Mortality associated with polymyalgia rheumatica in the United States in the 1999-2020 period: a multiple-cause-of-death study.

OBJECTIVE: Multicause-of-death methods were used to analyze mortality and leading causes of death associated with polymyalgia rheumatica (PMR) in the United States from 1999 to 2020. MATERIALS AND METHODS: We analyzed mortality data from the Centers for Disease Control and Prevention (CDC) Data analysis system and selected death certificates that listed PMR as the cause of death based on the International Statistical Classification of Diseases and Related Health Problems (ICD-10) category code. Relevant mortality rates, number of deaths and historical trends were analyzed. The number of PMR-related deaths and age-standardized mortality rate (ASMR) trend charts were made using Excel 2010 version and trend lines were added. RESULTS: Over the last 22 years, the total number of PMR-related deaths in the United States was 15,421 women (89.8%), a ratio of about 1:9 men to women. When PMR is listed as the underlying cause of death, the ASMR for women and men (per 100,000 people) is approximately 1.8-5.1:1, and when it is listed as the non-underlying cause of death, it is 1.8-3.3:1. PMR deaths are more frequent in individuals aged 70 years and above, with patients aged 80 years and above being most affected. Among different ethnicities, the highest number of deaths was found in Caucasians, followed by Black or African American. When it comes to causes of death, heart disease still ranks first, followed by cancer. In addition, we also found that when PMR combined with malignant tumors as a multiple cause of death, the number of female deaths was higher than that of male deaths, the overall number of deaths of both showed an upward trend, and the overall ASMR of both showed a downward trend. CONCLUSIONS: In the past 22 years, we have observed a low mortality rate of PMR in the United States. However, for patients with PMR, especially elderly women, medical workers should be vigilant and pay attention to whether they are combined with other complications, such as malignant neoplasms, and make timely diagnosis and treatment to further reduce the mortality rate of patients with PMR.

Prospects of targeting JAK/STAT signal transduction pathways for vasculitis.

Vasculitis is the inflammation of blood vessels caused by autoimmunity and/or autoinflammation, and its etiology and pathogenesis remain largely unknown. The Janus kinase (JAK) and Signal transduction Transcription Activator (STAT) signal transduction pathways are a group of molecules involved in the major pathways by which many cytokines exert and integrate their functions, and their dysregulation has been implicated in the pathogenesis of a variety of autoimmune diseases. However, current data supporting the role of the JAK/STAT pathway in the development of vasculitis is limited. In terms of treatment, glucocorticoids and immunosuppressants have been the standard therapy. However, because of the huge burden of treatment side effects, people have long waited for new treatment options. JAK inhibitors reduce the production of multiple cytokines and inhibit inflammation by targeting the JAK/STAT pathway, and have the advantage of rapidly acting in oral formulations, reducing glucocorticoid dependence and associated adverse events, especially in refractory cases. Therefore, JAK inhibitors are expected to be a promising drug for the treatment of vasculitis.

[Analysis of clinical data of necrotizing fasciitis secondary to intestinal fistulas and screening the mortality risk factors].

Objective: To analyze the clinical data and to screen the mortality risk factors of necrotizing fasciitis (NF) secondary to intestinal fistulas (NFsIF). Methods: This study was a retrospective observational study. The data of all NFsIF cases who met the inclusion criteria and were admitted into Shandong Provincial Hospital Affiliated to Shandong First Medical University (hereinafter referred to as our unit) from January 2000 to October 2023, and in PubMed, Web of Science, Scopus, China National Knowledge Infrastructure, and Chinese Medical Journal Network databases from its establishment to October 2023 were retrieved and screened. Based on clinical outcomes, the cases were divided into survival group (47 males and 24 females) and death group (16 males and 7 females), and the mortality rate was calculated. Clinical data of patients in the two groups including age, underlying diseases (most related to NF), symptom duration before presentation, white blood cell count, causes of NF, signs of peritonitis, scope of NF involvement, and intestinal management and wound management measures were compared and analyzed to screen the risk factors of death in 94 patients with NFsIF. Results: A total of 94 valid cases were collected, including 90 patients reported in the literature and 4 patients admitted to our unit, with the mortality rate of patients being 24.5% (23/94). Univariate analysis showed that there were no statistically significant differences in age, underlying diseases, symptom duration before presentation, white blood cell count, causes of NF, signs of peritonitis, scope of NF involvement between patients in the two groups (P>0.05); there were statistically significant differences in intestinal treatment and wound treatment between the two groups (with χ2 values of 17.97 and 8.33, respectively, P<0.05). Multivariate logistic regression analysis showed that both intestinal treatment measures and wound treatments measures were independent risk factors for death in 94 NFsIF patients, among which first-stage colostomy+late-stage reconstruction and negative presssure therapy had higher protective effects (with odds ratios of 0.05 and 0.27, respectively, 95% confidence intervals of 0.01-0.33 and 0.08-0.88, respectively, P<0.05). Conclusions: The mortality risk of patients with NFsIF is high. Based on comprehensive treatments, active intestinal and wound treatment may be the key to avoid death, with first-stage colostomy+late-stage reconstruction and negative pressure therapy having higher protective effects.

