Comprehensive and deep profiling of the plasma proteome with protein corona on zeolite NaY / 药物分析学报

Proteomic characterization of plasma is critical for the development of novel pharmacodynamic bio-markers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the"masking"effect caused by high-abundance proteins.The relative abundance of middle-and low-abundance proteins increased substantially from 2.54％to 54.41％,and the top 20 high-abundance proteins decreased from 83.63％to 25.77％.Notably,our method can quantify approxi-mately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins iden-tified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.

Clinical features and long-term prognosis of diabetic patients with low or intermediate complexity coronary artery disease post percutaneous coronary intervention / 中华心血管病杂志

Objective: To investigate the clinical features and long-term prognostic factors of diabetic patients with low or intermediate complexity coronary artery disease (CAD) post percutaneous coronary intervention (PCI). Methods: This was a prospective, single-centre observational study. Consecutive diabetic patients with SYNTAX score (SS)≤32 undergoing PCI between January and December 2013 in Fuwai hospital were included in this analysis. The patients were divided into two groups based on SS, namely SS≤22 group and SS 23-32 group. Multivariate Cox regression analysis was performed to identify independent factors related to poor 5-year prognosis. The primary outcomes were cardiac death and recurrent myocardial infarction, the secondary outcomes were all cause death and revascularization. Results: Of the 3 899 patients included in the study, 2 888 were men (74.1%); mean age was 59.4±9.8 years. There were 3 450 patients in the SS≤22 group and 449 patients in the SS 23-32 group. Compared with SS≤22 group, the incidence of revascularization was higher in SS 23-32 group (18.9% (85/449) vs. 15.2% (524/3450), log-rank P=0.019). There was no significant difference in all-cause death, cardiac death and recurrent myocardial infarction between the two groups (log-rank P>0.05). Multivariate Cox regression analysis showed that age (HR=1.05, 95%CI 1.02-1.08, P<0.001), chronic obstructive pulmonary disease (HR=3.12, 95%CI 1.37-7.07, P=0.007) and creatinine clearance rate (CCr)<60 ml/min (HR=3.67, 95%CI 2.05-6.58, P<0.001) were independent risk factors for 5-year cardiac death, while left ventricular ejection fraction (HR=0.94, 95%CI 0.91-0.96, P<0.001) was a protective factor. Previous PCI (HR=2.04, 95%CI 1.38-3.00, P<0.001), blood glucose level≥11.1 mmol/L on admission (HR=2.49, 95%CI 1.32-4.70, P=0.005) and CCr<60 ml/min (HR=1.85, 95%CI 1.14-2.99, P=0.012) were independent risk factors for 5-year recurrent myocardial infarction. The SS of 23-32 was independently associated with risk of revascularization (HR=1.54, 95%CI 1.09-2.16, P=0.014), after adjusting for residual SS. Residual SS was not a risk factor for 5-year prognosis. Conclusions: In diabetic patients with low-or intermediate complexity CAD, SS 23-32 is associated with increased risk of 5-year revascularization; the clinical characteristics of the patients are associated with the long-term mortality and recurrent myocardial infarction, but not related to revascularization.

Network Analysis of Meaning in Life and Coping Styles among College Students / 中国医学伦理学

【Objective:】 To explore the network structure characteristics and core items of meaning in life and coping styles among college students, and provide a basis for understanding their relationships and related interventions. 【Methods:】 A survey was conducted among college students using the Simplified Coping Style Questionnaire and Meaning in Life Questionnaire . The network analysis method was used to construct a network of college students’ meaning in life and coping styles, and R software was used for statistical analysis and visualization. 【Results:】 In the network of college students’ meaning in life and coping styles, "believing that time will change the status quo, and the only thing to do is to wait" and "trying to forget the whole thing" had the closest connection. "Learning from others to handle similar difficult situations" had the highest expected impact. "Seeking the meaning in life" and "pursuing hobbies and actively participating in cultural and sports activities" had the highest bridge expected influence. The average predictability value of all nodes was 0.775. 【Conclusions:】 Interventions aimed at "learning from others to handle similar difficult situations", "changing one’s own ideas and rediscovering what is important in life" and "changing some of the original practices or problems" may maximize the coping effect of college students. "Seeking the meaning in life" can furthest influence the coping styles, and "pursuing hobbies and actively participating in cultural and sports activities" can maximize the improvement of meaning in life.

