Effect of quality nursing care on wound pain and anxiety in burn patients: A meta-analysis.

To systematically evaluate the effects of quality nursing care on wound pain and anxiety in burn patients. Computerised searches of PubMed, Google Scholar, Cochrane Library, Embase, Wanfang, China Biomedical Literature Database and China National Knowledge Infrastructure databases randomised controlled trials (RCTs) on the application of quality nursing care to burn patients were carried out from database inception to October 2023. Literature was screened and evaluated by two researchers based on inclusion and exclusion criteria, and data were extracted from the final included literature. Stata 17.0 software was employed for data analysis. Overall, 15 RCTs and 1115 burn patients were included, including 563 and 552 in the quality care and routine care groups. It was found that, compared with routine care, burn patients who implemented quality care had significantly less wound pain (SMD: -1.79, 95% CI: -2.22 to -1.36, p < 0.001), anxiety (SMD: -2.71. 95% CI: -3.49 to -1.92, p < 0.001) and depression (SMD: -1.74, 95% CI: -2.35 to -1.14, p < 0.001) levels were significantly reduced post-trauma.

Causal effects of gut microbiota on the risk of erectile dysfunction: a Mendelian randomization study.

Erectile dysfunction ranks among the prevalent sexual disorders in men. Several studies have indicated a potential link between gut microbiota and erectile dysfunction. To validate this potential association, we were to screen statistical data from genome-wide association studies of gut microbiota and erectile dysfunction. p values of less than 1 × 10-5 were set as the threshold for screening instrumental variables that were strongly associated with gut microbiota. At the same time, in order to obtain more convincing findings, we further excluded instrumental variables with possible chain imbalance, instrumental variables with the presence of palindromes, instrumental variables with F-statistics less than 10, and instrumental variables associated with risk factors for erectile dysfunction. Five methods including inverse-variance weighted method, weighted median method, weighted mode, Mendelian randomization egger method and Mendelian randomization pleiotropy residual sum and outlier test were then used to analyse the 2591 instrumental variables obtained from the screening. We identified correlations between six gut microbiota and the risk of erectile dysfunction. The genus Ruminococcaceae UCG-013 exhibited an inverse association with the risk of developing erectile dysfunction (0.79 (0.65-0.97), P = 0.0214). Conversely, the genus Tyzzerella3 (1.13 (1.02-1.26), P = 0.0225), genus Erysipelotrichaceae UCG-003 (1.18 (1.01-1.38), P = 0.0412), genus LachnospiraceaeNC2004group (1.19 (1.03-1.37), P = 0.0191), genus Oscillibacter (1.23 (1.08-1.41), P = 0.0022), and family Lachnospiraceae (1.26 (1.05-1.52), P = 0.0123) demonstrated positive associations with an increased risk of erectile dysfunction. These sensitivity analyses of the gut microbiota were consistent. This study demonstrated a possible causal relationship between gut microbiota and erectile dysfunction risk through Mendelian randomization analysis, providing new potential possibilities for the prevention and treatment of erectile dysfunction.

Application of optical coherence tomography and optical coherence tomography angiography biomarkers in the prognosis and monitoring of diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic macular edema(DME)is a complication of diabetic retinopathy(DR), and is also the main cause of vision loss and blindness in DR patients. Optical coherence tomography(OCT)and optical coherence tomography angiography(OCTA)serve as the principal methods for the non-invasive assessment of microstructural and microvascular pathological changes in the retina. They are widely-used methods for detecting and evaluating DME. As OCT and OCTA technologies advance, various parameters have assumed the role of biomarkers, such as central subfield thickness(CST), cube average thickness(CAT), cube volume(CV), disorganization of retinal inner layers(DRIL), hyperreflective foci(HRF)and subfoveal neuroretinal detachment(SND). OCT and OCTA are widely used in clinical practice. OCT can visually show the layer changes and subtle structures of the retina and choroid in the macular area, while OCTA is more often used to detect microvascular changes. In this article, the role of OCT and OCTA-related biomarkers in prognosis and monitoring in DME is described, while the biomarkers visible in the test results can provide new ideas for monitoring and treatment strategies in DME, and provide new insights into the pathogenesis of DR and DME.

