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Abstract
Background The superiority of balloon angioplasty plus aggressive medical management (AMM) to AMM alone for symptomatic intracranial artery stenosis (sICAS) on efficacy and safety profiles still lacks evidence from randomised controlled trials (RCTs).
Aim To demonstrate the design of an RCT on balloon angioplasty plus AMM for sICAS.
Design Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS) trial is a multicentre, prospective, randomised, open-label, blinded end-point trial to investigate whether balloon angioplasty plus AMM could improve clinical outcome compared with AMM alone in patients with sICAS. Patients eligible in BASIS were 35–80 years old, with a recent transient ischaemic attack within the past 90 days or ischaemic stroke between 14 days and 90 days prior to enrolment due to severe atherosclerotic stenosis (70%–99%) of a major intracranial artery. The eligible patients were randomly assigned to receive balloon angioplasty plus AMM or AMM alone at a 1:1 ratio. Both groups will receive identical AMM, including standard dual antiplatelet therapy for 90 days followed by long-term single antiplatelet therapy, intensive risk factor management and life-style modification. All participants will be followed up for 3 years.
Study outcomes Stroke or death in the next 30 days after enrolment or after balloon angioplasty procedure of the qualifying lesion during follow-up, or any ischaemic stroke or revascularisation from the qualifying artery after 30 days but before 12 months of enrolment, is the primary outcome.
Discussion BASIS trail is the first RCT to compare the efficacy and safety of balloon angioplasty plus AMM to AMM alone in sICAS patients, which may provide an alternative perspective for treating sICAS.
Trial registration number NCT03703635; https://www.clinicaltrials.gov.
- Angioplasty
- Atherosclerosis
- Angiography
Data availability statement
All data are available to researchers on request for purposes of reproducing the results or replicating the procedure by directly contacting the corresponding author.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Optimal treatment for patients with symptomatic intracranial artery stenosis (sICAS), especially those accompanied by haemodynamic compromise, remains unclear.
WHAT THIS STUDY ADDS
Balloon angioplasty alone may be another feasible treatment option for sICAS for lower rates of perioperative complications.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
The Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis trial aims to explore whether balloon angioplasty plus aggressive medical management (AMM) is superior to AMM alone for sICAS patients.
Introduction
Intracranial atherosclerotic stenosis (ICAS) is a main aetiology of stroke worldwide, which is associated with stroke recurrence, substantial morbidity and mortality, accounting for up to 50% of ischaemic strokes in south and east Asia.1 Although receiving treatment with aspirin and standard medical management of vascular risk factors, patients with symptomatic ICAS (sICAS) still had as high as 23% at a 1-year stroke recurrence rate.2 3 Therefore, how to prevent stroke recurrence and death in patients with sICAS is a global major issue. Currently, treatment options for sICAS include aggressive medical management (AMM), balloon angioplasty and stenting (balloon angioplasty plus stenting); however, the optimal treatment for sICAS remains unclear.
SAMMPRIS (Stenting vs Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) and VISSIT (Vitesse Intracranial Stent Study for Ischemic Stroke Therapy) trials have shown high perioperative complication rates and no significant advantage of endovascular stents compared with AMM in the long term.4 5 However, the CASSISS (China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis) trial reported that stenting by experienced operators did not add additional risks of stroke and death within 30 days to AMM for sICAS, although it failed to demonstrate a benefit by stenting.6 As lower rates of short-term stroke or mortality (peri-procedural or mean follow-up ≤3 months) were found in balloon angioplasty than stenting,7 balloon angioplasty alone may be a feasible alternative treatment to stenting for sICAS treatment. Moreover, several previous meta-analyses also proved the safety and efficacy of balloon angioplasty for sICAS, which suggested that balloon angioplasty alone may be potentially promising for sICAS.8–10
To date, limited evidence is available from randomised controlled trials (RCTs) to determine the safety and efficacy of balloon angioplasty for patients with sICAS. Hence, we designed the Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS) RCT to explore whether balloon angioplasty plus AMM is superior to AMM alone in patients with sICAS.
Methods
Hypothesis
Balloon angioplasty combined with AMM may be superior to AMM alone in patients with sICAS.
