Frequency tripled semiconductor disk laser with over 0.5 W ultraviolet output power.

Semiconductor disk lasers can produce high output power and good beam quality simultaneously. The high intracavity circulating power of about hundreds of watts, along with the flexibility of tailorable emitting wavelengths, make it an attractive light source for obtaining ultraviolet (UV) radiation from near-infrared lasers through nonlinear frequency conversion. This work reports a frequency tripled 327 nm semiconductor disk laser with record output power and wavelength tuning range by using a type-I phase-matched LiB3O5 (LBO) crystal and a type-I phase-matched ß-BaB2O4 (BBO) crystal as the frequency-doubling and -tripling crystals respectively. Thanks to the obviously larger nonlinear coefficient of the type-I phase-matched BBO compared to the commonly used type-II phase-matched LBO, as well as the small spot size specifically designed at the crystal location, the maximum output power of UV lasers reaches 538 mW, corresponding to an optical-to-optical conversion efficiency from pump to UV laser of about 1.14%. A wavelength tuning range of about 8.6 nm and good power stability with a standard deviation of about 0.94 are also achieved.

Mode-Locked Operation of High-Order Transverse Modes in a Vertical-External-Cavity Surface-Emitting Laser.

Understanding the mechanism of mode-locking in a laser with high-order transverse mode is important for achieving an ultrashort pulses train under more complicated conditions. So far, mode-locking with high-order transverse mode has not been reported in other lasers except the multimode fiber laser. This paper demonstrates robust mode-locking with high-order transverse mode in a Kerr-lens mode-locked vertical-external-cavity surface-emitting laser for the first time, to the best of our knowledge. While the longitudinal modes are locked, continuous mode-locking accompanied by high-order transverse mode up to TEM40 is observed. The threshold of the mode-locking is only a little bigger than that of the lasing. After the laser oscillation is built up, the mode-locked pulse train can be obtained almost immediately and maintained until the thermal rollover of the laser. Output powers of 717 mW under fundamental mode and 666 mW under high-order transverse mode are achieved with a 4.3 ps pulse duration and 1.1 GHz pulses repetition rate, and some phenomenological explanations to the related characteristics of the mode-locked operation of high-order transverse mode in the vertical-external-cavity surface-emitting laser are proposed.

108 m Underwater Wireless Optical Communication Using a 490 nm Blue VECSEL and an AOM.

Advanced light sources in the blue-green band are crucial for underwater wireless optical communication (UWOC) systems. Vertical-external-cavity surface-emitting lasers (VECSELs) can produce high output power and good beam quality, making them suitable for UWOC. This paper presents a 108 m distance UWOC based on a 100 mW 490 nm blue VECSEL and an acousto-optic modulator (AOM). The high-quality beam, which is near diffraction-limited, undergoes relatively small optical attenuation when using a conventional avalanche photodiode (APD) as the detector and employing 64-pulse position modulation (PPM). At the time-slot frequency of 50 MHz, the bit error rate (BER) of the UWOC was 2.7 × 10-5. This is the first reported AOM-based UWOC system with a transmission distance over 100 m. The estimated maximum transmission distance may be improved to about 180 m by fully utilizing the detection accuracy of the APD according to the measured attenuation coefficient of the blue VECSEL used. This type of UWOC system, composed of a high-beam-quality light source and a conventional detector, make it more closely suited to practical applications.

Narrow linewidth semiconductor multi-wavelength DFB laser array simultaneously self-injection locked to a single microring resonator.

We experimentally demonstrate a narrow linewidth semiconductor multi-wavelength distributed feedback (DFB) laser array by simultaneously injection locking each laser to the corresponding resonance of a single on-chip microring resonator. The white frequency noises of all the DFB lasers is reduced by more than 40 dB once they are simultaneously injection locked to a single microring resonator with a quality factor (Q-factor) of 2.38 million. Correspondingly, the instantaneous linewidths of all the DFB lasers are narrowed by a factor of 104. In addition, frequency combs originating from non-degenerate four-wave mixing (FWM) between the locked DFB lasers are also observed. Simultaneously injection locking multi-wavelength lasers to a single on-chip resonator may enable the possibilities of integrating a narrow-linewidth semiconductor laser array on a single chip and having multiple microcombs in a single resonator, which are in high demand in wavelength division multiplexing coherent optical communication systems and metrological applications.

