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Background: Liver metastasis is an important cause of death in patients with colorectal cancer (CRC). Increasing evidence indicates that microRNAs (miRNAs) are involved in the pathogenesis of colorectal cancer liver metastasis (CRLM). This study is aimed at exploring the potential miRNA-mRNA regulatory network., Methods: From the GEO database, we downloaded the microarray datasets GSE56350 and GSE73178. GEO2R was used to conduct differentially expressed miRNAs (DEMs) between CRC and CRLM using the GEO2R tool. Then, GO and KEGG pathway analysis for differentially expressed genes (DEGs) performed via DAVID. A protein-protein interaction (PPI) network was constructed by the STRING and identified by Cytoscape. Hub genes were identified by miRNA-mRNA network. Finally, the expression of the hub gene expression was assessed in the GSE81558., Results: The four DEMs (hsa-miR-204-5p, hsa-miR-122-5p, hsa-miR-95-3p, and hsa-miR-552-3p) were identified as common DEMs in GSE56350 and GSE73178 datasets. The SP1 was likely to adjust the upregulated DEMs; however, the YY1 could regulate both the upregulated and downregulated DEMs. A total of 3925 genes (3447 upregulated DEM genes and 478 downregulated DEM genes) were screened. These predicted genes were mainly linked to Platinum drug resistance, Cellular senescence, and ErbB signaling pathway. Through the gene network construction, most of the hub genes were found to be modulated by hsa-miR-204-5p, hsa-miR-122-5p, hsa-miR-95-3p, and hsa-miR-552-3p. Among the top 20 hub genes, the expression of CREB1, RHOA, and EGFR was significantly different in the GSE81558 dataset., Conclusion: In this study, miRNA-mRNA networks in CRLM were screened between CRC patients and CRLM patients to provide a new method to predict for the pathogenesis and development of CRC., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2023 Si-ming Zhang et al.)

In this article, we report a high power quantum cascade laser (QCL) at λ∼7.4 µm with a broad tuning range. By carefully designing and optimizing the active region and waveguide structure, a continuous-wave (CW) output power up to 1.36 W and 0.5 W is achieved at 293 K and 373 K which shows the excellent temperature stability. A high wall-plug efficiency (WPE) of 8% and 13.6% in CW and pulsed mode at 293 K are demonstrated. The laser shows a characteristic temperature T 0 of 224 K and T 1 of 381 K over a temperature range from 283 K to 373 K. In addition, a far field of pure zero order transverse mode and a fairly wide external cavity (EC) tuning range (280 cm -1 ) from 6.54 µm to 8 µm are achieved in pulsed operation. In addition, an EC single mode output power of 226 mW is obtained under CW operation at 293K.

Insufficient nitrogen removal is a key challenge for the application of an osmotic membrane bioreactor (OMBR). The integration of a bioelectrochemical system (BES) and an OMBR was constructed to enhance nitrogen removal.To optimize the operation, five aeration intensities and three draw solutes (DSs) were applied in the proposed system. The results showed that the proposed system obtained the highest nitrogen removal efficiency of 77.36 ± 3.55 % with an aeration intensity of 0.6 L/min, and it was further increased to 94.99 ± 2.83 % and 99.92 ± 0.14 %with the NaOAc DS and the glucose DS, respectively.The analysis ofmetabolic pathways implied that species interactions existed,andthe following different mechanisms of enhanced nitrogen removal for the two organic DSs were proposed. The growth of denitrifying bacteria was enhanced by using reverse-fluxed organic NaOAc DS as a carbon source;glucoseDS stimulated electron transfer system activity to accelerate denitrification., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A second-order distributed feedback interband cascade laser emitting at 3.25 µm was designed, grown, and fabricated. By coherent epitaxy of a GaSb cap layer instead of the conventional thin InAs cap on top of the laser structure, a high-quality surface grating was made of GaSb and gold. Enough coupling strength and a significant inter-modal loss difference were predicted according to the simulation within the framework of couple-wave theory. Lasers having 2-mm-long cavities and 4.5-µm-wide ridges with high-/anti-reflection coatings were fabricated. The continuous-wave threshold current and maximum single-mode output power were 60 mA and 24 mW at 20°C, respectively. The output power of 5 mW was still kept at 55°C. Continuous tuning free from mode hopping and high single-mode suppression ratios (>20 dB) were realized at all injection currents and heat-sink temperatures, covering a spectral range of over 20 cm -1 .

A Gram-stain-negative, strictly aerobic, non-motile, rod-shaped bacterium, capable of producing poly-β-hydroxyalkanoate, designated DP3N28-2 T , was isolated from the sediment collected from Daya Bay, Guangdong, PR China. Optimal growth occurred at 37-40 °C, pH 6.0 and in the presence of 4 % NaCl. The 16S rRNA gene sequences analysis revealed that DP3N28-2 T showed highest similarities with Mameliella alba DSM 23384 T (98.3 %), Antarctobacter jejuensis 13-2-B6 T (97.2 %), Antarctobacter heliothermu s El-219 T (96.8 %), Maliponia aquimaris MM-10 T (96.7 %), Ponticoccus litoralis CL-GR66 T (96.4 %) and Aquicoccus porphyridii L1 8-17 T (96.1 %). The predominant fatty acids (>10 %) were summed feature 8 (C 18 : 1 ω6 c and/or C 18 : 1 ω7 c ; 72.1 %) and C 16 : 0 (11.0 %). The polar lipids contain phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylglycerol, one aminophosphlipid, one phospholipid and three unidentified lipids. The respiratory quinone was Q-10. The DNA G+C content was 63.0 mol% (data from the genome sequence). The estimated genome size was 5.12 Mb. The average nucleotide identity values between the DP3N28-2 T genome and the genome of M. alba was 81.1 %, while the digital DNA-DNA hybridization value was 23.4 %. The phenotypic, genotypic and chemotaxonomic differences between DP3N28-2 T and its phylogenetic relatives indicates that DP3N28-2 T should be regarded as representing a novel species of the genus Mameliella , for which the name Mameliella sediminis sp. nov. is proposed. The type strain is DP3N28-2 T (=MCCC 1K06218 T =KCTC 82804 T ).

