Normobaric Hyperoxia Combined With Endovascular Treatment Based on Temporal Gradient: A Dose-Escalation Study.

BACKGROUND: Normobaric hyperoxia (NBO) has neuroprotective effects in acute ischemic stroke. Thus, we aimed to identify the optimal NBO treatment duration combined with endovascular treatment. METHODS: This is a single-center, randomized controlled, open-label, blinded-end point dose-escalation clinical trial. Patients with acute ischemic stroke who had an indication for endovascular treatment at Tianjin Huanhu Hospital were randomly assigned to 4 groups (1:1 ratio) based on NBO therapy duration: (1) control group (1 L/min oxygen for 4 hours); (2) NBO-2h group (10 L/min for 2 hours); (3) NBO-4h group (10 L/min for 4 hours); and (4) NBO-6h group (10 L/min for 6 hours). The primary outcome was cerebral infarction volume at 72 hours after randomization using an intention-to-treat analysis model. The primary safety outcome was the 90-day mortality rate. RESULTS: Between June 2022 and September 2023, 100 patients were randomly assigned to the following groups: control group (n=25), NBO-2h group (n=25), NBO-4h group (n=25), and NBO-6h group (n=25). The 72-hour cerebral infarct volumes were 39.4±34.3 mL, 30.6±30.1 mL, 19.7±15.4 mL, and 22.6±22.4 mL, respectively (P=0.013). The NBO-4h and NBO-6h groups both showed statistically significant differences (adjusted P values: 0.011 and 0.027, respectively) compared with the control group. Compared with the control group, both the NBO-4h and NBO-6h groups showed significant differences (P<0.05) in the National Institutes of Health Stroke Scale scores at 24 hours, 72 hours, and 7 days, as well as in the change of the National Institutes of Health Stroke Scale scores from baseline to 24 hours. Additionally, there were no significant differences among the 4 groups in terms of 90-day mortality rate, symptomatic intracranial hemorrhage, early neurological deterioration, or severe adverse events. CONCLUSIONS: The effectiveness of NBO therapy was associated with oxygen administration duration. Among patients with acute ischemic stroke who underwent endovascular treatment, NBO therapy for 4 and 6 hours was found to be more effective. Larger-scale multicenter studies are needed to validate these findings. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05404373.

Safety and Tolerability of Direct Ischemic Postconditioning Following Thrombectomy for Acute Ischemic Stroke.

BACKGROUND: Experimental studies have demonstrated the neuroprotection of ischemic postconditioning (IPostC) in acute ischemic stroke by attenuating ischemia-reperfusion injury. This study aimed to investigate the safety and tolerability of direct IPostC in both a dog model and patients with acute ischemic stroke treated with thrombectomy. METHODS: The study involved 2 parts. First, IPostC was induced by repeated balloon inflation and deflation in dogs, where a low-pressure balloon was navigated to the anterior spinal artery, and 4 cycles of 5-minute ischemia followed by 5-minute reperfusion were performed. Vascular injuries were assessed using angiography and vascular tissue specimens. Then, a 3+3 dose-escalation trial was conducted in patients with acute ischemic stroke following successful thrombectomy recanalization. Patients received direct IPostC with ischemia and reperfusion durations in progressive increments of 0, 1, 2, 3, 4, and 5 minutes ×4 cycles. Major adverse responses were defined as vessel perforation, rupture, dissection, reocclusion, severe vasospasm, thrombotic events, and rupture of the balloon. RESULTS: IPostC was investigated in 4 dogs. No vessel perforation or rupture, dissection, or vasospasm was observed under the angiography. Only 1 vessel experienced mild injury between the intima and the internal elastic membrane detected on a histopathologic slide. Then, 18 patients were recruited. The duration of IPostC was progressively escalated with no major response happened. No patient experienced agitation, discomfort, or other tolerability issues. Five patients (27.8%) experienced any intracranial hemorrhage after thrombectomy, and 1 (5.6%) was symptomatic. At 3-month follow-up, no patient died, and 9 patients (50%) achieved functional independence. CONCLUSIONS: Direct IPostC inducing by 4 cycles of 5-minute ischemia followed by 5-minute reperfusion is safe, feasible, and tolerable in patients with acute ischemic stroke treated with thrombectomy. Further investigations are needed to determine the safety and preliminary efficacy of direct IPostC. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05153655.