Integration of metabolomics and proteomics reveals the underlying hepatotoxic mechanism of perfluorooctane sulfonate (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) in primary human hepatocytes.

Perfluorooctane sulfonate (PFOS) and its alternative 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) are ubiquitous in various environmental and human samples. They have been reported to have hepatotoxicity effects, but the potential mechanisms remain unclear. Herein, we integrated metabolomics and proteomics analysis to investigate the altered profiles in metabolite and protein levels in primary human hepatocytes (PHH) exposed to 6:2 Cl-PFESA and PFOS at human exposure relevant concentrations. Our results showed that 6:2 Cl-PFESA exhibited higher perturbation effects on cell viability, metabolome and proteome than PFOS. Integration of metabolomics and proteomics revealed that the alteration of glycerophospholipid metabolism was the critical pathway of 6:2 Cl-PFESA and PFOS-induced lipid metabolism disorder in primary human hepatocytes. Interestingly, 6:2 Cl-PFESA-induced cellular metabolic process disorder was associated with the cellular membrane-bounded signaling pathway, while PFOS was associated with the intracellular transport process. Moreover, the disruption effects of 6:2 Cl-PFESA were also involved in inositol phosphate metabolism and phosphatidylinositol signaling system. Overall, this study provided comprehensive insights into the hepatic lipid toxicity mechanisms of 6:2 Cl-PFESA and PFOS in human primary hepatocytes.

Ultra-narrow linewidth vertical-cavity surface-emitting laser based on external-cavity weak distributed feedback.

We demonstrate an ultra-narrow linewidth vertical-cavity surface-emitting laser (VCSEL) based on external-cavity weak distributed feedback from Rayleigh backscattering (RBS). A single longitudinal mode VCSEL with the linewidth as narrow as 435 Hz and a contrast of 55 dB are experimentally achieved by RBS fiber with a feedback level of RBS signal of -27.6 dB. By adjusting the thermal resistance of the VCSEL from 4.5 kΩ to 7.0 kΩ, the laser wavelength can be tuned from 1543.324 nm to 1542.06 nm with a linear tuning slope of -0.506 nm/kΩ. In the tuning process, the linewidth fluctuates in the range of 553-419 Hz.

Ultra-narrow-linewidth DFB laser array based on dual-cavity feedback.

Herein, we propose a structure to simultaneously compress the distributed feedback (DFB) laser array's linewidth. The proposed structure is meticulously designed to ensure single longitudinal mode operation via the interference phenomenon between the laser's primary cavity and the dual-cavity feedback. Given the weak feedback effect for each wavelength in the laser array, the proposed structure could realize the intense compression of the laser linewidths. The study results show that the side-mode suppression ratios of each DFB laser are over 40 dB, and the linewidths have been compressed from 3 MHz to ∼800 Hz. Thus, we believe the idea of an overall compression linewidth scheme in the present study can be adopted for integrated laser arrays.

Control of polarization switching in a VCSEL via resonant feedback from a whispering-gallery-mode cavity.

We report a method for flexibly switching the dominant polarization of a vertical-cavity surface-emitting laser (VCSEL) by introducing polarization-resolved resonant optical feedback from a whispering-gallery-mode (WGM) cavity to the lasing cavity. Switching between the originally dominant mode and a side mode is experimentally demonstrated under different bias currents once one of them is locked to the resonance mode of the WGM cavity. In addition to a controllable polarization state, the reported VCSEL also demonstrates a linewidth as narrow as tens of kilohertz, which is highly desirable for many applications, including high-speed data communication, light detection and ranging (lidar), and absorption spectroscopy.