[Correlations between plaque characteristics and cerebral blood flow in patients with moderate to severe carotid stenosis using magnetic resonance vessel wall imaging].

OBJECTIVE: To investigate the correlations between carotid plaque characteristics and cerebral blood flow (CBF) in patients with unilateral moderate to severe carotid stenosis using high-resolution magnetic resonance imaging (HR-MRI) and 3D pseudo-continuous arterial spin labeling (3D pcASL). METHODS: A total of 43 patients with unilateral moderate to severe carotid stenosis were recruited. The degree of carotid stenosis, maximum wall thickness (Max WT) and normalized wall index (NWI) were measured using HR-MRI. The plaque characteristics were analyzed. Presence or absence of plaque components including intraplaque hemorrhage (IPH), lipid-rich necrotic nucleus (LRNC), calcification and ulcer were identified, and the grades of calcification and LRNC were recorded. CBF values within the region of interest representing the bilateral middle cerebral artery distribution were acquired using 3D pcASL. Paired sample t test was used to compare the differences of CBF values between the index side and the contralateral side. Spearman correlation analysis was conducted to evaluate the correlations of CBF values with the degree of carotid stenosis, Max WT and NWI. The differences of CBF values between the patients with or without IPH and ulcer were compared using Mann-Whitney U test. Different levels of calcification and LRNC were compared by Kruskal-Wallis test, respectively. RESULTS: The ave-rage degree of carotid stenosis at the index side was 77.30%±11.79%. The mean CBF value of the index side was (46.77±11.65) mL/(100 g·min), and that of the contralateral side was (49.92±9.95) mL/(100 g·min), and the difference was statistically significant (t=-2.474, P=0.017). The mean Max WT and NWI of the carotid plaques at the index side was (6.40±1.87) mm and 62.91%±8.87%, respectively. There were no significant correlations of CBF values with the degrees of stenosis, Max WT and NMI (P>0.05). Plaque composition analysis showed that the CBF values of the index side were different when there was calcification or not and the degrees of calcification were different (P=0.030), but there were no differences between the CBF values on the index sides with or without IPH, ulcer and LRNC. CONCLUSION: In patients with unilateral moderate to severe carotid stenosis, calcification might affect CBF perfusion. When there is no calcification, the plaque components need attention.

Early adjunctive diagnostic value of contrast-enhanced ultrasound-related quantitative parameter and its relationship with micro-perfusion of nontraumatic necrosis of femoral head.

OBJECTIVE: The aim of this study is to explore the early diagnostic value of contrast-enhanced ultrasound (CEUS)-related quantitative parameter and its relationship with the micro-perfusion of nontraumatic necrosis of the femoral head. PATIENTS AND METHODS: According to the random and double-blind method, the patients with non-traumatic femoral head necrosis diagnosed and treated in our hospital from July 2019 to January 2022 were selected as the subjects (the research group). According to the staging of the International Society of Bone Circulation for Femoral Head Necrosis, 89 patients with stage Ⅱ and Ⅲ A were included (39 patients with stage Ⅱ and 50 patients with stage Ⅲ A). 25 patients who conducted physical examination in our hospital during the same time were taken as the control group. Quantitative parameters of CEUS were analyzed. The content of serum vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) were evaluated. The relationship among the quantitative parameters of CEUS, the expression of VEGF and BMP-2 in serum and the patient's condition, and the value for assisting the early diagnosis of nontraumatic femoral head necrosis were analyzed. RESULTS: The body mass, body mass index (BMI), blood lipid, and cholesterol levels were much higher in the research group than in the control group (p < 0.05). The research group had a markedly higher slope of ascending branch (AS), strength enhancement index (EI), and VEGF and obviously lower decay slope (DS), mean transit time (MTT), and time to peak (TTP) than the control group (p < 0.05). In the research group, compared to stage Ⅱ, the levels of AS, EI, and VEGF in stage Ⅲ A patients were memorably higher, and the levels of DS, MTT, TTP and BMP-2 were dramatically lower (p < 0.05). Pearson's correlation test showed that AS, EI, and VEGF were positively correlated with the patients' condition, while DS, MTT, TTP and BMP-2 were negatively correlated with the patients' condition (p < 0.05). The receiver operating characteristic (ROC) curve analysis showed that the diagnostic area under the curve (AUC) of quantitative parameters of CEUS was 0.961, with sensitivity and specificity of 88.0% and 97.4%, respectively. The AUC of the combined detection of VEGF and BMP-2 was 0.945 with sensitivity and specificity of 82.3% and 87.5%, respectively, and the combined detection had a high diagnostic value (p < 0.05). CONCLUSIONS: The quantitative parameters of CEUS were of great value in the early diagnosis of nontraumatic necrosis of the femoral head with microvascular perfusion and the patients' condition, and provided a reference for the clinical treatment of non-traumatic necrosis of the femoral head. These parameters were expected to be useful indicators for judging the efficacy before and after treatment.

