Effects of a diabetes education program integrated with text-message support for lifestyle change among older individuals with type 2 diabetes in communities: a randomised controlled trial.

OBJECTIVE: The objective of this study was to investigate the effects of self-management education integrated with text-message support (SME-TMS) on glycaemic control in individuals with type 2 diabetes. STUDY DESIGN: a randomized, controlled trial. METHODS: Patients from two communities were randomized into the intervention group (n = 53) or the control group (n = 52). The six-month intervention included the culturally tailored diabetes education and text-messaging support for behaviour changes. The control group received treatment as usual. The primary outcome was reductions in HbA1c and fasting blood glucose at six-month non-intervention follow-up. Secondary outcomes were reductions in body weight, body mass index (BMI), blood pressure, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, physical activity, and health beliefs. RESULTS: The intervention led to substantially increase days of weekly physical activity (42% vs. 0%, P < 0.001) and health beliefs (coefficient = 7.0, 95% confidence interval [CI]: 4.4 to 9.6, P < 0.001). However, no greater reduction was found in HbA1c at six months after the intervention, compared with the control group (0.13%, 95% CI: -0.20 to 0.46, P = 0.443). The reductions of blood pressure, TC, and LDL-C were greater in the control group than in the intervention group (all P < 0.050). Within the intervention group, participants had significant reduction in BMI, whereas the control group had greater reductions in TC and LDL-C (all P < 0.050). CONCLUSIONS: The SME-TMS intervention led to a greater increase in the weekly physical activity and health belief score in the older patients at 6-month follow-up than with the usual care. Further research is needed to ascertain how these benefits could be translated into favorable medium-and long-term glycaemic control. TRAIL REGISTRATION NUMBER: This study was registered on Chinese Clinical Trials Registry (ChiCTR2300075112).

Assessing hydrological connectivity for natural-artificial catchment with a new framework integrating graph theory and network analysis.

Anthropogenic activities alter the underlying surface conditions and arrangements of landscape features in a drainage basin, interfering with the pollutant (e.g., dissolved nitrogen, phosphorus) transport network configuration and altering the hydrological response. Assessing the impact of anthropogenic activities on hydrological connectivity for natural-artificial catchment is critical to understand the hydrological-driven ecosystem processes, services and biodiversity. However, quantifying this impact at catchment scale remains challenging. In this study, a new framework was proposed to quantify the impact of anthropogenic activities on hydrological connectivity combined with graph theory and network analysis. This framework was exemplified in a natural-artificial catchment of the Yangtze River basin of China. Based on remote sensing and field-investigated data, three transport networks were constructed, including natural transport network (N1), ditch-road transport network (N2), and terrace-dominated transport network (N3), which reflected the different human intervention. The results showed that human intervention improved the connectivity of the nodes and enhanced the complexity of the catchment transport network structure. Anthropogenic activities significantly decreased the hydrological structural connectivity of the catchment. In particular, compared with the N1 network, the critical nodes for hydrological connectivity which were judged by connectivity indexes were reduced by 92.94% and 95.29% in the N2 and N3 network, respectively. Furthermore, the ditch-road construction had a greater impact than terraces in decreasing hydrological structural connectivity at catchment scale. This framework has proven effective in quantifying the hydrological connectivity analysis under different human intervention at the catchment scale and facilitates the improvement of catchment management strategies.

[Survival and disease burden trend analysis of occupational pneumoconiosis from 1963 to 2020 in Shizuishan City].

