Yuan Wang

Background: While prior meta-analyses have demonstrated the benefits of lipid-lowering agents for atherosclerotic cardiovascular disease prevention in high-risk populations with definite risk, the applicability of these findings to global community-based populations, where hemorrhagic risk profiles and optimal serum lipid levels might differ, remains less defined. This gap underscores the need to clarify the relationship between serum lipids and hemorrhagic stroke (HS) risk in a broader community-based population. Methods: PubMed, Ovid, and the Cochrane Library were searched from inception to May 21, 2025, for observational prospective cohorts in populations with no major disease, baseline serum lipid assessment, and first-attack HS. Risk ratios (RRs) with 95% confidence intervals (95% CIs) of continuous variables and dose-response modeling were both analyzed. Potential nonlinear trends were validated through model comparison. Results: A total of 50,244,342 participants from 54 cohorts were included. Continuous variable analysis revealed that serum total cholesterol (sTC) was inversely related to total HS (RR = 0.94, 95% CI 0.90 ~ 0.97, P < 0.01) and intracerebral hemorrhage (ICH) (RR = 0.90, 95% CI 0.87 ~ 0.93, P < 0.01) risk; serum low-density lipoprotein cholesterol (sLDL-C) was inversely related to total HS (RR = 0.92, 95% CI 0.86 ~ 0.98, P = 0.012) and ICH (RR = 0.83, 95% CI 0.74 ~ 0.94, P < 0.01) risk; and serum high-density lipoprotein cholesterol (sHDL-C) was inversely related to subarachnoid hemorrhage (SAH) (RR = 0.77, 95% CI 0.63 ~ 0.92, P < 0.01) risk. In the dose-response analysis, linear trends were detected in total HS, with a decreasing risk of 7.8% (95% CI 3.6%~11.8%, P < 0.01) per mmol/L sTC increase and a decreasing risk of 9.6% (95% CI 2.4%~16.2%, P < 0.01) per mmol/L sLDL-C increase; in ICH, with a decreasing risk of 17.0% (95% CI 7.5%~25.6%, P < 0.01) per mmol/L sLDL-C increase; and in SAH, with a decreasing risk of 20.7% (95% CI 1.5%~36.1%, P = 0.036) per mmol/L sHDL-C increase and a decreasing risk of 54.0% (95% CI 5.5%~77.6%, P = 0.035) per mmol/L triglyceride increase. U-shaped trends were detected between sTC and ICH risk, with the lowest RR at 6.07 mmol/L; between sLDL-C and SAH risk, with a minimum RR of 3.69 mmol/L; between sHDL-C and total HS risk, with a minimum RR of 1.53 mmol/L; and between sHDL-C and ICH risk, with a minimum RR of 1.50 mmol/L. Conclusion: When the minimal important difference was set at an RR of 0.87 ~ 1.15, sTC between 3.48 ~ 5.20 mmol/L, sLDL-C between 1.09 ~ 3.40 mmol/L, and sHDL-C between 0.99 ~ 2.34 mmol/L might provide balanced lipid management, contributing to stroke prevention in global community-based populations. Trial registration: The protocol of this study was registered on PROSPERO (CRD420250650371).

