[Animal study on left bundle branch current of injury and anatomic location of leads in His-purkinje conduction system pacing].

Objective: Explore the relationship between tip of the left bundle branch pacing lead and anatomic location of left bundle branch as well as the mechanism of left bundle branch current of injury. To clarify the clinical value of left bundle branch current of injury during operation. Methods: The pacing leads were implanted in the hearts of two living swines. Intraoperative electrophysiological study confirmed that the left bundle branch or only the deep left ventricular septum was captured at low output. Immediately after operation, the gross specimen of swine hearts was stained with iodine to observe the gross distribution of His-purkinje conduction system on the left ventricular endocardium and its relationship with the leads. Subsequently, the swine hearts were fixed with formalin solution, and the pacing leads were removed after the positions were marked. The swine hearts were then sectioned and stained with Masson and Goldner trichrome, and the relationship between the anatomic location of the conduction system and the tip of the lead was observed under a light microscope. Results: After iodine staining of the specimen, the His-purkinje conduction system was observed with the naked eye in a net-like distribution, and the lead tip was screwed deeply and fixed in the left bundle branch area of the left ventricular subendocardium in the ventricular septum. Masson and Goldner trichrome staining showed that left bundle branch pacing lead directly passed through the left bundle branch when there was left bundle branch potential with left bundle branch current of injury, while it was not directly contact the left bundle branch when there was left bundle branch potential without left bundle branch current of injury. Conclusion: The left bundle branch current of injury observed on intracardiac electrocardiogram during His-purkinje conduction system pacing suggests that the pacing lead directly contacted the conduction bundle or its branches, therefore, the captured threshold was relatively low. Left bundle branch current of injury can be used as an important anatomic and electrophysiological evidence of left bundle branch capture.

Raspberry ketone glucoside suppresses melanin synthesis through IL6/JAK1/STAT3 signal pathway.

OBJECTIVE: This study aimed to evaluate the anti-melanogenic activity of raspberry ketone glucoside (RKG) and further explore the specific molecular mechanisms by which RKG affects melanogenesis. MATERIALS AND METHODS: The B16F10 cells model, the mushroom tyrosinase model and the zebrafish model were used to assess the whitening activity of RKG. We subsequently identified possible pathways related to RKG inhibition of melanogenesis by RNA-seq analysis and qRT-PCR on the zebrafish model, and further explored the effects of key genes on the pathway on the melanogenic effect of RKG by using related pathway inhibitors and Tg [mpeg: EGFP] transgenic zebrafish line. RESULTS: RKG could noticeably inhibit melanogenesis in B16F10 cells in vitro and on zebrafish in vivo. The RNA-Seq analysis and the qRT-PCR in zebrafish embryos indicated that the inhibition of melanogenesis by RKG could be achieved by activating JAK1/STAT3 signal pathway and inhibiting the expression levels of the MITFa, TYR, TYRP1a genes directly associated with melanogenesis. The inhibitor tests revealed that the inhibitory effect of the RKG on melanogenesis was restored by the IL6, JAK1/2, and STAT3 inhibitors, specifically STAT3 inhibitor. We further examine the relationship between the JAK1/STAT3 signal pathway and the MITFa. The achieved results indicate that the RKG could activate the zebrafish macrophages via the JAK1, but the inhibition of macrophage activation by loganin did not affect the anti-pigmentation effect of the RKG. CONCLUSIONS: RKG showed remarkable whitening activity on both B16F10 cells in vitro and zebrafish model in vivo. Furthermore, RKG could inhibit melanogenesis by activating the IL6/JAK1/STAT3 pathway, inhibiting the transcriptional activity of MITFa, and its downstream expression levels of the TYR and TYRP1a genes.

Correlation of serum levels of HIF-1α, SMAD3, and HDAC3 with the disease severity in stroke patients.