Objective: To understand the survival status and its influencing factors of occupational pneumoconiosis patients in Shizuishan City, and to analyze the disease burden of occupational pneumoconiosis and its trend, so as to provide scientific basis for formulating comprehensive prevention and treatment measures of occupational pneumoconiosis. Methods: A retrospective survey was conducted during July to December 2020 to explore the survival status of occupational pneumoconiosis patients who had been reported from 1963 to 2020 in Shizuishan City. The Kaplan-Meier method and Life-table method were used for survival analysis, and Cox proportional hazards regression model was used to analyze the influencing factors of survival time. The disability adjusted life years (DALY) was applied to analyze the disease burden of occupational pneumoconiosis and its temporal trend. Results: From 1963 to 2020, a total of 3263 cases of occupational pneumoconiosis were reported in Shizuishan City, of which 1467 died, so that the fatality rate was 44.96%. The median survival time was 26.71 years, average age of death was (70.55±10.92) years old. There were significant differences in the survival rates of occupational pneumoconiosis patients among different types, diagnosis age, exposure time, industry, initial diagnosis stage and whether upgraded (P<0.05) . As the survival time increased, the survival rate of patients decreased gradually. When the survival time was ≥50 years, the cumulative survival rate of patients was 4.20%. Cox regression analysis suggested that the type of pneumoconiosis, industry, diagnosis age, exposure time, initial diagnosis stage and whether upgraded were the influencing factors for the survival time of patients with occupational pneumoconiosis (P<0.05) . The total DALY attributable to occupational pneumoconiosis from 1963 to 2020 in Shizuishan City was 48026.65 person years, of which the years of life lost (YLL) was 15155.39 person years, and the average YLL was 10.33 years/person, and the years lost due to disability (YLD) was 32871.26 person years, and the average YLD was 10.07 years/person. The DALY attributed to coal worker's pneumoconiosis and silicosis were 39408.51 person years and 6565.02 person years, respectively, and they accounted for 82.06% and 13.67% of the total disease burden in Shizuishan City, respectively. The DALY caused by occupational pneumoconiosis in the age group of 40-49 years old and the first diagnosis of stage I occupational pneumoconiosis were higher, which were 20899.71 and 36231.97 person years, respectively. The average YLL and average YLD showed a volatility downtrend over time. Conclusion: The disease burden of occupational pneumoconiosis cannot be ignored in Shizuishan City, and timely targeted measures should be taken for key populations and key industries. It is recommended that life-cycle health management and hierarchical medical should be taken to improve the life quality of patients and prolong their lifes.

[Clinical diagnosis and treatment characteristics of pancreatic cystic neoplasms in pediatric patients: a report of 13 cases].

Objective: To investigate the clinical characteristics of pancreatic cystic neoplasms in pediatric patients. Methods: The clinical data of 13 patients with pancreatic cystic neoplasm at Wuhan Children's Hospital from July 2007 to November 2019 were collected.There were 5 males and 8 females, with a mean age of 133 months(range: 9 to 170 months). Eleven patients presented with abdominal pain, vomiting, and a palpable mass. Tumors were located in the pancreatic head(n=7), body(n=2) and tail(n=4), respectively. Results: The preoperative diagnosis was confirmed by imaging examination in 11 patients, CT and MRI was significantly superior to ultrasound in the exact diagnosis of the tumor types. In this group, surgical methods mainly included pancreaticoduodenectomy(n=3), pylorus-preserving pancreatoduodenectomy(n=1), duodenum-preserving pancreas head resection(n=3), spleen-preserving distal pancreatectomy (n=3), distal pancreatectomy plus splenectomy(n=2), and tumor enucleation(n=1). Postoperative complications including biochemical leakage(n=1), delayed gastric emptying(grade A) (n=1), adhesive intestinal obstruction(n=1), transient elevation of platelet count(n=2), all were cured by conservative treatment. In one patient biliary leakage occurred and later developed into biliary stricture, this patient underwent the second operation 6 weeks later and recovered smoothly. All patients were diagnosed by postoperative pathology, including solid pseudopapillary neoplasm(n=10), serous cystadenoma(n=1), mucinous cystadenoma(n=1) and cystic lymphangiom(n=1). Three cases were lost in this group, the rest of patients were all accepted outpatient or telephones follow-up. There was no evidence of recurrence or metastasis during 3 to 92 months follow-up. Conclusions: The incidence of pancreatic cystic neoplasm is low in the pediatric patients. Symptomatic patients should receive surgical treatment timely. It's safe and effective to choose the organs and functions-preserving surgical method.