The impact of image quality on the diagnostic performance of CT-derived fractional flow reserve / 中华放射学杂志

Objective:To explore the impact of coronary CT angiography (CCTA) image quality and related factors on the diagnostic performance of CT-derived fractional flow reserve (CT-FFR).Methods:Based on the CT-FFR CHINA trial, the prospective multicenter trial enrolled patients with suspected coronary artery disease who underwent CCTA, CT-FFR and FFR measurement. The subjective and objective assessments of CCTA image were performed on a per-vessel level. The objective assessments included the enhancement degree of coronary artery, the signal-to-noise ratio (SNR) of the aortic root. We used χ 2 test and DeLong test to compare the diagnostic performance of CT-FFR with FFR as the reference standard in different subjective groups (non-artifact vs. artifact), enhancement degree of coronary artery groups (≤400 vs. 401-500 vs.>500 HU), SNR of the aortic root groups (≤16.9 vs.>16.9), body mass index (BMI) groups (<25 kg/m 2 vs.≥25 kg/m 2) and heart rate groups (<75 bpm vs.≥75 bpm). FFR and CT-FFR values≤0.80 was identified as myocardial ischemia. Results:The study enrolled 317 patients with 366 vessels. All target vessels in CCTA images were successfully analyzed by CT-FFR. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value and AUC of the non-artifact group were 90.45%, 86.75%, 93.10%, 90.00%, 90.76% and 0.928, respectively, and those of the artifact group were 83.23%, 87.21%, 79.01%, 81.52%, 85.33% and 0.869, respectively. The differences in accuracy and specificity were statistically significant (χ 2=4.23, P=0.040; χ 2=8.55, P=0.003). The diagnostic efficacy of CT-FFR had no statistically significant differences among different objective groups (all P>0.05). Conclusions:The artifact of CCTA image has an effect on CT-FFR in the diagnosis of myocardial ischemia. The degree of vascular enhancement, SNR, BMI, and heart rate have no significant effect on the diagnostic performance of CT-FFR.

Short-term outcome of kidney transplantation from deceased donors with nephrolithiasis / 中南大学学报(医学版)

Objective: Shortage of kidney allografts is a major barrier to end-stage renal disease patients receiving kidney transplantation, and it is necessary to enlarge the donor pool and find better ways of using available allografts. The global incidence of nephrolithiasis is increasing, nephrolithiasis affects approximately 10％ of adults worldwide, and it also affects the kidney donors. However, there is little information about the use of cadaveric kidney allografts with nephrolithiasis. This study aims to evaluate the safety and outcome of kidney transplantation with allografts from the deceased donors with nephrolithiasis. Methods: A total of 520 deceased donors who was at least 10 years old, and 945 adult recipients with single kidney transplantation at the Department of Kidney Transplantation, the Second Xiangya Hospital from 2016 to 2020 were included in this study. The donors were divided into 2 groups according to nephrolithiasis diagnoses: The donors with nephrolithiasis (D+) and the donors without nephrolithiasis (D?). The recipients were assigned into 3 groups according to their donors and the allografts they received: The allografts from donors without nephrolithiasis (D?K?), the allografts without nephrolithiasis from donors with nephrolithiasis (D+K?), and the allografts with nephrolithiasis (D+K+). The demographic and clinical data of enrolled subjects were retrospectively analyzed. The allograft discard ratio between different donors were analyzed. The one-year survival of allografts and recipients, as well as the allograft function and the complications of kidney transplantation were compared. Results: Fifty out of 520 donors had nephrolithiasis, and the nephrolithiasis incidence was 9.6％. We recovered 1040 kidneys, and total discard rate was 4.4％ (46/1040). The D+ group had a rate of 7％ discard. The donors with kidney discard accounted for 12％ in the D+ group, and this was higher than that of donors in the D? group (5.1％, P<0.05). The total incidence of delayed graft function (DGF) was 7.5％, and there were no significant differences in the incidence of DGF in recipients among the D?K?, D+K?, and D+K+ group (7.5％ vs 6.5％ vs 8.2％, P>0.05). During the one-year follow-up, 8 allografts lost function and 19 recipients died with a functional allograft. Recipients in the D?K?, D+K?, and D+K+ groups also had no significant difference between a one-year allograft and patient survival rate (P>0.05). However, recipients in the D+K+ group had a higher level of serum creatinine [(139.2±62.46) μmol/L vs (117.19±51.22) μmol/L, P<0.05] and lower estimated glomerular filtration rate [eGFR; (56.67±23.31) mL/(min·1.73 m?2) vs (66.86±21.90) mL/(min·1.73 m?2), P<0.05] compared with recipients in the D?K? group at 12 months after transplantation. During the first year after transplantation, 4 recipients developed urolithiasis, and recipients who received allografts from the D+ group donors had a higher incidence of urolithiasis than those who received allografts from the D? group donors (2.2％ vs 0.2％, P<0.05). There were no significant differences in the incidence of urinary tract infections and ureteral strictures at 1 year between recipients of D+ and D? donors (both P>0.05).Conclusion: The cadaveric kidney allografts with nephrolithiasis could be safely used for transplantation, and the short-term outcome is acceptable. However, nephrolithiasis in donors may increase the rate of kidney discard, disturb the short-term function of allografts, and increase the risk of urolithiasis in recipients. Further research with a long-term study is needed to verify the long-term outcome of kidney transplantation using cadaveric kidney allografts with nephrolithiasis.