[Research advances of adipose stem cell matrix gel in promoting wound healing].

In recent years, with the problem of aging population in China being prominant, the number of patients with chronic wounds such as diabetic foot, pressure ulcer, and vascular ulcer is increasing. Those diseases seriously affect the life quality of patients and increase the economy and care burden of the patients' family, which have been one of the most urgent clinical problems. Many researches have confirmed that adipose stem cells can effectively promote wound healing, while exogenous protease is needed, and there are ethical and many other problems, which limit the clinical application of adipose stem cells. Adipose stem cell matrix gel is a gel-like mixture of biologically active extracellular matrix and stromal vascular fragment obtained from adipose tissue by the principle of fluid whirlpool and flocculation precipitation. It contains rich adipose stem cells, hematopoietic stem cells, endothelial progenitor cells, and macrophages, etc. The preparation method of adipose stem cell matrix gel is simple and the preparation time is short, which is convenient for clinical application. Many studies at home and abroad showed that adipose stem cell matrix gel can effectively promote wound healing by regulating inflammatory reaction, promoting microvascular reconstruction and collagen synthesis. Therefore, this paper summarized the preparation of adipose stem cell matrix gel, the mechanism and problems of the matrix gel in promoting wound repair, in order to provide new methods and ideas for the treatment of chronic refractory wounds in clinic.

Artificial Intelligence-Assisted Evaluation of the Spatial Relationship between Brain Arteriovenous Malformations and the Corticospinal Tract to Predict Postsurgical Motor Defects.

BACKGROUND AND PURPOSE: Preoperative evaluation of brain AVMs is crucial for the selection of surgical candidates. Our goal was to use artificial intelligence to predict postsurgical motor defects in patients with brain AVMs involving motor-related areas. MATERIALS AND METHODS: Eighty-three patients who underwent microsurgical resection of brain AVMs involving motor-related areas were retrospectively reviewed. Four artificial intelligence-based indicators were calculated with artificial intelligence on TOF-MRA and DTI, including FN5mm/50mm (the proportion of fiber numbers within 5-50mm from the lesion border), FN10mm/50mm (the same but within 10-50mm), FP5mm/50mm (the proportion of fiber voxel points within 5-50mm from the lesion border), and FP10mm/50mm (the same but within 10-50mm). The association between the variables and long-term postsurgical motor defects was analyzed using univariate and multivariate analyses. Least absolute shrinkage and selection operator regression with the Pearson correlation coefficient was used to select the optimal features to develop the machine learning model to predict postsurgical motor defects. The area under the curve was calculated to evaluate the predictive performance. RESULTS: In patients with and without postsurgical motor defects, the mean FN5mm/50mm, FN10mm/50mm, FP5mm/50mm, and FP10mm/50mm were 0.24 (SD, 0.24) and 0.03 (SD, 0.06), 0.37 (SD, 0.27) and 0.06 (SD, 0.08), 0.06 (SD, 0.10) and 0.01 (SD, 0.02), and 0.10 (SD, 0.12) and 0.02 (SD, 0.05), respectively. Univariate and multivariate logistic analyses identified FN10mm/50mm as an independent risk factor for long-term postsurgical motor defects (P = .002). FN10mm/50mm achieved a mean area under the curve of 0.86 (SD, 0.08). The mean area under the curve of the machine learning model consisting of FN10mm/50mm, diffuseness, and the Spetzler-Martin score was 0.88 (SD, 0.07). CONCLUSIONS: The artificial intelligence-based indicator, FN10mm/50mm, can reflect the lesion-fiber spatial relationship and act as a dominant predictor for postsurgical motor defects in patients with brain AVMs involving motor-related areas.

