillary hemorrhage on the fundus. A cerebral computed tomography (CT) scan showed a hemorrhagic stroke with ventricular flooding. A lumbar puncture was performed and a hematic cerebrospinal fluid (CSF) with 12 leukocytes and 8000 red blood cells was obtained. The evolution was marked by the extinction of the infectious and meningeal syndromes, the regression of the pyramidal syndrome and the persistence of the dysarthria justifying a neuropsychological and speech therapy follow-up. Several challenges (diagnostic, therapeutic) exist in the management of children with stroke. Prospective studies with a larger sample are needed to fill the observed gaps.

Clinical Study of Xingnaojing Injection Combined with Craniocerebral Hypothermia Apparatus in the Treatment of Acute Hemorrhagic Stroke

Objective:To investigate the clinical effect of Xingnaojing injection combined with craniocerebral hypothermia apparatus in the treatment of acute hemorrhagic stroke.Methods:Seventy-two patients with acute hemorrhagic stroke admitted to our hospital from March 2018 to September 2019 were randomly divided into two groups,with 36 cases in each group.The control group(n=36)was treated with craniocerebral hypothermia apparatus,and the observation group(n=36)was treated with Xingnaojing injection combined with craniocerebral hypothermia apparatus.The clinical efficacy,the National Institutes of Health Stroke Scale(NIHSS)score and the activity of daily living(MBI score)after 1 month of treatment were compared.Results:The effective rate of treatment in the observation group was higher than that in the control group(P<0.05);NIHSS score was decreased in both groups(P<0.05);MBI score was increased in both groups,and the change range of the observation group was greater than that of the control group,showing statistically significant differences(P<0.05).Conclusion:Xingnaojing injection combined with craniocerebral hypothermia apparatus can improve the clinical efficacy,the neurological impairment and activity of daily living in the treatment of acute hemorrhagic stroke,which is worthy of clinical application.

Advances in the knowledge on the role of apoptosis repressor with caspase recruitment domain in hemorrhagic stroke

The apoptosis repressor with caspase recruitment domain(ARC)plays a critical role in extrinsic apoptosis initiation via death receptor ligands,physiological stress,infection response in a tissue-dependent manner,endoplasmic reticulum(ER)stress,genotoxic drugs,ionizing radiation,oxidative stress,and hypoxia.Recent studies have suggested that regulating apoptosis-related pathways can improve outcomes for patients with neurological diseases,such as hemorrhagic stroke.ARC expression is significantly correlated with acute cerebral hemorrhage.However,the mechanism by which it mediates the anti-apoptosis pathway remains poorly known.Here,we discuss the function of ARC in hemorrhagic stroke and argue that it could serve as an effective target for the treatment of hemorrhagic stroke.

From hemorrhagic stroke to lipid paradox: a double-hit hypothesis underlying low low-density lipoprotein cholesterol related cardiovascular risk—a narrative review

Despite overwhelming evidence from large randomized clinical trials supporting a clear benefit of low-density lipoprotein cholesterol(LDL-C)lowering therapy on the primary and secondary prevention of atherosclerotic cardiovascular disease,data from epidemiological and clinical observations demonstrated an increased incidence of hemorrhagic stroke in patients with low LDL-C exposure(<70 mg/dL),especially among East Asians.Meanwhile,emerging studies have reported a paradoxical phenomenon in which hypercholesterolemia is associated with better short-term outcomes in acute coronary syndrome patients,the"lipid paradox."The underlying mechanism for these two closely connected clinical observations is not clear.This review aimed to summarize the evolution and clinical implications of these two low LDL-C related concepts,and proposed a"double-hit"hypothesis that may help explain these phenomena.It is worth noting that in the era of increasing use of high-intensity LDL-C lowering and dual antiplatelet strategies in atherosclerotic cardiovascular disease in patients receiving percutaneous coronary intervention,balancing the risk of thrombosis with bleeding complication should be a priority in clinical practice.Our hypothesis may raise clinicians’awareness to identify potential high risk patients with low LDL-C(<70 mg/dL),especially among East Asians.