Bidirectional transmission of a collimator with double-combined collimating lenses and thermally expanded core fibers.

The collimator is an essential part of the fiber optic rotary joint design. This study proposes the Large-Beam Fiber Collimator (LBFC) with a double collimating lens and a Thermally Expanded Core (TEC) fiber structure. The transmission model is constructed based on the defocusing telescope structure. The effects of TEC fiber's mode field diameter (MFD) on the coupling loss are investigated by deriving the loss function for the influence of collimator mismatch error and implementing it on a fiber Bragg grating temperature sensing system. The experimental results show that the coupling loss decreases with the increase of the MFD of TEC fiber, while the coupling loss is less than 1 dB when the mode field diameter is greater than 14 µm. TEC fibers can reduce the effect of angular deviation. Considering the coupling efficiency and deviation, the preferred mode field diameter for the collimator is 20 µm. The proposed LBFC enables bidirectional transmission of optical signals for temperature measurement.

Mechanical thrombectomy using the retrograde semi-retrieval technique for patients with underlying intracranial atherosclerotic stenosis.

Background: The retrograde semi-retrieval technique (RESET) has been described as a modified technique for endovascular thrombectomy (EVT) whose safety and efficacy for intracranial atherosclerosis stenosis (ICAS) patients remain uncertain. This article presents our single-center experience, comparing RESET vs. non-RESET in ICAS patients. Materials and methods: We analyzed 327 consecutive ICAS patients who underwent EVT at Tianjin Huanhu Hospital from January 2018 and December 2022. Patients were categorized into two groups: RESET and non-RESET. The primary outcome was the first-pass effect (FPE). Secondary outcomes included successful reperfusion, functional independence at 90 days, mortality, and symptomatic intracranial hemorrhage (sICH). Results: RESET was significantly associated with FPE [adjusted odds ratio (aOR) 2.00, 95% confidence interval (CI) 1.03-3.87, p = 0.040]. RESET was not significantly associated with successful reperfusion (aOR 1.5, CI 0.55-4.06, p = 0.425), an mRS of 0-2 at 90 days (aOR 1.36, CI 0.83-2.21, p = 0.223), sICH (aOR 0.39, CI 0.12-1.23, p = 0.108), and mortality (aOR 0.49, CI 0.16-1.44, p = 0.193). After propensity score matching, the results were consistent with the primary analysis. Conclusion: Compared to non-RESET, patients treated with RESET showed increased FPE incidence and significantly decreased puncture-to-reperfusion time. RESET was proven to be safe and effective in enhancing reperfusion for LVO patients receiving EVT with underlying ICAS.

Optical Coupling Efficiency of a Coupler with Double-Combined Collimating Lenses and Thermally Expanded Core Fibers.

Improving the coupling efficiency of two optical signals is a hot issue, where the efficiency of optical coupling has a significant effect on the signal transmission over the fiber link. To this end, the Large-Beam Fiber Coupler (LBFC) with a Double-combined Collimating Lens (DCL) and a single-mode TEC fiber structure are proposed in this study. Based on the propagation principle of Gaussian beams and the coupling requirements, the coupling mechanism of the fiber coupler and the coupling mismatch between the coupler is analytically modeled. The model and the optical path are optimized, then the ray tracing is used to calculate the coupling efficiency of inter-coupler signals for different SMF. The coupling efficiency is evaluated through experiments in terms of coupling efficiency and the radial, axial, and angular mismatches between the couplers. The results showed that with a large Mode Field Diameter (MFD), better coupling efficiency can be obtained, i.e., a large MFD of 28 µm is tested with its maximal efficiency of 95.16%. Moreover, the angular mismatch has the most significant impact on the coupling efficiency, while the axial mismatch has the least. The use of large MFD can alleviate the angular mismatch and thus improve the optical coupling efficiency.

[Effect of oral administration of tribendimidine at different dosages against Trichinella spiralis encapsulated larvae in mice].