Objective: Systematically assessing the safety and effectiveness of spraying rhubarb powder solution under gastroscope for the treatment of acute non-varicose upper gastrointestinal bleeding, and confirmation for further clinical research and application., Methods: We searched the following databases up till November 2019: PubMed, the Cochrane Library, EMBASE, CNKI, WanFang Data, VIP and SinoMed. Randomized controlled trials (RCTs) were used to compare the curative effect of spraying rhubarb powder solution with other drugs under gastroscope for the treatment of acute non-varicose upper gastrointestinal bleeding., Results: Out of 171 articles, 14 RCTs involving 1493 patients were included. All control groups included in the RCTs were treated with norepinephrine solution. The hemostatic effect of spraying rhubarb powder solution under gastroscope was examined for 24 h at high concentration (0.1 g/mL). The hemostatic effect at higher conc. (0.1 g/mL) found far more better than low conc.(RR = 1.48;95 %CI:1.25,1.75;P﹤0.00001) (0.03 g/mL)as homeostatic effect at low conc.is same that of norepinephrine solution (RR = 1.02;95 %CI:0.94,1.10;P = 0.62). Moreover within 48 h, rhubarb powder solution with 0.1 g/mL or 0.15 g/mL conc. have of significantly higher hemostatic effects than norepinephrine solution (RR = 1.18;95 % CI: 1.08, 1.30;P = 0.0003). Occurrence of rebleeding event within 48 h after successful hemostasis (RR = 0.42;95 %CI:0.24,0.74;P = 0.003) reduced exceptionally. After that the hemostatic effect of rhubarb powder solution with 0.1 g/mL conc.examined within 72 h again exhibited significant improvement than norepinephrine solution (RR = 1.19;95 %CI:1.12,1.26;P < 0.00001). On par with immediate hemostasis time, rhubarb powder solution took unprecedented less time than norepinephrine solution;(MD=-5.56S;95 %CI:-6.16, -4.95;P﹤0.00001). Additionally, the adverse reaction produced by rhubarb powder solution is much lower than norepinephrine solution (RR = 0.22;95 %CI:0.11,0.42;P < 0.00001)., Conclusions: According to meta-analysis, Spraying rhubarb powder solution under gastroscope in the treatment of acute non-varicose upper gastrointestinal bleeding is superior to norepinephrine solution in improving hemostasis effect. Shortening immediate hemostasis time and reducing rebleeding,and is safe to use. Based on the results of this study, physicians can treat patients with acute non-varicose upper gastrointestinal bleeding by spraying rhubarb powder solution under gastroscope according to the patients' condition.However, the sample size included in this study is small and of substandard quality qu, and a large sample size clinical trial with strict design and normative report is needed to verify the safety and efficacy of rhubarb powder solution under gastroscope for acute non-varicose upper gastrointestinal bleeding., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Toxoplasma gondii severely threaten the health of immunocompromised patients and pregnant women as this parasite can cause several disease, including brain and eye disease. Current treatment for toxoplasmosis commonly have high cytotoxic side effects on host and require long durations ranging from one week to more than one year. The regiments lack efficacy to eradicate T. gondii tissue cysts to cure chromic infection results in the needs for long treatment and relapsing disease. In addition, there has not been approved drugs for treating the pregnant women infected by T. gondii. Moreover, Toxoplasma vaccine researches face a wide variety of challenges. Developing high efficient and low toxic agents against T. gondii is urgent and important. Over the last decade, tremendous progress have been made in identifying and developing novel compounds for the treatment of toxoplasmosis. This review summarized and discussed recent advances between 2009 and 2019 in exploring effective agents against T. gondii from five aspects of drug discovery., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

In this paper, an anomalous spectral data of distributed Bragg reflector (DBR) quantum cascade lasers (QCLs) emitting around 7.6 μm is presented. The two-section DBR lasers, consisting of a gain section and an unpumped Bragg reflector, display an output power above 0.6 W in continuous wave (CW) mode at room temperature. The anomalous spectral data is defined as a longitudinal mode which moves toward shorter wavelengths with increasing temperature or injection current, which is unexpected. Although the longer wavelength modes are expected to start lasing when raising device temperature or injection current, occasional mode hops to a shorter wavelength are seen. These anomalous mode transitions are explained by means of modal analysis. The thermal-induced change of the refractive index implied by an increase in the temperature or injection current yields nearly periodic transitions between cavity modes.

Objective: The purpose of the present study was to explore the characteristics and differentiation of somatic cells in vitro undergoing a low pH treatment, so as to provide new therapeutic strategies for treating sensorineural hearing loss. Method: The human mature somatic cells were selected as the target cells, and the cells were treated with different pH values to observe the cell morphology. The cell characteristics were identified from alkaline phosphatase (AKP) activity, immunohistochemical staining and molecular biology, and the most suitable pH value was selected. In addition, a mouse model of the cochlear lesion was constructed using bilirubin. Subsequently, the characteristics and therapeutic effect of somatic cells undergoing low pH treatment were examined by morphology, AKP activity, immunofluorescence assay and Q-PCR. Result: The cell growth of the experimental group was significantly better than those in the control group. The activity of AKP in the experimental group was higher than that in the control group. The expression of Nanog and Oct4 was both positive in the two groups. When the cells were changed to neurobasol medium, the marker of Nestin was positive. Conclusion: The human somatic cells undergoing a low pH treatment showed the similar characteristics as those of induced pluripotent stem (iPS) cells; although the functions and therapeutic effect of these altered human somatic cells need to be further studied., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

High-power, low-threshold stable single-mode operation buried distributed feedback quantum cascade laser by incorporating sampled grating emitting at λ ~ 4.87 μm is demonstrated. The high continuous wave (CW) output power of 948 mW and 649 mW for a 6-mm and 4-mm cavity length is obtained at 20 °C, respectively, which benefits from the optimized optical field distribution of sampled grating. The single-mode yields of the devices are obviously enhanced by controlling cleaved positions of the two end facets precisely. As a result, stable single-mode emission and mode tuning linearly without any mode hopping of devices are obtained under the different heat sink temperatures or high injection currents.