Genetics of ischemic and hemorrhagic stroke in Chinese population

Stroke is a major cause of adult death and disability worldwide.Epidemiological and animal studies have provided strong evidence that the pathogenesis of stroke is multi-factorial and induced by a combination of environmental and genetic risk factors,but the identifica-tion of individual causative variants remains little known.Genetic influences are likely to be polygenic with small effect sizes,and stroke itself consists of a number of different subtypes which may each have different genetic profiles.In addition,various ethnic populations may have different stroke risk,such as Asian race.The reasons for high risk of stroke among the Chinese,especially hemorrhagic stroke,remain unknown.Most human studies have taken a candidate gene approach using case-control methodology.To be reliably detected,small relative risks require large sample sizes,probably 1000 patients or more.Genome-wide association(GWA)study is an unbiased and comprehensive approach to identify common risk alleles for complex diseases.Recently,a multistage GWA study has identified three loci on chromosomes 2q,8q and 9p to be associated with intracranial aneurysm in European and Japanese populations.Another GWAfinding is the identification of risk variants for cardioembolic stroke on chromosome 4q25 in European populations.In this review,we mainly focus on the results from case-control association studies on genetic factors that play a role in the risk of ischemic and hemorrhagic stroke in Chinese population.The combined effects of multiple susceptibility genes for stroke risk are also summarized.

Stroke Epidemiological Study at the Centre Hospitalier Universitaire (CHU) de Cocody in Abidjan, Côte D’Ivoire

Background: Recent literature reported a recurrent increase in hemorrhagic stroke (HS) rates in low- and middle-income countries. However, the causes and mechanisms of the rising HS rates are unknown. To address these issues, the present epidemiological study was carried out in the neurovascular unit of the neurology department at the Centre Hospitalier Universitaire (CHU) de Cocody in Abidjan (Africa). Methods: The study included 60 patients hospitalized from January 1 to December 31, 2016, who underwent brain CT (computerized tomography) scans. We examined the medical records and survey forms in these patients with acute stroke (within 7 days) admitted to the Neurovascular Unit receiving only stroke patients. In these patients, we explored stroke distribution according to socio-demographic variables: age, gender and socio-professional categories. In addition, common risk factors were assessed. Results: In Côte d’Ivoire, our studies showed an ischemic stroke (IS) rate of 66.67% and a hemorrhagic stroke (HS) rate of 33.33%. Our studies indicated that stroke particularly affects the 40 - 60 age group. Then, stroke frequency has fallen in the 30 - 40 and 60 - 70 age groups, becoming rare in relatively young (70 years) subjects. In the sample analyzed, stroke occurred in women (56.67%) compared with men (43.33%). However, there was no gender-specific predilection for stroke. In addition, 90% of strokes occur in the working population and 10% in the non-working population. Arterial hypertension was the highest medical risk factor among patients (66.13%), compared with the other risk factors i.e. alcohol (17.42%), smoking (12.90%), previous stroke (9.67%), diabetes (6.65%), heart disease (6.65%) and dyslipidemia (3.23%). Specifically, hypertension was the main risk factor causing HS (45%) and IS (21.66%) in patients. Conclusion: Stroke particularly affected socio-economically active subjects (aged 40 - 60) in Africa, which were subjected to high prevalence of hemorrhagic stroke (HS). Chronic stress related to working life and unfavorable socioeconomic conditions would be a triggering event for hemorrhagic stroke.

Role of N-formyl peptide receptor 2 in germinal matrix hemorrhage:an intrinsic review of a hematoma resolving pathway

Germinal matrix hemorrhage is one of the leading causes of morbidity,mortality,and acquired infantile hydrocephalus in preterm infants in the United States,with little progress made in its clinical management.Blood clots have been shown to elicit secondary brain injury after germinal matrix hemorrhage,by disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage causing post-hemorrhagic hydrocephalus development.Current evidence suggests that rapid hematoma resolution is necessary to improve neurological outcomes after hemorrhagic stroke.Various articles have demonstrated the beneficial effects of stimulating the polarization of microglia cells into the M2 phenotype,as it has been suggested that they play an essential role in the rapid phagocytosis of the blood clot after hemorrhagic models of stroke.N-formyl peptide receptor 2(FPR2),a G-protein-coupled receptor,has been shown to be neuroprotective after stroke.FPR2 activation has been associated with the upregulation of phagocytic macrophage clearance,yet its mechanism has not been fully explored.Recent literature suggests that FPR2 may play a role in the stimulation of scavenger receptor CD36.Scavenger receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix hemorrhage.FPR2 has been shown to phosphorylate extracellular-signal-regulated kinase 1/2(ERK1/2),which then promotes the transcription of the dual-specificity protein phosphatase 1(DUSP1)gene.In this review,we present an intrinsic outline of the main components involved in FPR2 stimulation and hematoma resolution after germinal matrix hemorrhage.