Risk factors and characteristics of ischemic stroke in patients with immune thrombocytopenia: A retrospective cohort study.

OBJECTIVES: Previous research has found that patients with immune thrombocytopenia (ITP) have an increased risk of thrombosis, such as venous thromboembolism (VT), ischemic stroke (IS)/transient ischemic attack (TIA), and cardiovascular disease (CVD), but the risk factors for stroke in patients with ITP have yet to be determined. This study aims to determine the risk factors and characteristics of ischemic stroke in patients with ITP. MATERIALS AND METHODS: This study included adults with incident primary ITP diagnosed in a tertiary medical center between 2010 and 2020. The t-test and Mann-Whitney U test were used to compare the variables between IS and non-IS groups, and the multivariate logistic regression model was employed to evaluate correlations. RESULTS: The study enrolled 1824 individuals, of whom 17 (0.93%) had IS, and 138 (1:8) were randomly chosen from 1807 non-IS patients. Age was found to be substantially associated with stroke in the multivariate analysis (OR 1.07, 95% CI: 1.026-1.116; p = 0.001). We found no correlation between platelet counts (PLT) (OR 1.013, 95% CI: 0.995-1.033; p = 0.164), mean platelet volume (MPV), platelet larger cell ratio (P-LCR), prothrombin time (PT) (OR 1.455, 95% CI 0.979-2.164; p = 0.064), activated partial thromboplastin time (APTT), D-dimer, fibrinogen or antinuclear antibody (ANA) and stroke. Of 17 ITP-IS patients, 7 (53.8%) were cryptogenic, greater than the general IS population. Three (23.1%) of them had an embolic pattern. CONCLUSION: For ITP patients, age was a significant predictor of stroke. ITP-IS patients had a more cryptogenic origin, with some showing an embolic pattern.

Simultaneous self-injection locking of two VCSELs to a single whispering-gallery-mode microcavity.

Simultaneous self-injection locking of two vertical-cavity surface-emitting lasers (VCSELs) to a single whispering-gallery-mode (WGM) microcavity is experimentally demonstrated. The linewidths of the two VCSELs are compressed from 3.5 MHz and 5 MHz to 20.9 kHz and 24.1 kHz, which is on the same order of magnitude as that of locking each VCSEL to the microcavity separately. Moreover, the frequency noises of the two simultaneously locked VCSELs are suppressed by more than 60 dB below the offset frequency of 100 kHz compared to that of the free-running VCSELs. The method demonstrated here might be used in the multi-wavelength laser array with low phase and frequency noises, especially the VCSELs with the unique architecture of a two-dimensional array.

Narrow linewidth VCSEL based on resonant optical feedback from an on-chip microring add-drop filter.

We demonstrate a narrow linewidth vertical-cavity surface-emitting laser (VCSEL) by injecting resonant optical feedback into the lasing cavity. A single longitudinal mode VCSEL with a Lorentzian linewidth of 32.6 kHz and a purified optical spectrum is experimentally achieved by an on-chip microring add-drop filter with a quality factor of 1.36 million, where the feedback level is ${-}{47.77}\;{\rm{dB}}$. The frequency noise spectrum of the VCSEL demonstrates that the thermo-optic effect in the microring resonator can also stabilize the lasing frequency. A VCSEL with narrow linewidth and stable frequency provides a high-performance light source for a single VCSEL or VCSEL array-based application.

Binding and activity of bisphenol analogues to human peroxisome proliferator-activated receptor ß/δ.

