Multifunctional Nano-Realgar Hydrogel for Enhanced Glioblastoma Synergistic Chemotherapy and Radiotherapy: A New Paradigm of an Old Drug.

Purpose: Realgar, as a kind of traditional mineral Chinese medicine, can inhibit multiple solid tumor growth and serve as an adjuvant drug in cancer therapy. However, the extremely low solubility and poor body absorptive capacity limit its application in clinical medicine. To overcome this therapeutic hurdle, realgar can here be fabricated into a nano-realgar hydrogel with enhanced chemotherapy and radiotherapy (RT) ability. Our objective is to evaluate the superior biocompatibility and anti-tumor activity of nano-realgar hydrogel. Methods: We have successfully synthesized nano-realgar quantum dots (QDs) coupling with 6-AN molecules (NRA QDs) and further encapsulated with a pH-sensitive dextran hydrogel carrier with hyaluronic acid coating (DEX-HA gel) to promote bioavailability, eventually forming a multifunctional nano-realgar hydrogel (NRA@DH Gel). To better investigate the tumor therapy efficiency of the NRA@DH Gel, we have established the mice in situ bearing GL261 brain glioblastoma as animal models assigned to receive intratumor injection of NRA@DH Gel. Results: The designed NRA@DH Gel as an antitumor drug can not only exert the prominent chemotherapy effect but also as a "sustainable reactive oxygen species (ROS) generator" can inhibit in the pentose phosphate pathway (PPP) metabolism and reduce the production of nicotinamide adenine dinucleotide phosphate (NADPH), thereby inhibiting the conversion of glutathione disulfide (GSSG) to glutathione (GSH), reducing GSH concentrations in tumor cells, triggering the accumulation of ROS, and finally enhancing the effectiveness of RT. Conclusion: Through the synergistic effect of chemotherapy and RT, NRA@DH Gel effectively inhibited the proliferation and migration of tumor cells, suppressed tumor growth, improved motor coordination, and prolonged survival in tumor-bearing mice. Our work aims to improve the NRA@DH Gel-mediated synergistic chemotherapy and RT will endow a "promising future" for the old drug in clinically comprehensive applications.

Perioperative and Short-Term Outcomes of Sinus Replacement and Conservative Repair for Aortic Root in Acute Type A Aortic Dissection: A Prospective Cohort Study.

Background: To compare outcomes between sinus replacement (SR) and conservative repair (CR) for dissected roots with normal size. Methods: From October 2018 to April 2021, a prospective cohort study was carried out. Patients were assigned to two groups (SR group and CR group) according to whether they underwent sinus replacement. Propensity score matching was applied to adjust preoperative variables and Kaplan-Meier method was used for survival analysis. Results: Three hundred and eighty-seven patients were enrolled. In the whole cohort, 18 patients (4.7%) died postoperatively. The operative mortality of SR group was comparable to CR group (3.2% vs. 6.0%, p = 0.192 before matching; 3.5% vs. 7.0%, p = 0.267 after matching) and the incidence of hemostasis management under restarted cardiopulmonary bypass for root bleeding was lower in SR group (1.6% vs. 7.0%, p = 0.002 before matching; 2.1% vs. 8.5%, p = 0.03 after matching). The median follow-up duration was 12 months. There were 3 reoperations in the CR group. The estimated cumulative event rate of reoperation was 1.1 % at 12 months and 1.6% at 24 months in CR group, with a trend of a lower rate in the SR group (log-rank p = 0.089 before matching, p = 0.075 after matching). There was one late death in each group. The estimated cumulative event rate of death was 3.8% at 12 months and 24 months in the SR group, and was 6.6% in the CR group with no significant difference (log-rank p = 0.218 before matching, p = 0.120 after matching). Aortic regurgitation significantly improved postoperatively and remained stable during follow-up. Conclusions: Sinus replacement is a simple, safe, and effective technique for repairing severely dissected sinus with a comparable time spent in operation and excellent immediate and short-term results. It had the advantages of eliminating false lumen and avoiding aortic root bleeding.

Comparison of Single Axillary vs. Dual Arterial Cannulation for Acute Type a Aortic Dissection: A Propensity Score Matching Analysis.