Safety outcomes following intravenous thrombolysis (IVT) impact overall efficacy in acute ischemic stroke (AIS), yet safety profiles of various IVT treatments remain less studied. In this study, we ranked safety profiles of various IVT treatments through a systematic review and meta-analysis of safety outcomes following IVT in AIS. This network meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO; no. CRD42024544617). Phase 3 randomized controlled trials on IVT in AIS from Embase, Ovid Medline, and Cochrane Library were included. Primary outcomes included total serious adverse events (SAEs), symptomatic intracranial hemorrhage (sICH), and 3-month mortality. Network meta-analysis involved 21 studies for total SAEs, 21 for sICH, and 34 for mortality with no heterogeneity (I² = 0%; I² = 0%; I² = 15.86%). Compared with non-thrombolysis, alteplase 0.9 mg/kg and tenecteplase 0.25 mg/kg were associated with more SAEs (risk difference [RD] 0.03, 95% confidence interval [CI] 0.01-0.05; RD 0.04, 95% CI 0.01-0.06), sICH (RD 0.02, 95% CI 0.01-0.03; RD 0.02, 95% CI 0.01-0.03), and mortality (RD 0.01, 95% CI 0.00-0.03; RD 0.02, 95% CI 0.00-0.03). Nonimmunogenic recombinant staphylokinase (nSta) 10 mg resulted in fewer SAEs than non-thrombolysis (RD - 0.11, 95% CI - 0.21 to - 0.01), recombinant human prourokinase (rhPro-UK) 35 mg (RD - 0.12, 95% CI - 0.22 to - 0.02), alteplase 0.9 mg/kg (RD - 0.14, 95% CI - 0.23 to - 0.04), and tenecteplase 0.25 mg/kg (RD - 0.15, 95% CI - 0.24 to - 0.05) and less sICH than tenecteplase 0.25 mg/kg (RD - 0.05, 95% CI - 0.10 to 0.00). Although rhPro-UK 35 mg resulted in more sICH than non-thrombolysis (RD 0.01, 95% CI 0.00-0.02), it was associated with a lower rate of sICH compared with alteplase 0.9 mg/kg (RD - 0.01, 95% CI - 0.02 to 0.00) and tenecteplase 0.25 mg/kg (RD - 0.01, 95% CI - 0.02 to - 0.01). Compared with alteplase 0.6 mg/kg, alteplase 0.9 mg/kg and tenecteplase 0.25 mg/kg resulted in more SAEs (RD 0.04, 95% CI 0.01-0.07; RD 0.05, 95% CI 0.01-0.08) and sICH (RD 0.01, 95% CI 0.00-0.02; RD 0.02, 95% CI 0.01-0.03). When administered beyond 4.5 h with tissue window assessment, tenecteplase 0.25 mg/kg and alteplase 0.6 mg/kg were not associated with higher rates of mortality compared with non-thrombolysis. Alteplase 0.6 mg/kg, rhPro-UK 35 mg, and nSta 10 mg were safer IVT options. Tenecteplase 0.25 mg/kg and alteplase 0.6 mg/kg were preferable beyond 4.5 h with tissue window assessment.

Objective: Brief exposure to intermittent hypoxia has been shown to potentially induce protective effects in the body. Animal studies suggest that intermittent hypoxia could increase cerebral blood flow and confer resistance to subsequent hypoxic–ischemic injury, yet clinical investigations are limited. This study aimed to evaluate the impact of a moderate short‐term intermittent hypoxia protocol on cerebral blood flow and cognitive performance.Methods: Subjects who met the inclusion criteria were recruited to this study and randomized into the intermittent hypoxia group or the control group, which receives intermittent hypoxia training and sham‐intermittent hypoxia training, respectively. Cerebral hemodynamics, cognitive performance, cerebral perfusion pressure, and oxygen saturation were assessed before and after the intervention.Results: A total of 100 healthy participants were included in this study. Compared to the control group, the intermittent hypoxia group exhibited higher peak systolic blood flow velocity (108.64 ± 22.53 vs. 100.21 ± 19.06, p = 0.049) and cerebrovascular conduction index (0.74 ± 0.17 vs. 0.66 ± 0.21, p = 0.027), and lower cerebrovascular resistance index (1.41 ± 0.29 vs. 1.54 ± 0.36, p = 0.044) following intermittent hypoxia training. Additionally, within‐group comparisons revealed that intermittent hypoxia training led to increased cerebral blood flow velocity, elevated cerebrovascular conductance index, and decreased cerebrovascular resistance index (p < 0.05). Other indicators including cognitive function, cerebral perfusion pressure, and oxygen saturation did not exhibit significant differences between groups.Interpretation: These findings revealed that intermittent hypoxia may represent a safe and effective strategy for improving cerebral blood flow.

Brain temperature, a crucial yet under-researched neurophysiological parameter, is governed by the equilibrium between cerebral oxygen metabolism and hemodynamics. Therapeutic hypothermia has been demonstrated as an effective intervention for acute brain injuries, enhancing survival rates and prognosis. The success of this treatment hinges on the precise regulation of brain temperature. However, the absence of comprehensive brain temperature monitoring methods during therapy, combined with a limited understanding of human brain heat transmission mechanisms, significantly hampers the advancement of hypothermia-based neuroprotective therapies. Leveraging the principles of bioheat transfer and MRI technology, this study conducted quantitative analyses of brain heat transfer during mild hypothermia therapy. Utilizing MRI, we reconstructed brain structures, estimated cerebral blood flow and oxygen consumption parameters, and developed a brain temperature calculation model founded on bioheat transfer theory. Employing computational cerebral hemodynamic simulation analysis, we established an intracranial arterial fluid dynamics model to predict brain temperature variations across different therapeutic hypothermia modalities. We introduce a noninvasive, spatially resolved, and optimized mathematical bio-heat model that synergizes model-predicted and MRI-derived data for brain temperature prediction and imaging. Our findings reveal that the brain temperature images generated by our model reflect distinct spatial variations across individual participants, aligning with experimentally observed temperatures.

