ObjectiveTo explore the protective effect and mechanism of Yangxin Dingji capsules on isoproterenol （ISO）-induced ventricular arrhythmia in SD rat cardiomyocytes based on the transforming growth factor-β activated kinase 1 （TAK1）-mitogen-activated protein kinase kinase 3 （MKK3）-p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodFifty male SPF-grade SD rats were randomly divided into a normal group， a model group， a propranolol group， a low-dose Chinese medicine group， and a high-dose Chinese medicine group. The ventricular arrhythmia model was constructed using the ISO "6+1" method. The propranolol group received propranolol at 0.015 g·kg^-1·d^-1. The Chinese medicine groups received Yangxin Dingji capsules at doses of 0.5、 2 g·kg^-1·d^-1， respectively. The normal and model groups were given an equal volume of 0.9% NaCl solution. Electrocardiogram （ECG） changes in SD rats were recorded using the BL-420F biological function experimental system. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the heart. Serum levels of cardiac troponin I （cTnI）， creatine kinase-MB （CK-MB）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and transforming growth factor-β₁ （TGF-β₁） were measured using enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of IL-1β and TNF-α was assessed using real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Reactive oxygen species （ROS） expression was detected using immunofluorescence. Protein expression levels of TAK1， phosphorylated TAK1 （p-TAK1）， MKK3， phosphorylated MKK3 （p-MKK3）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， IL-1β， and TNF-α were measured using Western blot or immunohistochemistry. ResultCompared with normal group， the model group showed significant ventricular arrhythmia in ECG， with an increased arrhythmia score （P<0.01）. Pathological damage to myocardial tissue was evident， and serum levels of cTnI， CK-MB， IL-1β， TNF-α， and TGF-β₁ were elevated （P<0.01）. The mRNA and protein expression of IL-1β and TNF-α in myocardial tissue was also increased （P<0.01）. ROS level and protein expression of p-TAK1， p-MKK3， p-p38 MAPK， and p-NF-κB were elevated in myocardial tissue （P<0.01）. In the propranolol and Chinese medicine groups， the incidence of sustained ventricular tachycardia （SVT） and arrhythmia scores were significantly reduced compared to model group （P<0.05， P<0.01）. Pathological damage to cardiomyocytes was alleviated， and levels of myocardial injury markers and inflammatory factors in serum and myocardial tissue were decreased. The ROS level in myocardial tissue was also reduced （P<0.01）， with a noticeable reduction in related molecules in the p38 MAPK pathway （P<0.05， P<0.01）. ConclusionThe expression of p38 MAPK pathway molecules was up-regulated in myocardial tissue of ISO-induced ventricular arrhythmia rats. Yangxin Dingji capsules may inhibit cardiac inflammation damage by regulating the expression of related molecules in the p38 MAPK pathway， thereby exerting a protective effect on myocardial cells， with TAK1 being a potential target.

OBJECTIVE：To study the effects of augmented renal clearance （ARC）on blood trough concentration of patients receiving high-dose regimen of teicoplanin. METHODS ：Patients who received high-dose regimen of teicoplanin in the ICU were prospectively collected from the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital during Jul. 2018-Jun. 2020. They were divided into ARC group and normal renal function group according to corrected creatinine clearance. The dosage regimen of teicoplanin in the two groups were loading dose of 600 mg，q12 h×3 doses，maintenance dose of 6-10 mg/kg，qd，and the dosage was adjusted in combination with creatinine clearance rate and blood trough concentration. The trough concentration of blood samples which were collected 30 min before the 4th and 8th-10th dosage of teicoplanin were determined by HPLC. Trough concentration ，clinical efficacy ，Gram-positive bacterial clearance rate and the occurrence of ADR were compared between 2 groups. RESULTS ：A total of 56 patients were included and divided into ARC group （18 cases）and normal renal function group （38 cases）. ARC group had younger age （P＜0.001）and lower serum albumin level （P＝0.025）than normal renal function group. The trough concentrations before administration of the 4th and 8th-10th dosage in ARC group were lower than normal renal function group （P＝0.034；P＝0.035）. The trough concentrations in the ARC group and normal renal function group before 8th-10th dosage were all higher than 30 min before the 4th dosage （P＝0.003；P＜0.001）. The clinical efficacy rate and the clearance rate of Gram-positive bacteria in ARC group were 77.8％ and 76.2％，which were lower than those of the normal renal function group ，but there was no statistical difference （P＝0.195；P＝0.223）. There was no liver function damage ，hemocytopenia and allergic reaction in both groups ，but in the normal renal function group ，the causal relationship between acute renal damage and teicoplanin was assessed as “very likely ”in one patient. CONCLUSIONS ：ARC patients are younger ，most of them have hypoproteinemia，and the blood trough concentrations of teicoplanin in high-dose regimen are significantly lower than those of normal renal function patients. For critical ill ARC patients ，it is advisable to increase the loading dose of teicoplanin to make the trough concentration reach the target concentration range quickly.