Research progress of optical coherence tomography and optical coherence tomography angiography in the prediction of postoperative visual acuity in patients with idiopathic epiretinal membrane / 国际眼科杂志(Guoji Yanke Zazhi)

Idiopathic epiretinal membrane(IERM)is a kind of epiretinal membrane without any other known ocular conditions, which occurs mostly in the middle-aged and elderly people over the age of 50. As IERM worsens, the structure and function of the retina in the macular region are altered, leading to symptoms like reduced vision and metamorphopsia. The pathogenesis of IERM remains unclear, and surgery is the primary treatment option. However, there is no consensus on the best time to have surgery, and there are differences in how well patients recover their vision following surgery. Optical coherence tomography(OCT)and OCT angiography(OCTA), as non-invasive and rapid diagnostic tools to observe retinal microstructure and blood flow changes in the macula, have been extensively utilized in clinical settings. The use of OCT and OCTA parameters to predict postoperative visual acuity has emerged as a hot topic in IERM research. This article provides a comprehensive review of current research on the correlation between various OCT and OCTA parameters and the prediction of postoperative visual acuity in IERM, aiming to assist clinicians in determining the optimal timing for surgery and balancing the benefits and risks involved.

Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Cardiovascular diseases (CVDs) are a leading factor driving mortality worldwide. Iron, an essential trace mineral, is important in numerous biological processes, and its role in CVDs has raised broad discussion for decades. Iron-mediated cell death, namely ferroptosis, has attracted much attention due to its critical role in cardiomyocyte damage and CVDs. Furthermore, ferritinophagy is the upstream mechanism that induces ferroptosis, and is closely related to CVDs. This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy, and the regulatory pathways and molecular targets involved in ferritinophagy, and to determine their roles in CVDs. Furthermore, we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs. Collectively, this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

Meta-analysis of Huangqi (Astragalus membranaceus) and Chinese Yam (Rhizoma Dioscoreae) for Diabetic Nephropathy.

Context: Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), has caused enormous economic pressure and serious health problems worldwide. TCM practitioners commonly use a combination of Astragalus membranaceus (A. membranaceus) and Rhizoma Dioscoreae (R. Dioscoreae) in the treatment of DN. Research is still lacking on the therapeutic effects of TCM for DN. Objective: The systematic review and meta-analysis intended to evaluate whether the combination of A. membranaceus and R. Dioscoreae together with Western medicine can provide better efficacy against DN than treatment with traditional Western medicine alone, to provide a clinical medical basis for the use of the TCM combination. Design: The research team performed a performed a systematic narrative review by searching the Web of Science, Science Direct, Pubmed, China National Knowledge Infrastructure (CNKI), VIP, Wanfang, Chinese Science and Technology Journal Database, and Biomedical Literature Chinese Database from databases' inceptions to May 2023. The team used the keywords astragalus and yam, diabetic nephropathy, antidiabetic, and 24-h urinary protein. Setting: The review and meta-analysis occurred at Jiangxi Hospital of Integrated Traditional China and Western Medicine in Nanchang, Jiangxi, China. Intervention: To perform a subgroup analysis, the research team divided the studies into two groups based on the TCM treatment course, with one subgroup receiving treatment for ≤4 weeks and the second receiving treatment for >4 weeks, to judge whether a time-dependence existed for the effects of the TCM combination on UP. Outcome Measure: All studies used 24-h urinary protein (UP) as the outcome measure. Results: In all studies, all heterogeneous (P < .01, I2 = 94%, the intervention groups had a significantly greater reduction in 24-h UP than the control groups did (P < .05). The heterogeneity for a treatment course of ≤4 weeks was P < .01, I2 = 97%, and for a course of >4 weeks was P < .01, I2 = 87%. For both ≤4 weeks and >4 weeks, the intervention groups had a significantly greater reduction in 24-h UP than the control groups did, with P < .01 and P < .01, respectively. The protein effect wasn't time dependent. Conclusions: A. membranaceus and R. Dioscoreae can significantly reduce UP production, and inhibition of UP wasn't time-dependent.