Myeloperoxidase: a new target for the treatment of stroke?

Myeloperoxidase is an important inflammatory factor in the myeloid system,primarily expressed in neutrophils and microglia.Myeloperoxidase and its active products participate in the occurrence and development of hemorrhagic and ischemic stroke,including damage to the blood-brain barrier and brain.As a specific inflammatory marker,myeloperoxidase can be used in the evaluation of vascular disease occurrence and development in stroke,and a large amount of experimental and clinical data has indicated that the inhibition or lack of myeloperoxidase has positive impacts on stroke prognosis.Many studies have also shown that there is a correlation between the overexpression of myeloperoxidase and the risk of stroke.The occurrence of stroke not only refers to the first occurrence but also includes recurrence.Therefore,myeloperoxidase is significant for the clinical evaluation and prognosis of stroke.This paper reviews the potential role played by myeloperoxidase in the development of vascular injury and secondary brain injury after stroke and explores the effects of inhibiting myeloperoxidase on stroke prognosis.This paper also analyzes the significance of myeloperoxidase etiology in the occurrence and development of stroke and discusses whether myeloperoxidase can be used as a target for the treatment and prediction of stroke.

Neonatal hemorrhage stroke and severe coagulopathy in a late preterm infant after receiving umbilical cord milking:A case report

BACKGROUND Umbilical cord milking(UCM)is an alternative placental transfusion method for delayed umbilical cord clamping in routine obstetric practice,allowing prompt resuscitation of an infant.Thus,UCM has been adopted at some tertiary neonatal centers for preterm infants to enhance placental-to-fetal transfusion.It is not suggested for babies less than 28 wk of gestational age because it is associated with severe brain hemorrhage.For late preterm or term infants who do not require resuscitation,cord management is recommended to increase iron levels and prevent the development of iron deficiency anemia,which is associated with impaired motor development,behavioral problems,and cognitive delays.Concerns remain about whether UCM increases the incidence of intraventricular hemorrhage.However,there are very few reports of late preterm infants presenting with neonatal hemorrhage stroke(NHS)and severe coagulopathy after receiving UCM.Here,we report a case of a late preterm infant born at 34 wk of gestation.She abruptly deteriorated,exhibiting signs and symptoms of NHS and severe coagulopathy after receiving UCM on the first day of life.CASE SUMMARY A female preterm infant born at 34 wk of gestation received UCM after birth.She was small for her gestational age and described as vigorous with Apgar scores of 9 and 10 at one minute and five minutes of life,respectively.After hospitalization in the neonatal intensive care unit,she showed hypoglycemia and metabolic acidosis.The baby was administered glucose and sodium bicarbonate infusions.Intramuscular vitamin K1 was also used to prevent vitamin K deficiency.The baby developed umbilical cord bleeding and gastric bleeding on day 1 of life;a physical examination showed bilateral conjunctival hemorrhage,and a blood test showed thrombocytopenia,prolonged prothrombin time,prolonged activated partial thromboplastin time,low fibrinogen,raised D-dimer levels and anemia.A subsequent cranial ultrasound and computed tomography scan showed a left parenchymal brain hemorrhage with extension into the ventricular and subarachnoid spaces.The patient was diagnosed with NHS in addition to disseminated intravascular coagulation(DIC).Fresh frozen plasma(FFP)and prothrombin complex concentrate were given for coagulopathy.Red blood cell and platelet transfusions were provided for thrombocytopenia and anemia.A bolus of midazolam,intravenous calcium and phenobarbital sodium were administered to control seizures.The baby’s clinical condition improved on day 5 of life,and the baby was hospitalized for 46 d and recovered well without seizure recurrence.Our case report suggests that preterm infants who receive UCM should undergo careful clinical assessment for intracranial hemorrhage,NHS and severe coagulopathy that may develop under certain circumstances.Supportive management,such as intensive care,FFP and blood transfusion,is recommended when the development of massive NHS and associated DIC is suspected.CONCLUSION Our case report suggests that for late preterm infants who are small for gestational age and who receive UCM for alternative placental transfusion,neonatal health care professionals should be cautious in assessing the development of NHS and severe coagulopathy.Neonatal health care professionals should also be more cautious in assessing the complications of late preterm infants after they receive UCM.