OBJECTIVE: Explore serum levels of hypoxia-inducible factor-1α (HIF-1α), signal transduction molecule 3 (SMAD3), and histone deacetylase (HDAC) and their correlation with the severity of the condition of stroke patients. PATIENTS AND METHODS: Clinical records of 93 stroke patients and 93 healthy individuals were retrospectively analyzed. Serum levels of HIF-1α, SMAD3, and HDAC3 in patients with different disease degrees and lesion areas were compared between the two groups. Correlation between serum levels of HIF-1α, SMAD3, and HDAC3 and the severity and lesion area of the observation group were analyzed. RESULTS: Serum levels of HIF-1α, SMAD3, and HDAC3 in the observation group were higher than those in the control group (p<0.05). Serum levels of HIF-1α, SMAD3, and HDAC3 in patients with moderate and severe disease were significantly higher than those in patients with mild disease and were the highest in patients with severe disease (p<0.05). Serum levels of HIF-1α, SMAD3, and HDAC3 in patients with moderate and large areas of cerebral infarction were significantly higher than those in patients with small areas of cerebral infarction and the highest in patients with large areas of cerebral infarction (p<0.05). Spearman correlation analysis showed that serum levels of HIF-1α, SMAD3, and HDAC3 significantly positively correlated with the severity of stroke and lesion area (p<0.05). CONCLUSIONS: Serum levels of HIF-1α, SMAD3, and HDAC3 in stroke patients are highly expressed, and the increase positively correlates with the severity of the disease and the area of the lesion.

Accelerating TB diagnosis during the COVID-19 pandemic.

SETTING: The COVID-19 pandemic has caused significant disruption worldwide to economies and healthcare systems, even those with well-developed infrastructure.OBJECTIVE: To examine the effects of COVID-19 on TB diagnosis in Singapore, and to identify any factors that could facilitate early detection of TB among persons screened.DESIGN: To assess the impact of testing and diagnosis of the pandemic on TB, the number of TB-related tests from January 2018 to December 2020 were collected. We also conducted a retrospective case-control study of all adult patients admitted for COVID-19, TB or coinfection from 23 January to 31 May 2020.RESULTS: Nationwide testing for TB from 2018 to 2020 increased by 24.2%. We analysed 253 adult inpatients, of whom 107 (42.3%) were diagnosed with COVID-19, 134 (53.0%) had TB, while 12 (4.7%) had co-infection. Patients with TB were more likely to have chest X-ray abnormalities than those with COVID-19 (89.9% vs. 76.0%; P < 0.01). Patients with TB were more likely to have prolonged cough vs. those with COVID-19 infection (28 vs. 5 days; P < 0.01).CONCLUSION: Early screening for TB, even among patients with COVID-19, could lead to earlier diagnosis and treatment, thereby breaking the chain of transmission.

Clinical standards for the diagnosis, treatment and prevention of TB infection.

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.

Identification of potential crucial genes associated with vasculogenic mimicry in human osteosarcoma based on gene expression profile.

We previously reported the presence of vasculogenic mimicry (VM) in human osteosarcoma. However, the mechanistic basis of osteosarcoma VM remains unclear. Three hundred eighty-one upregulated differentially expressed genes (DEGs) and 526 downregulated DEGs between human osteosarcoma cell line 143B and HOS cell exposed to Matrigel were screened out by microarray. GO categories such as "cell adhesion", "angiogenesis" were enriched in 143B group. PATHWAY analysis showed enriched TGF-beta, Wnt and VEGF signaling pathway in 143B group. The hub gene ITGA2 in signal-network of DEGs exhibited pro-VM and pro-metastasis effect. Our study provides fundamental data for further studies regarding molecules involved in osteosarcoma VM.

[The ratio of tuberculosis-specific antigen to phytohemagglutinin in T-SPOT assay in the diagnosis of active tuberculosis].