Several studies have indicated metabolic function disruption effects of bisphenol analogues through peroxisome proliferator-activated receptor (PPAR) alpha and gamma pathways. In the present study, we found for the first time that PPARß/δ might be a novel cellular target of bisphenol analogues. By using the fluorescence competitive binding assay, we found seven bisphenol analogues could bind to PPARß/δ directly, among which tetrabromobisphenol A (TBBPA, 18.38-fold) and tetrachlorobisphenol A (TCBPA, 12.06-fold) exhibited stronger binding affinity than bisphenol A (BPA). In PPARß/δ-mediated luciferase reporter gene assay, the seven bisphenol analogues showed transcriptional activity toward PPARß/δ. Bisphenol AF (BPAF), bisphenol F (BPF) and bisphenol B (BPB) even showed higher transcriptional activity than BPA, while TBBPA and TCBPA showed comparable activity with BPA. Moreover, in human liver HL-7702 cells, the bisphenol analogues promoted the expression of two PPARß/δ target genes PDK4 and ANGPTL4. Molecular docking simulation indicated the binding potency of bisphenol analogues to PPARß/δ might depend on halogenation and hydrophobicity and the transcriptional activity might depend on their binding affinity and hydrogen bond interactions. Overall, the PPARß/δ pathway may provide a new mechanism for the metabolic function disruption of bisphenol analogues, and TBBPA and TCBPA might exert higher metabolic disruption effects than BPA via PPARß/δ pathway.

Lipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through Hsa-miRNA-532-3p/Acyl-CoA oxidase 1(ACOX1) pathway.

6:2 Chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an alternative product of perfluorooctane sulfonate (PFOS), has been frequently detected in various environmental, wildlife, and human samples. A few studies revealed the hepatotoxicity of 6:2 Cl-PFESA in animals, but the underlying toxicity mechanisms remain largely unknown. In this study, we investigated the lipid metabolism disorders of 6:2 Cl-PFESA through miRNA-gene interaction mode in Huh-7 cells. Our results showed that 6:2 Cl-PFESA significantly promoted cellular lipid accumulation and increased the expression of Acyl-CoA oxidase 1 (ACOX1), with the lowest effective concentrations (LOECs) of 3 µM. In silico analysis showed that hsa-miR-532-3p is a potential miRNA molecule targeting ACOX1. Fluorescent-based RNA electrophoretic mobility shift assay (FREMSA) and ACOX1-mediated luciferase reporter gene assays showed that hsa-miR-532-3p could directly bind to ACOX1 and inhibit its transcription activity. Besides, 6:2 Cl-PFESA decreased the expression of hsa-miR-532-3p in the PPARα-independent manner. Overexpression of hsa-miR-532-3p promoted 6:2 Cl-PFESA-induced cellular lipid accumulation and decreased the ACOX1 production in Huh-7 cells. Taken together, at human exposure relevant concentrations, 6:2 Cl-PFESA might upregulate the expression levels of ACOX1 through downregulating hsa-miR-532-3p, and disturbed lipid homeostasis in Huh-7 cells, which revealed a novel epigenetic mechanism of 6:2 Cl-PFESA-induced hepatic lipid toxic effects.