Background: The optimal arterial cannulation site for acute aortic dissection repair is unclear, especially for complex arch surgery. Axillary artery cannulation is widely accepted but adding femoral artery cannulation to it was considered to potentially improve perfusion and early outcomes. To clarify this point, a comparison of perioperative outcomes for these two different cannulation strategies was conducted regarding the pathological features of dissection. Methods: From January 2010 to December 2019, 927 consecutive patients underwent a total arch replacement combined with frozen elephant trunk for acute type A aortic dissection. The data, including detailed pathological features, were retrospectively collected and analyzed. Propensity score matching and multivariate logistic regression analysis were used for adjusting confounders that are potentially related to the outcome. Results: A total of 523 patients (56.3%) accepted a dual arterial cannulation (DAC group), and 406 patients (43.7%) received a single axillary artery cannulation (SAC group). In total, 388 pairs of patients were well-matched. Whether before or after adjusting the preoperative characteristics by matching, there were no significant differences in operative mortality (6.7 vs. 5.4%, P = 0.420 before matching; 5.4 vs. 5.4%, P = 1 after matching), stroke (6.7 vs. 5.4%, P = 0.420 before matching; 6.4 vs. 5.2%, P = 0.435 after matching), spinal cord injury (5 vs. 5.7%, P = 0.640 before matching; 5.4 vs. 5.7%, P = 1. After matching), and acute renal failure requiring dialysis (13.8 vs. 9.6%, P =0.050 before matching; 12.6 vs. 9.5%, P = 0.174) between the two groups. Dual arterial cannulation was not an independent protective factor of operative mortality (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.55-1.86), stroke (OR 1.17, 95% CI 0.65-2.11), spinal cord injury (OR 1.17, 95% CI 0.65-2.11), and acute renal failure requiring continuous renal replacement therapy (CRRT) (OR 1.24, 95% CI 0.78-1.97) after adjusting for confounding factors by multivariable logistic regression analysis. In the subgroup analysis, no advantage of dual arterial cannulation was found for a particular population. Conclusions: Single axillary artery cannulation was competent in the complex arch repair for acute aortic dissection, presenting with a satisfactory result as dual arterial cannulation. Adding femoral artery cannulation was necessary when a sufficient flow volume could not be achieved by axillary artery cannulation or when a lower limb malperfusion existed.

Comparison of the Metabolic Profiles in the Plasma and Urine Samples Between Autistic and Typically Developing Boys: A Preliminary Study.

Background: Autism spectrum disorder (ASD) is defined as a pervasive developmental disorder which is caused by genetic and environmental risk factors. Besides the core behavioral symptoms, accumulated results indicate children with ASD also share some metabolic abnormalities. Objectives: To analyze the comprehensive metabolic profiles in both of the first-morning urine and plasma samples collected from the same cohort of autistic boys. Methods: In this study, 30 autistic boys and 30 tightly matched healthy control (HC) boys (age range: 2.4~6.7 years) were recruited. First-morning urine and plasma samples were collected and the liquid chromatography-mass spectrometry (LC-MS) was applied to obtain the untargeted metabolic profiles. The acquired data were processed by multivariate analysis and the screened metabolites were grouped by metabolic pathway. Results: Different discriminating metabolites were found in plasma and urine samples. Notably, taurine and catechol levels were decreased in urine but increased in plasma in the same cohort of ASD children. Enriched pathway analysis revealed that perturbations in taurine and hypotaurine metabolism, phenylalanine metabolism, and arginine and proline metabolism could be found in both of the plasma and urine samples. Conclusion: These preliminary results suggest that a series of common metabolic perturbations exist in children with ASD, and confirmed the importance to have a comprehensive analysis of the metabolites in different biological samples to reveal the full picture of the complex metabolic patterns associated with ASD. Further targeted analyses are needed to validate these results in a larger cohort.

Safety and durability of single-stage type I hybrid total aortic arch repair for extensive aortic arch disease: early- and long-term clinical outcomes from a single center and our 10-year of experience.