Fourier based partial least squares algorithm: new insight into influence of spectral shift in "frequency domain".

Developments in analytical chemistry technology, especially the combination between the partial least squares and spectroscopy, have contributed significantly to predicting the chemical concentrations and discriminating similar chemical analytes. However, spectral shift is an unwanted but inevitable factor for the spectroscopic analyzer, especially in practical application, which decreases the method's accuracy and stability. To remove the term of spectral shift completely and increase the robustness of spectroscopic analysis method, Fourier transform based partial least squares method was proposed. The approach used Fourier transform first to transform the spectral shift in the "time domain" to the phase term in the "frequency domain." The module of the Fourier transformed spectra was then calculated. As a result, the phase term was removed (the module of the phase term is 1), which means the spectral shift term was removed completely. Finally, the spectra modules were used to build the model and validate. The approach's advantages are: (i) that the approach provides a new insight to treat the spectral shift in spectroscopic analyzer; (ii) that the model is insensitive to spectral shift; (iii) that the approach makes partial least squares combined with spectroscopy more suitable for practical application, rather than lab experiment, because spectral shift is permitted, which means the decreased requirements of measure environment. As an example, blood species discrimination, using Raman spectroscopy, was used in order to demonstrate this approach's effectiveness.

Endoscopic submucosal dissection of distal intestinal tumors using grasping forceps for traction.

BACKGROUND: The aim of this study was to assess the efficacy of traction device-assisted endoscopic submucosal dissection (ESD) of the rectum and the distal segment of sigmoid colon using grasping forceps. METHODS: A total of 43 patients scheduled for colonic ESD at our institution were enrolled between January 2013 and June 2017. The patients were randomly allocated to receive conventional ESD (group A) or traction device-assisted ESD (group B). The procedure time, complication rate, and en-block resection rate in the two groups were compared. RESULTS: A total of 41 patients completed the study. The procedure time, complication rate and en-block resection rate were, respectively, 104.1 ± 34.7 min, 15%, 90% in the routine group (group A) and 84.7 ± 23.5 min, 9.5%, 90.5% in traction device-assisted ESD (group B). The procedure time in group B was significantly less than that in group A (F = 4.442, p < 0.05). CONCLUSIONS: Traction device-assisted ESD using grasping forceps is safe and effective in distal colon ESD.

[Cerebral hyper perfusion syndrome after carotid artery stenting].

OBJECTIVE: To explore the risk factors, clinical characteristics, precaution and treatment of hyper perfusion syndrome (HPS) after carotid artery stenting (CAS). METHODS: From September 2014 to March 2018, the clinical data of 226 patients with severe carotid stenosis (70%-99%) treated with carotid artery stenting (CAS)at Department of Interventional Radiology and Vascular Surgery, Peking University Third Hospital, were analyzed retrospectively．Five of them developed HPS after CAS．The relationship between the clinical baseline data, imaging characteristics, perioperative management and HPS were assessed. RESULTS: In this group, 5 patients of them (2.21%, 5/226) developed HPS after CAS, and 2 patients of them (0.88%, 2/226) were hyper perfusion induced intracranial hemorrhage (HICH). The 5 patients consisted of 4 men and 1 woman whose age ranged from 58 to 74 years. The symptoms of HPS occurred within 4 hours to 3 days after CAS. Among the 5 cases, the clinical manifestations were that 2 cases with headache, 1 case with delirium,1 case with hemiparesis of left limbs, and 1 case with coma(died ultimately).The main manifestations of case 1 and case 2 were headache in the frontal parietal temporal region of the operative side, accompanied by nausea and vomiting. The symptoms were relieved after blood pressure lowering treatment and mannitol dehydration. The main manifestations of case 3 were excitement and delirium. The symptoms were relieved by a small dose of sedatives, also with blood pressure lowering treatment and mannitol dehydration. The initial symptoms of case 4 were excitement and delirium, accompanied by mild headache of the operative side, and hemiplegia of the contralateral limb occurred within a short time. The main manifestation of case 5 was severe headache and went into deep coma within a short time. This patient died of massive cerebral hemorrhage ultimately. CONCLUSION: HPS is an uncommon but serious complication after CAS. Improving our understanding and heightening vigilance of HPS is necessary. The earlier diagnosis, the earlier treatment.