Design and patient population
BASIS trial is an investigator-initiated, multicentre, prospective, randomised, open-label, blinded end-point trial that plans to enrol 512 patients with a 3-year follow-up, including a neurovascular imaging examination (digital subtraction angiography (DSA), CT angiography (CTA) or magnetic resonance angiography (MRA)) at 1 year after enrolment. Patients with sICAS (defined as a recent transient ischaemic attack (TIA) or ischaemic stroke attributed to a 70%–99% atherosclerotic stenosis of a major intracranial artery) determined by DSA and conform to the inclusion/exclusion criteria of BASIS trial will be considered for enrolment at 31 comprehensive stroke centres across China (online supplemental table 1). The ethics committee of each participating centre approved the BASIS trial study protocol. The inclusion and exclusion criteria are listed in table 1.
Supplemental material
Inclusion and exclusion criteria of BASIS trial
Randomisation
BASIS trial used an interactive web response system (IWRS) for central randomisation stratified by study centres. After inputting eligible patients’ necessary information into the web-based system, the researchers in each centre will obtain a random code as well as the corresponding group allocation information from the IWRS. Eligible patients will be randomly, at a 1:1 ratio, assigned to the following one treatment group (figure 1).
The flowchart of BASIS trial. *Neurovascular imaging includes digital subtraction angiography (DSA), CT angiography (CTA) or magnetic resonance angiography (MRA). AMM, aggressive medical management; BA, basilar artery; BASIS, Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis; ICA, internal carotid artery; MCA, middle cerebral artery; TIA, transient ischaemic attack; VA, vertebral artery.
Experimental group: patients with sICAS will undergo balloon angioplasty plus AMM.
Control group: patients with sICAS will undergo AMM alone.
Intervention
Endovascular treatment
Antithrombotic protocol
Preprocedure
All patients who are scheduled to undergo balloon angioplasty should receive dual antiplatelet therapy (aspirin 100 mg per day and clopidogrel 75 mg per day) for ≥3 days prior to the procedure.
Intraprocedure
Intravenous anticoagulant such as heparin during the procedure.
Postprocedure
Aspirin 100 mg per day must be used throughout the follow-up duration, and clopidogrel 75 mg per day or ticagrelor 90 mg two times per day must be used for 90 days after randomisation.
Anesthesia strategy and arterial access
The procedure should be performed under general anaesthesia. Femoral artery access is recommended (radial artery access is allowed for patients with tortuosity of the aortic arch or aorta abdominals).
Procedure steps
A stable vascular access with a long sheath or guiding catheter (an intermediate catheter is recommended for participants with tortuous access), which should be placed as distal as possible, is suggested to provide adequate support for performing the balloon angioplasty. Collateral status assessment based on a whole brain DSA is recommended before balloon angioplasty according to ASITN/SIR (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology) collateral flow grading system (poor collateral: ASITN/SIR <3).11
A 0.014-inch microwire with a microcatheter or not passes through the lesion to reach the distal branch of the target artery.
The microwire guides a balloon to the lesion of the target artery (the Neuro RX and Neuro LPS Intracranial Balloon Dilation Catheter (Sinomed, Tianjin, China) is recommended).
Balloon size selection: balloon length should cover the lesion completely and cover at least 2 mm beyond each end of the lesion. The balloon diameter is determined according to surgeon’s opinion (submaximal angioplasty is suggested: balloon with a diameter no more than 70% of the proximal artery diameter).
The balloon should be slowly inflated to the nominal pressure and maintain this pressure for 10–30 s before deflating slowly. This step can be repeated 2–3 times if the dilation effect of balloon angioplasty is not satisfactory. For patients with extremely severe stenosis, a relatively smaller balloon can be used for predilation.
Technical success: residual stenosis ≤50% of the proximal artery diameter with modified Thrombolysis in Cerebral Infarction (mTICI)12 of 3 grade without arterial dissection that impairs the distal blood flow.
Rescue stent implantation is allowed when: (1) residual stenosis ≥70% after balloon dilation or the antegrade flow is unstable (mTICI <2 b); (2) arterial dissection impairing the distal blood flow (mTICI <2 b); (3) development of thrombosis or embolisation that jeopardises distal perfusion. Other measures such as intravenous/intraarterial thrombolysis, infusion of glycoprotein IIb/IIIa inhibitors, are based on the surgeon’s experience, which can be used alone or in combination with rescue stenting.