Impact of interventional therapy on top of standard drug therapy on left ventricular structure and function in HFrEF patients complicating with middle aortic syndrome caused by Takayasu arteritis / 中华心血管病杂志

Objective: To evaluate the impact of interventional therapy on top of drug therapy on cardiac function and structure in heart failure with reduced ejection fraction (HFrEF) patients complicating with middle aortic syndrome caused by Takayasu arteritis (TA-MAS). Methods: It was a retrospective longitudinal study. The data of patients with TA-MAS and HFrEF, who received interventional therapy on top of drug therapy in Fuwai Hospital from January 2010 to September 2020, were collected and analyzed. Baseline clinical data (including demographic data, basic treatment, etc.) were collected through the electronic medical record system. Changes of indexes such as New York Heart Association (NYHA) classification, N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) before and after therapy were analyzed. Results: A total of 10 patients were collected. There were 8 females in this patient cohort, age was (18.4±5.0) years and onset age was (15.3±5.0) years. All 10 patients received standard heart failure medication therapy in addition to hormone and/or immunosuppressive anti-inflammatory therapy, but cardiac function was not improved, so aortic balloon dilatation and/or aortic stenting were performed in these patients. The median follow-up was 3.3(1.3, 5.6) years. On the third day after interventional therapy, the clinical symptoms of the 10 patients were significantly improved, NYHA classfication was restored from preoperative Ⅲ/Ⅳ to Ⅱ at 6 months post intervention(P<0.05). Compared with preoperation, NT-proBNP (P=0.028), LVEDD (P=0.011) and LVMI (P=0.019) were significantly decreased, LVEF was significantly increased (P<0.001) at 6 months after operation. Compared with preoperation, NT-proBNP (P=0.016), LVEDD (P=0.023) and LVMI (P=0.043) remained decreased, LVEF remained increased (P<0.001) at 1 year after operation. Conclusion: Results from short and medium term follow-up show that interventional therapy on top of heart failure drug therpay can effectively improve left cardiac function and attenuate cardiac remodeling in patients with TA-MAS comorbid with HFrEF.

Predictive value of SYNTAX-Ⅱ score on prognosis of patients with chronic total occlusion undergoing percutaneous coronary intervention / 中华心血管病杂志

Objective: To investigate the predictive value of SYNTAX-Ⅱ score on long term prognosis of patients diagnosed with chronic total occlusion (CTO) and received percutaneous coronary intervention (PCI). Methods: Patients undergoing CTO-PCI in Fuwai hospital from January 2010 to December 2013 were enrolled in this retrospective analysis. The SYNTAX-Ⅱ score of the patients was calculated. According to SYNTAX-Ⅱ score tertiles, patients were stratified as follows: SYNTAX-Ⅱ≤20, 20<SYNTAX-Ⅱ≤27, SYNTAX-Ⅱ>27. Primary endpoint was major adverse cardiac events (MACCE), including all-cause death, myocardial infarction, stroke and any revascularization. Secondary endpoints included stent thrombosis, heart failure and target lesion failure (TLF). Patients were followed up by outpatient visit or telephone call at 1 month, 6 months and 1 year after PCI, and annually up to 5 years. Multivariate Cox regression model was used to analyze the independent risk factors of all-cause death in patients undergoing CTO-PCI. The predictive value of SYNTAX score with SYNTAX-Ⅱ score for all-cause death was evaluated by the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results: A total of 2 391 patients with CTO and received PCI were enrolled in this study. The mean age was (57.0±10.5) years, 1 994 (83.40%) patients were male. There were 802 patients in lower tertile group (SYNTAX-Ⅱ≤20), 798 patients in intermediate group (20<SYNTAX-Ⅱ≤27) and 791 patients in upper tertile group (SYNTAX-Ⅱ>27). At the end of 5-year follow-up, the loss to follow-up rate of the three groups was 9.10%(73/802), 10.78%(86/798)and 8.85%(70/791), respectively. The rate of all-cause mortality (1.78% (13/729) vs. 3.65% (26/712) vs. 9.02% (65/721), P<0.001), cardiac death (1.37% (10/729) vs. 2.11% (15/712) vs. 4.85% (35/721), P<0.001), target vessel myocardial infarctions (4.25% (31/729) vs. 4.49% (32/712) vs. 7.07% (51/721), P=0.03), probable stent thrombosis (1.51% (11/729) vs. 2.81% (20/712) vs. 3.61% (26/721), P=0.04) and heart failure (1.78% (13/729) vs. 1.97% (14/712) vs. 5.41% (39/721), P<0.001) increased in proportion to increasing SYNTAX-Ⅱ score (all P<0.05). Multivariable Cox regression analysis indicated that female (HR=2.05, 95%CI 1.12-3.73, P=0.01), left ventricular ejection fraction (HR=0.97, 95%CI 0.95-1.00, P=0.05) and SYNTAX-Ⅱ score (HR=1.07, 95%CI 1.02-1.11,P=0.01) were independent predictors for all-cause mortality in patients undergoing CTO-PCI. The predicted value of the SYNTAX-Ⅱ score for all-cause death was significantly higher than the SYNTAX score (AUC 0.71 vs. 0.60, P=0.003). Conclusion: For CTO patients who underwent percutaneous coronary intervention, SYNTAX-Ⅱ score is an independent predictor for 5-year all-cause death, and SYNTAX-Ⅱ serves as an important predictor for all-cause death in these patients.