The effect of bivalirudin on coagulation function in male patients with coronary heart disease undergoing percutaneous coronary intervention.

Aim of this study was to explore the effect of bivalirudin on coagulation function with the treatment of percutaneous coronary intervention (PCI) in male coronary heart disease (CHD) patients. There were 90 male CHD cases treated with PCIas study object and were randomly divided into bivalirudin and unfractionated heparin group (n=45). Unfractionated heparin group patients were given unfractionated heparin and bivalirudin group cases were treated with bivalirudin. Activated clotting time (ACT), thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), platelet count (PLT) were determined and the major adverse cardiovascular events (MACCE) were observed in two group patients. There was no significant (p<0.05) difference with ACT, TT, PT, PLT, APTT and Fib between the two groups before and after 6h, 24h and 72h of operation. The incidence of stent thrombosis and general bleeding with in 24h after PCI in bivalirudin group was lower than in heparin group. After 13 months of follow-up, there was no significant (p<0.05) difference in the incidence of MACCE between the two groups. Compared with the treatment of unfractionated heparin in CHD patients after PCI in 24h, the bivalirudin had more remarkable effect, such as rapid onset, short half-life, lower incidence of thrombosis and bleeding.

Laparoscopic resection of focal nodular hyperplasia in the hepatic caudate lobe.

OBJECTIVE: To investigate the safety and feasibility of laparoscopic resection of focal nodular hyperplasia (FNH) in the hepatic caudate lobe. METHODS: The clinical data of eight patients who underwent laparoscopic hepatic caudate lobe FNH resection at the Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of Army Medical University, were retrospectively analyzed. RESULTS: The laparoscopic procedures were successful in all eight patients, and no patients required conversion to open surgery. Five patients underwent partial caudate lobe resection, one patient underwent caudate lobe resection, and two patients underwent combined left hemihepatectomy with caudate lobe resection. Tumor resection was performed using the left approach in five cases, the right approach in one case, the middle hepatic fissure approach in one case, and the left and right combined approach in one case. The operation time ranged from 120 to 360 min, with a mean of 225 min. The intraoperative blood loss ranged from 50 to 600 ml, with a mean of 235 ml. No postoperative bleeding, bile leakage or abdominal infection occurred. CONCLUSIONS: Laparoscopic resection of hepatic caudate lobe FNH was safe and feasible in appropriate patients. Skilled laparoscopic hepatectomy techniques, adequate preoperative evaluation, appropriate choice of surgical approach and the control of intraoperative bleeding are critical to perform this surgery.

Research progress of microfluidic chips in age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Age-related macular degeneration(ARMD)is the primary cause of severe visual impairment and blindness in people over 60 years old. With the aging of the global population, the incidence of the disease is also rising year by year. However, the pathogenesis and treatment strategy of ARMD need to be further explored. As a cutting-edge science and technology, microfluidic chips can build a comprehensive microsystem that simulates the condition and function of human tissues and organs, which has the advantages of less sample consumption and short analysis time. In recent years, many studies have confirmed that microfluidic chips can bring brand new technology solutions to the basic and clinical research of ARMD. This article will discuss and review the application progress of microfluidic chips in the areas of ARMD mechanism research, drug evaluation and clinical translation, providing a theoretical reference for further research on the diagnosis and treatment of ARMD.