A final DSA should be performed after 10–15 min of observation.
Aggressive medical management
Antiplatelet treatment
AMM will be identical in both arms. All the necessary blood and imaging tests are precollected in the screening period before randomisation for the following management of risk factors. Both arms are prescribed with an AMM regime (includes aspirin 100 mg per day throughout the follow-up duration and clopidogrel 75 mg per day for the first 90 days after enrollment). For the record: clopidogrel can be replaced with ticagrelor or cilostazol with appropriate dosage for patients with clopidogrel resistance (platelet aggregation rate of ADP >40% or loss-of-function alleles of CYP2C19 is detected).
Risk factors management
Neurologists and study investigators at each site will be responsible for the management of patients’ risk factors. They receive training on risk factors management according to Chinese Stroke Association guidelines for the clinical management of cerebrovascular disorders.13 All study investigators are regularly trained according to BASIS protocol every 6 months. If a patient fails to reach the target, a face-to-face follow-up with the local neurologist to modify their medical regime will be necessary.
Blood pressure management
Blood pressure will be checked at screening, randomisation, discharge, 30 days, 90 days, 180 days, 1 year and the end of the trial. Patients may need to visit local sites for blood pressure measurement and medical regime modification if necessary. The target blood pressure is no more than 140 mm Hg/90 mm Hg for patients without diabetes mellitus (DM) and no more than 130 mm Hg/80 mm Hg for patients with DM. Antihypertensive drugs include angiotensin-converting enzyme inhibitor (lisinopril 10 mg or 40 mg), angiotensin receptor blocker (candesartan 16 mg or 32 mg), beta-blocker (atenolol 50 mg or 100 mg), calcium channel antagonist (felodipine 5 mg or 10 mg), diuretic, vasodilator (hydralazine 50 mg), etc.
Achieving target LDL cholesterol
The baseline serum low-density lipoprotein cholesterol (LDL-c) level is recorded before enrolment. The target LDL-c level is <1.8 mmol/L or 70 mg/dL. If the patient’s LDL level is higher than the target level, he/she should modify the lipid-lowering drugs. Liver enzyme (Aspartate aminotransferase/Alaninetransaminase) levels will be measured at the beginning of the study and at each visit point.
Non-HDL cholesterol
The target level of nonhigh-density lipoprotein (HDL) cholesterol is <100 mg/dL. Non-HDL cholesterol includes low-density lipoproteins (LDL), very-low-density lipoproteins and intermediate-density lipoproteins. When a larger statin dosage fails to lower LDL level, while non-HDL cholesterol ≥100 mg/dL and triglycerides ≥200 mg/dL, other lipid-lowering drugs in addition to statin are recommended, such as ezetimibe or PCSK9 inhibitors.
Diabetes management
The target of DM management is to achieve HbA1c<7.0%. Fasting plasma glucose and HbA1c levels will be measured at baseline, 30 days, 90 days, and 1 year.
Lifestyle modification
Smoking cessation: investigators at each site will evaluate smoking status at each follow-up and encourage all subjects to quit smoking as soon as possible.
Weight management: investigators at each site will evaluate the weight according to body mass index.
Activity level: activity level for each patient is also assessed at each follow-up by trained investigators or coordinators, and moderate exercise of 30 minutes a day, three times per week is strongly recommended to all patients with athletic ability.
Follow-up schedule
All the participants will be followed up by the on-site neurologists at baseline, the day of DSA, discharge, 30±7 days, 90±7 days, 6 months±14 days, 1 year±30 days and up to 3 years (at 6 months intervals after 1 year). Follow-up visits will be conducted by telephone at 6-month and post-1-year period and will be evaluated in person at other visits. At each follow-up visits, the participants’ medications, laboratory tests, risk factors management (as described above) and possible adverse event (AEs)/endpoints are reviewed by experienced neurologist and/or neurointerventionalist. All patients are required to undergo a neurovascular imaging examination including DSA, CTA or MRA at 1-year follow-up. Table 2 shows the complete study assessment schedule.