Impact of prolonging dual antiplatelet therapy on long-term prognosis of elderly patients with coronary heart disease complicated with diabetes mellitus undergoing drug-eluting stent implantation / 中华心血管病杂志

Objective: To explore and compare the effect of standard or prolonged dual antiplatelet therapy (DAPT) on the long-term prognosis of elderly patients with coronary heart disease complicated with diabetes mellitus after drug-eluting stent (DES) implantation. Methods: Consecutive patients with diabetes mellitus, ≥65 years old, underwent DES implantation, and had no adverse events within 1 year after operation underwent percutaneous coronary intervention (PCI) from January to December 2013 in Fuwai Hospital were enrolled in this prospective cohort study. These patients were divided into three groups according to DAPT duration: standard DAPT duration group (11 ≤ DAPT duration≤ 13 months) and prolonged DAPT duration group (13<DAPT duration≤ 24 months; DAPT duration>24 months). All the patients were followed up at 1, 6 months, 1, 2 and 5 years in order to collect the incidence of major adverse cardiovascular and cerebrovascular events (MACCE), and type 2 to 5 bleeding events defined by the Federation of Bleeding Academic Research (BARC). MACCE were consisted of all cause death, myocardial infarction, target vessel revascularization or stroke. The incidence of clinical adverse events were compared among 3 different DAPT duration groups, and Cox regression model were used to analyze the effect of different DAPT duration on 5-year long-term prognosis. Results: A total of 1 562 patients were enrolled, aged (70.8±4.5) years, with 398 female (25.5%). There were 467 cases in standard DAPT duration group, 684 cases in 13<DAPT duration≤ 24 months group and 411 cases in DAPT duration>24 months group. The patients in standard DAPT duration group and the prolonged DAPT duration groups accounted for 29.9% (467/1 562) and 70.1% (1 095/1 562), respectively. The 5-year follow-up results showed that the incidence of all-cause death in 13<DAPT duration≤ 24 months group (4.8%(33/684) vs. 8.6%(40/467),P=0.011) and DAPT duration>24 month group(4.1%(17/411) vs. 8.6%(40/467),P=0.008) were significantly lower than in standard DAPT group. The incidence of myocardial infarction in 13<DAPT duration≤ 24 months group was lower than in standard DAPT duration group (1.9%(13/684) vs. 5.1%(24/467),P=0.002). The incidence of MACCE in 13<DAPT duration≤ 24 months group was the lowest (standard DAPT duration group, 13<DAPT duration≤ 24 months group and DAPT duration>24 month group were 19.3% (90/467), 12.3% (84/684), 20.2% (83/411), respectively, P<0.001). There was no significant difference in the incidence of stroke and bleeding events among the three groups (all P>0.05). Multivariate Cox analysis showed that compared with the standard DAPT group, prolonged DAPT to 13-24 months was negatively correlated with MACCE (HR=0.601, 95%CI 0.446-0.811, P=0.001), all-cause death (HR=0.568, 95%CI 0.357-0.903, P=0.017) and myocardial infarction (HR=0.353, 95%CI 0.179-0.695, P=0.003). DAPT>24 months was negatively correlated with all-cause death (HR=0.687, 95%CI 0.516-0.913, P=0.010) and positively correlated with revascularization (HR=1.404, 95%CI 1.116-1.765, P=0.004). There was no correlation between prolonged DAPT and bleeding events. Conclusions: For elderly patients with coronary heart disease complicated with diabetes mellitus underwent DES implantation, and had no MACCE and bleeding events within 1 year after operation, appropriately prolonging of the DAPT duration is related to the reduction of the risk of cardiovascular adverse events. Patients may benefit the most from the DAPT between 13 to 24 months. In addition, prolonging DAPT duration does not increase the incidence of bleeding events in this patient cohort.