A comparative study of three internal fixation techniques for split fractures of humeral greater tuberosity / 中华创伤骨科杂志

Objective:To compare the clinical effectiveness between arthroscopic hollow screws combined with a suture anchor, hollow screws and proximal humerus internal locking system (PHILOS) in the treatment of split-type fractures of humeral greater tuberosity.Methods:A retrospective study was conducted to analyze the 54 patients with split-type fracture of humeral greater tuberosity who had been admitted to Department of Joint Surgery, Hospital of Traditional Chinese Medicine, Affiliated to Southwest Medical University from May 2015 to August 2020. There were 17 males and 37 females with an age of (58.4±12.1) years. According to different treatment methods, they were divided into 3 groups. Group A of 18 cases was treated with arthroscopic hollow screws combined with a suture anchor, group B of 18 cases with hollow screws, and group C of 18 cases with PHILOS. The length of surgical incision, and range of shoulder motion, visual analogue scale (VAS), and American Shoulder and Elbow Surgeons (ASES) score at the last follow-up were recorded and compared between the 3 groups.Results:There was no statistically significant difference in the preoperative general information between the 3 groups, indicating the 3 groups were comparable ( P>0.05). The surgical incision in group A [(0.7±0.1) cm] was the shortest, followed by (5.0±1.4) cm in group B, and (12.8±2.1) cm in group C, showing statistically significant differences in pairwise comparison ( P<0.05). In the 3 groups at the last follow-up, respectively, the shoulder forward flexion was 159.7°±13.4°, 154.9°±16.2°, and 160.5°±12.9°, and the shoulder abduction 149.6°±11.3°, 142.4°±12.0°, and 145.1°±10.4°, showing no statistically significant difference among the 3 groups ( P>0.05); the external rotation was 41.1°±8.1°, 38.1°±7.8° and 43.7°±6.2°, showing a statistically significant difference between groups B and C ( P<0.05); the dorsal extension was T 12 (L 5 to T 6), T 12 (L 5 to T 7), and T 12 (L 3 to T 6), showing no statistically significant difference among the 3 groups ( P>0.05). There was no statistically significant difference among the 3 groups in the VAS score or ASES score at the last follow-up ( P>0.05). Respectively, there were 2, 6, and 4 patients in groups A, B and C who developed complications, showing statistically significant differences between the 3 groups ( P<0.05). Conclusions:In the treatment of split fractures of humeral greater tuberosity, arthroscopic hollow screws combined with a suture anchor, hollow screws and PHILOS can all relieve pain and restore joint function of the shoulder. However, arthroscopic hollow screws combined with a suture anchor are the most recommendable due to their advantages in minimally invasiveness and reduction in complications.

Study on incidence and disease burden of foreign body in eyes in 1990 and 2019 of China / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the incidence and disease burden of foreign body in eyes in 1990 and 2019 of China.METHODS: Using the global burden of disease database in 2019, the incidence and disability adjusted life years(DALY)of foreign body in eyes in 1990 and 2019 of China were analyzed among the total population and different age groups of China.RESULTS: In 2019, the number of cases of foreign body in eyes in China was 11.2535 million, and the incidence was 79.12/10 000. The number and incidence of foreign body in eyes in 2019 decreased 12.87% and 27.49% respectively compared with those in 1990. In 2019, the DALY of foreign body in eyes in China was 181 200 person-years, and the DALY of foreign body in eyes in 2019 increased by 6.14% compared with 1990. In 2019, the age groups with the highest number of cases, incidence and DALY were all 20-54 years old, which were 8 012 600, 103.97/10 000 and 102 500 person-years, respectively. From 1990 to 2019, the incidence of foreign body in eyes in China showed a decreasing trend, average annual percentage change(AAPC)=-1.2%(95%CI: -1.8～-0.7, P&#x0026;#x003C;0.05), and DALY rate also showed a decreasing trend, AAPC=-0.6%(95%CI:-2.1～0, P&#x0026;#x003C;0.05). From 1990 to 2019, the incidence and DALY rate of foreign body in eyes in China and the World showed a downward trend. In 2019, the incidence and DALY rate of foreign body in eyes in China were significantly higher than those in the World and regions with different sociodemographic index(SDI).CONCLUSION: Although the incidence and DALY rates of foreign body in eyes in China have been decreasing in recent years, China has a large population base and the burden of foreign body in eyes is still large in the World. Active preventive measures should be taken to reduce the disease burden of foreign body in eyes.