Assessment schedule
Study outcomes
Primary outcome
Stroke or death in the next 30 days after enrolment or after balloon angioplasty procedure of the qualifying lesion during follow-up or any ischaemic stroke or revascularisation from the qualifying artery after 30 days but before 12 months of enrolment. We defined ischaemic stroke as a new focal, sudden onset neurologic deficit, which is confirmed on brain NCCT or MRI. We define symptomatic intracranial haemorrhage as subarachnoid, parenchymal or intraventricular haemorrhage identified on brain MRI or NCCT, which leads to new neurologic symptoms (consciousness level change, headache or focal neurologic symptoms), lasting over 24 hours or a seizure. If symptomatic intracranial haemorrhage occurs in the next 30 days after enrolment or in the next 30 days after the balloon angioplasty during follow-up, we will consider it as a primary outcome. Revascularisation of the culprit artery will be considered a primary outcome if it occurs from 30 days though 12 months after enrolment and fulfils one of the following requirements:
Acute revascularisation: acute culprit artery occlusion accompanied by neurological deficit, requiring intravenous thrombolysis, intraarterial thrombolysis, mechanical thrombectomy or balloon/stent angioplasty (including intracranial–extracranial bypass grafting operations).
Selective revascularisation: neurologic symptom-driven selective revascularisation, including balloon angioplasty or stent implantation (including intracranial–extracranial bypass grafting operations), if the participants fulfil one of the following conditions:
Ischaemic stroke caused by the culprit artery stenosis: a new focal neurological deficit of sudden onset attributed to the territory of the culprit artery, which is confirmed as a recurrent stroke on brain CT or MRI (follow-up imaging will be compared with baseline imaging for the detection of new lesions).
Culprit artery stenosis that causes recurrent transient ischaemic attack lasting longer than 10 min or new disabling neurological symptoms (paroxysmal limb weakness/numbness, inarticulateness, diplopia or dyspraxia) compared with the baseline qualifying symptoms. All symptoms must be detected after 1 month of AMM (as described above).
Secondary outcomes
Any stroke (ischaemic or haemorrhagic stroke) or death due to any cause in the next 1 month after enrolment or after balloon angioplasty of the qualifying lesion during follow-up.
Any stroke (ischaemic or haemorrhagic stroke) within the lesion arterial territory or death from any cause in the next 3 months after enrollment.
Any stroke (ischaemic or haemorrhagic stroke) that occurs beyond the lesion arterial territory in the next 3 months after enrolment.
Modified Rankin Scale (mRS) at 3 months.
Any stroke (ischaemic or haemorrhagic stroke) within the lesion arterial territory or death from any cause in the next 1 year after enrollment.
Lesion arterial revascularisation in the next 1 year after enrollment.
Any stroke (ischaemic or haemorrhagic stroke) that occurs beyond the lesion arterial territory in the next 1 year after enrolment.
mRS at 1 year.
Restenosis rate of the lesion artery in the next 1 year after enrolment (defined as based on subsequent neurovascular imaging, stenotic degree >70% or increased by 30%).
Combined events such as myocardial infarction, stroke and vascular death in the next 1 year after enrolment.
EuroQol-5-Dimensions Scale questionnaire in the next 1 year after enrollment.
Any stroke (ischaemic or haemorrhagic stroke) within the lesion arterial territory or death from any cause in the next 2 years after enrolment.
Any stroke (ischaemic or haemorrhagic stroke) that occurs beyond the lesion arterial territory in the next 2 years after enrolment.
mRS at 2 years.
Combined events such as myocardial infarction, stroke and vascular death in the next 2 years after enrolment.
Any stroke (ischaemic or haemorrhagic stroke) within the lesion arterial territory or death from any cause in the next 3 years after enrolment.
Any stroke (ischaemic or haemorrhagic stroke) that occurs beyond the lesion arterial territory in the next 3 years after enrolment.
mRS at 3 years.
Combined events such as myocardial infarction, stroke and vascular death in the next 3 years after enrolment.