The short-term and long-term prognostic analysis in patients with chronic total occlusion acute non-ST segment elevation myocardial infarction / 中华内科杂志

Objectives:To investigate the clinical impacts of chronic total occlusion (CTO) in acute non-ST segment elevation myocardial infarction (NSTEMI) patients underwent primary percutaneous coronary intervention (PCI).Methods:A total of 2 271 acute NSTEMI patients underwent primary PCI from China Acute Myocardial Infarction Registry were enrolled in this study and divided into the CTO group and the non-CTO group according to the angiography. The primary endpoint was in-hospital mortality and mortality during a 2-year follow-up. The secondary endpoint was major adverse cardiovascular events (MACE) including revascularization, death, re-myocardial infarction, heart failure readmission, stroke and major bleeding.Results:Thirteen-point four percent of the total acute NSTEMI patients had concurrent CTO. In-hospital mortality (3.6% vs. 1.4%, P<0.01) and 2-year mortality (9.0% vs. 5.1%, P<0.01) were significantly higher in the CTO group than those in the non-CTO group, respectively. Multiple regression analyses showed that chronic obstructive pulmonary disease ( HR 7.28, 95% CI 1.50-35.35, P=0.01) was an independent risk factor of in-hospital mortality, and advanced age ( HR 1.04, 95% CI 1.01-1.07, P<0.01), and low levels of ejection fraction ( HR 0.95, 95% CI 0.93-0.98, P<0.01) were independent risk factors of 2-year mortality. CTO ( HR1.67, 95% CI 1.10-2.54, P=0.02) was an independent risk factor of revascularization, but not a risk factor of mortality. Conclusions:Although acute NSTEMI patients concurrent with CTO had higher mortality, CTO was only an independent risk factor of revascularization, but not of mortality. Advanced age and low levels of ejection fraction were independent risk factors of long-term death among acute NSTEMI patients.

Comparison of the long-term outcomes of focused ultrasound ablation surgery for uterine fibroids and myomectomy / 中华妇产科杂志

Objective:To compare the long-term outcomes after focused ultrasound ablation surgery (FUAS) versus myomectomy for uterine fibroids.Methods:A retrospective study was conducted on women who were treated by FUAS or myomectomy for uterine fibroids at First Medical Center of Chinese PLA General Hospital from January 2007 to January 2015. Regular follow-up was conducted to evaluate the symptoms relief, symptoms recurrence, the need for re-interventions and complications of the two groups.Results:The effective rates were 95.7% (730/763) and 95.5% (1 151/1 205) in women who were treated by FUAS and myomectomy, no statistical difference was seen between the two groups ( χ2 =0.027, P=0.869). The cumulative rates of symptoms recurrence at 1 year, 3 years, 5 years, 8 years and 10 years of follow-up in FUAS group were 1.8%, 6.8%, 11.9%, 15.2% and 15.9%, respectively; and the cumulative re-intervention rates were 0.7%, 4.1%, 6.8%, 9.9% and 11.0%, respectively. The cumulative rates of symptoms recurrence at 1 year, 3 years, 5 years, 8 years and 10 years of follow-up in myomectomy group were 1.8%, 5.9%, 10.6%, 14.2% and 14.9%, respectively; and the cumulative re-intervention rates were 0.9%, 4.5%, 7.8%, 10.3% and 11.4%, respectively. No statistical differences were seen between the two groups (all P>0.05). There were no significant differences in the effective rate, symptoms recurrence rate and re-intervention rate between the two groups in patients with intermural fibroids; but the effective rate of FUAS (95.9%, 235/245) was higher than that of myomectomy (89.1%, 115/129), the symptoms recurrence rate (11.9%, 28/235) was lower than that of myomectomy (27.8%, 32/115), and the re-intervention rate (7.7%, 18/235) was lower than that of myomectomy (17.4%, 20/115) in patients with submucosal fibroids, there were significant different (all P<0.05). The effective rate of FUAS (91.0%, 132/145) was lower than that of myomectomy (97.0%, 322/332), the symptoms recurrence rate (32.6%, 43/132) was higher than that of myomectomy (9.9%, 32/322), and the re-intervention rate (22.0%, 29/132) was higher than that of myomectomy group (6.2%, 20/132) in patients with subserosal fibroids, there were significant different (all P<0.01). The incidences of total [1.8% (14/763) vs 21.9% (264/1 205)], minor and moderate adverse events were lower in FUAS group than myomectomy group (all P<0.001). Conclusion:Satisfaction with long-term outcomes after FUAS treatment or myomectomy for uterine fibroids is comparable.

Prestin-Mediated Frequency Selectivity Does not Cover Ultrahigh Frequencies in Mice / 神经科学通报·英文版

