Hearing analysis in heterozygous and homozygous klotho gene deficient mice

Objective: To understand the crucial role of the klotho gene in hearing development in mouse models.Methods: PCR was used to identify CBA mice with different genotypes, i.e. WT, heterozygous(klotho +/-)or homozygous(klotho-/-). Mice phenotype and weight were recorded postnatal 25 days(P-25) and auditory brainstem responses(ABR) were used to determine auditory function at P-60.Results: klotho-/-mice tended to have smaller size, lighter weight and higher ABR thresholds at P-60,showing early onset age-related hearing loss(ARHL).Conclusion: Heterozygous and homozygous klotho deficient mice exhibit different degrees of hearing loss at young age, with homozygous mice(klotho-/-) showing more severe hearing loss. Our results indicate that persisted expression of klotho protein in the inner ear may potentially delay the onset of ARHL and play an important role in the protection of auditory function.

Study and observation of ultrasound on hemorheology of continuous renal replacement therapy in ICU

Objective: To observe the influence of bedside ultrasound on Hemodynamics of Continuous Renal Replacement Therapy,and explore the clinical value of bedside ultrasound technique in acute kidney injury (AKI) Patients with continuous renal replacement therapy (CRRT) and capacity management. Methods 311 cases of AKI patients with CRRT were divided randomly into Observe group and Control group. the observe group was used bedside ultrasound technique, by monitoring tricuspid annular plane systolic excursion (TAPSE), internal diameter of inferior vena cava (IVC), respiratory variation index of the inferior vena cava internal diameter (RVI) and left vertical Tei index changes. Meanwhile, each parameter change was mediated by ultrasound detection from before, to 30min, 6h, 12h, 36h, 48h after of CRRT to sustain liquid balance in observe group, however, central venous pressure (CVP) change was modulated in control group. The difference of kidney length in pre-CRRT were examined to exclude, and of renal aortic diameter, renal resistance index (RRI)and renal blood flow in post-48h of CRRT were compared in two groups. Results Renal length, Renal parenchyma thickness and Echo strength of renal parenchyma weren't different statistically in pre-CRRT of two groups(P>0.05). In observe group, the RVI level was started to increase significantly and IVC internal diameter to decrease at 6h, which would tend to stable at 36h(F=27.746 and 15.446 respectively);the TAPSE level was gradual ascending and Tei index was descending at 12h with a stable tendency at 24h of CRRT(F=36.213 and 17.127 respectively), and there was difference statistical among time of obvious change in TAPSE, IVC internal diameter, RVI and Tei index(P<0.05);In control group, there was no difference statistical among each time in CVP(F=2.189, P>0.05). Compared with control group, renal aortic diameter and renal blood flow were increased significantly(t=2.356 and 2.075), RRI was decreased obviously in observe group(t=2.244), which was different in statistics (P<0.05). Conclusion the application of bedside ultrasound technique in AKI patient's capacity management with CRRT was more effective and evaluated the kidney perfusion.

Investigation of feasibility of alkali-cosolvent flooding in heavy oil reservoirs

Cold production is a challenge in the case of heavy oil because of its high viscosity and poor fluidity in reservoir conditions.Alkali-cosolvent-polymer flooding is a type of microemulsion flooding with low costs and possible potential for heavy oil reservoirs.However,the addition of polymer may cause problems with injection in the case of highly viscous oil.Hence,in this study the feasibility of alkali-cosolvent(AC)flooding in heavy oil reservoirs was investigated via several groups of experiments.The interfacial tension between various AC formulations and heavy crude oil was measured to select appropriate formulations.Phase behavior tests were performed to determine the most appropriate formulation and conditions for the generation of a microemulsion.Sandpack flooding experiments were carried out to investigate the displacement efficiency of the selected Ac formulation.The results showed that the interfacial tension between an AC formulation and heavy oil could be reduced to below 1o-3 mN/m but differed greatly between different types of cosolvent.A butanol random polyether series displayed good performance in reducing the water-oil interfacial tension,which made it possible to form a Type Il microemulsion in reservoir conditions.According to the results of the phase behavior tests,the optimal salinity for different formulations with four cosolvent concentrations(0.5 wt%,1 wt%,2 wt%,and 3 wt%)was 4000,8000,14000,and 20000 ppm,respectively.The results of rheological measurements showed that Type Ill microemulsion had a viscosity that was ten times that of water.The results of sandpack flooding experiments showed that,in comparison with waterflooding,the injection of a certain Ac formulation slug could reduce the injection pressure.The pressure gradient during waterflooding and AC flooding was around 870 and 30-57 kPa/m,respectively.With the addition of an AC slug,the displacement efficiency was 30%-50%higher than in the case of waterflooding.