[Exploration on the construction of analysis indicators system for antibiotic resistance monitoring].

Antibiotic resistance (AR) is a severe and fast-growing public health challenge with rapid globalization, especially in China. Although some monitoring systems were established in different fields, fragmentation of information failed to show the overall trend and spread of AR. It is necessary to establish a national monitoring system to reveal the occurrence, development, and spread of AR. The new AR monitoring system needs an updated analysis indicators system. We intend to recommend a new analysis indicators system for AR was constructed and applied to AR data monitoring and analysis for humans, animals, the environment, and foods. After investigating and analyzing the 5 Chinese major AR monitoring systems and literature, we have formulated 15 AR monitoring analysis indicators and initially established an evaluation system for the country's new AR monitoring system.

[A prospective randomized controlled study of the application effect of hydrogel dressings on deep partial-thickness burn wounds after dermabrasion and tangential excision].

Objective: To investigate the clinical effect of applying hydrogel dressings in deep partial-thickness burn wounds after dermabrasion and tangential excision. Methods: A prospective randomized controlled study was conducted. From November 2015 to August 2019, 168 patients with deep partial-thickness burns hospitalized in Zibo Sixth People's Hospital met the inclusion criteria. According to the random number table, the patients were divided into hydrogel dressing+vaseline gauze group (84 cases, 67 males and 17 females) and vaseline gauze only group (84 cases, 65 males and 19 females) who were aged (31±16) and (35±17) years, respectively, and were given corresponding treatment after dermabrasion and tangential excision. The dressings were changed every 3-5 days. Autologous skin grafting was performed with split-thickness or medium-thickness skin grafts taken from trunk or thigh if the wounds failed to heal over 21 days or the wounds were less than 21 days but located in the joints, which might affect the functional activities at later stage. After operation, the general condition of the wounds was observed continuously and dynamically till the wounds were healed. The degree of dressing adhesion was evaluated during the first 4 dressing changes after operation, and the degree of pain was evaluated using Numerical Rating Scale (NRS). The wound healing rate on post operation day (POD) 3, 6, and 15 was calculated. The positive proportion of bacterial culture of wound exudates/cleanout fluid on admission and at dressing change on POD 3, 6, and 15 was calculated. The number of dressing changes were recorded, the rate of skin grafting operation was calculated, and the time of complete wound healing was recorded. Vancouver Scar Scale (VSS) was used in 6 months of follow-up to evaluate the hyperplasia of scar. Data were statistically analyzed with analysis of variance for repeated measurement, independent sample t test, Mann-Whitney U test, chi-square test or Fisher's exact probability test, and Bonferroni correction. Results: During the observation period after operation, the wound was moist with less exudates and the wound healed much faster in patients of hydrogel dressing+vaseline gauze group, with the inner dressing being easier to remove with mild pain, while the wounds showed more exudates and slower healing in patients of vaseline gauze only group with the obvious adhesions of inner dressing, stronger pain, and bleeding in the wounds. Compared with those in vaseline gauze only group, the degree of dressing adhesion and pain NRS score of patients in hydrogel dressing+vaseline gauze group decreased significantly during the first 4 dressing changes after operation (χ2=52.625, Z=-10.854, P<0.01), the wound healing rate increased significantly at dressing change on POD 3, 6, and 15 (t=10.347, 41.150, 167.627, P<0.01), the positive proportion of wound exudates/cleanout fluid bacterial culture did not change significantly on admission or at dressing change on POD 3 (P>0.05) but decreased significantly at dressing change on POD 6 and 15 (χ2=15.616, 15.226, P<0.01), the dressing change times was significantly reduced (t=-11.986, P<0.01), and the rate of skin grafting operation was significantly decreased (χ2=35.850, P<0.01). The complete wound healing time of patients in hydrogel dressing+vaseline gauze group was (17.6±2.8) d, significantly shorter than (27.1±3.0) d in vaseline gauze only group (t=-21.288, P<0.01). During the follow-up of 6 months, the VSS score of scar hyperplasia of patients in hydrogel dressing+vaseline gauze group was significantly lower than that in vaseline gauze only group (Z=-11.287, P<0.01). Conclusions: Compared with the use of vaseline gauze only, the application of vaseline gauze coated with hydrogel dressing in deep partial-thickness burn wounds after dermabrasion and tangential excision is more effective in moisturizing, significantly reducing the degree of dressing adhesion and patients' pain during dressing change, increasing wound healing rate, decreasing wound infection rate and the rate of skin grafting operation, and reducing the number of dressing changes. It shortens the time for complete wound healing, and effectively relieves scar hyperplasia.