[Application of Neuroform EZ stent in the treatment of severe intracranial arterial stenosis with complex symptomatic].

OBJECTIVE: To assess the safety and efficacy of Neuroform EZ stent used in treatment of symptomatic complex severe intracranial atherosclerotic stenosis (ICAS). METHODS: Clinical data of 18 patients with symptomatic complex severe ICAS undergoing Neuroform EZ stent angioplasty from January 2016 to December 2017 were retrospectively analyzed. All the lesions of the patients in this group were considered as complex ICAS, i.e. with severe tortuous access, long (>10 mm) or occlusive or bifurcation lesions, with concurrent aneurysms near the stenotic lesion. The primary outcome was defined as any stroke (including ischemic or hemorrhagic) or deaths from any cause after stenting procedure within 30 days. The secondary outcome was defined as successful revascularization and occurrence of >50% in-stent restenosis during the follow-up period. RESULTS: All the 18 patients achieved technical success (100%) and mean stenosis rate was reduced from 85%±7% to 18%±6%. Of the 18 patients included, the 30-day stroke or death was 5.6% (1/18), which presented as basal ganglia region infarction in a patient with tandem lesions on the left vertebral artery. There was no hemorrhagic and death complications that occurred in the patients of this group. One concurrent aneurysm was embolized with micro coil (stent assisted) by stages after 1 month. In this group 12 patients were followed up with digital subtraction angiography (DSA) after hospital discharge. The follow-up period ranged from 8 months to 26 months [mean: (16±8) months]．During the follow-up period 2 patients in the 12 patients (2/12, 16.7%) developed in-stent restenosis (ISR) confirmed by DSA, and one of them was symptomatic restenosis and restored unobstructed blood flow after balloon angioplasty. CONCLUSION: Neuroform EZ stent for the treatment of highly screened symptomatic complex severe ICAS is safe and effective. It has its advantages over traditional stent.

Alteration of N-glycoproteins/N-glycosites in human hepatic stellate cells activated with transforming growth factor-ß1.

Proteins N-glycosylation is significantly increased in the activated human hepatic stellate cells (HSCs) stimulated by transforming growth factor-ß1 (TGF-ß1) compared to the quiescent HSCs according to our previous study. However, little is known about the alteration of N-glycoprotein profiles in the activated HSCs. Profiles of N-glycopeptides / N-glycoproteins / N-glycosites in LX-2 cells, with and without activation by TGF-ß1, were identified and compared using hydrazide chemistry enrichment coupled with liquid chromatography - mass spectrometry analysis. Western blot and immunohistochemistry were further used for validation. A total of 103 non-redundant N-glycopeptides, with 107 glycosylation sites from 86 N-glycoproteins, were identified in activated and quiescent LX-2 cells respectively. Among these, 23 proteins were known N-glycoproteins, and 58 were newly identified N-glycoproteins. In addition, 43 proteins (e.g., pigment epithelium-derived factor and clathrin heavy chain 1) were solely identified or up-regulated in the activated LX-2 cells, which participated in focal adhesion and glycosaminoglycan degradation pathways and were involved in interaction clusters of cytoskeletal proteins (e.g., myosin light chains and keratins). The increased expression of glucosamine (N-acetyl)-6-sulfatase and phospholipase C beta 2 and the decreased expression of zinc finger and BTB domain-containing protein 1 were validated in the activated compared to the quiescent LX-2 cells. In conclusion, increased expression of N-glycoproteins and N-glycosites play important roles in cellular contractility, signal transduction, and responses to stimuli in the activated HSCs, which might provide useful information for discovering novel molecular mechanism of HSC activation and therapeutic targets in liver fibrosis.

Proteolysis and cathepsin activities in the processing of dry-cured duck.