星状神经节阻滞对重症急性胰腺炎患者肺损伤的影响

目的探讨星状神经节阻滞对重症急性胰腺炎(SAP)合并急性肺损伤(ALI)患者炎症介质及功能的影响。方法选取2016年6月—2018年12月河北北方学院附属第一医院重症医学科确诊SAP患者34例,随机分为常规治疗组(对照组)19例和超声引导下星状神经节阻滞组(SGB组)15例。对照组予禁食、水等常规治疗,而SGB组在常规治疗基础上行超声引导下星状神经节阻滞。酶联免疫吸附试验检测TNF-α、IL-1β、IL-6、IL-10的变化,血液细胞分析法检测CRP和WBC的水平。观察两组在治疗前后肺水指数、氧合指数、治疗后ICU住院时间及呼吸机拔管时间的差异,以及入院0 h(T0)、第3天(SGB治疗后2 d,T1)、第7天(SGB治疗后6 d,T2)和第15天(SGB治疗后14 d,T3)时间点炎症介质的改变。结果治疗前两组患者肺水指数和氧合指数比较,差异无统计学意义(P>0.05)。治疗2周后SGB组的肺水指数较对照组下降(P<0.05),氧合指数较对照组升高(P<0.05),SGB组ICU住院时间、呼吸机拔管时间较对照组缩短(P<0.05)。不同时间点间IL-6、TNF-α、IL-1β、IL-10、WBC和CRP有差异(P<0.05);两组患者IL-6、TNF-α、IL-1β、CRP和IL-10有差异(P<0.05);两组患者TNF-α、IL-1β、IL-10、WBC、CRP随时间变化趋势有差异(P<0.05)。结论SGB有可能减轻SAPALI的炎症反应而利于改善肺损伤。

Role of autophagy in acute myeloid leukemia therapy

Despite its dual role in determining cell fate in a wide array of solid cancer cell lines, autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis. However, autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein, though the molecular mechanism remains elusive. Nevertheless, since it can induce cooperation with apoptosis and differentiation in response to autophagic signals, autophagy can be manipulated for a better therapy on acute myeloid leukemia.

Novel high- with low specific on-resistance high voltage lateral double-diffused MOSFET

A novel voltage-withstand substrate with high-K（HK, k 〉 3.9, k is the relative permittivity） dielectric and low specific on-resistance（Ron,sp） bulk-silicon, high-voltage LDMOS（HKLR LDMOS）is proposed in this paper. The high-K dielectric and highly doped interface N＋-layer are made in bulk silicon to reduce the surface field drift region. The high-K dielectric can fully assist in depleting the drift region to increase the drift doping concentration（Nd） and reshape the electric field distribution. The highly doped N＋-layer under the high-K dielectric acts as a low resistance path to reduce the Ron,sp. The new device with the high breakdown voltage（BV）, the low Ron,sp, and the excellent figure of merit（FOM = BV^2/Ron,sp） is obtained. The BV of HKLR LDMOS is 534 V, Ron,sp is 70.6 m？·cm^2, and FOM is 4.039 MW·cm^（-2）.

Efficacy and safety of short duration radiotherapy combined with chemotherapy for advanced rectal cancer

BACKGROUND Radiotherapy or chemoradiotherapy is widely used for the treatment of rectal cancer preoperatively.Although the combination of radiotherapy and chemotherapy as an established preoperative neoadjuvant therapy shows high efficacy in the treatment of rectal cancer,some patients experience a response of poor tolerance and outcomes due to the long duration radiotherapy.The study compared short duration radiotherapy plus chemotherapy vs long duration radiotherapy plus chemotherapy for rectal cancer to determine whether short duration radiation treatment should be considered to diminish complications,reduce risk of recurrence and improve survival in patients with rectal cancer.AIM To evaluate the efficacy and safety of short duration radiotherapy combined with chemotherapy for the treatment of advanced rectal cancer.METHODS One hundred patients with stage IIIB or higher severe rectal cancer were selected as the study subjects at The First Affiliated Hospital of Hebei North University between December 2018 and December 2019.The patients were assigned to different groups based on the treatment regimens.Fifty patients who received preoperative short durations of radiotherapy plus chemotherapy were enrolled in an observation group and fifty patients who received conventional radiotherapy and chemotherapy were enrolled in a control group.Colonoscopic biopsy was performed for all patients with pathological diagnosis of rectal cancer.The expression of tumor-related factors such as RUNX3 and Ki-67 was quantitatively analyzed using immunohistochemistry in the tissues of the patients before and after treatment.Moreover,the duration of procedure,the amount of bleeding during the operation,the anus-conserving rate,the incidence of postoperative complications(wound infection,anastomotic leakage,postoperative intestinal obstruction,etc.)and postoperative pathology were compared between the two groups.The overall survival rate,recurrence rate and distant metastasis rate were also compared through postoperative reexamination and regular follow-up.RESULTS There was no significant difference in the positive expression rate of RUNX3 and Ki-67 between the two groups before the treatment(P>0.05).Compared with the pretreatment value,the positive rate of RUNX3 was increased and the positive rate of Ki-67 was decreased in both groups after the treatment(all P<0.05).The incidence of leukopenia,thrombocytopenia,neutropenia and diarrhea were higher in the observation group than in the control group(all P<0.05).There was no significant difference in the incidence of anemia,fatigue,neurotoxicity and nausea and vomiting between the two groups(all P>0.05).No significant difference was observed in the duration of procedure,intraoperative bleeding,the anus-conserving rate and the incidence of postoperative complications between the two groups(P>0.05).After 1 year of follow-up,the 1-yr survival rate was 80.0%in the observation group and 68.0%in the control group,the recurrence rate was 8.0%in the observation group and 10.0%in the control group,the distant metastasis rate was 6.0%in the observation group and 8.0%in the control group difference(all P<0.05).CONCLUSION Short duration radiotherapy combined with chemotherapy can improve the cure rate,prolong the survival time and reduce the incidence of complications in patients with advanced rectal cancer.