Repeat hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma: retrospective multicentre study.

BACKGROUND: The therapeutic value of repeat hepatic resection (rHR) or radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) is unknown. This study aimed to investigate the safety and efficacy of rHR or RFA. METHODS: This was a retrospective multicentre study of patients with recurrent HCC within the Milan criteria who underwent rHR or RFA at nine university hospitals in China and Italy between January 2003 and January 2018. Survival after rHR or RFA was examined in unadjusted analyses and after propensity score matching (1 : 1). RESULTS: Of 847 patients included, 307 and 540 underwent rHR and RFA respectively. Median overall survival was 73.5 and 67.0 months after rHR and RFA respectively (hazard ratio 1.01 (95 per cent c.i. 0.81 to 1.26)). Median recurrence-free survival was longer after rHR versus RFA (23.6 versus 15.2 months; hazard ratio 0.76 (95 per cent c.i. 0.65 to 0.89)). These results were confirmed after propensity score matching. RFA was associated with lower morbidity of grade 3 and above (0.6 versus 6.2 per cent; P < 0.001) and shorter hospital stay (8.0 versus 3.0 days, P < 0.001) than rHR. CONCLUSION: rHR was associated with longer recurrence-free survival but not overall survival compared with RFA.

[Integrated analysis of DNA methylation and gene expression profiles of hepatocellular carcinoma to construct miR-1180-3p relevant ceRNA regulatory network].

Objective: This study analyzes the expression level of miR-1180-3p and constructs the regulatory network of relevant ceRNA by integrating the DNA methylation and gene expression profile of hepatocellular carcinoma from the Cancer Genome Atlas (TCGA). Methods: Firstly, the expression level of miR-1180-3p in hepatocellular carcinoma and adjacent tissues was analyzed by TCGA database, and the differential expression of lncrna and mRNA was screened. Secondly, the LncBase database and the TargetScan database were used to predict the relationship between miR-1180-3p and lncRNA and mRNA, and the DNA methylation-mediated lncRNA was screened by the DNA methylation profile of lncRNA. Finally, Cytoscape software was used to construct miR-1180-3p relevant ceRNA network, and WebGestalt website was used to perform GO and KEGG analysis of related mRNA in ceRNA. Results: Compared with patients with low expression of miR-1180-3p (mean overall survival duration, 5.69 ± 0.35 years), patients with high expression of miR-1180-3p had shorter overall survival time (mean overall survival duration, 3.99 ± 0.47 years), indicating that the high expression of miR-1180-3p was hepatocellular carcinoma risk factor affecting the prognosis (HR = 1.28, 95% CI = 1.1 ~ 1.5, P < 0.01). A miR-1180-3p related ceRNA regulatory network was constructed in this study, which contained 2 lncRNAs (F11-AS1 and LINC01511) and 37 mRNAs. Conclusion: This study has successfully constructed miR-1180-3p relevant ceRNA regulatory network, and DNA methylation-mediated F11-AS1 and F11-AS1/miR-1180-3p/C11of54 ceRNA regulatory axis has played an important role in the occurrence and development of hepatocellular carcinoma.

[Summary of the 2019 Academic Annual Meeting of the Society of Burn Surgery of Chinese Medical Doctor Association].

The 2019 Academic Annual Meeting of the Society of Burn Surgery of Chinese Medical Doctor Association, sponsored by the Chinese Medical Doctor Association, was successfully held in Jinan, Shandong Province from May 22th to 24th. More than 300 representatives of burn department attended the meeting. With the theme of " Standardization and Innovation" , the conference focused on academician lectures and invited reports, thematic reports, thematic discussions, and discussion of difficult and complex cases in view of the current situation and challenges of burn specialty in China, and closely combined with the actual clinical needs. In order to reserve the reserve force, the Youth Committee of the Society of Burn Surgery of Chinese Medical Doctor Association was established.

[Retrospect on 60 years' history and prospect of Department of Burns and Plastic Surgery of Provincial Hospital Affiliated to Shandong University].

The Department of Burns and Plastic Surgery of Provincial Hospital Affiliated to Shandong University is the leading team in Shandong province. It is integrated with clinical treatment, scientific research, teaching, personnel training, and medical service for social crisis, which undertakes the tasks of giving lessons and offering chances for noviciate and internship of burns and plastic surgery in College of Medicine of Shandong University. It is not only the training unit affiliated to College of Medicine of Shandong University for master students and doctoral students major in burns and plastic surgery, but also the national training base for specialists of burns and plastic surgery. It is the national key clinical subject of burn surgery. Over the past 60 years, with the concerted efforts of several generations, it has made significant contributions to the development and innovation of burns and plastic surgery in Shandong province and the whole China.