Objective: The aim of this study was to determine the performance of the ratio of tuberculosis-specific antigen (TBAg) to phytohemagglutinin (PHA) (TBAg/PHA ratio) in T-SPOT assay in the diagnosis of active tuberculosis (ATB). Methods: Between January 2014 and January 2017, 378 Mycobacterium tuberculosis (MTB) culture positive patients (268 cases of pulmonary tuberculosis, 110 extra-pulmonary tuberculosis) and 824 healthy individuals were recruited from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. T-SPOT assay was performed and TBAg/PHA ratio was calculated in all the participants. To validate the study, another group of 223 MTB culture positive TB patients with positive T-SPOT results were recruited from Guangzhou Chest Hospital between January 2017 and December 2017. This was a retrospective case-control study and differences between groups were analyzed using the Mann-Whitney U-test. Results: Of the 378 culture positive ATB patients, 344 patients had positive T-SPOT results. Of the 824 healthy individuals, 204 individuals had positive T-SPOT results. Using healthy individuals as the control group, the sensitivity and specificity of T-SPOT assay in the diagnosis of ATB were 91.0% (344/378) and 75.2% (620/824). Directly using T-SPOT results had a limited accuracy in distinguishing ATB from latent tuberculosis infection (LTBI). The area under the receiver operating characteristic (ROC) curve was between 0.7 and 0.8. However, a further calculation of the TBAg/PHA ratio showed a better performance than TBAg in distinguishing these two conditions, and the area under the ROC curve was 0.881 (95% CI: 0.853-0.909). If using the threshold value of 0.234, the sensitivity and specificity of the TBAg/PHA ratio in distinguishing ATB from LTBI were 69.5% (239/344) and 94.12% (192/204). The validation data showed that the performance of the TBAg/PHA ratio in distinguishing ATB from LTBI was also satisfactory, and the area under the ROC curve was 0.901 (95% CI: 0.872-0.931). Furthermore, the TBAg/PHA ratio had an important role in the diagnosis of extra-pulmonary tuberculosis. If using the threshold value of 0.234, the sensitivity and specificity of the TBAg/PHA ratio in the diagnosis of extra-pulmonary tuberculosis were 79.2% (76/96) and 94.1% (192/204). The area under the ROC curve was 0.932 (95% CI: 0.897-0.967). Conclusions: The TBAg/PHA ratio in T-SPOT assay was better than directly using T-SPOT results in distinguishing ATB from LTBI. This ratio also showed a potential use in the diagnosis of extra-pulmonary tuberculosis.

[Electrocardiographic characteristics of idiopathic ventricular arrhythmias originating from the tricuspid annulus regions].

Object: To explore the electrocardiographic characteristics of ventricular arrhythmias (VAs) originating from tricuspid annulus region. Methods: Present study included 169 consecutive patients undergoing catheter ablation of VAs from tricuspid annulus origin in our department from August 2007 to September 2016. Based on the origin sites, the patients were divided into two subgroups, the free wall group (81 cases) and septal wall group (88 cases). Based on the location, patients in the free wall group were classified into anterolateral (22 cases), lateral (26 cases) and posterolateral (33 cases) subgroups. Patients in the septal group were classified into anteroseptal (10 cases), midseptal (71 cases) and posteroseptal (7 cases) subgroups. We analyzed the electrocardiographic features of these patients and in 87 patients with PVCs/VT originating from right ventricular outflow tract. Results: (1) A positive R wave inⅠ, aVL, V(5)-V(6) leads were found among most of patients, only few cases originating from tricuspid annulus anteroseptum group and tricuspid annulus anterolateral group demonstrated qr or qs pattern in aVL lead. 97.53% (79/81) patients demonstrated rS pattern in V(1)-V(3) leads with VAs originating from tricuspid annulus free wall, and 9/10 patients demonstrated rS pattern in V(1) lead with VAs originating from anteroseptum, and 97.44% (76/78) patients demonstrated QS pattern in V(1) lead with VAs originating from midseptum and posteroseptum. Precordial lead transition zone was on or behind V(3) for tricuspid annulus free wall group (96.3%, 78/81), but in front of V(3) for tricuspid annulus septum wall group (47.73%, 42/88) (P<0.01). The S wave's amplitude smaller than-1.81 mV in lead V(2) can be used as a cutoff value to identify if PVC/VT is originating from free wall or septum of TA. R wave in inferior wall leads was found among 98.85% (86/87) patients with PVCs/VT originating from right ventricular outflow tract. Conclusion: A positive R wave in Ⅰ, aVL, V(5)-V(6) leads was found among most of patients with idiopathic ventricular arrhythmias originating from the tricuspid annulus regions, but VAs originating from different portions of tricuspid annulus area have distinct electrocardiographic characteristics.

[Analysis of corneal and conjunctival sensitivities and its related factors of premature babies].