Changes in sarcoplasmic and myofibrillar proteins, free amino acids, and cathepsin activities were measured to evaluate the contribution of cathepsins to the proteolysis of muscle proteins in dry-cured duck processing. Thirty-six dry-cured ducks were processed with the traditional method, and samples were collected at different stages. Sarcoplasmic and myofibrillar proteins were found to be degraded to some degree at different stages, whereas content of free amino acids increased from 43.9 to 133.97 mg/100 g during the whole process. Cathepsin B, D, and L activities decreased significantly, and the activities in the end product were 22.4, 26.2, and 40.5% of those in the raw material, respectively. Statistical analysis showed there were significant correlations among changes in proteins, free amino acids, and cathepsin activities. The results indicated that cathepsins are involved in the proteolysis of muscle proteins in dry-cured duck processing.

[An artificial neural network diagnostic model for scleroderma and immune cell infiltration analysis based on mitochondria-associated genes].

OBJECTIVE: To establish a diagnostic model for scleroderma by combining machine learning and artificial neural network based on mitochondria-related genes. METHODS: The GSE95065 and GSE59785 datasets of scleroderma from GEO database were used for analyzing expressions of mitochondria-related genes, and the differential genes were identified by Random forest, LASSO regression and SVM algorithms. Based on these differential genes, an artificial neural network model was constructed, and its diagnostic accuracy was evaluated by 10-fold crossover verification and ROC curve analysis using the verification dataset GSE76807. The mRNA expressions of the key genes were verified by RT-qPCR in a mouse model of scleroderma. The CIBERSORT algorithm was used to estimate the bioinformatic association between scleroderma and the screened biomarkers. RESULTS: A total of 24 differential genes were obtained, including 11 up-regulated and 13 down-regulated genes. Seven most relevant mitochondria-related genes (POLB, GSR, KRAS, NT5DC2, NOX4, IGF1, and TGM2) were screened using 3 machine learning algorithms, and the artificial neural network diagnostic model was constructed. The model showed an area under the ROC curves of 0.984 for scleroderma diagnosis (0.740 for the verification dataset and 0.980 for cross-over validation). RT-qPCR detected significant up-regulation of POLB, GSR, KRAS, NOX4, IGF1 and TGM2 mRNAs and significant down-regulation of NT5DC2 in the mouse models of scleroderma. Immune cell infiltration analysis showed that the differential genes in scleroderma were associated with follicular helper T cells, immature B cells, resting dendritic cells, memory activated CD4+T cells, M0 macrophages, monocytes, resting memory CD4+T cells and mast cell activation. CONCLUSION: The artificial neural network diagnostic model for scleroderma established in this study provides a new perspective for exploring the pathogenesis of scleroderma.

Disordered gut microbiota in postmenopausal stage amplifies intestinal tight junction damage to accelerate atherosclerosis.

The causes and characteristics of gut microbiota abnormalities and whether microbiota manipulation can prevent atherosclerosis in the postmenopausal stage remain to be determined. Aortic oestrogen receptor expression, histological changes and gut microbiota in women before and after menopause were detected. Serum oestrogen levels, systemic inflammation, intestinal oestrogen receptor expression and histological changes, atherosclerosis, and gut microbiota in low density lipoprotein deletion (LDLR-∕-) female mice before and after ovariectomy were tested. This study examined aortic oestrogen receptor expression, histological changes, and gut microbiota in women before and after menopause, and tested serum oestrogen levels, systemic inflammation, intestinal oestrogen receptor expression, histological changes, atherosclerosis, and gut microbiota in low-density lipoprotein receptor knockout (LDLR-∕-) female mice before and after ovariectomy. We demonstrated that the downregulation of oestrogen and oestrogen receptors after menopause promotes gut microbiota disturbance in both women and female mice. We found that gut microbiota disturbance amplifies the intestinal barrier damage and aggravates systemic inflammation, thereby promoting atherosclerosis in female mice. Faecal microbiota transplantation and antibiotics inhibit the proinflammatory properties of gut microbiota and prevent atherosclerosis by reducing intestinal barrier damage in postmenopausal mice. Together, our study highlights the causes of gut microbiota disturbances and the role of microbiota manipulation in preventing atherosclerosis in postmenopausal stage.