Assessment of AEs
We defined AE as the presence of all unexpected medical conditions during or after being treated with medical devices. It includes symptoms, signs or abnormal laboratory parameters that can be unrelated to treatment. We define severe AE as an AE meeting at least one criterion as follows: lead to death; need hospitalisation or extend the existing hospitalisation time; life-threatening; lead to serious disability or need medical intervention to prevent one of the above-mentioned outcomes. If a potential endpoint occurs, the committee board meeting will be convened to evaluate whether such an event can be categorised as the primary endpoint.
Data safety and monitoring board
An independent statistician and academic members consist of the data safety and monitoring board (DSMB) of the BASIS trial. DSMB is scheduled to have meetings annually to review the study progress to make sure that the trial is consistent with the standards of ethics and to guarantee all enrolled patients’ safety. After every DSMB meeting, a report including all recommendations will be generated by the DSMB members and handed to the steering committee immediately after the meeting.
Sample size
According to VISSIT trial and a previous randomised trial in China, the composite event rate of the primary outcome in the control group is anticipated to be 15%.4 14 As to the balloon angioplasty group, we assume a 7% of the primary outcome based on studies of angioplasty without stenting9 15 and investigators’ clinical practice experience in China. As a result, the sample size needs to detect an 8% absolute difference. A total of 512 patients (256 per group) will be enrolled considering an 80% statistical power at a one-sided α of 2.5% and a 10% dropout rate.
Statistical analyses
The composite event rates and corresponding 95% CIs of the primary outcome in the two treatment groups will be estimated by Kaplan-Meier survival analysis and compared by log-rank test. We will perform a Cox proportional hazards regression model to calculate the HR between the two groups and its 95% CI. Time-to-event endpoints of secondary outcomes will also be analysed by Kaplan-Meier survival analysis and Cox regression, and common ORs of mRS will be estimated using ordinal logistic regression. The widths of the intervals will not be adjusted for multiplicity for secondary outcomes. The main analysis of this study will be conducted based on intention-to-treat principle, and a per-protocol analysis will also be conducted as a sensitivity analysis. Subgroup analyses on the primary outcome will be performed in the following subgroups: age (<65 years old vs ≥65 years old), sex (men vs women), hypertension (yes vs no), DM (yes vs no), smoking (yes vs no), baseline renal function (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 vs eGFR≥60 mL/min/1.73 m2), target vessel stenosis degree (<80% vs ≥80%), body mass index (<25 Kg/m2 vs 25–30 Kg/m2 vs ≥30 Kg/m2), hypoperfusion (yes vs no), lesion location (anterior circulation vs posterior circulation) and mechanism (ischaemic stroke vs TIA). We will use SAS software, V.9.4 (SAS Institute) to conduct all analyses. Detailed statistical methods, missing data imputation and subgroup analyses are described in the statistical analysis plan.
Study organisation
Twice a year, the steering committee will meet to oversee the trial and provide strategic guidance. Periodically, the clinical research team of the leading centre will meet online with the project team of the clinical research organisation to review the trial progress and data monitoring each week. An independent clinical events adjudication committee will ensure that defined outcomes are reported and judged uniformly using the same definition by experts who are blinded to the treatment status (online supplemental table 2).
Core lab and quality assurance
Imaging will be adjudicated by an independent neuroimaging core laboratory (China National Clinical Research Center for Neurological Diseases, Tiantan Neuroimaging Center of Excellence). We will collect, transport and persevere all blood samples and imaging data according to the study protocol. The diagnosis of sICAS and regional hypoperfusion that is attributed to the target artery will be blindly assessed by experienced neuroradiologists and neurologists (over 10-year working experience). To make sure that the collected data reveal what is illustrated in the protocol, each subcentre of the BASIS trial will be regularly scrutinised, and by comparing data in the Electronic Data Capture System and data in the original documents (case report form vs source documents) to confirm data consistency. If a patient develops AE/severe AE or completes a 1-year observation after receiving treatment from non-study sites, duplicate copies of the medical documents will be collected for future reviews.