A quantum cascade laser emitting at λ∼8.5  μm based on the excited-state injection is presented. The operating voltage is reduced for a low-voltage defect in the excited-state design, compared with the conventional ground-state injection design. The threshold voltage and voltage defect are as low as 6.3 V and 54 mV for a 30-stage active region, respectively. Devices were fabricated through standard buried-heterostructure processing to decrease the heat accumulation. A continuous-wave optical power of 340 mW is obtained at 283 K with a threshold current density of 2.7  kA/cm 2 . Such a design has the potential to further improve the wall plug efficiency for increased voltage efficiency.

Power scaling in broad area quantum cascade laser (QCL) usually leads to the deterioration of the beam quality with an emission of multiple lobes far-field pattern. In this letter, we demonstrate a tapered QCL array integrated with Talbot cavity at one side of the array. Fundamental supermode operation is achieved in the arrays with taper straight-end connected to the Talbot cavity. Lateral far-field of the fundamental supermode shows a near diffraction limited beam divergence of 2.7 ° . The output power of a five-element array is about three times as high as a single-ridge laser with an emission wavelength of around 4.8 μm. However, arrays with the taper-end connected to the Talbot cavity always show a high-order supermode operation whatever Talbot cavity length is.

Aims: To evaluate the evidence of the effectiveness and safety of Chinese herbal medicine skin-patches for patients with acute gouty arthritis., Background: Acute gouty arthritis is a problem that can limit the level of activity and impair the quality of life. In China, many clinical studies have demonstrated that skin-patches of Chinese herbal medicines benefit patients with acute gouty arthritis. However, the reported clinical effects vary., Design: A systematic review and meta-analysis of randomized controlled trials., Data Sources: Three English databases including CENTRAL (1993 to February 2017), PubMed (1966 to February 2017) and EMBASE (1974 to February 2017) and four Chinese databases including Chinese National Knowledge Infrastructure, Chinese VIP Information, SinoMed and Wanfang (all, 1949 - February 2017) were searched. Randomized controlled trials that compared skin-patches of Chinese herbal medicine with or without conventional treatments to conventional treatments, no treatment or a placebo treatment for patients with acute gouty arthritis were included., Review Methods: We conducted a systematic review and meta-analysis following the Cochrane process. Two authors selected the studies, extracted the data and evaluated the risk of bias of the included trials., Results: Nineteen studies met our inclusion criteria. After synthesizing the data, the results showed that skin-patches of CHM combined with Western medicine seemed to be more effective than Western medicine alone for pain relief in patients with acute gouty arthritis and had fewer adverse events., Conclusion: Due to the quality of the data, larger and more rigorously designed clinical trials with proper outcome measures are necessary., (© 2018 The Authors. Journal of Advanced Nursing Published by John Wiley & Sons Ltd.)

In this work, quantum cascade lasers (QCLs) based on strain compensation combined with two-phonon resonance design are presented. Distributed feedback (DFB) laser emitting at ~ 4.76 μm was fabricated through a standard buried first-order grating and buried heterostructure (BH) processing. Stable single-mode emission is achieved under all injection currents and temperature conditions without any mode hop by the optimized antireflection (AR) coating on the front facet. The AR coating consists of a double layer dielectric of Al 2 O 3 and Ge. For a 2-mm laser cavity, the maximum output power of the AR-coated DFB-QCL was more than 170 mW at 20 °C with a high wall-plug efficiency (WPE) of 4.7% in a continuous-wave (CW) mode.

Very low power-consumption distributed feedback (DFB) quantum cascade lasers (QCLs) at the wavelength around 4.9 μm were fabricated by conventional process without lateral regrowth of InP:Fe or using sidewall grating. Benefitted from the optimized materials and low waveguide loss, very low threshold current density of 0.5 kA/cm 2 was obtained for a device with cavity length of 2 mm. Combined with the partial-high-reflection coating, the 1-mm-long DFB QCL achieved low power-consumption continuous wave (CW) operation up to 105 °C. The CW threshold power-consumptions were 0.72 and 0.78 W at 15 and 25 °C, respectively. The maximum CW output power was over 110 mW at 15 °C and still more than 35 mW at 105 °C. At 15 °C, wall-plug efficiency of 5.5% and slope efficiency of 1.8 W/A were deduced, which were very high for low power-consumption DFB QCLs.

In the present work, an ultra-low power consumption substrate-emitting distributed feedback (DFB) quantum cascade laser (QCL) was developed. The continuous-wave (CW) threshold power dissipation is reduced to 0.43 W at 25 °C by shortening the cavity length to 0.5 mm and depositing high-reflectivity (HR) coating on both facets. As far as we know, this is the recorded threshold power dissipation of QCLs in the same conditions. Single-mode emission was achieved by employing a buried second-order grating. Mode-hop free emission can be observed within a wide temperature range from 15 to 105 °C in CW mode. The divergence angles are 22.5 o and 1.94 o in the ridge-width direction and cavity-length direction, respectively. The maximum optical power in CW operation was 2.4 mW at 25 °C, which is sufficient to spectroscopy applications.

We demonstrate a quantum cascade laser with active regions consisting of InAs quantum dots deposited on GaAs buffer layers that are embedded in InGaAs wells confined by InAlAs barriers. Continuous wave room temperature lasing at the wavelength of 7.2 μm has been demonstrated with the threshold current density as low as 1.89 kA/cm 2 , while in pulsed operational mode lasing at temperatures as high as 110 °C had been observed. A phenomenological theory explaining the improved performance due to weak localization of states had been formulated.