In mammals, the piezoelectric protein, Prestin, endows the outer hair cells (OHCs) with electromotility (eM), which confers the capacity to change cellular length in response to alterations in membrane potential. Together with basilar membrane resonance and possible stereociliary motility, Prestin-based OHC eM lays the foundation for enhancing cochlear sensitivity and frequency selectivity. However, it remains debatable whether Prestin contributes to ultrahigh-frequency hearing due to the intrinsic nature of the cell's low-pass features. The low-pass property of mouse OHC eM is based on the finding that eM magnitude dissipates within the frequency bandwidth of human speech. In this study, we examined the role of Prestin in sensing broad-range frequencies (4-80 kHz) in mice that use ultrasonic hearing and vocalization (to >100 kHz) for social communication. The audiometric measurements in mice showed that ablation of Prestin did not abolish hearing at frequencies >40 kHz. Acoustic associative behavior tests confirmed that Prestin-knockout mice can learn ultrahigh-frequency sound-coupled tasks, similar to control mice. Ex vivo cochlear Ca2+ imaging experiments demonstrated that without Prestin, the OHCs still exhibit ultrahigh-frequency transduction, which in contrast, can be abolished by a universal cation channel blocker, Gadolinium. In vivo salicylate treatment disrupts hearing at frequencies <40 kHz but not ultrahigh-frequency hearing. By pharmacogenetic manipulation, we showed that specific ablation of the OHCs largely abolished hearing at frequencies >40 kHz. These findings demonstrate that cochlear OHCs are the target cells that support ultrahigh-frequency transduction, which does not require Prestin.

MiR-133b regulates the proliferation, colony formation, and invasion of bladder cancer cells via inhibiting SOX4 / 中南大学学报(医学版)

OBJECTIVES@#Bladder cancer is one of the most common urothelial tumors with high incidence and mortality rates. Although it has been reported that microRNA (miR)-133b can regulate tumorigenesis of bladder cancer, the mechanism remains unclear. Sex-determining region Y-box transcription factor 4 (SOX4) exhibits an important role in tumorigenesis, but it is unclear whether SOX4 and miR-133b are associated with regulation of pathogenesis of bladder cancer. This study aims to determine the expressions of SOX4 and miR-133b in bladder cancer tissues and cells, investigate their effects on the proliferation, colony formation, and invasion of bladder cancer cells, and to explore the association between miR-133b and SOX4 in regulating biological featurss of bladder cancer cells.@*METHODS@#The bladder cancer and adjacent tissue samples of 10 patients who underwent surgical resection in the Second Xiangya Hospital of Central South Universty from Januray to June 2015 were obtained. The levels of miR-133b were tested by real-time PCR, and the protein levels of SOX4 were evaluated using Western blotting in bladder cancer tissues, matched adjacent tissues, and cell lines. The correlation between miR-133b expression and SOX4 expression in bladder cancer tissues was analyzed. Using the online database TargetScan, the relationship between SOX4 and miR-133b was predicted. MiR-133b mimics, miR-133b inhibitor, and short hairpin RNA (shRNA)-SOX4 were transfected into T24 cells by Lipofectamine 2000. The relationship between miR-133b and SOX4 was also verified by a dual-luciferase reporter assay. The proliferation of T24 cells cultured for 0, 12, 48, 72, and 96 h was evaluated by cell counting kit-8 (CCK-8) assay. The colony formation capacity of bladder cancer cells was tested after 14-day culture, and cell invasion capacity was evaluated with Transwell invasion assay.@*RESULTS@#Bladder cancer tissue and bladder cancer cells had low level of miR-133b but high level of SOX4, compared with matched adjacent tissues and normal bladder epithelial cells. A negative correlation between miR-133b mRNA and SOX4 protein levels in bladder cancer tissues was also found (r=-0.84). The results of online database TargetScan showed that miR-133b targets at SOX4, and overexpression of miR-133b significantly attenuated the expression of SOX4 in T24 cells. Both overexpression of miR-133b and knockdown of SOX4 significantly inhibited the proliferation, colony formation, and invasion capacity of bladder cancer cells in vitro. SOX4 down-regulation restored the effects of miR-133b inhibitor on the proliferation, colony formation, and invasion capacity of T24 cells.@*CONCLUSIONS@#The up-regulation of SOX4 contributes to the progression of bladder cancer, and miR-133b can regulate the proliferation, colony formation, and invasion of bladder cancer cells via inhibiting SOX4.

Lingbao Huxin Pill Alleviates Apoptosis and Inflammation at Infarct Border Zone through SIRT1-Mediated FOXO1 and NF- κ B Pathways in Rat Model of Acute Myocardial Infarction / 中国结合医学杂志