[Therapeutic effect of human umbilical cord mesenchymal stem cells on airway remodeling in an asthma model of rat and its possible mechanism].

Objective: To observe the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on airway remodeling in asthma model of rat and its possible mechanism. Methods: hUC-MSCs were isolated and cultured, and surface markers of hUC-MSCs were identified by flow cytometry. Forty Wistar male rats were divided into 4 groups: Control, Model, MSCs, Budesonide. The rats of Control group were sensitized and challenged by normal saline. The rats of Model, MSCs and Budesonide group were sensitized and challenged by ovalbumin (OVA) for 8 weeks. The MSCs group rats were given a tail vein injection of MSCs 0.2 ml (1×10(6) /ml) on days 35, 45, and 55 half an hour befor each OVA exposure. The Budesonide group rats were given aerosol inhalation of budesonide 2 mg two hours before each OVA exposure. Specimens were collected within 24 hours after the last OVA challenge. The parameters of airway morphological changes and the degree of airway remodeling were analyzed using Image-pro plus computer graphics. The levels of transformation growth factor (TGF) -ß(1) in bronchoalveolar lavage fluid (BALF) and serum were detected by enzyme linked immunosorbent assay (ELISA). The expressions of E-cadherin, α-smooth muscle actin (α-SMA) and fibronectin (Fn) were measured by immunohistochemistry. Results: The thickness of airway wall and smooth muscle of Model, MSCs and Budesonide group rats were significantly thicker than Control group. The levels of TGF-ß(1) in both BALF and serum of Model, MSCs and Budesonide group rats were significantly higher than Control group. The expression of E-cadherin of Model, MSCs and Budesonide group rats was significantly lower than Control group, while the expression of α-SMA and Fn were significantly higher. The thickness of airway wall and smooth muscle of MSCs and Budesonide group rats were significantly lower than Model group[(38.40±2.50, 45.34±0.33) vs (80.18±1.75) µm and (15.71±0.89, 18.57±0.67) vs (40.97±0.90) µm]. The levels of TGF-ß(1) in both BALF and serum of MSCs and Budesonide group were significantly lower than Model group[(3.53±0.43, 3.11±0.05) vs (20.88±0.37) µg/L and (31.07±0.89, 31.12±0.50) vs (70.58±0.39)µg/L](all P<0.01). The expressions of α-SMA, Fn of MSCs and Budesonide group rats were significantly lower than Model group[(0.438±0.057, 0.445±0.027) vs (0.521±0.030) and (0.459±0.041, 0.458±0.029) vs (0.527±0.022)], While the expression of E-cadherin was significantly higher[(0.308±0.023, 0.296±0.010) vs (0.256±0.087)](all P<0.01). Conclusion: MSCs could alleviate asthmatic airway remodeling, the mechanism of which may be associated with the inhibition of TGF-ß(1) induced epithelial-mesenchymal transition.

Systematic review of risk factors of hepatocellular carcinoma after hepatitis B surface antigen seroclearance.

There is no consensus about factors that increase risk of hepatocellular carcinoma (HCC) among patients with chronic hepatitis B who have achieved seroclearance of hepatitis B surface antigen (HBsAg). To assess the available evidence about risk factors for HCC after HBsAg seroclearance, Scopus, EMBASE, PubMed and Cochrane Library databases were systematically searched for relevant studies published through 15 September 2017. A total of 28 studies involving more than 105 411 patients with chronic hepatitis B were included. HBsAg seroclearance occurred spontaneously in 7656, while it occurred after interferon or nucleos(t)ide analogue therapy in 1248. The rate of HBsAg seroclearance was 6.77%. Incidence of HCC was significantly lower among patients who experienced HBsAg seroclearance than among those who remained HBsAg-positive (1.86% vs 6.56%, P < .001). Risk factors of HCC occurrence included cirrhosis (incidence with vs without: 9.51% vs 1.66%), male gender (2.34% vs 0.64%) and age ≥ 50 year at HBsAg seroclearance (2.34% vs 0.63%) (all P < .001). The available evidence suggests that HCC can develop at a low rate after HBsAg seroclearance, so periodic surveillance is recommended, especially for male patients, patients with cirrhosis and patients who experience HBsAg seroclearance when at least 50 years old.