Advances in the diagnosis, treatment, and prognosis of acute decompensatory cirrhosis / 中华肝脏病杂志

Acute decompensatory cirrhosis is a common cause of hospital admission, readmission, and death, causing a heavy burden on patients, their families, and society. This article reviews the research advancement from the perspectives of concept evolution, pathogenesis, treatment, outcome, and prognosis models, providing new ideas for preventing and treating acute decompensatory cirrhosis.

Comparison of efficacy between intravitreal injection of conbercept with and without macular photocoagulation for diabetic macular edema / 中华实验眼科杂志

Objective:To compare the clinical efficiency and safety between intravitreal injection of conbercept with and without macular photocoagulation for diabetic macular edema (DME).Methods:A non-random controlled study was conducted.Sixty patients (60 eyes) with DME treated in Shenzhen People's Hospital from January 2017 to January 2020 were enrolled.The patients receiving intravitreal injection of conbercept alone were divided into conbercept injection group (33 cases, 33 eyes), and those who underwent macular photocoagulation combined with intravitreal injection of conbercept were divided into combined treatment group (27 cases, 27 eyes). Best corrected visual acuity (BCVA) was examined using Early Treatment of Diabetic Retinopathy Study.The BCVA, central macular thickness (CMT) and fluorescein fundus angiography (FFA) examination were performed to observe the changes of macular edema and leakage area before and at 1, 3, 6, 9 and 12 months after treatment.The injection frequency, ocular and systemic complications were recorded.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Shenzhen Pepole's Hospital (No.LL-YK-20170405). Written informed consent was obtained from each patient prior to any medical examination.Results:There were better mean BCVA and lower CMT at 1, 3, 6, 9 and 12 months after treatment compared with the BCVA and CMT before treatment in the two groups (all at P<0.05). At 12 months after treatment, FFA showed that the improvement rate of macular edema was 91.0% (30/33) in the conbercept injection group and 96.3% (26/27) in the combined treatment group, showing a statistically significant difference between them ( χ2=3.430, P<0.05). The injection frequency was (4.36±1.62) times in the conbercept injection group, which was significantly higher than (3.41±0.64) times in the combined treatment group ( t=9.211, P<0.05). No ocular adverse events, including ocular hypertension, endophthalmitis and retinal pigment epithelial tears or systemic complications were found during the follow-up. Conclusions:Intravitreal injection of conbercept with or without macular photocoagulation can both maintain or improve visual acuity and alleviate exudative macular edema.They both show good safety, and the combined therapy has better long-term efficacy than conbercept alone.

Expression and clinical significance of CC motif chemokine ligand 20 in esophageal carcinoma based on the Cancer Genome Atlas data mining / 解剖学报

Objective To explore the expression and significance of CC mokif chemokine ligand 20(CCL20) gene in esophageal carcinoma and its influence on the progression and prognosis of the disease. Methods The expression data of esophageal cancer were obtained from the Cancer Genome Atlas (TCGA) database, and were collected from cBioPortal(www.cbioportal.org).The survival curve was analyzed by Kaplan-Meier method. Through the website (http://ualcan.path.uab. edu) the objective was to analyze the expression of CCL20 gene in esophageal cancer tissues, the relationship between CCL20 and obesity and the methylation level of CCL20 in esophageal cancer. cBioPortal was used to analyze the copy number and mRNA expression of CCL20 gene. Finally, the expression differences of CCL20 in esophageal cancer tissues and adjacent tissues were analyzed by mRNA and protein levels. Results CCL20 was highly expressed in esophageal cancer, especially adenocarcinoma. The survival rate of patients with high expression of CCL20 was reduced. The expression of CCL20 was directly proportional to the degree of obesity in patients with esophageal cancer and inversely proportional to the degree of methylation. The expression of CCL20 in esophageal cancer tissues increased significantly. Conclusion CCL20 gene expression level is associated with poor prognosis of esophageal cancer patients.