Objective: To analyse the corneal and conjunctival sensitivities of premature babies and to study the relevant influencing factors. Methods: Cross-sectional study. One hundred premature infants born at Women's Hospital School of Medicine Zhejiang University between May 2015 and September 2015 were enrolled, among which 51 were male (51%) and 49 were female (49%), the mean gestational age was (30.93±1.75)w, the mean corrected gestational age was (33.65±1.53)w, the mean birth weight was (1 592±336)g. The thresholds of cornea and conjunctiva of infants' left or right eyes were measured with Cochet-Bonnet aesthesiometer at 8-10 o'clock every morning when they naturally woke up, the minimum length of nylon wire that induced three successive times of eye-blink responses was recorded. Paired sample t test was used to compare the corneal and conjunctival sensitivities, the ocular surface sensitivities of preterm infants of different gender were compared using independent samples t-test, Pearson correlation and multiple linear regression analysis was conducted to analyze the correlation of corneal and conjuncitval sensitivities with gestational age, birth weight, age and corrected gestational age. Results: The mean corneal sensitivity was (44.85±5.53) mm and the mean conjunctival sensitivity was (23.50±5.48)mm in premature babies, corneal sensitivity was significantly higher than conjunctival sensitivity (t=25.620, P<0.001). No statistical significance was found between male and female preterm infants in corneal sensitivity [(44.80±5.83) mm vs. (44.90±5.25) mm, t=-0.085, P=0.933] and conjunctival sensitivity[(23.14±5.83) mm vs. (23.88±5.13) mm, t=-0.673, P=0.502]. Pearson correlation analysis showed that corneal sensitivity was significantly associated with conjunctival sensitivity in prematurity(r=0.676, P<0.001). There was significant correlation between corneal sensitivity and age, corrected gestational age (r=0.238, P=0.017; r=0.679, P<0.001), however no significant correlation was found between corneal sensitivity and gestational age, birth weight in preterm infants (r=0.067, P=0.510; r=-0.179, P=0.075). There was significant correlation between conjunctival sensitivity and corrected gestational age (r=0.490, P<0.001), however no significant correlation was found between conjunctival sensitivity and gestational age, birth weight and age in preterm infants (r=0.078, P=0.439; r=-0.096, P=0.344; r=0.151, P=0.133). Multiple linear regression revealed that corneal sensitivity(Y1) was positively correlated with corrected gestational age(X), the regression equation was Y1=2.45X-37.52, the conjunctical sensitivity(Y2) was also positively correlated with corrected gestational age(X), the regression equation was Y2=1.75X-35.41. Conclusions: The corneal sensitivity is higher than conjunctival sensitivity in premature babies.No statistical significance is found between male and female preterm infants in corneal sensitivity and conjunctival sensitivity. The corneal sensitivity and conjunctival sensitivity are correlated with corrected gestational age in preterm infants. The corneal and conjunctival sensitivities of premature babies tend to increase along with the increase of corrected gestational age. (Chin J Ophthalmol, 2018, 54: 115-119).

[A cross-sectional study on dyslipidemia in migrants in Inner Mongolia Autonomous Region].

Objective: To investigate the prevalence of dyslipidemia in migrants in Inner Mongolia Autonomous Region. Methods: A stratified multi-stage cluster equal size sampling was performed among the migrants aged ≥18 years who were engaged in manufacturing, wholesale retail, accommodation and catering service, social service, construction and other and 1 501 migrants from five area in Inner Mongolia Autonomous Region was investigated by means of questionnaires survey, physical measurements and laboratory detection. Results: Complete data was obtained in 1 496 study subjects. The prevalence of dyslipidemia was 42.65% (638/1 496), the age-standardized prevalence was 42.05%; the prevalence of hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia and low high-density lipoprotein hyperlipidemia were 4.90% (73/1 491), 14.76% (220/1 491), 4.83% (72/1 496), 25.27% (378/1 496), respectively. Dyslipidemia characterized by high triglyceride (HTG) and low high-density lipoprotein cholesterol (LHDL-C) accounted for 81.97% (523/638). The prevalence of dyslipidemia and HTG/LHDL-C dyslipidemia were similar, which increased significantly with age in both females and males, but was significantly higher in males. The prevalence among migrants with other occupations was highest. The prevalence of HTG/LHDL-C dyslipidemia didn't significantly increase with the duration of migration. However, the prevalence of high TG and dyslipidemia increased significantly with the duration of migration, the prevalence of high TG in age group <45 years showed the same characteristics. Conclusions: The prevalence of dyslipidemia in migrants in Inner Mongolia was high, and the main form was HTG/LHDL-C dyslipidemia. The prevalence in males, the middle aged and aged as well as those with other occupations were high. Migrants with longer duration of migration had higher prevalence of dyslipidemia.