The effect of remote ischemic conditioning on blood coagulation function and cerebral blood flow in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To explore the effect of remote ischemic conditioning (RIC) on blood coagulation function and cerebral blood flow in patients with aneurysmal subarachnoid hemorrhage. PATIENTS AND METHODS: According to inclusion and exclusion standards, from October 2017 to June 2018, 30 consecutive patients of aneurysmal subarachnoid hemorrhage admitted to Intensive Care Unit, Department of Neurosurgery at Xuanwu Hospital, were given remote ischemic conditioning 5 times intervention to each patient within 7 days, and blood coagulation function testing, including prothrombin activity (PTA), prothrombin time (PT), activated partial prothrombin time (APTT), fibrinogen (Fib), D-dimer, and thromboelastogram (TEG, including R, K, Angle, MA, EPL, LY30, A, CI, G, and A30) were performed for each patient before and after the RIC intervention, as well as venous ultrasound monitoring before and after the RIC intervention for detection of deep vein thrombosis (DVT). Transcranial Doppler evaluation (TCD), including cerebral blood flow of bilateral ACA, MCA, PCA and intracranial segments of VA, as well as BA and the ratios of MCA cerebral blood flow/terminal segment of ipsilateral ICA cerebral blood flow, was performed before and after RIC intervention; and fresh infarction was evaluated by head CT or MRI recheck after RIC intervention. Thirty cases without RIC intervention of matched age, gender, and Hunt Hess grade with aneurysmal subarachnoid hemorrhage were selected to compare coagulation function and cerebral blood flow using TCD with RIC group. RESULTS: (1) Comparing the data before and after the RIC intervention, there was no significant difference for APTT, Fib, and D-dimer (P > 0.05), while PTA decreased and PT increased slightly after intervention as well as INR (P < 0.05) but all still in normal reference values. (2) Comparing the data before and after the RIC intervention, within TEG parameters, only the R value increased with significant difference (P < 0.05) but still in normal reference value, while K, Angle, MA, EPL, LY30, A, CI, G, and A30 had no significant difference (P > 0.05). (3) Comparing the data before and after the RIC intervention, DVT was not detected on the pressurized limbs of patients. (4) Comparing the data before and after the RIC intervention, the cerebral blood flow of bilateral MCA, L-ACA, L-VA, and BA increased (P < 0.05), while the elevation ranges were all in 25%, and the other parameters showed no significant difference. (5) Head CT or MRI showed no fresh cerebral infarction after the RIC intervention. (6) Compared with the group without RIC intervention, the coagulation function and the cerebral blood flow evaluated by TCD of the RIC group showed no statistical difference (P > 0.05) except APTT and D-dimer decreased after RIC but still in normal reference values. CONCLUSION: RIC showed no obvious effect on blood coagulation function and cerebral blood flow in patients with aneurysmal subarachnoid hemorrhage both after the intervention and compared with the non-intervention group. DVT was not detected on the pressurized limbs of patients and no fresh cerebral infarction was detected. This preliminary study confirmed the safety of RIC on blood coagulation function and cerebral blood flow in patients with aneurysmal subarachnoid hemorrhage, and the application of RIC on patients with aneurysmal subarachnoid hemorrhage needs further study to confirm and validate the safety and effectiveness.

Analysis of factors influencing hospital-acquired infection in postoperative patients with intracranial aneurysm.

BACKGROUND: Hospital-acquired infection (HAI) is a serious complication of neurosurgery. In recent years, the medical body has paid increasing attention to this issue. AIM: We investigated the status of HAIs in patients who had undergone surgery for intracranial aneurysms and analysed their risk factors. METHODS: A retrospective analysis was carried out on the medical records of 542 patients with intracranial aneurysms after they were admitted for neurosurgery at Xuanwu Hospital of Capital Medical University between January and December 2016. Cases studied were divided into an infection group and a control group. Logistic regression analysis of the data was carried out. FINDINGS: Of the 542 patients with intracranial aneurysms who underwent surgery, 77 HAIs occurred in 64 patients, with an infection prevalence of 11.8% and prevalence of infection cases of 14.2%. Logistic regression showed that an admission Glasgow Coma Scale (GCS) score of less than 8 points (odds ratio = 4.261, 95% confidence interval 1.102-16.476), hyperglycaemia (2.759, 1.159-6.564), hypothermia treatment (6.557, 2.244-19.159), and central venous catheterisation (CVC) (8.853, 2.860-27.398) were independent risk factors for HAIs in patients with intracranial aneurysm who underwent surgery. CONCLUSION: Being comatose upon hospital admission, having hyperglycaemia or hypothermia, and indwelling CVC are major risk factors for HAIs in patients undergoing surgery for intracranial aneurysms.

Role of Decompressive Craniectomy in the Treatment of Malignant Cerebral Venous Sinus Thrombosis: A Single Center Consecutive Case Series Study in China.