Synaptosomal Actin Dynamics in the Developmental Visual Cortex Regulate Behavioral Visual Acuity in Rats.

Purpose: Synaptosomal actin dynamics are essential for synaptic structural stability. Whether actin dynamics are involved in structural and functional synaptic plasticity within the primary visual cortex (V1) or behavioral visual acuity in rats has still not been thoroughly investigated. Methods: Synaptosome preparation and western blot analysis were used to analyze synaptosomal actin dynamics. Transmission electron microscopy was used to detect synaptic density and mitochondrial area alterations. A visual water maze task was applied to assess behavioral visual acuity. Microinjection of the actin polymerization inhibitor or stabilizer detected the effect of actin dynamics on visual function. Results: Actin dynamics, the mitochondrial area, and synaptic density within the area of V1 are increased during the critical period for the development of binocularity. Microinjection of the actin polymerization inhibitor cytochalasin D into the V1 decreased the mitochondrial area, synaptic density, and behavioral visual acuity. Long-term monocular deprivation reduced actin dynamics, the mitochondrial area, and synaptic density within the V1 contralateral to the deprived eye compared with those ipsilateral to the deprived eye and impaired visual acuity in the amblyopic eye. In addition, the mitochondrial area, synaptic density, and behavioral visual acuity were improved by stabilization of actin polymerization by jasplakinolide microinjection. Conclusions: During the critical period of visual development of binocularity, synaptosomal actin dynamics regulate synaptic structure and function and play roles in behavioral visual acuity in rats.

Impact of edaravone on serum CXC chemokine ligand-13 levels and perioperative neurocognitive disorders in elderly patients with hip replacement.

BACKGROUND: Perioperative neurocognitive disorders (PND) are a series of severe complications in the perioperative and anesthetic periods with a decline in memory, execution ability, and information processing speed as the primary clinical manifestation. This study aimed to evaluate the impact of edaravone (EDA) on PND and peripheral blood C-X-C motif chemokine ligand 13 (CXCL13) levels in elderly patients with hip replacement. METHODS: A total of 160 elderly patients undergoing hip arthroplasty in Affiliated Dongguan People's Hospital of Southern Medical University (from March 2016 to March 2018) were randomly and double-blindly categorized into an EDA group and a control group (CON). Group EDA was administered intravenously EDA 30 min before surgery, and group CON was administered intravenously saline. The cognitive function of the two groups was evaluated 1-day before the operation and at 1 and 12 months after surgery, and the incidence of post-operative delirium was tested on days 1, 3, and 7 after surgery using the Chinese version of the confusion assessment method. Serum CXCL13 and interleukin (IL)-6 concentrations were measured before anesthesia, during surgery (30 min after skin incision), and on days 1, 3, and 7 after surgery. The continuous variables in accordance with normal distribution were tested using the Student's t test, the continuous variables without normal distribution using the Mann-Whitney U test, and categorical variables by the χ2 test or Fisher exact test. RESULTS: The incidence of post-operative delirium within 7 days after surgery was significantly higher in group CON than that in group EDA (31.3% vs. 15.0%, t = -5.6, P < 0.001). The modified telephone interview for cognitive status and activities of daily life scores were significantly higher in the group EDA than those in the group CON at 1 month (39.63 ±â€Š4.35 vs. 33.63 ±â€Š5.81, t = -2.13, P < 0.05 and 74.3 ±â€Š12.6 vs. 61.2 ±â€Š13.1, t = -1.69, P < 0.05) and 12 months (40.13 ±â€Š5.93 vs. 34.13 ±â€Š5.36, t = -3.37, P < 0.05 and 79.6 ±â€Š11.7 vs. 65.6 ±â€Š16.6, t = -2.08, P < 0.05) after surgery; and the incidence of neurocognitive dysfunction was significantly lower in the group EDA than that in the group CON (P < 0.05). Serum CXCL13 and IL-6 concentrations were significantly lower in the group EDA than those in the group CON during and after surgery (P < 0.05). CONCLUSION: EDA can significantly reduce the serum concentrations of CXCL13 and IL-6 and improve the PND of patients.