[Clinical characteristics of 11 patients with Vibrio vulnificus infection and the establishment of a rapid diagnosis procedure for this disease].

Objective: To analyze the clinical characteristics of patients with Vibrio vulnificus infection, share diagnosis and treatment experience, and establish a rapid diagnosis procedure for this disease. Methods: This study was a retrospective case series study. From January 2009 to November 2022, 11 patients with Vibrio vulnificus infection who met the inclusion criteria were admitted to the Department of Burns and Wound Repair of Guangdong Provincial People's Hospital Affiliated to Southern Medical University. The gender, age, time of onset of illness, time of admission, time of diagnosis, route of infection, underlying diseases, affected limbs, clinical manifestations and signs on admission, white blood cell count, hemoglobin, platelet count, C-reactive protein (CRP), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, procalcitonin, albumin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and blood sodium levels on admission, culture results and metagenomic next-generation sequencing (mNGS) results of pathogenic bacteria and the Vibrio vulnificus drug susceptibility test results during hospitalization, treatment methods, length of hospital stay, and outcomes of all patients were recorded. Comparative analysis was conducted on the admission time and diagnosis time of patients with and without a history of exposure to seawater/marine products, as well as the fatality ratio and amputation of limbs/digits ratio of patients with and without early adequate antibiotic treatment. For the survived patients with hand involvement, the hand function was assessed using Brunnstrom staging at the last follow-up. Based on patients' clinical characteristics and treatment conditions, a rapid diagnosis procedure for Vibrio vulnificus infection was established. Results: There were 7 males and 4 females among the patients, aged (56±17) years. Most of the patients developed symptoms in summer and autumn. The admission time was 3.00 (1.00, 4.00) d after the onset of illness, and the diagnosis time was 4.00 (2.00, 8.00) d after the onset of illness. There were 7 and 4 patients with and without a history of contact with seawater/marine products, respectively, and the admission time of these two types of patients was similar (P>0.05). The diagnosis time of patients with a history of contact with seawater/marine products was 2.00 (2.00, 5.00) d after the onset of illness, which was significantly shorter than 9.00 (4.25, 13.00) d after the onset of illness for patients without a history of contact with seawater/marine products (Z=-2.01, P<0.05). Totally 10 patients had underlying diseases. The affected limbs were right-hand in 8 cases, left-hand in 1 case, and lower limb in 2 cases. On admission, a total of 9 patients had fever; 11 patients had pain at the infected site, and redness and swelling of the affected limb, and 9 patients each had ecchymosis/necrosis and blisters/blood blisters; 6 patients suffered from shock, and 2 patients developed multiple organ dysfunction syndrome. On admission, there were 8 patients with abnormal white blood cell count, hemoglobin, and albumin levels, 10 patients with abnormal CRP, procalcitonin, and NT-proBNP levels, 5 patients with abnormal creatinine and blood sodium levels, and fewer patients with abnormal platelet count, ALT, and AST levels. During hospitalization, 4 of the 11 wound tissue/exudation samples had positive pathogenic bacterial culture results, and the result reporting time was 5.00 (5.00, 5.00) d; 4 of the 9 blood specimens had positive pathogenic bacterial culture results, and the result reporting time was 3.50 (1.25, 5.00) d; the mNGS results of 7 wound tissue/exudation or blood samples were all positive, and the result reporting time was 1.00 (1.00, 2.00) d. The three strains of Vibrio vulnificus detected were sensitive to 10 commonly used clinical antibiotics, including ciprofloxacin, levofloxacin, and amikacin, etc. A total of 10 patients received surgical treatment, 4 of whom had amputation of limbs/digits; all patients received anti-infection treatment. The length of hospital stay of 11 patients was (26±11) d, of whom 9 patients were cured and 2 patients died. Compared with that of the 6 patients who did not receive early adequate antibiotic treatment, the 5 patients who received early adequate antibiotic treatment had no significant changes in the fatality ratio or amputation of limbs/digits ratio (P>0.05). In 3 months to 2 years after surgery, the hand function of 8 patients was assessed, with results showing 4 cases of disabled hands, 2 cases of incompletely disabled hands, and 2 cases of recovered hands. When a patient had clinical symptoms of limb redness and swelling and a history of contact with seawater/marine products or a pre-examination triage RiCH score of Vibrio vulnificus sepsis ≥1, the etiological testing should be initiated immediately to quickly diagnose Vibrio vulnificus infection. Conclusions: Vibrio vulnificus infection occurs most frequently in summer and autumn, with clinical manifestations and laboratory test results showing obvious infection characteristics, and may be accompanied by damage to multiple organ functions. Both the fatality and disability ratios are high and have a great impact on the function of the affected limbs. Early diagnosis is difficult and treatment is easily delayed, but mNGS could facilitate rapid detection. For patients with red and swollen limbs accompanied by a history of contact with seawater/marine products or with a pre-examination triage RiCH score of Vibrio vulnificus sepsis ≥1, the etiological testing should be initiated immediately to quickly diagnose Vibrio vulnificus infection.