Pattern of Stroke Admissions, Radiodiagnostic Compliance, and Outcomes in the Intensive Care Unit of a Tertiary Hospital, South-South, Nigeria

Background: Stroke patients form an integral part of patients admitted into the intensive care unit (ICU);and may need airway maintenance, supplemental oxygen and even endotracheal intubation for mechanical ventilation. Method: In this retrospective study, the medical records and radiological investigations of the patients were assessed. Also, their socio-demographics, and clinical diagnosis and background co-morbidities were noted. The radiological diagnosis post CT was used to determine the type of stroke for those compliant;while clinical assessment alone was used to determine the diagnosis in those who did not do CT. They were also classified into 2 groups: those requiring mechanical ventilation (for ICU care) and those without the need for mechanical ventilation (for high dependency Unit (HDU) care). The eventual clinical outcome was noted. Result: A total of eighty-eight cases, 67% (n = 59) were males and 33% (n = 29) females. 89.8% (n = 79) had hypertension, 3.4% (n = 3) had diabetes while 6.8% (n = 6) had both hypertension and diabetes. Of the hypertensives, 36.7% (n = 29) had hemorrhagic stroke and 66.3% (n = 50) had ischaemic stroke. 53.3% (n = 46) patients had High dependency Unit (HDU care while 47.7% (n = 42) were mechanically ventilated. Of the number in HDU, 51.5% (n = 17) were haemorrhagic, while 52.7% (n = 29) were ischaemic. Clinical diagnosis of ischemic stroke was done in 55 (62.5%) and hemorrhagic stroke in 37.5% (n = 33). Of the lot, only 19.3% (n = 17) of them did CT and 80.7% (n = 71) did not have CT done. None did MRI. Late presentation (beyond 24 hrs) was a common feature for most of the patients, for whom immediate cardio-respiratory support became necessary. Overall mortality rate was 62.5% (n = 55). 39.1% (n = 18) of the HDU (46) patients died, while 88.1% (n = 37) of the ventilated (42) patients died. 56.6% (n = 26) were discharged from the HDU and 4.3% (n = 2) referred to another facility. Of the 42 patients on mechanical ventilation 88.1% (37) died, 9.5% (n = 4) discharged, and 2.4% (n = 1) referred to another health facility. Summary: Low neuroimaging compliance by Stroke patients in our environment and late presentation to hospital, impacts negatively on good outcome of the disease. This, coupled with the high cost of these facilities, makes their use unaffordable, suggesting a strong indication for comprehensive quality and affordable health care and health insurance in the country.

Withaferin A inhibits ferroptosis and protects against intracerebral hemorrhage

Recent studies have indicated that suppressing oxidative stress and ferroptosis can considerably improve the prognosis of intracerebral hemorrhage(ICH).Withaferin A(WFA),a natural compound,exhibits a positive effect on a number of neurological diseases.However,the effects of WFA on oxidative stress and ferroptosis-mediated signaling pathways to ICH remain unknown.In this study,we investigated the neuroprotective effects and underlying mechanism for WFA in the regulation of ICH-induced oxidative stress and ferroptosis.We established a mouse model of ICH by injection of autologous tail artery blood into the caudate nucleus and an in vitro cell model of hemin-induced ICH.WFA was injected intracerebroventricularly at 0.1,1 or 5μg/kg once daily for 7 days,starting immediately after ICH operation.WFA markedly reduced brain tissue injury and iron deposition and improved neurological function in a dose-dependent manner 7 days after cerebral hemorrhage.Through in vitro experiments,cell viability test showed that WFA protected SH-SY5Y neuronal cells against hemin-induced cell injury.Enzyme-linked immunosorbent assays in vitro and in vivo showed that WFA markedly decreased the level of malondialdehyde,an oxidative stress marker,and increased the activities of anti-oxidative stress markers superoxide dismutase and glutathione peroxidase after ICH.Western blot assay,quantitative polymerase chain reaction and immunofluorescence results demonstrated that WFA activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling axis,promoted translocation of Nrf2 from the cytoplasm to nucleus,and increased HO-1 expression.Silencing Nrf2 with siRNA completely reversed HO-1 expression,oxidative stress and protective effects of WFA.Furthermore,WFA reduced hemin-induced ferroptosis.However,after treatment with an HO-1 inhibitor,the neuroprotective effects of WFA against hemin-induced ferroptosis were weakened.MTT test results showed that WFA combined with ferrostatin-1 reduced hemin-induced SH-SY5Y neuronal cell injury.Our findings reveal that WFA treatment alleviated ICH injury-induced ferroptosis and oxidative stress through activating the Nrf2/HO-1 pathway,which may highlight a potential role of WFA for the treatment of ICH.