Vestibular-evoked myogenic potentials in miniature pigs

Objective:To report detection of vestibular-evoked myogenic potentials (VEMPs) in the miniature pig. Methods:Potentials evoked by 1000 Hz tone bursts were recorded from neck extensor muscles and the masseter muscles in normal adult Bama miniature pigs anesthetized with 3%pentobarbital sodium and Carbachol II. Results:The latency of the first positive wave P from neck extensor muscles was 7.65 ± 0.64 ms, with an amplitude of 1.66 ± 0.34 uv and a rate of successful induction of 75%at 80 dB SPL. The latency of potentials evoked from the masseter muscles was 7.60 ± 0.78 ms, with an amplitude of 1.31 ± 0.28 uv and a rate successful induction of 66%at 80 dB SPL. Conclusion:The latencies and thresholds of VEMPs recorded from the neck extensor muscle and the masseter muscle appear to be comparable in normal adult Bama miniature pigs, although the amplitude recorded from the neck extensor muscle seems to be higher than that from the masseter muscle. However, because of their usually relatively superficial and easily accessible location, as well as their large volume and strong contractions, masseter muscles may be better target muscles for recording myogenic potentials.

Polymorphism of the 86th amino acid in CX26 protein and hereditary deafness

Objective:To investigate the membrane localization function of the CX26 protein when its 86th amino acid is Thr, Ser or Arg, and its relations to deafness. Methods:CX26-GFP protein with either Thr, Ser or Arg as the 86th amino acid was expressed in mouse SGN cells via the GFP fusion type lenti-virus expression system. The membrane localization of the fusion protein was observed under a fluorescence microscope. Results:The mutated protein of CX26 T86S was localized to cell membrane and form gap conjunction structures, showing no difference to the wild type CX26 protein (with Thr as the 86th amino acid). However, the gap conjunction structure disappeared when the mutation was CX26 T86A. Conclusion:These results indicate that the CX26 T86R mutation may be a cause of hearing loss, but CX26 T86S as a non-pathogenic poly-morphism mutation does not affect functions of the CX26 protein. The results are in accordance with the results of clinical screening.

Electroclinical characteristics and therapies of tonic spasms

Backgroud Epileptic spasms followed by a tonic component have been frequently observed in patients with late-onset spasms(LOS).However,there is a lack of comprehensive analysis and summary of clinical data related to tonic spasms(TS),including seizures,video-electroencephalogram(V-EEG),synchronous electromyography(EMG)and follow-up data.Methods To investigate the characteristics of TS,we prospectively collected the clinical data,including 24-h V-EEG and synchronous EMG data of 32 enrolled patients who suffered from epileptic spasms followed by a TS onset at least once during the 24-h V-EEG in the epilepsy center of Xijing Hospital between June 2015 and July 2020.The patients were prescribed anti-seizure medications(ASMs)and followed up for 2–7 years.Results The average age of epilepsy onset was 48.06±16.07 months(range:25 to 88 months).Among the enrolled patients,22 patients presented with mild intellectual deficits.During the 24-h video-EEG monitoring,an average of 6.94 TS events(range:3 to 21)were recorded,and these TS seizures often occurred in clusters.In addition to TS,26 patients experienced generalized tonic-clonic seizures(GTCS),atypical absence seizures,myoclonic seizure,and epileptic spasms.None of the 32 patients with TS displayed hypsarrhythmia during the 24-h video-EEG recording.A total of 28 patients showed normal EEG backgrounds.Interictal epileptic discharges,including slow waves(SW),spike/sharp slow waves(SSW),and spikes,often displayed multifocally.Notably,two patients achieved seizure freedom for more than 2 years through monotherapy with oxcarbazepine(OXC),which was associated with normalization of the EEG.Conclusions It is difficult to classify the patients with TS as any existing epileptic syndromes,which were distinct from West syndrome or Lennox-Gastaut syndrome.TS might be an underreported seizure type and further studies are needed to gain a more comprehensive understanding of the electro-clinical features and appropriate choice of ASMs for treating tonic spasms.

Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome

To unravel the genetic mechanisms of disease and physiological traits,it requires comprehensive sequencing analysis of large sample size in Chinese populations.Here,we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative(CASPMI)project launched by the Chinese Academy of Sciences,including the de novo assembly of a northern Han reference genome(NH1.0)and whole genome analyses of 597 healthy people coming from most areas in China.Given the two existing reference genomes for Han Chinese(YH and HX1)were both from the south,we constructed NH1.0,a new reference genome from a northern individual,by combining the sequencing strategies of PacBio,10×Genomics,and Bionano mapping.Using this integrated approach,we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1.In order to generate a genomic variation map of Chinese populations,we performed the whole-genome sequencing of 597 participants and identified 24.85 million(M)single nucleotide variants(SNVs),3.85 M small indels,and 106,382 structural variations.In the association analysis with collected phenotypes,we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males.Moreover,significant genetic diversity in MTHFR,TCN2,FADS1,and FADS2,which associate with circulating folate,vitamin B12,or lipid metabolism,was observed between northerners and southerners.Especially,for the homocysteine-increasing allele of rs1801133(MTHFR 677T),we hypothesize that there exists a “comfort”zone for a high frequency of 677T between latitudes of 35–45 degree North.Taken together,our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

Performance optimization of dye-sensitized solar cells by gradient-ascent architecture of SiO_2@Au@TiO_2 microspheres embedded with Au nanoparticles

Highly homogeneous, well dispersed SiO_2@Au@TiO_2(SAT) microspheres decorated with Au nanoparticles(AuNPs) were prepared and incorporated into the photoanode with an optimized concentration gradientascent. The effects of SAT microspheres and the gradient-ascent architecture on the light absorption and the photoelectric conversion efficiency(PCE) of the dye-sensitized solar cells(DSSCs) were investigated.Studies indicate that the introduction of SAT microspheres and the gradient-ascent architecture in the photoanode significantly enhance the light scattering and harvesting capability of the photoanode. The DSSC with the optimized SAT gradient-ascent photoanode has the maximum short circuit current density(J_(sc)) of 17.7 mA cm^(-2) and PCE of 7.75%, remarkably higher than those of the conventional DSSC by 23.7%and 28.0%, respectively. This significantly enhancement of the performance of the DSSC can be attributed to the excellent light reflection/scattering of SAT, the localized surface plasma resonance(LSPR) effect of AuNPs within the microspheres, and the gradient-ascent architecture of SAT microspheres inside the photoanode. This study demonstrates that the tri-synergies of the scattering of SAT microspheres, the LSPR of AuNPs and the gradient-ascent architecture can effectively improve the PCE of DSSC.

A High-Sensitivity and Broad-Range SPR Glucose Sensor Based on Improved Glucose Sensitive Membranes

An improved glucose sensitive membrane(GSM)is prepared by immobilizing glucose oxidase(GOD)onto a mixture of silica mesocellular foams(SiMCFs)and SiO2 nanoparticles(SiNPs)and then trapping it in a polyvinyl alcohol(PVA)gel.The membrane is coated onto a gold-glass sheet to create a surface plasmon resonance(SPR)sensor.A series of experiments are conducted to determine the optimized parameters of the proposed GSM.For a GSM with a component ratio of SiMCFs:SiNPs=7:3(mass rate),the resonance angle of the sensor decreases from 68.57°to 63.36°,and the average sensitivity is 0.026°/(mg/dL)in a glucose concentration range of 0 mg/dL‒200 mg/dL.For a GSM with a component ratio of SiMCFs:SiNPs=5:5(mass rate),the resonance angle of the sensor decreases from 67.93°to 63.50°,and the sensitivity is 0.028°/(mg/dL)in a glucose concentration range of 0 mg/dL‒160 mg/dL.These data suggest that the sensor proposed in this study is more sensitive and has a broader measurement range compared with those reported in the literature to date.