We demonstrate a quantum dash quantum cascade photodetector (QDash-QCD) by incorporating self-assembled InAs quantum dashes into the active region of a long wave infrared QCD. Sensitive photoresponse to normal incident light at 10 μm was observed, which is attributed to the intersubband (ISB) transitions in the quantum well/quantum dash (QW/QDash) hybrid absorption region and the following transfer of excited electrons on the extraction stair-like quantum levels separated by LO-phonon energy. The high density InAs quantum dashes were formed in the Stranski-Krastanow mode and stair-like levels were formed by a lattice matched InGaAs/InAlAs superlattice. A stable responsivity from 5 mA/W at 77 K to 3 mA/W at as high as 190 K was observed, which makes the QDash-QCD promising in high temperature operation.

The design, fabrication, and characterization of a polarization-dependent normal incident quantum cascade detector coupled via complementary split-ring metamaterial resonators in the infrared regime are presented. The metamaterial structure is designed through three-dimensional finite-difference time-domain method and fabricated on the top metal contact, which forms a double-metal waveguide together with the metallic ground plane. With normal incidence, significant enhancements of photocurrent response are obtained at the metamaterial resonances compared with the 45° polished edge coupling device. The photocurrent response enhancements exhibit clearly polarization dependence, and the largest response enhancement factor of 165% is gained for the incident light polarized parallel to the split-ring gap.

We demonstrate a surface-emitting quantum cascade laser (QCL) based on second-order buried distributed feedback/distributed Bragg reflector (DFB/DBR) gratings for feedback and outcoupling. The grating fabricated beneath the waveguide was found to fundamentally favor lasing in symmetric mode either through analysis or experiment. Single-lobe far-field radiation pattern with full width at half maximum (FWHM) of 0.18° was obtained along the cavity-length direction. Besides, the buried DFB/DBR grating structure successfully provided an efficient vertical outcoupling mechanism with low optical losses, which manages to achieve a high surface outcouping efficiency of 46% in continuous-wave (CW) operation and 60% in pulsed operation at room temperature. Single-mode emission with a side-mode suppression ratio (SMSR) about 25 dB was continuously tunable by heat sink temperature or injection current. Our work contributes to the realization of high efficiency surface-emitting devices with high far-field beam quality that are significantly needed in many application fields.

Objective: To assess the beneficial and adverse effects of Wendan Decoction (温胆汤, WDD) for the treatment of schizophrenia., Methods: Five electronic databases were searched until May 2014, including the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the Chinese Scientist Journal Database, PubMed, and the Cochrane Central Register of Controlled Trials in the Cochrane Library. The randomized controlled trials (RCTs) testing WDD against placebo, antipsychotic drugs, or WDD combined with antipsychotic drugs against antipsychotic drugs alone were included. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards., Results: Thirteen RCTs (involving 1,174 patients) were included and the methodological quality was evaluated as generally low. The pooled results showed that WDD combined with antipsychotic drugs were more effective in clinical comprehensive effect, Positive and Negative Syndrome Scale (PANSS) scores and Brief Psychiatric Rating Scale scores compared with antipsychotic drugs alone. However, WDD had less effectiveness compared with antipsychotics in clinical comprehensive effect; and WDD was not different from antipsychotic drugs for PANSS scores. The side effects were significantly reduced in the intervention group compared with the control group., Conclusions: WDD appears to be effective on improving symptoms in patients with schizophrenia. However, due to poor methodological quality in the majority of the included trials, the potential benefit from WDD needs to be confirmed in rigorous trials and the design and reporting of trials should follow the international standards.

Objective: There is no effective therapy for blast-induced hearing loss in the clinic. The present report summaries our case series with using nerve growth factor in the treatment of patients with various blast-induced hearing loss., Patients and Methods: This retrospective study analyzed the clinical outcomes of 21 patients (33 ears) seen in our Outpatient Service Clinic who were treated with nerve growth factor (NGF) by intramuscular injection for 10 days. The pure tone audiometry changes before and after NGF treatments were measured for five frequencies., Results: Among the 21 patients with blast-induced hearing loss (33 ears) treated with 10-d NGF injection, the mean value of pure tone audiometry for the 5 frequencies for all the 33 ears after NGF treatment was significantly improved (p = 0.01). Three patients (6 ears) had hearing improved in different degrees, with average hearing being recovered by 15 dB HL. The total effective rate of the treatment was 18%., Conclusions: Nerve growth factor can be used to treat blast-induced hearing loss in clinic. The key to clinical success is early treatment; the efficacy on the patients with late treatment (more than one-month after injury is poor).

Low-frequency (Hz~kHz) squeezing is very important in many schemes of quantum precision measurement. But it is more difficult than that at megahertz-frequency because of the introduction of laser low-frequency technical noise. In this paper, we propose a scheme to obtain a low-frequency signal beyond the quantum limit from the frequency comb in a non-degenerate frequency and degenerate polarization optical parametric amplifier (NOPA) operating below threshold with type I phase matching by frequency-shift detection. Low-frequency squeezing immune to laser technical noise is obtained by a detection system with a local beam of two-frequency intense laser. Furthermore, the low-frequency squeezing can be used for phase measurement in Mach-Zehnder interferometer, and the signal-to-noise ratio (SNR) can be enhanced greatly.

The purpose of this review was to analyze recent studies, both clinical and experimental, on diagnosis and treatment of autoimmune sensorineural hearing loss (ASNHL). Relevant studies were identified by searching Chinese Biomedical Literature Database and China Academic Journals Full-text Database for articles published nationally during the period of 1993-2013. The manuscripts were analyzed for the following aspects: selection of patients, sample size, presence of control group, experimental methods, study outcomes including audiological evaluation results, and efficacy of treatment. Forty-one manuscripts were identified including 12 reviews, 2 case reports, 20 experimental studies, and 7 clinical studies. The patient numbers in clinical studies ranged from 14 to 71 patients. Five clinical studies included control group of healthy individuals, while further two studies had no control group. Patients with ASNHL were treated with corticosteroids (prednisone or dexamethasone) in all seven clinical studies. However, statistical analyses of therapeutic efficacy were not carried out. Animal models were developed by immunization with allogeneic inner ear antigen, and some pathological changes were not specific to the disease. Experimental animals also had various degrees of changes in auditory brainstem response. Treatment guidelines need to be developed, while specific criteria of treatment efficacy need to be established. Further research is needed to demonstrate that experimental ASNHL resembles pathophysiologically the clinical situation.