OBJECTIVE: Patients with cerebral venous sinus thrombosis (CVST) may die during the acute phase due to increased intracranial pressure and cerebral herniation. The purpose of this study was to assess the role of decompressive craniectomy in the treatment of patients with malignant CVST. METHODS: Patients who underwent decompressive craniectomy and were consequently admitted to the Critical Care Unit, Department of Neurosurgery, at Capital Medical University Xuanwu Hospital from March 2010 to January 2021 were retrospectively examined with follow-up data at 12 months. RESULTS: In total, 14 cases were reviewed, including 9 female and 5 male patients, aged 23-63 years (42.7 ± 12.3 years). Prior to surgery, all patients had a GCS score <9. 6 patients had a unilateral dilated pupil, while 4 patients had bilateral dilated pupils. According to the head computed tomography (CT), all patients had hemorrhagic infarction, and the median midline shift was 9.5 mm before surgery. Thirteen patients underwent unilateral decompressive craniectomy, and 1 patient underwent bilateral decompressive craniectomy, among whom, 9 patients underwent hematoma evacuation. Within 3 weeks of surgery, 3 cases (21.43%) resulted in death, with 2 patients dying from progressive intracranial hypertension and 1 from acute respiratory distress syndrome (ARDS). Eleven patients (78.57%) survived after surgery, of whom 4 (28.57%) patients recovered without disability at 12-month follow-up (mRS 0-1), 2 (14.29%) patients had moderate disability (mRS 2-3), and 5 (35.71%) patients had severe disability (mRS 4-5). CONCLUSIONS: Emergent decompressive craniectomy may provide a chance for survival and enable patients with malignant CVST to achieve an acceptable quality of life (QOL).

Impact of immediate postrecanalization cooling on outcome in acute ischemic stroke patients with a large ischemic core: prospective cohort study.

BACKGROUND: Patients with large acute ischemic strokes (AIS) often have a poor prognosis despite successful recanalization due to multiple factors including reperfusion injury. The authors aim to describe our preliminary experience of endovascular cooling in patients with a large AIS after recanalization. METHODS: From January 2021 to July 2022, AIS patients presenting with large infarcts (defined as ASPECTS ≤5 on noncontrast CT or ischemic core ≥50 ml on CT perfusion) who achieved successful recanalization after endovascular treatment were analyzed in a prospective registry. Patients were divided into targeted temperature management (TTM) and non-TTM group. Patients in the TTM group received systemic cooling with a targeted core temperature of 33° for at least 48 h. The primary outcome is 90-day favorable outcome [modified Rankin Scale (mRS) 0-2]. The secondary outcomes are 90-day good outcome (mRS 0-3), mortality, intracranial hemorrhage and malignant cerebral edema within 7 days or at discharge. RESULTS: Forty-four AIS patients were recruited (15 cases in the TTM group and 29 cases in the non-TTM group). The median Alberta Stroke Program Early CT Score (ASPECTS) was 3 (2-5). The median time for hypothermia duration was 84 (71.5-147.6) h. The TTM group had a numerically higher proportion of 90-day favorable outcomes than the non-TTM group (46.7 vs. 27.6%, P=0.210), and no significant difference were found regarding secondary outcomes (all P>0.05). The TTM group had a numerically higher rates of pneumonia (66.7 vs. 58.6%, P=0.604) and deep vein thrombosis (33.3 vs. 13.8%, P=0.138). Shivering occurred in 4/15 (26.7%) of the TTM patients and in none of the non-TTM patients (P=0.009). CONCLUSIONS: Postrecanalization cooling is feasible in patients with a large ischemic core. Future randomized clinical trials are warranted to validate its efficacy.

Intravenous delivery of adeno-associated viral vector serotype 9 mediates effective gene expression in ischemic stroke lesion and brain angiogenic foci.