BACKGROUND: Single-stage type I hybrid total aortic arch repair is a surgical treatment for extensive aortic arch disease, but the clinical outcomes were distinguishing. The purposes of this study were to share our experience and evaluate the perioperative safety and long-term durability. METHODS: Thirty-six patients who underwent single-stage type I hybrid total aortic arch repair in Fuwai Hospital between January 2010 and June 2020 were respectively reviewed. Early primary endpoint was defined as early composite adverse events, including mortality, multiple organ dysfunction syndrome (MODS), unplanned reoperation, stroke, paraplegia, acute renal failure (ARF) necessitating continuous renal replacement therapy (CRRT), respiratory failure and stents related complications. Long-term endpoints included late mortality, late aortic related reintervention and late adverse aortic events. When evaluating the early- and long-term outcomes, all patients were stratified into two subgroups by age (65 years). RESULTS: All patients acquired technical success. Early composite adverse events rate was 11.1% (4/36), in-hospital mortality was 8.3% (3/36). Average follow-up period was 48.0±35.3 months. Overall survival rate was 83.3% and 51.9% at 5 and 10 years respectively. Late aortic related reintervention occurred at one (3.0%, 1/33) patient and this patient died after reintervention. Overall freedom from adverse aortic events was 79.2% and 47.5% at 5 and 10 years respectively. Significant difference was not observed between the elderly and young subgroups, no matter in early- and long-term outcomes. CONCLUSIONS: Single-stage type I hybrid total aortic arch repair has achieved desirable outcomes in our center, which does not increase perioperative risk in the elderly patients, meanwhile, also acquire acceptable durability in the young patients. In conclusion, this surgery is a practical mini-invasive treatment for extensive aortic arch disease with strict and limited indications.

Wavelength-tunable all-fiber mode-locked laser based on supermode interference in a seven-core fiber.

A wavelength-tunable all-fiber mode-locked erbium-doped fiber laser has been proposed and realized by using a supermode interference filter (SMIF). The SMIF is fabricated by splicing a segment of seven-core fiber (SCF) to two standard single-mode fibers. Since two supermodes of the propagating light are excited in the SCF, the transmission spectrum of the SMIF shows a clean broadband comb-shape characteristic. By bending the SMIF in the proposed mode-locked laser, the output spectrum can be continuously tuned in a wavelength range up to 22 nm while keeping mode-locking operation. The self-starting laser produces 230 fs pulses with a spectral width of 14 nm.

Widely wavelength-tunable 2 µm Brillouin fiber laser incorporating a highly germania-doped fiber.

We present, for the first time to our knowledge, a wavelength-tunable 2 µm Brillouin fiber laser based on a homemade thulium-doped fiber laser pump and a segment of highly germania-doped fiber (HGDF). The laser wavelength can be continuously tuned over 110 nm from 1920 to 2030 nm with single frequency operation, and the linewidth is estimated to be less than 0.9 kHz at 1950 nm. Benefiting from the high nonlinearity and low loss of the HGDF, a low lasing threshold of 47 mW is also achieved.

[Efficacy and safety of intravenous recombinant human brain natriuretic peptide in patients with severe heart failure: a prospective multicenter clinical study].