Conclusion: The hearing conditions of the centenarians were quite poor as regards hearing thresholds and speech detection ability., Objective: To investigate hearing conditions of centenarians., Methods: A total of 54 centenarians in Rizhao and Linyi Districts in Shandong Province were investigated to assess hearing conditions of centenerians comprehensively by questionnaire investigation, pure-tone audiometry, acoustic immitance, intelligence evaluation, and speech detection scores. Also, 135 individuals were recruited as controls and divided into four groups according to their age: 45-59 years, 60-69 years, 70-79 years, and 80-89 years., Results: The hearing thresholds of the centenarians were dramatically higher than those of the control group (p < 0.05) and all centenarians suffered moderate to profound hearing loss according to the World Health Organization (WHO) criteria. Few centenarians had normal level of speech detection scores. All centenarians showed descending hearing curve, and the hearing threshold of the male centenarians at 8000 Hz was higher than that of the females (p = 0.047). There was a significant air-bone conduction gap in the centenarians (p < 0.05).

High-power broad area substrate emitting photonic-crystal distributed feedback (DFB) quantum cascade lasers (QCLs) emitting around 4.73 μm is reported. Two-dimensional centered rectangular photonic-crystal (CRPC) grating is introduced to enhance optical coherence in large area device. Main lobe far-field radiation pattern with a very small divergence angle of about 0.65° × 0.31° is obtained. A record peak output power for vertical emitting QCLs exceeding 10 W is obtained with high reflectivity (HR) coating. Robust single longitudinal mode emission with a side mode suppression ratio (SMSR) of 30 dB is continuously tunable by the heat sink temperature up to 65°C.

To investigate the pharmacodynamic effects of Binghuang ear drop on acute suppurative otitis externa in guinea pig model. Thirty guinea pigs were randomly divided into three groups, with ten animals in each group. Group A animals had normal ear canal and Binghuang ear drops (two drops, B.I.D) were applied in both ears for 7 days; Group B animals had induced otitis externa and received identical prescription as group A; Group C had normal ear canal and were treated with normal saline (two drops, B.I.D) for 7 days. After the treatments, the external morphology of ear canals was observed and the paraffin sections of external auditory canal were prepared and examined under the microscope. The inflammatory manifestation and cell infiltration into the skin of group B was significantly attenuated after the Binghuang ear drops treatment. In contrast, no allergy or side effects were produced by Binghuang ear drops application in the animals with normal ear canals. Binghuang ear drops could be used to treat acute otitis externa by eliciting anti-bacterial effects.

A large portion of the global carbon pool is stored in peatlands, which are sensitive to a changing environment conditions. The hydrological loss of dissolved organic carbon (DOC) is believed to play a key role in determining the carbon balance in peatlands. Zoige peatland, the largest peat store in China, is experiencing climatic warming and drying as well as experiencing severe artificial drainage. Using a fully crossed factorial design, we experimentally manipulated temperature and controlled the water tables in large mesocosms containing intact peat monoliths. Specifically, we determined the impact of warming and water table position on the hydrological loss of DOC, the exported amounts, concentrations and qualities of DOC, and the discharge volume in Zoige peatland. Our results revealed that of the water table position had a greater impact on DOC export than the warming treatment, which showed no interactive effects with the water table treatment. Both DOC concentration and discharge volume were significantly increased when water table drawdown, while only the DOC concentration was significantly promoted by warming treatment. Annual DOC export was increased by 69% and 102% when the water table, controlled at 0 cm, was experimentally lowered by -10 cm and -20 cm. Increases in colored and aromatic constituents of DOC (measured by Abs(254 nm), SUVA(254 nm), Abs(400 nm), and SUVA(400 nm)) were observed under the lower water tables and at the higher peat temperature. Our results provide an indication of the potential impacts of climatic change and anthropogenic drainage on the carbon cycle and/or water storage in a peatland and simultaneously imply the likelihood of potential damage to downstream ecosystems. Furthermore, our results highlight the need for local protection and sustainable development, as well as suggest that more research is required to better understand the impacts of climatic change and artificial disturbances on peatland degradation.

We demonstrated an unambiguous quantum dot cascade laser based on InGaAs/GaAs/InAs/InAlAs heterostructure by making use of self-assembled quantum dots in the Stranski-Krastanow growth mode and two-step strain compensation active region design. The prototype generates stimulated emission at λ ~ 6.15 μm and a broad electroluminescence band with full width at half maximum over 3 μm. The characteristic temperature for the threshold current density within the temperature range of 82 to 162 K is up to 400 K. Moreover, our materials show the strong perpendicular mid-infrared response at about 1,900 cm-1. These results are very promising for extending the present laser concept to terahertz quantum cascade laser, which would lead to room temperature operation., Pacs: 42.55.Px; 78.55.Cr; 78.67.Hc.

The acupoints and meridians selected in the treatment of depression with acupuncture and moxibustion recorded in the domestic clinical literatures from 2001 to 2011 were summarized and analyzed so as to provide the references for the treatment of depression with acupuncture and moxibustion and discuss the relationship between meridians and mental state. SPSS 17.0 statistical analyzing software was used and the statistical description of enumeration data was applied for statistical analysis. It was found that all of the twelve regular meridians and the eight extraordinary meridians were involved in the treatment of depression with acupuncture and moxibustion, of which the application frequency of the Governor Vessel was the highest and that of the Foot-Taiyang Meridian, Foot-Yangming Meridian, Foot-Shaoyang Meridian and the Conception Vessel were followed. It is concluded that depression is Yin disease treated by regulating Yang meridians and it is found that the Governor Vessel, three foot yang-meridians and the Conception Vessel are closely related to mental disorders.