BACKGROUND AND PURPOSE: Adeno-associated viral vector (AAV) is a powerful tool for delivering genes to treat brain diseases. Intravenous delivery of a self-complementary but not single-stranded AAV9 (ssAAV9) mediates robust gene expression in the adult brain. We tested if ssAAV9 effectively mediates gene expression in the ischemic stroke lesion and angiogenic foci. METHODS: Focal ischemic stroke was induced by permanent occlusion of the left middle cerebral artery (MCAO) and focal angiogenesis was induced by injecting an AAV expressing vascular endothelial growth factor (AAV-VEGF) into the basal ganglia. ssAAV vectors that have cytomegalovirus (CMV) promoter driving (AAV-CMVLacZ) or hypoxia response elements controlling (AAV-H9LacZ) LacZ expression were packaged in AAV9 or AAV1 capsid and injected into mice through the jugular vein 1 hour after MCAO or 4 weeks after the induction of angiogenesis. LacZ gene expression was analyzed in the brain and other organs 5 days after LacZ vector injection. RESULTS: LacZ expression was detected in the peri-infarct region of AAV9-CMVLacZ and AAV9-H9LacZ-injected MCAO mice and the brain angiogenic foci of AAV9-CMVLacZ-injected mice. Minimum LacZ expression was detected in the brain of AAV1-CMVLacZ-injected mice. Robust LacZ expression was found in the liver and heart of AAV-CMVLacZ-injected mice, but not in AAV9-H9LacZ-injected mice. CONCLUSIONS: ssAAV9 could be a useful tool to deliver therapeutic genes to the ischemic stroke lesion or brain angiogenic foci.

Human health risk assessment of 6:2 Cl-PFESA through quantitative in vitro to in vivo extrapolation by integrating cell-based assays, an epigenetic key event, and physiologically based pharmacokinetic modeling.

Human health risk assessment of chemicals is essential but often relies on time-consuming and animal and labor-extensive procedures. Here, we develop a population-based, quantitative in vitro to in vivo extrapolation (QIVIVE) approach which depended on cellular effects monitored by in vitro assays, considered chemical internal concentration determined by LC-MS/MS, extrapolated into in vivo target tissue concentration through physiologically based pharmacokinetic (PBPK) modelling, and assessed populational health risk using in silico modelling. By applying this QIVIVE approach to 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), as a representative of the emerging pollutants, we find that 6:2 Cl-PFESA disturbed lipid homeostasis in HepG2 cells through enhancement of lipid accumulation and fatty acid ß-oxidation, during which miR-93-5p served as a key event towards toxicity and thus, could serve as an efficient toxicity marker for risk assessment; further, the disruption potency of lipid homeostasis of 6:2 Cl-PFESA for the most of studied populations in China might be of moderate concern. Together, our approach improved the reliability of QIVIVE during human health risk assessment, which can readily be used for other chemicals.

Randomized controlled trial of symptomatic middle cerebral artery stenosis: endovascular versus medical therapy in a Chinese population.

BACKGROUND AND PURPOSE: To investigate the efficacy and safety of percutaneous transluminal angioplasty and stenting (PTAS) for symptomatic middle cerebral artery stenosis compared with standard medical treatment in a low-risk Chinese population. METHODS: A prospective, randomized, controlled, single-center clinical trial was conducted comparing PTAS with medical treatment for symptomatic middle cerebral artery stenosis (≥70%). Patients were enrolled according to 1:1 enroll ratio (PTAS: medical). The PTAS group received stenting or balloon angioplasty, whereas the medical treatment group received standard medical treatment (aspirin 100mg plus clopidogrel 75 mg/d), and all the patients were under strict control of the risk factors. The end point events were any kind of ipsilateral stroke or transient ischemic attack, or death from any origin during 1-year follow-up. RESULTS: The enrollment was stopped after 70 patients were enrolled from August 2007 to December 2010, with a 30-day rate of end point events of 8.3% versus 5.9% (P=0.69) for PTAS and medical group, respectively, and 1-year rate of end point events of 19.4% versus 17.6% (P=0.85), respectively. There was no significant difference in baseline characteristics between the 2 groups. The mean follow-up time, which was ongoing, was 9.9±3.9 and 9.7±4.4 months, respectively. Among the risk factors, hypertension was the independent related to the outcome (P=0.015). CONCLUSIONS: This study showed that endovascular treatment is as safe but not better than medical treatment for symptomatic middle cerebral artery stenosis in a low-risk Chinese population. History of hypertension increases the risk of recurrent ischemic events.