Background: Intermittent hypoxia (IH) is emerging as a cost‐effective nonpharmacological method for vital organ protection. We aimed to assess the effects of a short‐term moderate intermittent hypoxia preconditioning protocol (four cycles of 13% hypoxia lasting for 10 min with 5‐min normoxia intervals) on acute hypoxic injury induced by sustained hypoxic exposure (oxygen concentration of 11.8% for 6 h).Methods: One hundred healthy volunteers were recruited and randomized to the IH group and the control group to receive IH or sham‐IH preconditioning for 5 days, respectively, and then were sent to a hypoxic chamber for simulated acute high‐altitude exposure (4500 m).Results: The overall incidence of acute mountain sickness was 27% (27/100), with 14% (7/50) in the IH group and 40% (20/50) in the control group (p = 0.003). After 6‐h simulated high‐altitude exposure, the mean Lake Louise Score was lower in the IH group as compared to controls (1.30 ± 1.27 vs. 2.04 ± 1.89, p = 0.024). Mean peripheral oxygen saturations (SpO₂) and intracranial pressure (ICP) measures after acute hypoxic exposure exhibited significant differences, with the IH group showing significantly greater SpO₂ values (85.47 ± 5.14 vs. 83.10 ± 5.15%, p = 0.026) and lower ICP levels than the control group (115.59 ± 32.15 vs. 130.36 ± 33.83 mmH₂O, p = 0.028). IH preconditioning also showed greater effects on serum protein gene product 9.5 (3.89 vs. 29.16 pg/mL; p = 0.048) and C‐reactive protein (−0.28 vs. 0.41 mg/L; p = 0.023).Conclusion: The short‐term moderate IH improved the tolerance to hypoxia and exerted protection against acute hypoxic injury induced by exposure to sustained normobaric hypoxia, which provided a novel method and randomized controlled trial evidence to develop treatments for hypoxia‐related disease.

Severe hypoxia can induce a range of systemic disorders; however, surprising resilience can be obtained through sublethal adaptation to hypoxia, a process termed as hypoxic conditioning. A particular form of this strategy, known as intermittent hypoxia conditioning hormesis, alternates exposure to hypoxic and normoxic conditions, facilitating adaptation to reduced oxygen availability. This technique, originally employed in sports and high-altitude medicine, has shown promise in multiple pathologies when applied with calibrated mild to moderate hypoxia and appropriate hypoxic cycles.

Stroke remains a major cause of long-term disability and mortality worldwide. The immune system plays an important role in determining the condition of the brain following stroke. As the resident innate immune cells of the central nervous system, microglia are the primary responders in a defense network covering the entire brain parenchyma, and exert various functions depending on dynamic communications with neurons, astrocytes, and other neighboring cells under both physiological or pathological conditions. Microglia activation and polarization is crucial for brain damage and repair following ischemic stroke, and is considered a double-edged sword for neurological recovery. Microglia can exist in pro-inflammatory states and promote secondary brain damage, but they can also secrete anti-inflammatory cytokines and neurotrophic factors and facilitate recovery following stroke. In this review, we focus on the role and mechanisms of microglia-mediated neuroinflammation and neuroplasticity after ischemia and relevant potential microglia-based interventions for stroke therapy.

Background: Although recommendations on gastric residual volume (GRV) have been applied to the clinical practice of patients who are intubated, evidence-based data about the GRV of patients who are neurocritically ill are still lacking. We conducted this study to investigate the safety of increased GRV in patients who are neurocritically ill on enteral nutrition (EN) support.Methods: Patients who are neurocritically ill feeding through intragastric enteral tubes were recruited consecutively between July 2018 and June 2021. Patients were divided into a control group (GRV 100 ml) and a study group (GRV 200 ml). Demographic data, admission diagnosis, and severity scores were collected from the patient medical records. The frequency of diet volume ratio (diet received/diet prescribed), the incidence of gastrointestinal complications, and outcome variables were evaluated.Results: There were 344 patients enrolled, of whom 197 had mechanical ventilation support. High GRV events in the control group were more frequent than those in the study group (38.1 vs. 22.8%, p = 0.002). The total gastrointestinal complication rate did not differ significantly between the two groups (study group: 61.1%, 102/167 vs. control group: 67.9%, 114/168). In the study group, two patients had aspiration (1.2 vs. 0%, p = 0.245). The study group showed a superior diet volume ratio, but the difference was not significant. The outcomes of the study group were slightly better than those of the control group; however, no significant differences were observed between the two groups concerning the length of stay in the neurointensive care unit (19.5 days vs. 25.3 days) and mortality (10.8 vs. 14.9%) at discharge.Conclusion: Our results suggest that 200 ml may be a safe normal limit for GRV in patients who are neurocritically ill.