To establish an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtain laryngocarcinoma cells with high metastatic potential, laryngeal squamous cell carcinoma cell line HEP-2 in logarithmic phase were inoculated under the lingual margin mucosa of nude mice. HEP-2 cells metastasized to the cervical lymph nodes were isolated, cultured, and re-inoculated under the lingual margin mucosa of nude mice twice. The tumor formation in the tongue and in the cervical lymph nodes was confirmed by pathological examination. Carcinoma cells' ability of invasion and migration was detected by transwell assay. Human specific Alu sequences were detected by PCR, which indicated that the tumor cells originated from human laryngeal squamous cell carcinoma cell line HEP-2. Finally, an animal model of spontaneous lymph node metastasis of laryngeal squamous cell carcinoma was successfully established. Laryngeal squamous cell carcinoma cells with high metastatic potential to lymph nodes were obtained through repeated inoculations. .

Conclusion: Bone marrow mesenchymal stem cells (MSCs) have the ability to differentiate into hair cells, and this method of culturing MSCs provides a useful tool for studies on mammalian cochlear hair cell regeneration., Objective: To investigate a method to induce bone marrow MSCs to differentiate into inner ear hair cells., Methods: Rat bone marrow MSCs were isolated from healthy rats and cultured in vitro. To make sure that the cultured cells were bone marrow MSCs, the expression of MSC markers such as SH2, CD31, CD34, and CD44 genes on the cultured cells was assessed by RT-PCR. Adipogenic cells and osteogenic cells were induced by the differentiation of the cultured cells, respectively, suggesting that the cultured cells have the characteristic of pluripotent differentiation. Then they were induced to differentiate into neural stem cells and hair cell progenitor cells. Immunohistochemistry experiments were carried out to detect the expression of molecular markers. Scanning electron microscope samples were prepared for observation of the morphology of the cells., Results: Rat bone marrow MSCs were successfully isolated, purified, cultured, and identified in vitro. They were also successfully induced to differentiate into neural progenitor cells and then hair cell-like cells that expressed myosin VIIa.

Objective: To explore the protective effects of brain-derived neurotrophic factor on the noise-damaged cochlear spiral ganglion., Methods: Recombinant adenovirus brain-derived neurotrophic factor vector, recombinant adenovirus LacZ and artificial perilymph were prepared. Guinea pigs with audiometric auditory brainstem response thresholds of more than 75 dB SPL, measured seven days after four hours of noise exposure at 135 dB SPL, were divided into three groups. Adenovirus brain-derived neurotrophic factor vector, adenovirus LacZ and perilymph were infused into the cochleae of the three groups, variously. Eight weeks later, the cochleae were stained immunohistochemically and the spiral ganglion cells counted., Results: The auditory brainstem response threshold recorded before and seven days after noise exposure did not differ significantly between the three groups. However, eight weeks after cochlear perfusion, the group receiving brain-derived neurotrophic factor had a significantly decreased auditory brainstem response threshold and increased spiral ganglion cell count, compared with the adenovirus LacZ and perilymph groups., Conclusion: When administered via cochlear infusion following noise damage, brain-derived neurotrophic factor appears to improve the auditory threshold, and to have a protective effect on the spiral ganglion cells.

The regulation of the bone morphogenetic protein (BMP) signal transduction pathway is important in the development of the inner ear and vestibular system. We reported previously that small mothers against decapentaplegic homolog-4 (Smad4) is required for inner ear cochlear development and normal auditory function in mammals; however, the distribution and functional mechanisms of Smad4 at various stages of vestibular development remained unclear. To investigate the relationship between the Smad4 gene and vestibular organ development, we measured changes in the expression of BMP4 and Smad4 during vestibular development in C57BL/6 mice. In addition, vestibular structures, pathologic changes, and the vestibular function of chondrocyte-specific Smad4 knockout mice were compared to those of the control group. We found that the expression of Smad4 in the inner ear was delayed compared with that of BMP4. Moreover, chondrocyte-specific Smad4 knockout homozygous mice showed stunted growth and partial vestibular deformities, but it showed less histologic changes in the vestibular end-organs and saccule dysfunction. These results suggest that Smad4 participates in late-stage shaping of the configuration of the vestibule and development of vestibular functional, but a Smad4-independent pathway for the inner ear vestibular BMP4 signal transduction could not be rule out., (Copyright © 2010 ISDN. Published by Elsevier Ltd. All rights reserved.)

Mammalian cochlear hair cells don't regenerate naturally after injury, which usually leave permanent hearing loss. Math1 gene is a positive regulator of hair cell differentiation during cochlear development and was proved to be very critical in hair cell regeneration in deaf animals. Generating new cochlear hair cells by forced Math1 expression may be a cure for hearing loss. However, satisfying gene delivering vectors in gene therapy are not available. We combined quaternized chitosan (QCS) with Na-carboxymethyl-beta-cyclodextrin (CM-beta-CD) as novel non-viral vector, which adsorbs pRK5-Math1-EGFP perfectly at the mass ratio of 4:1. In vitro cell transfection can reach a 40% transfect efficiency and relatively low cytotoxity than liposomes. These results suggest that QCS/CM-beta-CD nanoparticle complexes could be a novel non-viral gene carrier in further clinical application.

Objective: To explore the safety and efficacy of cochlear implantation among elderly patients with severe to profound hearing loss., Methods: Eight pre-elderly and elderly patients with an medium age of 58 years who suffered from bilateral severe to profound sensorineural hearing loss received cochlear implantation between November 2008 and November 2009. The patients' tolerance to implant surgery and the occurrence of complications were observed. Three months after switch-on, aided threshold and speech performance were measured., Results: The surgery was uneventful in all cases with normal intraoperative neural response telemetry elicited. Three months after switch-on, average aided threshold across speech frequencies was 35 - 50 dB HL measured in sound field with warble tone. The results of speech audiometry showed large variation between individuals. Some patients achieved good performance in monosyllable recognition test, disyllables threshold test and sentences recognition test under both bubble noise and quiet conditions., Conclusions: Pre-elderly and elderly patients can endure a state of general anesthesia for cochlear surgery without complications. Cochlear implant can provide reconstruction of speech recognition capabilities for elderly patients suffering from severe to profound hearing loss. Cochlear implantation can improve the quality of life of elderly patients with hearing loss.