OBJECTIVE: To explore the efficacy and safety of recombinant human brain natriuretic peptide (rhBNP) in the patients with severe heart failure (HF). METHODS: A prospective multicenter study was conducted. Patients whose age > 18 years old, and with the New York Heart Association (NYHA) cardiac function grade over III-IV, acute cardiac insufficiency and the acute exacerbation of chronic cardiac insufficiency admitted to intensive care unit/cardiovascular care unit (ICU/CCU) of 58 Hospitals in China were enrolled. On the basis of the conventional treatment, all patients would be given rhBNP (neo adjuvant) with a loading dose of 1.5 µg/kg for 3-5 minutes, and followed by a maintenance dose of 0.010-0.015 µg×kg-1×min-1 for 3-7 days. Before the treatment and 1, 3, 7 days after treatment, researchers detected indexes of cardiac and renal function, the levels of N-terminal B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), cardiac output (CO), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), urea nitrogen (BUN), serum creatinine (SCr), and urine output; the renal function index was re-evaluated at 30 days after administration, and the time entering ICU again, re-admission, cardiovascular events were recorded. RESULTS: 408 patients were enrolled, with 241 males and 167 females. Age range was 28-95 years, the average age was (63.0±15.8) years, and 50-70 years old accounted for 46.8%. Compared with the data before treatment, NT-proBNP, PCWP and CVP significantly decreased at 6 hours after treatment [NT-proBNP (µg×kg-1×min-1): 4 378.58±4 082.29 vs. 6 403.41±5 759.48, PCWP (mmHg, 1 mmHg = 0.133 kPa): 12.41±2.21 vs. 14.26±2.85 , CVP (mmHg): 10.63±2.62 vs. 11.45±3.45, all P < 0.05], and with the prolongation of injection, NT-proBNP, PCWP and CVP were gradually declined; CO 1 day after treatment (mL: 4.89±0.81 vs. 4.40±0.92) and LVEF 3 days after treatment (0.465±0.100 vs. 0.431±0.107) were significantly increased (both P < 0.05), and with the prolongation of injection, CO and LVEF were gradually increased. There were no obvious changes in BUN and SCr during the treatment, but 30 days after treatment, SCr was significantly lower than that pre-treatment (µmol/L: 110.98±47.40 vs. 132.62±75.60, P < 0.01). Compared with the data pre-treatment, urine output per hour was significantly increased at 3 hours after treatment (mL: 129.59±82.16 vs. 89.60±53.49, P = 0.000); urine output every 24 hours was significantly increased at day 1 and day 2 after administration (mL: 2 676.54±1 006.83, 2 678.74±975.97 vs. 2 150.36±283.76, both P < 0.01). In 7 days, the re-entry ICU rate was 2.7%, and the re-hospitalization rate was 2.88% within 30 days, re-cardiac failure rate was 1.43% in 30 days, and the overall fatality rate was 9.55% in 30 days. CONCLUSIONS: The rhBNP can significantly improve heart function in patients with HF. And, it has a certain effect on renal function. The rhBNP is effective and safe for the treatment of cardiac insufficiency.

Microchip dual-frequency laser with well-balanced intensity utilizing temperature control.

A continuous-wave microchip dual-frequency laser (DFL) with well balanced intensity was presented. In order to obtain such a balanced intensity distribution of the two frequency components, the DFL wavelengths were precisely tuned and spectrally matched with the emission cross section (ECS) spectrum of the gain medium by employing a temperature controller. Finally, when the heat sink temperature was controlled at -5.6°C, a 264 mW DFL signal was achieved with frequency separation at 67.52 GHz and intensity balance ratio (IBR) at 0.991.

Broadband mid-infrared fiber optical parametric oscillator based on a three-hole suspended-core chalcogenide fiber.

A mid-infrared fiber optical parametric oscillator is proposed and designed based on a three-hole As(2)S(5) suspended-core fiber (SCF). The eigenmodes of the SCF are depicted and the pump condition for single-mode operation is analyzed. The zero-dispersion wavelength is shifted to 2 µm by tuning the core diameter of the SCF. Using the degenerate four-wave mixing coupled-wave equations, a tuning range of the idler wavelength from 2 to 5 µm and a maximum conversion efficiency of 19% are numerically predicted in a 0.1-m-long SCF pumped by a 2.7 W thulium-doped fiber laser.

CW dual-frequency MOPA laser with frequency separation of 45 GHz.

A CW dual-frequency master oscillator power amplifier (MOPA) laser system with dozens of gigahertz (GHz) frequency separation is presented. The MOPA system consists of a monolithic microchip seed laser and a double-end pumped traveling wave power amplifier. The short length of seed laser cavity guarantees the seed signal with a large frequency separation (above 53 GHz) but low output power (below 247.8 mW). By adding a long and low-doped active medium laser amplifier stage, a significant increase in laser power and an improvement in beam quality are obtained. After fine temperature tuning of seed laser cavity for "spectra matching", a 2.40 W dual-frequency laser signal with 45 GHz frequency separation is achieved.

Optical logic gates based on electro-optic modulation with Sagnac interferometer.