TUG-891 inhibits neuronal endoplasmic reticulum stress and pyroptosis activation and protects neurons in a mouse model of intraventricular hemorrhage

Pyroptosis plays an important role in hemorrhagic stroke.Excessive endoplasmic reticulum stress can cause endoplasmic reticulum dysfunction and cellular pyroptosis by regulating the nucleotide-binding oligomerization domain and leucine-rich repeat pyrin domain-containing protein 3(NLRP3)pathway.However,the relationship between pyroptosis and endoplasmic reticulum stress after intraventricular hemorrhage is unclear.In this study,we established a mouse model of intraventricular hemorrhage and found pyroptosis and endoplasmic reticulum stress in brain tissue.Intraperitoneal injection of the selective GPR120 agonist TUG-891 inhibited endoplasmic reticulum stress,pyroptosis,and inflammation and protected neurons.The neuroprotective effect of TUG-891 appears related to inhibition of endoplasmic reticulum stress and pyroptosis activation.

Epidemiology,pathogenesis,and management of coronavirus disease 2019-associated stroke

The coronavirus disease 2019(COVID-19)epidemic has triggered a huge impact on healthcare,socioeconomics,and other aspects of the world over the past three years.An increasing number of studies have identified a complex relationship between COVID-19 and stroke,although active measures are being implemented to prevent disease transmission.Severe COVID-19 may be associated with an increased risk of stroke and increase the rates of disability and mortality,posing a serious challenge to acute stroke diagnosis,treatment,and care.This review aims to provide an update on the influence of COVID-19 itself or vaccines on stroke,including arterial stroke(ischemic stroke and hemorrhagic stroke)and venous stroke(cerebral venous thrombosis).Additionally,the neurovascular mechanisms involved in SARS-CoV-2 infection and the clinical characteristics of stroke in the COVID-19 setting are presented.Evidence on vaccinations,potential therapeutic approaches,and effective strategies for stroke management has been highlighted.

Circulating Vitamin D and Risk of Cerebrovascular Disease:A Meta-analysis

Objective:This scoping review aims to perform a meta-analysis to harmonize the existing results on circulating vitamin D and cerebrovascular disease.Methods:Three scientific databases,PubMed,the Cochrane Library and EMBASE,were systematically searched.The overall relative risk(RR)and the corresponding 95%confidence interval(CI)were calculated using a random-effects model,and sensitivity analysis and publication bias tests were performed.Results:Of the 4,138 articles retrieved,28 studies were included in our analysis,with a cumulative sample size of 284,840.Subsequent random-effects meta-analysis showed an association between low levels of vitamin D and cerebrovascular disease:RR=1.39,95%CI:1.26,1.53.In subgroup analyses,low levels of vitamin D were associated with both ischemic stroke(RR=1.35,95%CI:1.17,1.55)and hemorrhagic stroke(RR=1.70,95%CI:1.03,2.79).The funnel plot was asymmetric.Sensitivity analysis showed that one literature article had a significant impact on the results.There was a statistically significant correlation between low levels of vitamin D and cerebrovascular disease.Conclusion:Vitamin D levels are associated with both ischemic and hemorrhagic stroke.

Endoscopic surgery for thalamic hemorrhage breaking into ventricles: Comparison of endoscopic surgery, minimally invasive hematoma puncture, and external ventricular drainage

Purpose:Thalamic hemorrhage breaking into ventricles(THBIV)is a devastating disease with high morbidity and mortality rates.Endoscopic surgery(ES)may improve outcomes,although there is no consensus on its superiority.We investigated the efficacy and safety of ES and compared the outcomes of different management strategies by ES,hematoma puncture and drainage(HPD),and external ventricular drainage(EVD)in patients with THBIV.Methods:We retrospectively analyzed patients with THBIV treated by ES,HPD,or EVD at our hospital from June 2015 to June 2018.Patients were categorized into anteromedial and posterolateral groups based on THBIV location,and then the two groups were further divided into ES,HPD,and EVD subgroups.Individualized surgical approach was adopted according to the location of the hematoma in the ES subgroups.Patient characteristics and surgical outcomes were investigated.Results:We analyzed 211 consecutive patients.There were no significant differences in clinical characteristics or incidence of perioperative procedure-related complications(postoperative rebleeding and intracranial infection)in either anteromedial or posterolateral groups.Compared with other therapeutic methods,the ES subgroups had the highest hematoma evacuation rate,shortest drainage time,and lowest incidence of chronic ventricular dilatation(all p<0.05).Among the three anteromedial subgroups,ES subgroup had the best clinical outcomes which was assessed by the modified Rankin Scale,followed by HPD and EVD subgroups(p<0.01);while in the posterolateral subgroups,clinical outcomes in the ES and HPD subgroups were similar and better than that in the EVD subgroup(p=0.037).Conclusion:Individualized surgical ES approach for removal of thalamic and ventricular hematomas is a minimally invasive,safe,and effective strategy for the treatment of THBIV with a thalamic hematoma volume of 10-30 mL.