Discussion
Up till now, no consensus has been achieved on the optimal treatment for patients with sICAS to prevent stroke recurrence and death. The SAMMPRIS trial failed to show positive results and suggested stenting could add additional perioperative risks of stroke or death within 30 days to the AMM for sICAS patients (14.7% vs 5.8%, p=0.002).5 16 However, in the AMM group of the SAMMPRIS trial, patients in the haemodynamic insufficiency subgroup still had as high as 37% rate of stroke recurrence.17 As a result, the phenomenon indicates that further RCT with more rigorous patient selection and an eligible endovascular strategy with an acceptable safety and efficacy profile may be necessary for the treatment of sICAS. The subsequent VISSIT study also showed no advantage of balloon-expandable stenting over medical therapy.4 A registry study of stenting for symptomatic intracranial artery stenosis in China reported the rate of TIA, death or stroke within 1 month after stenting for sICAS was only 4.3%, which may suggest the safety of stenting for sICAS in real-world practice.18 Eleven years after SAMMPRIS, the CASSSIS study reported that stenting plus AMM had a similar effect on preventing stroke and death with AMM alone in patients with sICAS (8.0% vs 7.2%, p=0.82).6
Patients with sICAS, especially those accompanied by haemodynamic disorders, not only have a high risk of recurrent stroke but may also be associated with cognitive decline.19 For such patients, it is necessary to identify safer and more effective revascularisation methods to improve blood flow and further reduce stroke recurrence. Balloon angioplasty alone may be another feasible treatment option for sICAS due to its easy operation and lower rates of perioperative morbidity and mortality.7 Three recent meta-analyses all suggested that submaximal balloon angioplasty may be a potentially promising intervention for sICAS.8–10 However, compared with medical therapy, the long-term effectiveness of balloon angioplasty, including recurrent stroke and restenosis of target vessels, is still unknown.
Therefore, we designed the BASIS trial to investigate a new perspective on endovascular treatment for sICAS. BASIS trial has several unique aspects that may contribute to previous clinical trials and cohort studies. First, unlike previous trials, balloon angioplasty (submaximal angioplasty and slow inflation/deflation of the balloon are recommended) alone is performed in the experimental group instead of balloon angioplasty plus stenting; and a 1-year neurovascular imaging follow-up is used to assess its long-term efficacy. Second, before the BASIS trial, our centre conducted a prospective, multicentre registry study of stenting for symptomatic intracranial artery stenosis in China,20 which helped us screen the comprehensive centres with rich experience in angioplasty to ensure consistency in performing the procedure in the BASIS trial. Finally, stricter patient selection criteria and preprocedure assessments will be conducted in the BASIS trial, such as perfusion imaging or collateral assessment. Participants with perforator stroke will fulfil the inclusion criteria only with simultaneous perfusion compromise and poor collateral duo to the culprit stenosis.
Conclusions
BASIS trial will provide objective evidence on whether balloon angioplasty plus AMM is superior to AMM alone in patients with sICAS, which may propose an alternative perspective for treating sICAS.
Data availability statement
All data are available to researchers on request for purposes of reproducing the results or replicating the procedure by directly contacting the corresponding author.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by Ethics Committee of Beijing Tiantan Hosptial and corresponding branch centres. Participants gave informed consent to participate in the study before taking part.
Acknowledgments
We thank all the participants in the BASIS program for their hard work.
References
Supplementary material
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Twitter @yilong
Contributors ZM, YW and YW designed the study; XS, MY and DS drafted the manuscript; GP, YD, XZ, LL, NM, FG, DM and WY provided critical comments/revisions of the manuscript.
Funding The BASIS trial is funded by the National Natural Science Foundation of China (Number 81825007), Beijing Outstanding Young Scientist Program (Number BJJWZYJH01201910025030), Capital's Funds for Health Improvement and Research (2022-2-2045), National Key R&D Program of China (2022YFF1501500, 2022YFF1501501, 2022YFF1501502, 2022YFF1501503, 2022YFF1501504, 2022YFF1501505), Youth Beijing Scholar Program (Number 010), Beijing Laboratory of Oral Health (PXM2021_014226_000041), Beijing Talent Project - Class A: Innovation and Development (No. 2018A12), National Ten-Thousand Talent Plan—Leadership of Scientific and Technological Innovation, and National Key R&D Program of China (Number 2017YFC1307900, 2017YFC1307905), and Long-Term Reliability Study of the Sensors System Under Minimally Invasive Surgery Biological Conditions (Number 2021YFB3200604).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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