Scaffold evaluation of liguzinediol analogs as novel cardiotonic agents.

Liguzinediol (LZDO) could mediate the positive inotropic effects through sarcoplasmic reticulum Ca2+ ATPase-dependent mechanism without the risk of arrhythmia. However, the pharmacophore of LZDO contributed to the activities was not clear. The aim of this work was to explore the relationship between positive inotropic effect and scaffold of LZDO as well as to check whether the pharmacophore of LZDO on anti-heart failure activity was located at the pyrazine ring. A series of LZDO analogs (3a-b, 4a-b, 9-19) were designed and synthesised, and their activities were evaluated on isolated heart contractility by Langendorff perfusion. The results showed that the efficacy of LZDO was reduced when the hydroxyl, carboxyl or ester moieties at the side chain position of LZDO were induced, and the para-dihydroxy in LZDO was necessary for its activity. Thus, the pharmacophore of the positive inotropic effect might be located at the whole scaffold of LZDO, but not at the pyrazine ring. The finding may provide an important clue of the pharmacophore for the development of novel cardiotonic agents.

Atmospheric nourishment of global ocean ecosystems.

Over the vast open ocean, vital nutrients for phytoplankton growth in the sunlit surface layer are largely provided through physical transport from deep waters, but some nutrients are also provided through atmospheric deposition of desert dust. The extent and magnitude of dust-mediated effects on surface ocean ecosystems have been difficult to estimate globally. In this work, we use global satellite ocean color products to demonstrate widespread responses to atmospheric dust deposition across a diverse continuum of phytoplankton nutritional conditions. The observed responses vary regionally, with some areas exhibiting substantial changes in phytoplankton biomass, whereas in other areas, the response reflects a change in physiological status or health. Climate-driven changes in atmospheric aerosols will alter the relative importance of this nutrient source.

[Guizhi Fuling Capsule inhibits migration and induces apoptosis of human ovarian cancer cells by regulating the NF-κB signaling pathway].