In this work, we present a new structure to realize optical logic operation in a Sagnac interferometer with electro-optical modulation. In the scheme, we divide two counterpropagation signals in a Sagnac loop to two different arms with the electro-optical crystal by using two circulators. Lithium niobate materials whose electro-optical coefficient can be as large as 32.2×10(-12) m/V make up the arms of the waveguides. Using the transfer matrix of the fiber coupler, we analyze the propagation of signals in this system and obtain the transmission characteristic curves and the extinction ratio. The results indicate that this optical switching has a high extinction ratio of about 60 dB and an ultrafast response time of 2.036 ns. In addition, the results reveal that the change of the dephasing between the two input signals and the modification of the modulation voltage added to the electro-optical crystal leads to the change of the extinction ratio. We also conclude that, in cases of the dephasing of two initial input signals Δφ=0, we can obtain the various logical operations, such as the logical operations D=A¯·B, D=A·B¯, C=A+B, and D=A⊕B in ports C and D of the system by adjusting the modulation voltage. When Δφ≠0, we obtain the arithmetic operations D=A+B, C=A⊕B, D=A·B¯, and C=A¯·B in ports C and D. This study is significant for the design of all optical networks by adjusting the modulation voltage.

Hybrid total arch repair without deep hypothermic circulatory arrest for acute type A aortic dissection (R1).

OBJECTIVE: To investigate the surgical outcomes of hybrid total arch repair without deep hypothermic circulatory arrest for patients with acute Stanford type A aortic dissection. METHODS: Retrospective review of clinical data of patients with acute Stanford type A aortic dissection who underwent surgical repair at our institution between November 2009 and December 2011 identified 21 patients who underwent hybrid total arch repair without deep hypothermic circulatory arrest. The in-hospital and follow-up data were investigated. Postoperative serial computed tomography angiography was used to evaluate the fate of true and false lumen in arch and descending aorta. RESULTS: Mean follow-up was 13.8 months (range, 3 to 21 months). The 1- and 12-month survival rates (by Kaplan-Meier analysis) were 95.2% (95% confidence interval, 86.2%-100%) and 90.5% (95% confidence interval, 78.0%-100%), respectively. No endograft caudal migration occurred. One patient with type I endoleak was successfully resolved during operation. There was no late rupture or paraplegia. CONCLUSIONS: Hybrid total arch repair without deep hypothermic circulatory arrest offers a promising alternative to risk reduction of complications during the postoperative period and late adverse events resulting from false lumen enlargement in the arch and descending aorta.

Double-pumped multiwavelength fiber optical parametric oscillator based on a Sagnac loop filter.

We propose a double-pumped ring cavity multiwavelength fiber optical parametric oscillator (MW-FOPO) using a highly nonlinear dispersion-shifted fiber (HNL-DSF) as the gain medium and a polarization maintained fiber based Sagnac loop filter as the comblike filter. 22-wavelength lasing of the double-pumped MW-FOPO with a ripple less than ±2.5 dB and a wavelength spacing of about 0.8 nm in a wavelength range from 1541 nm to 1558 nm is experimentally demonstrated. We discussed the power stability of the multiwavelength lasing of the double-pumped MW-FOPO. A comparison of the output spectra between the double-pumped MW-FOPO and single-pumped MW-FOPO is also presented.

[Stented elephant trunk and femoral artery bypass grafting surgery for extended aneurysmal dilation of Stanford A aortic dissection or aortic aneurysm].

OBJECTIVES: To summarize the clinical experience of stented elephant trunk with femoral artery bypass grafting procedure to treat severe aneurysmal dilation of Stanford A aortic dissection or aortic aneurysm. To study the surgical indication and surgical strategy of chronic Stanford A aortic dissection and aneurysmal dilation, also to summarize the early follow-up results. METHODS: From February 2006 to November 2011, 19 patients with Stanford A aortic dissection or aortic aneurysm with extented aneurysmal dilation (megaaorta) received stented elephant trunk with femoral artery bypass grafting procedure. There were 3 acute cases and 16 chronic cases with 14 male patients and 5 female patients. Average age of this group was (42 ± 8) years and average body weight was (70 ± 15) kg. One patient was aortic aneurysm and all the other were Stanford A aortic dissection. Eight patients were Mafan's syndrome. Ascending aorta replacement or Bentall's operation was done first and total arch replacement and stented elephant trunk operation was done under deep hypothermia and circulatory arrest. After the patient was weaned from cardiopulmonary bypass, bypass from ascending aorta to femoral artery was done subcutaneously using the 10 mm graft in the same femoral incision. RESULTS: There was no operative mortality. One patient had chylothorax which recovered with medical treatment and one patient got paraplegia after surgery. The cardiopulmonary bypass time was (176 ± 42) minutes, aortic cross clamping time was (88 ± 25) minutes and deep hypothermia and low flow rate time was (23 ± 8) minutes. The blood pressure of the lower extremities were normal after operation. Follow-up time was (22 ± 19) months. All patients survived. False lumen closure rate at the stent level was 100%. CT scan at 3 to 6 months after operation showed no obvious dilation of the descending aorta. Two patient successfully received second stage operation of total (subtotal) thoracoabdominal aorta replacement. CONCLUSIONS: Stented elephant trunk and aorta to femoral artery bypass is a safe procedure to treat aortic dissection or aortic aneurysm with extended aneurysmal dilation. This procedure can effectively increase the blood supply of the lower extremities due to small true lumen of the descending aorta, and may decrease the speed of dilation of the false lumen. It is also a practical procedure to lay the foundation for the second stage operation of normothemia thoracoabdominal aorta replacement.