OBJECTIVE: To observe the efficacy of oral administration of tribendimidine (TBD) at different dosages against Trichinella spiralis encapsulated larvae in murine striated muscle. METHODS: A total of 88 BALB/c mice were divided equally into 11 groups. Each mouse was infected orally with 50 T spiralis encapsulated larvae. At day 29 after infection, TBD was each orally administered to mice of the 11 groups with doses of 0 (control group), 50, 100, 150, 200, 250, 300, 350, 400, 450, and 500 mg/(kg x d), respectively. All mice were administered once a day and lasted for 6d, and untoward drug reactions for mice were observed. Mice were sacrificed at the 7th day after administration of TBD, the encapsulated larvae in diaphragmatic muscle, jugomaxillary muscle, pectoral muscle and gastrocnemius muscle were examined by pellet method, and the total, survival and dead worms were counted. The therapeutic effect was estimated on the basis of average quantity of encapsulated larvae per gram muscle. RESULTS: During the administration period, no untoward reaction were observed in mice of 50-300 mg/(kg x d) groups. Mice in 350 and 400 mg/(kg x d) groups showed body hair dishevelment, emaciation and food-intake decrease, death rates were 25% and 50%, respectively. All mice in 450 and 500 mg/(kg x d) groups died on day 4 and 5 after TBD administration, respectively. In control group, the highest total burden (per gram) was found in diaphragmatic muscle, followed by jugomaxillary muscle, gastrocnemius muscles and pectoral muscles. TBD at dose of 50 mg/(kg x d) was unable to kill encapsulated larvae. In the rest groups, with the increase of drug dose, the total worm burden and the number of survival worms showed a decreasing trend in four kinds of muscles, and were significantly lower than that of the control group (P < 0.05 or P < 0.01). In 300 mg/(kg x d) group the number of survival worms in diaphragmatic muscle, jugomaxillary muscle, pectoral muscle and gastrocnemius muscle [8.6 +/- 1.7, 2.8 +/- 0.7, 3.9 +/- 0.8, and 0, respectively] were significantly lower than that of the control group [3648.1 +/- 989.2, 1266.4 +/- 812.3, 701.9 +/- 196.4, and 711.6 +/- 34.6] (P < 0.01). All encapsulated larvae in the four kinds of muscle died in 350 and 400 mg/(kg x d) groups. With the increase of TBD dosage, the mortality of encapsulated larvae increased in the muscles, reached up to 98.6%--100% in 300 m (kg x d) group (P < 0.01), and 100% in 350 and 400 mg/(kg x d) groups (P < .01). CONCLUSION: Oral tribendimidine administered at 50 mg/(kg x d) to mice for 6 d is unable to reduce worm burden in muscle. Tribendimidine 300 mg/(kg x d) effectively kill encapsulated larvae and is a suitable dose against encapsulated larva stage. However, tribendimidine at doses of 350 mg/(kg x d) and above for 6d is toxic to mice and even causing death.

p53 upregulated modulator of apoptosis sensitizes drug-resistant U251 glioblastoma stem cells to temozolomide through enhanced apoptosis.

Malignant glioma is a highly aggressive brain tumor with a poor prognosis. Chemotherapy has been observed to prolong overall survival rate and temozolomide (TMZ), a promising chemotherapeutic agent for treating glioblastoma (GBM), possesses the most effective clinical activity at present, although drug resistance limits its clinical outcome. Growing evidence supports the concept that initial and recurrent GBM may derive from glioblastoma stem cells, which may be responsible for drug resistance. However, the molecular mechanisms underlying this resistance remain to be elucidated. In the present study, a TMZ­resistant GBM cell line, U251R, was developed and subsequently divided into two subpopulations according to the CD133 immunophenotype. No significant difference was identified in the expression of O6­methylguanine­DNA­methyltransferase (MGMT) between CD133+ U251R cells and CD133­ U251R cells, whereas the CD133+ cell population was more resistant to TMZ­induced growth inhibition and cell death. TMZ achieves its cytotoxic effect by inducing DNA lesions and p53 upregulated modulator of apoptosis (PUMA) is an essential mediator of DNA damage­induced apoptosis independently of p53 status. Therefore, whether PUMA effectively enhances growth suppression and induces apoptosis when combined with TMZ was investigated. Consequently, it was found that adenoviruses expressing wild­type­PUMA not only lead to the apoptosis of CD133+ U251R cells alone, but also significantly increase their sensitivity toward TMZ by elevating the Bcl­2­associated X protein/B­cell lymphoma­2 ratio without alterations in MGMT expression. Therefore, PUMA may be a suitable target for intervention to improve the therapeutic efficacy of TMZ.