OBJECTIVE: To observe the status of protein kinase B(Akt) signaling pathway in Akt phosphorylation induced by free silica(SiO_2) in mouse monocyte macrophage cell RAW264.7, and the role of Akt signaling pathway in early inflammatory response of silicosis. METHODS: i) RAW264.7 cells were routinely cultured and divided into SiO_2 stimulation groups at 5 different time points, and were stimulated for 15, 30, 60, 120 and 240 minutes with SiO_2 suspension with a final concentration of 100 mg/L, and a control group without SiO_2 treatment. At the end of treatment, the cells were collected and the expression of phospho-(Ser/Thr) Akt(p-Akt) was detected by Western blotting to select the optimal time of treatment. ii) RAW264.7 cells were divided into control group(no treatment), SiO_2 exposure group(previous concentration of 100 mg/L SiO_2 suspension) and intervention group(pre-treated with Akt activation inhibitor deguelin for one hour and then treated with 100 mg/L SiO_2 suspension), samples were collected after incubation for 60 minutes. The p-Akt expression and distribution in cells were detected by cellular immunofluorescence assay, the relative expression of p-Akt in cells was detected by Western blotting, and the levels of tumor necrosis factor-α(TNF-α) and transforming growth factor-β1(TGF-β1) in the supernatant of cells were detected by enzyme-linked immunosorbent assay. RESULTS: i) The optimal treatment time of RAW264.7 cells for SiO_2 exposure model was 60 minutes in vitro. ii) The results of cellular immunofluorescence assay showed that Akt phosphorylation was activated in RAW264.7 cells after stimulant with SiO_2, and the fluorescence of p-Akt was enhanced in the SiO_2 exposure group than the control group, and in the intervention group it was relatively weaker than the SiO_2 exposure group. The relative expression of p-Akt as well as the levels of TNF-α and TGF-β1 in the SiO_2 exposure group and the intervention group were higher than that in the control group(P<0.05), and the above three idexes in the intervention group were lower than the SiO_2 exposure group(P<0.05). CONCLUSION: Akt signaling pathway is involved in the process of SiO_2-induced macrophages phosphorylation, and participates in the early inflammatory response of silicosis.

OBJECTIVE: To explore the effect of wearing earphone to listen to music on the high-frequency noise-induced hearing loss(NIHL) in noise-exposure workers. METHODS: A total of 651 male noise-exposure workers in an automobile manufacturer were selected as study subjects by using judgment sampling method. The level of noise exposure in the individuals and the pure tone hearing threshold were tested. According to the frequency of wearing earphone to listen to music after work, the subjects were divided into low-, medium-and high-frequency earphone-using groups, with 60, 436 and 155 workers in each group, respectively. The effects of wearing earphone to listen to music combined with occupational noise exposure on high-frequency NIHL were analyzed. RESULTS: The high-frequency NIHL detection rate of the study subjects was 31.3%(204/651). The detection rate of high-frequency NIHL in these three groups from low to high was low-, medium-and high-frequency earphone-using groups(P<0.01). The detection rate of high-frequency NIHL in the high-frequency earphone-using group was higher than that of the low-and medium-frequency earphone-using groups(43.2% vs 25.0%, 43.2% vs 28.0%, P<0.01). Multivariate logistic regression analysis showed that wearing earphones to listen to music was a risk factor for high-frequency NIHL in noise-exposure workers(P<0.01) after eliminating the influence of confounding factors such as age, length and level of noise-exposure, and wearing anti-noise ear plugs. The higher frequency of wearing earphone to listen to music, the higher risk of high-frequency NIHL. CONCLUSION: Wearing earphone to listen to music after work and occupational noise exposure had a synergistic effect on high-frequency NIHL in noise-exposure workers.