Background: Our previous studies have shown that both apoptosis and necrosis are involved in hair cell (HC) pathogenesis in aging cochleae. To better understand the biological mechanisms responsible for the regulation of HC death, we examined the activity of succinate dehydrogenase (SDH), a mitochondrial bioenergetic enzyme, in the HCs of aging cochleae., Methods: The auditory brainstem response thresholds elicited by tone bursts at 4, 10 and 20 kHz were measured in both young (2-3 months) and aging (22-23 months) Wistar rats. SDH activity was evaluated with a colorimetric assay using nitroblue tetrazolium monosodium salt. The SDH-labeled organs of Corti were double stained with propidium iodide, a DNA intercalating fluorescent probe for illustration of HC nuclei. All the specimens were examined with fluorescence microscopy and confocal microscopy., Results: Aging rats exhibited a significant elevation of ABR thresholds with threshold shifts being 34 dB at 20 kHz, 28 dB at 10 kHz, and 25 dB at 4 kHz. Consistent with the reduction in the cochlear function, aging cochleae exhibited the reduction of SDH staining intensity in the apical and the basal ends of the cochleae, where a large number of apoptotic, necrotic, and missing HCs were evident. The reduction in SDH staining appeared in a cell-death-mode dependent fashion. Specifically, SDH labeling remained in apoptotic HCs. In contrast, SDH staining was markedly reduced or absent in necrotic HCs., Conclusions: In the aging cochlea, SDH activity is preserved in HCs undergoing apoptosis, but is substantially reduced in necrosis. These results suggest that mitochondrial energetic function is involved in the regulation of cell death pathways in the pathogenesis of aging cochleae.

The Smads are a group of related intracellular proteins critical for transmitting the signals to the nucleus from the transforming growth factor-beta superfamily at the cell surface. Knockout of the Smad5 is embryonic lethal. However, the Smad5 knockout of single allele (+/-) could survive. We used Smad5 heterozygous knockout (+/-) to determine the role of Smad5 in the development of inner ear morphology and function. In situ hybridization showed that Smad5 was expressed predominantly in hair cells, spiral ganglion, and supporting cells. Measurements of hearing thresholds using auditory brainstem response showed that Smad5 defect resulted in progressive hearing loss between 4 and 24 weeks after birth. Morphological examination revealed apoptosis in the inner ear, with significant loss of outer hair cells in adult Smad5 mutant mice. Our results indicated that deficiency in the Smad5-mediated signaling resulted in apoptosis of hair cells, suggesting Smad5 is a gene that may be related with presbycusis.

Objective: To investigate the effect of Hath1 (human atonal homolog 1) overexpression on greater epithelial ridge (GER) cells from postnatal rat cochlea in vitro., Methods: GER cells were isolated by using a combinatorial approach of enzymatic digestion and mechanical separation from P1 rat cochlear. The GER cell cultures were infected by adenovirus containing Hath1 and enhanced green fluorescent protein (ad-Hath1-EGFP), while transfecting EGFP(ad-EGFP) was as controls. Immunostaining were performed at different time points after adenovirus infection., Results: Some of the infected GER cells became myosin VIIa-positive following ad-Hath1-EGFP infection. The earliest time point to see induction of hair cell differentiation (hair cell marker expression) by ad-Hathl was 5 days post-infection. In contrast, infection of the GER sheet cultures with ad-EGFP control virus did not show any myosin VIIa-positive cells at 3-12 days post-infection in all cultures examined., Conclusions: GER cells may potentially serve as hair cell progenitors and they are capable of differentiating hair cell-like cells when forced to express Hath1.

Objective: To establish in vitro culture systems of greater epithelial ridge (GER) cells from rat cochlear and to investigate the characterization, growth pattern and ultrastructure of GER cells., Methods: Using a combinatorial approach of enzymatic digestion and mechanical separation to allow isolation and culture of GER cells from P1 rat cochleae. The dissociated GER cells were cultured in serum-free or 10% fetal bovine serum DMEM respectively. BrdU, phalloidin, ZO1, calretinin and myosin VIIa immunostaining and scanning electron microscope observation were performed in GER cell cultures., Results: The dissociated GER cell cultures showed positive to ZO1, phalloidin and BrdU staining, but negative to myosin VIIa and calretinin. They assumed a polygonal morphology which was similar to epithelial cells and grew in islands-like patches in medium containing 10% fetal bovine serum while forming spheres in serum-free medium. The GER cells presented significant ability to proliferate in both conditions. Scanning electron microscope showed that there was microvillus and centre bodies but not hair cell specific stereociliary bundles on the surface of GER cultures., Conclusions: The GER cell cultures showed significant ability to proliferate and grew in islands-like patches in medium containing 10% fetal bovine serum while forming spheres in serum-free medium. The dissociated GER cells expressed epithelial cell specific marker but not marker of hair cells.

There is a worldwide interest in studying SLC26A4 mutations that are responsible for enlarged vestibular aqueduct (EVA) in different ethnic background and populations. The spectrum of SLC26A4 mutations in Chinese population is yet to be fully characterized. In this study, all the 21 exons of SLC26A4 were screened in 107 Chinese patients with hearing loss associated with EVA or both EVA and Mondini dysplasia (MD), taken from six multiplex and 95 simplex families. The two types of control populations consisted of 84 normal-hearing subjects and 46 sensorineural hearing loss subjects without inner ear malformations. Biallelic mutations were found in 12 patients from multiplex families and 84 patients (88.4%) from the simplex families. In addition, monoallelic variant was detected in nine patients in the remaining 11 simplex families. Overall, up to 97.9% patients were found having at least one possible pathogenic variant in SLC26A4, with most having biallelic variants consistent with recessive inheritance of this disorder. A total of 40 mutations including 25 novel mutations were identified in the Chinese patients but were not detected in all the controls except for one normal subject. For the Chinese mutation spectrum of SLC26A4 gene, IVS 7-2A>G mutation was the most common form accounting for 57.63% (102/177) of all the mutant alleles.