[Efficacy of standardized sublingual immunotherapy of allergic asthma with rhinitis in children between different age groups].

Objective:The aim of this study is to evaluate the efficacy of standardized sublingual immunotherapy of allergic asthma with rhinitis in children between two different age groups. Method:Retrospective analysis of 250 patients with allergic asthma and rhinitis who received SLIT treatment. According to the age divided into younger children group (aged 3-6 years, 128 patients) and older children group (aged 7-13 years, 122 patients). Evaluate the asthma daytime, nocturnal symptom, medication score, VAS score and pulmonary function FEV1, PEF% level and rhinitis symptom and medication score before and after treatment of two groups of children. Result:The DASS, NASS, TAMS, VAS, FEV1, PEF, TNSS, TRMS had continuously improved significantly after SLIT for half a year, 1 year and 2 years in two groups as compared with baseline (P<0.05). The treatment after 1 year and 2 years, curative effect strengthened continuously, and TAMS, VAS, TNSS and TRMS further reduced. After treatment of each point in time, only at SLIT treatment after half a year, the TAMS, VAS score of younger children group was lower than of older children group (Z values were 4.58 and 4.58, P<0.05). The rest of the indicators were no statistical significance difference between the two age groups (P>0.05). Conclusion:Sub-lingual immunotherapy with Dermatophagoides farinae drops in younger children and older children allergic with asthma and rhinitis can play a significant and similar effect.

[Experimental study of using chitosan nerve conduit combined with PRP to repair facial nerve defect].

Objective:The purpose of this study was to produce chitosan nerve conduit in order to investigate the feasibility of chitosan nerve conduit combined with autologous platelet-rich plasma (PRP) for repairing facial nerve defects.Method:Forty New Zealand white rabbits were randomly divided into four groups (n=10 in each group).Establishment of the facial nerve defect model of the upper buccal branches was placed in the nerve regeneration catheter and injected with the same amount of PRP and saline. The PRP was injected into the chitosan nerve conduit as group A. The physiological saline was injected into the chitosan nerve conduit as group B. The physiological saline was injected into the silicone tube as group C. The PRP was injected into the silicone tube as group D. Eight weeks later,facial nerve gross observation,facial nerve electrophysiological tests,histological observation,image analysis,valuation of nerve regeneration recovery were detected.Result:Five patients were lost to follow up (all five in the modified Semont group),and three patients failed to complete treatment (all three in the Epley group). The sequelae at the 3rd day and one week after modified Semont maneuver were 27 and 9,while 41 and 15 in Epley group. The efficacy rates at the 3rd day and one week after modified Semont maneuver were 91.7% and 98.3%,and 91.9% and 96.8% in Epley group retrospectively. The sequelae and short-term effective rate of patients in modified Semont group was no difference when compared with that in Epley group (P>0.05).Conclusion:The chitosan nerve conduit combined with PRP has a certain effect on the repair of facial nerve defects and is expected to be applied to the repair of clinical facial nerve defects.

[An analysis of the subcutaneous immunotherapy on the pulmonary function and symptoms of asthma and rhinitis in children].

Objective:To evaluate the effect of subcutaneous immunotherapy on allergic asthma and rhinitis in children.Method:A prospective study was adopted to analysis 3 years SCIT treatment of 144 cases of children with allergic asthma and rhinitis. Before and after SCIT treatment for 1 year, 2 and 3 years, FEV1, daytime and night symptoms of asthma and rhinitis were evaluated.Result:After 3 years of SCIT treatment, the FEV1 had significantly increased (F= 243.05, P< 0.01), and with the duration of the treatment was further improvement (P< 0.01). Compared with the baseline, treatment 1 year in daytime, nighttime symptoms scores of asthma and nighttime symptoms scores of rhinitis had significantly reduced (P< 0.01). All symptoms were reduced further by 2 years of treatment (P< 0.01) compared with 1 year. Compared with the 2 years of treatment, daytime symptoms of asthma and rhinitis of 3 years SCIT treatment was improved significantly (P< 0.05).Conclusion:Subcutaneous immunotherapy with 3 years in children allergic with asthma and rhinitis can play a significant effect.