Stroke has increasingly become one of the three major diseases threatening human beings,among which acute ischemic stroke is the most common.Intravenous thrombolysis has become the first choice for acute ischemic stroke,but a large number of studies have shown that intravenous thrombolysis increases the risk of hemorrhagic transformation.The latest advances in clinical types,incidence,mechanism and risk factors of hemorrhagic transformation after thrombolysis with recombinant human tissue plasminogen activator are reviewed in this article,and the possible predictors of hemorrhagic transformation are discussed,aiming to provide new reference for clinical thrombolytic therapy.

OBJECTIVE: To explore the relationship between noise-induced hearing loss, hypertension and abnormal electrocardiogram(ECG) in noise-exposed workers. METHODS: A judgment sampling method was adopted to select 555 male workers with hearing loss as study group and 555 male workers with normal hearing as control group in the similar environment in an automobile manufacturing enterprise in Guangzhou. Pure tone audiometry,blood pressure measurement and ECG examination were performed in both groups to analyze the relationship between hearing loss and hypertension and abnormal ECG. RESULTS: The prevalence rate of hypertension and abnormal ECG was higher in the hearing loss group than the control group(P < 0. 05). The multiple logistic regression analysis showed that after adjusting confounding factors such as age,seniority,body mass index,drinking et al,the risk of hypertension in hearing loss group was higher than the control group(P < 0. 05) and the odds ratio(OR) was 2. 255 [95% confidence interval(CI) : 1. 093-4. 655 ],while adjusting the confounding factor of drinking,the risk of ECG abnormalities in hearing loss group was higher than the control group(P < 0. 05) and the OR was 1. 408(95% CI: 1. 027-1. 930). CONCLUSION: Workers exposed to noise with hearing loss increase the risk of hypertension and abnormal ECG.

Objective To explore the morphological characteristics of intraepidermal nerve fibers in healthy Chinese by skin biopsy,to provide reference basis for the early diagnosis of peripheral neuropathy.Methods Skin biopsies samples were obtained from 192 healthy volunteers (half male and half female,collected in our hospital from June 2009 to August 2013),and these samples were divided into 6 groups according to different anatomic sites (far-end of the upper arm,far-end of the forearm,opisthenar,near-end of thigh,far-end of crus and acrotarsium) and 4 groups according to age (patients of younger than 20,patients of 21-40 years old,patients of 41-60 years old and patients of older than 61).Morphological observation of the intraepidermal nerve fibers was performed by skin biopsy and immunohistochemical technique.Results Various branch models emerged at each location:non-branching,branching at the epidermis-dermis junction,branching near the epidermis-dermis junction,branching at faraway side of epidermis-dermis junction,and branching near the cuticle.Branch models showed no significant diferences among patients of different ages.The above branch models appeared in far-end of the upper arm,far-end of the forearm,opisthenar,near-end of thigh,far-end of crus and acrotarsium,and as body based site famess,skin nerve fibers usually had more branches,and more axon expansion and varicose.Conclusions The age and lanatomic sites do not affect the branching pattems of intraepidermal nerve fibers.The closer to the extremities,the more branches of the intraepidermal nerve fiber.