Frequency characteristics of horizontal semicircular canals damage and the ultrastructure analysis of crista ampullaris in patients with Meniere's disease / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the frequency characteristics and the pathological characteristics of the horizontal crista ampullaris in patients with Meniere's disease,and to analyse its structural basis. Methods: Between March, 2019 and November, 2019, seventy-two patients diagnosed as Meniere's disease (27 males and 45 females, aged from 13 to 74 years, with a course of disease ranging from 4 months to 32 years)in Shandong Provincial ENT Hospital were included.Caloric test, sinusoidal harmonic acceleration test (SHA), video-head impulse test (v-HIT), Gadolinium-enhanced inner-ear 3D-FLAIR MRI and pure tone audiometry were conducted in the patients. The function of the horizontal semicircular canal in these patients were analysed as well as its relationship with the degree of endolymphatic hydrops,clinical stage and duration. Light microscopy and transmission electron microscopy were used to observe the ultrastructure of horizontal semicircular canal crista ampullaris from six patients with refractory Meniere's disease who underwent labyrinthectomy. The number of type Ⅰ and type Ⅱ vestibular hair cells, the common pathophysiological changes of horizontal semicircular canal crista ampullaris were investigated in these patients. Statistical analysis was performed using SPSS 19.0. Results: With the increase of detection frequency, the abnormal rate decreased gradually. The abnormal rate of caloric test was 69.4% (50/72), SHA 51.4% (37/72), V-HIT 36.1% (26/72), comparation of the positive rate among the three tests showed statistically significant differences(P<0.05).Neither caloric test nor SHA had correlation with the degree of hydrops(P>0.05), but v-HIT(r=0.434,P<0.01).There was correlation with clinical stage to SHA and v-HIT(r=0.338,0.462,P<0.01), except caloric test(P>0.05).No significant relation was found with caloric test, SHA, v-HIT and course of disease(P>0.05).Morphological observation found abnormal monolayer epithelialization of the horizontal semicircular canal crista ampullaris significantly decreased number of type Ⅱ hair cells compared with type Ⅰhair cells. Hair cells showed perinuclear vacuolization, cytoplasmic vacuoles, mitochondrial electron density increasement and loss of stereocilia. Conclusions: The horizontal semicircular canal damage in the patients with Meniere's disease has a frequency-dependent characteristic, mainly occurres in low frequency area. With progress of the disease, the high frequency area of ampulla will be impaired gradually, and it is related to the degree of endolymphatic hydrops and hearing level. Hair cell injury would be observed,the frequency characteristics may be more associated with the disorder of type Ⅱ hair cells.

Impact of edaravone on serum CXC chemokine ligand-13 levels and perioperative neurocognitive disorders in elderly patients with hip replacement / 中华医学杂志(英文版)