Mammalian cochlear hair cell loss is irreversible and leads to permanent hearing loss. To restore hearing physiologically, it is necessary to generate new functional hair cells either from endogenous cells or from exogenously transplanted hair cells/progenitors. Previous studies suggest that cochlear greater epithelial ridge (GER) and lesser epithelial ridge (LER) cells are capable of differentiating into hair cells. While it was recently possible to obtain and culture pure LER progenitors, isolation of pure GER progenitors has not been reported. Here we describe a method that allows isolation of pure GER cells from neonatal rat cochleae. The cochlear epithelial sheet (CES) containing GER progenitor cells was mechanically separated from the underlying mesenchymal tissue after digestion with thermolysin. The GER area could then be dissected following mechanical removal of organ of Corti as well as all the lateral area. The isolated GER cells showed significant proliferation and expressed markers for GER cells but not markers for hair cells or LER. When the GER cells were cultured in serum-free medium containing epidermal growth factor, spheres were formed where they continued to proliferate. Furthermore, when GER cells were induced to express Hath1 or co-cultured with mesenchymal cells prepared from neonate rat cochleae, they showed the potential to differentiate into hair cell-like cells. Successful isolation, culture and differentiation of GER hair cell progenitors will shed additional light on the mechanism of hair cell differentiation and potential hair cell replacement.

Objective: To analyze the molecular pathogenesis of deaf couples by means of genetic testing. To provide accurate genetic counseling and instruction for deaf couples with different etiology based upon results of genetic testing., Methods: Four deaf families from July 2005 to May 2006. Each subject was with moderate to profound hearing loss. Genomic and mitochondrial DNA (mtDNA) of each subject were extracted from whole blood. Genetic testing of GJB2, SLC26A4 (PDS) and mtDNA A1555G mutation were offered to each individuals., Results: The husband from family 1 didn't carry GJB2, SLC26A4 and mtDNA A1555G mutation while his wife was confirmed to carry compound SLC26A4 mutations. The possibility of their offspring's to be SLC26A4 single mutation carrier was 100%. The couple from family 2 both didn't carry GJB2, SLC26A4 and mtDNA A1555G mutation. The possibility of their offspring's having hereditary deafness caused by GJB2, SLC26A4 and mtDNA A1555G mutation was excluded. The husband from family 3 was confirmed to carry homozygous GJB2 mutations and a single SLC26A4 mutation while his wife who was diagnosed with enlarged vestibular aqueduct syndrome (EVAS) by CT scan was proven to carry a single SLC26A4 mutation. The risk of their offspring's suffering EVAS was 50%. The husband from family 4 was mtDNA A1555G positive while his wife who was diagnosed with cochlear malformation by CT scan didn't carry GJB2, SLC26A4 and mtDNA A1555G mutation. The risk of their offspring's having hereditary deafness caused by GJB2, SLC26A4 and mtDNA A1555G mutation was excluded., Conclusions: Genetic testing could be applied to offer the more accurate genetic counseling and instruction to deaf couples.

Objective: To analyze the molecular genetic mechanisms of pathogenesis of deafness in the families with deaf-mute patients and analyze the strategies of genetic counseling and intervention for these families., Methods: Peripheral blood samples were collected from the probands with deaf-muteness and their parents of five families and genetic tests were conducted to analyze the GJB2, SLC26A4 (PDS), and mitochondrial DNA (mtDNA) A 1555G genes for the existence of mutation. Families 1-3 had one child with hearing loss each while the parents had normal hearing and the mothers had been pregnant for 6-18 weeks. Both parents of family 4 were deaf-mute, and the wife of family 5 was deaf-mute while her husband had normal hearing., Results: The proband from family 1 was proven to carry compound GJB2 mutations while his parents carried a single GJB2 mutation; prenatal testing showed that the fetus only carried the paternal mutation. The proband from family 2 was proven to carry compound SLC26A4 (PDS) mutations while his parents carried a single SLC26A4 (PDS) mutation; prenatal testing showed that the fetus only carried the paternal mutation. The proband from family 3 and his parents didn't carry any GJB2, SLC26A4 and mtDNA A1555G mutation. Observation showed that the new born babies of these three families all had normal hearing revealed by new born hearing screening and ABR test. The husband from family 4 was homozygous GJB2 235delC while his wife was mtDNA A1555G positive. This couple was advised to strictly avoid the administration of aminoglycoside antibiotics to their future offspring. In family 5, the wife carried compound SLC26A4 (PDS) mutations while her husband carried a single SLC26A4 (PDS) mutation; and they were told about the 50% risk of their offspring's suffering from enlarged vestibular aqueduct syndrome., Conclusion: Genetic testing with prenatal testing and relevant intervention for the families with deaf-mute patients can be applied to prevent another deaf-mute member from being born.

Objective: Transducing PEDF-GFP plasmid to the retina of the BN rats with cationic liposome through different gene delivery route, then observe the expression and location of the PEDF-GFP., Methods: PEDF-GFP plasmid with cationic liposome was delivered to the retina of the BN rat through subretinal injection and intravitreal injection. The expression of GFP was observed under fluorescence microscope, and the mRNA of PEDF gene was detected by RT-PCR., Results: Green fluorescence was emitted from the total retina include RPE cell under fluorescent microscope after 24 h in two gene delivery route, The fluorescence intensity was stronger with time changing. Gradual fluorescence increase in the retina and RPE cells occurred and lasted 4 weeks. The expression of PEDF mRNA was also detected by RT-PCR after 24 h, and maintained stable 4 weeks after infection., Conclusions: Cationic liposome can mediate PEDF-GFP gene into the retina of the BN rat effectively; subretinal injection and intravitreal injection both are effective gene delivery route; and their stable expression can maintain 4 weeks after transfection.