BACKGROUND:Bipolar femoral head prosthesis has achieved the desired repair effect in patients with femoral neck fracture, but there is stil much controversy on the biomechanical properties of bipolar artificial femoral head prosthesis. OBJECTIVE:To compare biomechanical properties of the bipolar femoral head prosthesis replacement and internal fixation in the repair of femoral neck fracture in the elderly. METHODS:Twenty-three (46 sides) senile femoral neck fracture specimens were analyzed and randomized into internal fixation group(n=23)and bipolar femoral head prosthesis replacement group (n=23). Specimens in the internal fixation group underwent conventional metal implant fixation. Specimens in the bipolar femoral head prosthesis replacement group underwent bipolar femoral head prosthesis replacement. Mechanical properties of femoral prosthesis stem were tested on universal testing machine. Biomechanical properties after bipolar femoral head prosthesis replacement and internal fixation were compared. RESULTS AND CONCLUSION:(1) The maximum loadwassignificantly higher in the bipolar femoral head prosthesis replacement group than in the internal fixation group (P< 0.05). The maximum load trend images showed that the maximum load was significantly higher in the bipolar femoral head prosthesis replacement group than in the internal fixation group (P< 0.05). (2) The displacement in axial pul test was significantly shorter in the bipolar femoral head prosthesis replacement group than in theinternal fixation group (P< 0.05). The displacement trend images exhibited that the displacement in axial pul test was significantly shorter in the bipolar femoral head prosthesis replacement group than in the internal fixation group (P< 0.05). (3) These findings suggest that compared with the implant, bipolar femoral head prosthesis replacement in the repair of femoral neck fracture in the elderly is more stable, has better repair effects, can elevate hip function and obtain good initial stability.

Objective To improve detectable rate of gastric schwannoma by endoscopic ultrasonography (EUS). Method Clinical data and endoscopic ultrasonography (EUS) imaging features of 4 cases were retrospectively ana-lyzed which diagnosed as gastric schwannoma pathologically and immunohistochemically while diagnosed as gastric stromal tumor by EUS from May 2008 to June 2015 and reviewed the literature. Results 4 cases of gastric schwan-nomas are female and benign, all 4 lesions are solitary, 3 in gastric body, and 1 in fundus by endoscopic. By EUS, all lesions are originated from muscularis propria, hypoechoic change, even echoes and clear board without calcifica-tion or cystic changes. 2 cases have halo artifacts around the lesion. Literature review found that gastric schwannoma tended to occur in female, halo artifacts could be the feature of gastric schwannoma, calcification or cystic changes were rare in gastric schwannoma which were common in gastric stromal tumors. Conclusion It was difficult to distin-guish gastric schwannoma and gastric stromal tumors that originated from muscularis propria by EUS. For female patients with lesions originated from muscularis propria, originated from muscularis propria and occurred in gastric body, it was necessary to observe lesions whether there was being calcification or cystic and halo artifacts. Integrated all these performance, we should be in consideration of gastric stromal tumors, meanwhile, excluding the possibility of gastric schwannoma.

Objective To establish the quantitative standard of intraepidermal nerve fibers in healthy Chinese and provide reference basis for the early diagnosis of peripheral neuropathy through the large sample system of quantitative research by skin biopsy.Methods Adult skin samples of different anatomical locations,age and gender were obtained from 192 healthy volunteers who performed skin biopsies in our hospital from May 2009 to July 2013;they were divided into 6 groups according to different anatomic sites (distal upper arm,distal forearm,opisthenar,proximal thigh,distal crus and acrotarsium) and 4 groups according to the ages (patients under 20 years old,patients of 21-40 years old,patients of 41-60 years old and patients older than 61 years).Quantitative observation of the intraepidermal nerve fibers was performed by skin biopsy and immunohistochemical technique.Half males and half females were chosen.Results The comparison of intra epidermal nerve fiber density (IENFD) among thigh,leg,dorsum of foot and the comparison among upper arm,forearm,dorsum of hand showed statistical significance (P＜0.05).Along with the limbs part from proximal to distal,the IENFD in the upper and lower limbs both manifested a degressive tendency by degrees (normal reference value ranges of each anatomic site:upper arm＞320.00 fibers/mm2,forearm＞190.57 fibers/mm2,opisthenar＞184.37 fibers/mm2,thigh＞418.36 fibers/mm2,crus＞157.35 fibers/mm2,and acrotarsium＞ 140.00 fibers/mm2).The IENFD among patients under 20 years old,patients of 21-40 years old,patients of 41-60 years old and patients older than 61 years did not show statistically significant differences (P＞0.05).The IENFD between patients under 20 years old and patients older than 61 years showed statistical significance (P＜0.05).The IENFD in male and female adults did not show statistical significance (P＞0.05).Conclusions A significant difference of IENFD is observed among different anatomic sites.Ages has small effect on IENFD,and gender has no effect on IENFD.