Temporal trend in mortality of cardiovascular diseases and its contribution to life expectancy increase in China, 2013 to 2018

Backgrounds::Cardiovascular disease(CVD)remains the leading cause of deaths nationwide.However,little is understood about its temporal trend and corresponding influence on longevity improvements.We aimed to describe the updated tendency in CVD mortality and to quantify its impact on life expectancy(LE)increase in China.Methods::All-cause mortality rates were calculated with population sizes from the National Bureau of Statistics and death counts from the National Health Commission.We estimated CVD mortality rates by allocating age-and sex-based mortality envelopes to each CVD subtype based on its proportion derived from the Disease Surveillance Points system.The probability of CVD premature deaths and LE were calculated with life tables and we adopted Arriaga’s method to quantitate age-and cause-specific contributions to LE gains.Results::During 2013 to 2018,the age-standardized mortality rate of CVD decreased from 289.69(95%confidence interval[CI]:289.03,290.35)/100,000 to 272.37(95%CI:271.81,272.94)/100,000,along with a decline in probability of CVD premature deaths from 9.05%(95%CI:9.02%,9.09%)to 8.13%(95%CI:8.10%,8.16%).The gap in CVD mortality across sexes expanded with more remarkable declines in females,especially for those aged 15 to 64 years.Among major subtypes,the probability of premature deaths from hemorrhage stroke declined fastest,while improvements of ischemic stroke and ischemic heart disease were limited,and there was an increase in stroke sequelae.LE in China reached 77.04(95%CI:76.96,77.12)years in 2018 with an increase of 1.38 years from 2013.Of the total LE gains,21.15%(0.29 years)were attributed to reductions of CVD mortality in the overall population,mostly driven by those aged>65 years.Conclusions::The general process in reducing CVD mortality has contributed to longevity improvements in China.More attention should be paid to prevention and control of atherosclerotic CVD and stroke sequelae,especially for the elderly.Working-age males also deserve additional attention due to inadequate improvements.

Registration of intervention trials of Traditional Chinese Medicine for four neurological diseases on Chinese Clinical Trial Registry and Clinical Trials.gov:a narrative review

OBJECTIVE:To analyze the current status of clinical trial registration of Traditional Chinese Medicine(TCM)for the treatment of neurological diseases.METHODS:Interventional clinical trials of TCM treatment for ischemic stroke,hemorrhagic stroke,vascular cognitive impairment,tension-type headache before September 22,2020 on the platform of Chinese Clinical Trial Registry(Chi CTR),and Clinical Trials.gov were searched.Two researchers independently selected the literature and extracted data.RESULTS:A total of 180 interventional clinical trials were included for analysis.Out of 180 trials,127 were from Chi CTR and 53 from Clinical Trials.gov.The countries primary sponsoring the included trials were China(176,97.8%),and the common categories of primary sponsors were hospital(131,72.8%).Among the study design,the largest proportion of allocation was randomized(172,95.6%),interventional model assignment was parallel(163,90.6%),masking was double blind 49(27.2%),and the sample size was≤400(144,80.0%).The trials were most carried out at a single center(102,56.7%).Among the included studies,112(62.2%)registered on Chi CTR attached the ethical approval documents.In terms of trial stages,50(27.7%)studies were in phaseⅣ.The mostly used intervention was Chinese herbal medicines(99,55%),acupuncture(68,37.8%)was the second.By searching the registration number on China National Knowledge Infrastructure Database and Pub Med,38(21.1%)registered trials were published,including 25 protocol studies and 14 research results with one(NCT02275949)published both the protocol and the results.CONCLUSIONS:Irregular and inadequate reporting,untimely update and publication,insufficient information on traditional medicine unique characteristics,and lack of international collaborations are the problems existing in the interventional clinical registration trials of traditional medicine treatment on neurological diseases.More efforts need to be made from the above aspects to standardize and improve the registration of traditional medicine trials.