BACKGROUND@#Perioperative neurocognitive disorders (PND) are a series of severe complications in the perioperative and anesthetic periods with a decline in memory, execution ability, and information processing speed as the primary clinical manifestation. This study aimed to evaluate the impact of edaravone (EDA) on PND and peripheral blood C-X-C motif chemokine ligand 13 (CXCL13) levels in elderly patients with hip replacement.@*METHODS@#A total of 160 elderly patients undergoing hip arthroplasty in Affiliated Dongguan People's Hospital of Southern Medical University (from March 2016 to March 2018) were randomly and double-blindly categorized into an EDA group and a control group (CON). Group EDA was administered intravenously EDA 30 min before surgery, and group CON was administered intravenously saline. The cognitive function of the two groups was evaluated 1-day before the operation and at 1 and 12 months after surgery, and the incidence of post-operative delirium was tested on days 1, 3, and 7 after surgery using the Chinese version of the confusion assessment method. Serum CXCL13 and interleukin (IL)-6 concentrations were measured before anesthesia, during surgery (30 min after skin incision), and on days 1, 3, and 7 after surgery. The continuous variables in accordance with normal distribution were tested using the Student's t test, the continuous variables without normal distribution using the Mann-Whitney U test, and categorical variables by the χ2 test or Fisher exact test.@*RESULTS@#The incidence of post-operative delirium within 7 days after surgery was significantly higher in group CON than that in group EDA (31.3% vs. 15.0%, t = -5.6, P < 0.001). The modified telephone interview for cognitive status and activities of daily life scores were significantly higher in the group EDA than those in the group CON at 1 month (39.63 ± 4.35 vs. 33.63 ± 5.81, t = -2.13, P < 0.05 and 74.3 ± 12.6 vs. 61.2 ± 13.1, t = -1.69, P < 0.05) and 12 months (40.13 ± 5.93 vs. 34.13 ± 5.36, t = -3.37, P < 0.05 and 79.6 ± 11.7 vs. 65.6 ± 16.6, t = -2.08, P < 0.05) after surgery; and the incidence of neurocognitive dysfunction was significantly lower in the group EDA than that in the group CON (P < 0.05). Serum CXCL13 and IL-6 concentrations were significantly lower in the group EDA than those in the group CON during and after surgery (P < 0.05).@*CONCLUSION@#EDA can significantly reduce the serum concentrations of CXCL13 and IL-6 and improve the PND of patients.

Crystal structure of SARS-CoV-2 papain-like protease

The pandemic of coronavirus disease 2019 (COVID-19) is changing the world like never before. This crisis is unlikely contained in the absence of effective therapeutics or vaccine. The papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays essential roles in virus replication and immune evasion, presenting a charming drug target. Given the PLpro proteases of SARS-CoV-2 and SARS-CoV share significant homology, inhibitor developed for SARS-CoV PLpro is a promising starting point of therapeutic development. In this study, we sought to provide structural frameworks for PLpro inhibitor design. We determined the unliganded structure of SARS-CoV-2 PLpro mutant C111S, which shares many structural features of SARS-CoV PLpro. This crystal form has unique packing, high solvent content and reasonable resolution 2.5 Å, hence provides a good possibility for fragment-based screening using crystallographic approach. We characterized the protease activity of PLpro in cleaving synthetic peptide harboring nsp2/nsp3 juncture. We demonstrate that a potent SARS-CoV PLpro inhibitor GRL0617 is highly effective in inhibiting protease activity of SARS-CoV-2 with the IC

Acrylamide Fragment Inhibitors that Induce Unprecedented Conformational Distortions in Enterovirus 71 3C and SARS-CoV-2 Main Protease

RNA viruses are critically dependent upon virally encoded proteases that cleave the viral polyproteins into functional mature proteins. Many of these proteases are structurally conserved with an essential catalytic cysteine and this offers the opportunity to irreversibly inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that selectively target the active site cysteine of the 3C protease (3Cpro) of Enterovirus 71, the causative agent of hand, foot and mouth disease in humans, altering the substrate binding region. Further, we effectively re-purpose these hits towards the main protease (Mpro) of SARS-CoV-2 which shares the 3C-like fold as well as similar catalytic-triad. We demonstrate that the hit fragments covalently link to the catalytic cysteine of Mpro to inhibit its activity. In addition, we provide the first demonstration that targeting the active site cysteine of Mpro can also have profound allosteric effects, distorting secondary structures required for formation of the active dimeric unit of Mpro. These new data provide novel mechanistic insights into the design of EV71 3Cpro and SARS-CoV-2 Mpro inhibitors and identify acrylamide-tagged pharmacophores for elaboration into more selective agents of therapeutic potential.