OBJECTIVE@#To investigate whether Lingbao Huxin Pill (LBHX) protects against acute myocardial infarction (AMI) at the infarct border zone (IBZ) of myocardial tissue by regulating apoptosis and inflammation through the sirtuin 1 (SIRT1)-mediated forkhead box protein O1 (FOXO1) and nuclear factor-κ B (NF-κ B) signaling pathways.@*METHODS@#Six-week-old Wistar rats with normal diet were randomized into the sham, the model, Betaloc (0.9 mg/kg daily), LBHX-L (0.45 mg/kg daily), LBHX-M (0.9 mg/kg daily), LBHX-H (1.8 mg/kg daily), and LBHX+EX527 (0.9 mg/kg daily) groups according to the method of random number table, 13 in each group. In this study, left anterior descending coronary artery (LADCA) ligation was performed to induce an AMI model in rats. The myocardial infarction area was examined using a 2,3,5-triphenyltetrazolium chloride solution staining assay. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was conducted to assess cardiomyocyte apoptosis in the IBZ. The histopathology of myocardial tissue at the IBZ was assessed with Heidenhain, Masson and hematoxylineosin (HE) staining assays. The expression levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1 β, and intercellular adhesion molecule-1 were measured using enzyme-linked immunosorbent assays (ELISAs). The mRNA expressions of SIRT1 and FOXO1 were detected by real-time qPCR (RT-qPCR). The protein expressions of SIRT1, FOXO1, SOD2, BAX and NF- κ B p65 were detected by Western blot analysis.@*RESULTS@#The ligation of the LADCA successfully induced an AMI model. The LBHX pretreatment reduced the infarct size in the AMI rats (P<0.01). The TUNEL assay revealed that LBHX inhibited cardiomyocyte apoptosis at the IBZ. Further, the histological examination showed that the LBHX pretreatment decreased the ischemic area of myocardial tissue (P<0.05), myocardial interstitial collagen deposition (P<0.05) and inflammation at the IBZ. The ELISA results indicated that LBHX decreased the serum levels of inflammatory cytokines in the AMI rats (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that the LBHX pretreatment upregulated the protein levels of SIRT1, FOXO1 and SOD2 (P<0.05) and downregulated NF- κ B p65 and BAX expressions (P<0.05). The RT-qPCR results showed that LBHX increased the SIRT1 mRNA and FOXO1 mRNA levels (P<0.05). These protective effects, including inhibiting apoptosis and alleviating inflammation in the IBZ, were partially abolished by EX527, an inhibitor of SIRT1.@*CONCLUSION@#LBHX could protect against AMI by suppressing apoptosis and inflammation in AMI rats and the SIRT1-mediated FOXO1 and NF- κ B signaling pathways were involved in the cardioprotection effect of LBHX.

Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study / 中国当代儿科杂志

OBJECTIVES@#To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment.@*METHODS@#A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group.@*RESULTS@#Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05).@*CONCLUSIONS@#This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

Postsynaptic Targeting and Mobility of Membrane Surface-Localized hASIC1a / 神经科学通报·英文版

Acid-sensing ion channels (ASICs), the main H

Long noncoding RNA small nucleolar RNA host gene 1 promotes gemcitabine resistance by targeting microRNA330 in pancreatic cancer cells / 中华胰腺病杂志

Objective:To investigate the role of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in the resistance of pancreatic cancer PANC1 cells to gemcitabine (GEM), and clarify the relationship between SNHG1 and miR-330.Methods:The clinical data of 179 pancreatic tissue samples and 171 adjacent normal pancreas tissues were collected from the Cancer Genome Atlas (TCGA), and bioinformatics analysis was performed to analyze the expression of SNHG1 and miR-330 in pancreatic cancer tissue and adjacent normal tissue. PANC1 cell line with the resistance to GEM was established by the intermittent gradient doubling method in vitro. The GEM-resistant cells were divided into three groups: si-NC-GEM (negative control) group, si-SNHG1-GEM (transfected with siRNA targeting SNHG1) group, and GEM-resistant group. At the same time, to validate the role of miR-330 in targeting SNHG1 expression, the GEM-resistant cells were further divided into three groups: NC-inh+ si-NC group (co-transfected with negative control miR-330 inhibitor and si-NC), NC-inh+ si-SNHG1 group (co-transfected with negative control miR-330 inhibitor and si-SNHG1), and miR-330-inh + si-SNHG1 group (co-transfected with miR-330 inhibitor and si-SNHG1). qRT-PCR was used to detect the expression of SNHG1 and miR-330 in GEM-resistant cells. CCK-8 and immunofluorescence (Ki67) were used to test GEM-resistant cell growth and proliferation. Transwell and wound healing were used to test the migration and invasion in GEM-resistant cells. Bioinformatics analysis and luciferase reporter assay were used to verify the regulatory relationship between SNHG1 and miR-330. Results:Compared to the adjacent normal tissues of pancreatic cancer, the expression of lncRNA SNHG1 in pancreatic cancer tissues was significantly increased (6.543±0.72 vs 5.31±0.96), and the expression of miR-330 was greatly decreased (2.54±1.85 vs 3.01±1.23); and all the differences were statistically significant ( P<0.05). The expression of lncRNA SNHG1 in si-NC-GEM group, si-SNHG1-GEM group, and GEM-resistant group was 2.43±0.10, 0.26±0.08 and 3.25±0.310, which in si-SNHG1-GEM group was lower than those in si-NC-GEM group or GEM-resistant group. While the expression of miR-330 in si-NC-GEM group, si-SNHG1-GEM group, and GEM-resistant group was 0.47±0.13, 0.84±0.12 and 0.38±0.21, which in si-SNHG1-GEM group was higher than those in si-NC-GEM group or GEM-resistant group. All the differences were statistically significant ( P<0.05). Compared to the si-NC-GEM group or GEM-resistant group, A450, Ki67, number of migrated cells and the distance of invasion in si-SNHG1-GEM group were all decreased, and the differences were statistically significant ( P<0.05). Otherwise, luciferase activity of miR-330-WT in si SNHG1-GEM group was significantly higher than that in NC siRNA group (3.21±0.22 vs 1.03±0.18). The luciferase activity of SNHG1-WT in miR-330 inhibitor group was significantly lower than that in NC inhibitor group (0.97±0.21 vs 2.32±0.17). In miR-330-inh+ si-SNHG1 GEM-resistant group, the cell A450, Ki67, migration cell and distant of invasion was higher than those in NC-inh+ si-SNHG1 group, and the difference was statistically significant (all P value<0.05). Conclusions:lncRNA SNHG1 targeting miR-330 could promote GEM resistance in pancreatic cancer PANC1 cells.

Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network

Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.

Alternating Hemiplegia of Childhood Caused by / 中国医学科学杂志(英文版)

Alternating hemiplegia of childhood is a rare neurodevelopmental disorder. Most cases are reported as sporadic disorder due to

Application of scenario simulation in prevention of needlestick injuries based on Kirkpatrick model / 中华医学教育探索杂志

Objective:To evaluate the application method and effect of standardized scenario simulation teaching based on Kirkpatrick model in vocational protection education for nursing students.Methods:A historical controlled trial study was designed. Practical nursing students enrolled in 2018-2019 and 2017-2018 were selected into the experimental group ( n=203) and control group ( n=196), respectively. The experimental group adopted standardized scenario simulation teaching in the prevention and control education of needlestick injuries, and the control group adopted traditional classroom lecture. Using the Kirkpatrick model, the teaching effect of needlestick injuries protection for nursing students were compared between the 2 groups from such 4 levels as in reaction level, learning level, behavior level and results level. Results:There was no significant difference in the baseline data between the two groups in terms of age, gender, educational background and test scores of nursing professional knowledge as compared to that before practice. In reaction level: the nursing students' satisfaction of experimental group in teaching methods ( t=25.149, P<0.001) and teaching environment ( t=12.827, P<0.001) are higher than that of the control group, with statistical significance. In learning level: the test scores of needlestick injury knowledge in experimental group were significantly higher than those in control group ( t=8.221, P<0.001). In behavior level: the level of needlestick injury protection behavior in the experimental group was significantly higher than that in the control group ( t=9.250, P<0.001), and the knowledge conversion rate in the experimental group was higher than that in the control group ( t=6.054, P<0.001). In results level: the needlestick injuries incidence of experimental group was significantly lower than that of the control group ( χ2=15.815, P<0.001), the reported rate of needlestick injuries of experimental group was significantly lower than that of the control group ( χ2=14.185, P<0.001). Conclusion:The implementation of standardized scenario simulation teaching can effectively improve the effectiveness of vocational protection learning and reduce the incidence of needlestick injuries.

Ultrasound-guided placement of midline catheter reduces the incidence rate of catheter-related bloodstream infection / 中华急诊医学杂志

Objective:To investigate the effect of ultrasound-guided midline catheter placement on the incidence of catheter-related bloodstream infection (CRBSI) in severe emergency patients.Methods:Five hundred and twenty-nine patients were chosen as the research objects from March 2018 to December 2019 at Emergency Intensive Care Unit, which was divided into the experimental group ( n=278) and the control group ( n=251). In the experimental group, ultrasound-guided midline catheter was used as central venous catheter (CVC) removal method of sequential, and in the control group, peripheral venous indwelling needle was used as sequential method after removal of CVC. CVC, midline catheter and the indwelling time of indwelling needle were counted. The utilization rate of CVC was compared between the two groups. Kaplan-Meier survival curve was plotted to describe the CVC indwelling time of the two groups and log-rank test was performed. Cox regression analysis was performed to analyze the influencing factors of CVC indwelling time and compare the incidence of CRBSI and other catheter-related complications. Results:The CVC indwelling time of the experimental group was significantly shorter than that of the control group (8 d vs. 13 d, P=0.000). The CVC utilization rate of the experimental group was significantly lower than that of the control group (49.83% vs. 80.45%, P=0.000). Multivariate Cox regression analysis showed that difficult intravenous access, length of ICU stay, the site of catheter placement, and midline catheter implantation without ultrasound-guidance were independent risk factors for prolonged CVC indwelling time ( P=0.000). The CRBSI rate of the experimental group was significantly lower than that of the control group (0.571‰ vs. 3.802‰, P=0.038). There was no significant difference in the incidence of other catheter-related complications between the two groups ( P=0.403). Conclusions:Ultrasound-guided midline catheter implantation can shorten the indwelling time of CVC, reduce the utilization rate of CVC, and reduce the incidence of CRBSI, which is worthy of clinical promotion.