Propranolol inhibits the proliferation, migration and tube formation of hemangioma cells through HIF-1α dependent mechanisms.

The aim of this study was to investigate the mechanism of propranolol on the regression of hemangiomas. Propranolol-treated hemangioma tissues were collected and the expression of hypoxia inducible factor-1α (HIF-1α) was examined. We also established HIF-1α overexpression and knockdown hemangioma cells, and determined the effects of HIF-1α on the hemangioma cells proliferation, apoptosis, migration and tube formation. Significantly increased HIF-1α level was found in the hemangioma tissues compared to that in normal vascular tissues, whereas propranolol treatment decreased the HIF-1α level in hemangioma tissues in a time- and dose-dependent manner. Moreover, propranolol treatment significantly decreased cell proliferation, migration and tube formation as well as promoted cell apoptosis in HIF-1α overexpression and knockdown hemangioma cells. Propranolol suppressed the cells proliferation, migration and tube formation of hemangioma cells through HIF-1α dependent mechanisms. HIF-1α could serve as a novel target in the treatment of hemangiomas.

Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients.

Nowadays, risperidone is an atypical antipsychotic drug that has been increasingly used for treatment and maintenance therapy in schizophrenia. However, partially affected by genetic or environmental factors, there is significant difference in treatment outcomes among patients. In this study, we aimed to interpret the difference between good and poor responders treated with risperidone in both genetic and epigenetic levels in 288 mainland Chinese patients. We recruited a Henan cohort including 98 patients as initial discovery group and then confirmed our results in Shanghai cohort. In genetic studies, we found 10 candidate single-nucleotide polymorphisms (SNPs) and 2 rare variants in Henan cohort by next-generation sequencing of 100 risperidone-response-related genes. After replication in Shanghai cohort by massarray platform, ultimately, rs6706232 and rs4818 were significantly associated with risperidone response in the two cohort meta-analysis (P=0.024 and 0.04, respectively). Besides, we also selected another reported 17 candidate SNPs associated with risperidone drug response to replicate in our mainland Chinese samples, while, we found no significant SNPs after Bonferroni correction. In epigenetic studies, we investigated the methylation status in promoters or gene-coding region of risperidone drug response-related genes including CYP3A4, CYP2D6, ABCB1, HTR2A, DRD2. Totally we found seven significant CpG sites in the meta-analysis with Bonferroni-corrected PCYP3A4_CpG_-36=0.0014, PCYP3A4_CpG_-258=0.0013, PCYP3A4_CpG_-296=0.0014, PCYP3A4_CpG_-367:-372:-374=0.028, PCYP2D6_CpG_193=0.012, PCYP2D6_CpG_242:244:250=0.00076 and PCYP2D6_CpG_284=0.034, respectively. As genetic and epigenetic factors may interactively affect drug response, we finally carried out a multivariant interaction analysis with multifactor dimensionality reduction and discovered a significant four-locus model (CYP3A4_CpG_-82:-86 +rs6280+rs1800497+rs6265, P=0.038) affecting drug response. These findings could partially explain different risperidone response outcome in Chinese population in a systematic level.

[Human selenium-containing single-chain variable fragment with glutathione peroxidase activity protects NIH3T3 fibroblast against oxidative damage].

Ultraviolet B (UVB medium wave, 280-315 nm) induces cellular oxidative damage and apoptosis by producing reactive oxygen species (ROS). Glutathione peroxidase functions as an antioxidant by catalyzing the reduction of hydrogen peroxide, the more important member of reactive oxygen species. A human selenium-containing single-chain variable fragment (se-scFv-B3) with glutathione peroxidase activity of 1288 U/µmol was generated and investigated for its antioxidant effects in UVB-induced oxidative damage model. In particular, cell viability, lipid peroxidation extent, cell apoptosis, the change of mitochondrial membrane potential, caspase-3 activity and the levels of intracellular reactive oxygen species were assayed. Human se-scFv-B3 protects NIH3T3 cells against ultraviolet B-induced oxidative damage and subsequent apoptosis by prevention of lipid peroxidation, inhibition of the collapse of mitochondrial membrane potential as well as the suppression of the caspase-3 activity and the level of intracellular ROS. It seems that antioxidant effects of human se-scFv-B3 are mainly associated with its capability to scavenge reactive oxygen species, which is similar to that of the natural glutathione peroxidase.