High sensitivity third-order autocorrelation measurement by intensity modulation and third harmonic detection.

We demonstrate a novel (to our knowledge) method for high sensitivity measurement of pulsed light at the telecommunication wavelength of 1558 nm using a GaAsP photomultiplier tube. By modulating the input power and analyzing the harmonic components, high sensitivity third-order autocorrelation is obtained in the wavelength and power regimes where a mixture of two-photon absorption and three-photon absorption in the photomultiplier tube is present.

[Diagnostic value of echocardiography for cardiac tumors in infancy and childhood].

OBJECTIVE: The present study was designed to evaluate the clinical manifestations, surgical findings, pathologic types and treatment of cardiac tumor and to analyze the echocardiographic characteristics of the cases. METHODS: Records of 19 patients with cardiac tumors confirmed by operations and pathology at Fuwai Cardiovascular Hospital in Beijing, China between Jan, 1983 and Dec, 2003 were reviewed. Clinical and echocardiographic data of all patients were analyzed. RESULTS: The median age of patients was 7 +/- 5 years, ranging from 5 months to 14 years. There were 8 male and 11 female cases. The surgical findings revealed that 57.9% (11 cases) of cardiac tumors were found in left heart, 36.8% (7 cases) in right heart, 5.3% (1 case) in two ventricles. The pathological study revealed that 17 cases (89.5%) were diagnosed as primary cardiac benign tumors including myxoma in 10 cases (52.6%), rhabdomyoma in 4 cases (21.1%), fibroma in 2 cases (10.5%) and lipoma in 1 case (5.3%). Two cases were diagnosed (10.5%) as cardiac malignant tumors including a primary cardiac rhabdomyosarcoma and a metastatic epithelioid sarcoma. By using echocardiography 11 cases were diagnosed as myxomas and rhabdomyoma (11/19, 57.9%), 8 cases were diagnosed as space occupying lesions of the heart or myxoma (8/19, 42.1%). CONCLUSIONS: Myxomas are the most common heart tumors seen in infancy and childhood, followed in frequency by rhabdomyomas, fibromas and lipomas. Surgery is recommended for patients with refractory and severe clinical symptoms.

Autotransfusion of shed mediastinal blood after open heart surgery.

OBJECTIVE: To determine the safety and effectiveness of autotransfusion of shed mediastinal blood after open heart surgery. METHODS: Sixty patients undergoing coronary artery bypass grafting (CABG) were selected randomly to receive either nonwashed shed mediastinal blood (Group 1, n = 30) or banked blood (Group 2, n = 30). Drainage and transfusion volume were determined after the operation. Hb, RBC, HCT and PLT were detected immediately before and after the operation, as well as 24 hours and 7 days after the operation. Data were analyzed using Fisher's exact test. A P < 0.05 was considered significant. RESULTS: There were no significant differences in Hb, HCT, PLT or length of cardiopulmonary bypass (CPB) (P > 0.05). In the two groups, no significant difference in the mean blood loss was observed during 24 hours after the operation (660 +/- 300 ml in Group 1 and 655 +/- 280 ml in Group 2, P > 0.05). In Group 1, the mean volume autotransfused was 280 +/- 160 ml, and the patients required 360 +/- 80 ml banked blood compared with 660 +/- 120 ml in Group 2. In other words, the banked blood requirement in Group 1 was 40% lower. CONCLUSIONS: Autotransfusion of shed mediastinal blood after an open heart operation is safe and effective.