Propranolol inhibits the proliferation, migration and tube formation of hemangioma cells through HIF-1α dependent mechanisms

The aim of this study was to investigate the mechanism of propranolol on the regression of hemangiomas. Propranolol-treated hemangioma tissues were collected and the expression of hypoxia inducible factor-1α (HIF-1α) was examined. We also established HIF-1α overexpression and knockdown hemangioma cells, and determined the effects of HIF-1α on the hemangioma cells proliferation, apoptosis, migration and tube formation. Significantly increased HIF-1α level was found in the hemangioma tissues compared to that in normal vascular tissues, whereas propranolol treatment decreased the HIF-1α level in hemangioma tissues in a time- and dose-dependent manner. Moreover, propranolol treatment significantly decreased cell proliferation, migration and tube formation as well as promoted cell apoptosis in HIF-1α overexpression and knockdown hemangioma cells. Propranolol suppressed the cells proliferation, migration and tube formation of hemangioma cells through HIF-1α dependent mechanisms. HIF-1α could serve as a novel target in the treatment of hemangiomas.

[Regulation effect of ß-catenin pathway on TGF-ß1 induced pulmonary pro-fibrosis].

OBJECTIVE: To investigate the regulation effect of ß-catenin pathway on transforming growth factor beta1 (TGF-ß1) induced pulmonary pro-fibrosis. METHODS: The rat alveolar typeⅡ cells (RLE-6TN) were divided into four groups: A1.control group; B1.TGF-ß1 group was treated with 5 µg/L TGF-ß1; C1.pcDNA+ TGF-ß1 group was transiently transfected with eukaryotic expression vector pcDNA3.0 (pcDNA) and followed by TGF-ß1 treatment (5 µg/L); D1.F-(ß-TrCP)-Ecad+ TGF-ß1 group was transiently transfected with ß-catenin protein knockout vector [F-(ß-TrCP)-Ecad] and followed by TGF-ß1 treatment (5 µg/L). After 24 hours, cells were observed under the inverted phase contrast microscope, then the expressions of E-cadherin, α-smooth muscle actin (α-SMA) and fibronectin (Fn) in each group were measured by Western blot and the mRNA levels of Snail which was the downstream profibrotic transcription production in cell culture supernatants of each group were detected by real-time fluorescence quantification-polymerase chain reaction (RT-PCR) .The rat alveolar macrophages (CRL-2192) were divided into five groups: A2.control group; B2.Interferon gamma (IFN-γ) group was treated by 20 µg/L IFN-γ; C2.TGF-ß1+ IFN-γ group was treated by 20 µg/L IFN-γ with 10 µg/L TGF-ß1; D2.F-(ß-TrCP)-Ecad+ TGF-ß1+ IFN-γ group was transfected with F-(ß-TrCP)-Ecad and other dispose was the same as group C2; E2.WTß-catenin+ TGF-ß1+ IFN-γ group was transfected with WTß-catenin and other dispose was the same as group C2.After 24 hours, protein levels of ß-catenin in group A2, B2, C2 were determined by Western blot.Inducible nitric oxide synthase (iNOS) mRNA levels of each group were detected by RT-PCR. RESULTS: The RLE-6TN cells of group B1, C1 showed a change in morphology to spindle-shaped cells, the cells of group D1 maintained a cobblestone morphology. Protein expressions of the fibroblast markers α-SMA and Fn, and mRNA expressions of the downstream profibrotic transcription production Snail of group B1, C1 were significantly higher than group A1, while protein expressions of the epithelial marker E-cadherin were significantly lower.The protein expressions of α-SMA, Fn and mRNA expressions Snail of group D1 were significantly lower than group C1 (0.352±0.076 vs 0.937±0.303, 0.319±0.072 vs 0.903±0.211, 3.675±0.642 vs 9.708±2.031), while the protein expressions of E-cadherin were significantly higher (1.482±0.227 vs 0.604±0.121) (all P<0.05). The steady state protein levels of ß-catenin in CRL-2192 cells was low and ß-catenin protein expressions of CRL-2192 cells in group A2, B2 and C2 had no significantly statistical differences.The mRNA expressions of iNOS of group B2 cells were significantly higher than group A2, C2, D2, E2 (64.95±4.47 vs 9.87±0.73, 21.32±2.41, 18.35±3.61, 22.87±3.14) (all P<0.01), the expressions of iNOS of group C2, D2, E2 were all higher than group A2 (all P<0.05), but there were no significant differences among group C2, D2 and E2. CONCLUSIONS: Inhibition of ß-catenin pathway inhibits TGF-ß1-induced epithelial-mesenchymal transition (EMT) and has no effect on its anti-inflammation effect.Therefore, ß-catenin pathway regulates the pulmonary pro-fibrosis effect of TGF-ß1.