OBJECTIVE: To study the inhibitory effect of Guizhi Fuling Capsule (GFC) on migration of human ovarian cancer cells and explore the possible mechanism. METHODS: Sixty Wistar rats were randomized into 4 groups for daily gavage of saline or 4, 8, or 16 g/kg GFC suspension for 5 days to prepare blank and low-, medium- and high-dose GFC-medicated sera. Cisplatinresistant ovarian cancer SKOV3/DDP cells were treated with these sera with nuclear factor-κB (NF-κB) inhibitor SN50 as the positive control, and the changes in migration ability and apoptosis of the cells were examined using scratch assay and flow cytometry, respectively; the changes in the mRNA and protein expressions of CDH1, CDH2, caspase 3 and NF- κB were detected using RT-qPCR and Western blotting. ATAC-seq was used to analyze the changes in expressions of CDH1, CDH2, caspase 3 and NF-κB genes in the open chromatin. RESULTS: Treatment with GFC-medicated sera dose-dependently inhibited the migration (P < 0.05), increased apoptosis (P < 0.01), inhibited CDH2 and NF-κB mRNA expression (P < 0.05), and enhanced caspase 3 and CDH1 mRNA expressions (P < 0.01) in SKOV3/DDP cells. The effects of high-dose GFC-medicated serum were comparable to those of SN50 (P>0.05), but its effect for enhancing DH1 protein expression was weaker than that of SN50 (P < 0.01). GFC-medicated sera significantly lowered the expressions of NF-κB and CDH2 and increased CDH1 expression in the open chromatin without obviously affecting caspase 3 expression. CONCLUSION: GFC- medicated sera inhibits the migration ability of SKOV3/DDP cells possibly by promoting cell apoptosis and caspase 3 and CDH1 expressions, inhibiting CDH2 and NF-κB expressions, and regulating the expressions of NF-κB, CDH2 and CDH1 in the open chromatin.

[Analysis of the clinical features and prognostic influencing factors of toxic epidermal necrolysis].

Objective: To investigate the clinical features and prognostic influencing factors of toxic epidermal necrolysis (TEN). Methods: A retrospective observational study was conducted. From January 2008 to March 2019, a total of 46 TEN patients who met the inclusion criteria were admitted to Guangdong Provincial People's Hospital. The gender, age, and hospital admission diagnosis of the 46 patients, the category of department admitted of patients complicated with sepsis, death ratio of the sepsis patients with or without treatment history in intensive care unit (ICU)/department of burns and wound repair, and the cause of death of the deceased patients were recorded. Depending on whether complicated with sepsis, the patients were divided into sepsis group (32 cases) and non-sepsis group (14 cases). According to whether died or not, the patients were divided into death group (9 cases) and survival group (37 cases). The specific conditions of suspected pathogenic agents and combined underlying diseases, the abnormality of transaminase/bilirubin, creatinine, and platelet count in blood on admission, and the detection of pathogenic microorganisms and drug resistance during the course of disease of patients were recorded in both sepsis group and non-sepsis group. The gender, age, lesion area, severity of illness score for TEN (SCORTEN) system score, combined underlying diseases on admission, and blood microbial culture positivity, hormone use, and gamma globulin use during the course of disease of patients between sepsis group and non-sepsis group, death group and survival group were compared respectively. Data were statistically analyzed with chi-square test, Fisher's exact probability test, and Mann-Whitney U test. The factors with statistically significant differences between sepsis group and non-sepsis group, death group and survival group were selected for binary multivariate logistic regression analysis, so as to screen the independent risk factors affecting sepsis and death in TEN patients. Results: Of the 46 TEN patients, 30 were male and 16 were female, aged from 8 months to 92.0 years, with 11 cases (23.91%) of epidermolysis bullosa, 9 cases (19.57%) of exfoliative dermatitis, 9 cases (19.57%) of TEN, 7 cases (15.22%) of epidermolysis bullosa, 6 cases (13.04%) of Stevens-Johnson syndrome, and 4 cases (8.70%) of severe drug rash for hospital admission diagnosis. The patients complicated with sepsis were admitted to 11 departments, and the death ratio of patients with treatment history in ICU/department of burns and wound repair was similar to that of patients without such department treatment history (P>0.05). All the deceased patients were complicated with sepsis, which was also the main cause of death. On admission, the suspected pathogenic agents of patients in sepsis group were mainly allopurinol (8 cases) and non-steroidal anti-inflammatory drugs (4 cases), while those in non-sepsis group were allopurinol (3 cases) and psychotropic drugs (3 cases). Patients in sepsis group combined as many as 10 underlying diseases, while those in non-sepsis group combined only 4 underlying diseases. The proportions of patients with increased creatinine (χ2=13.349, P<0.01) and decreased platelet count (P<0.01) in sepsis group were significantly higher than those in non-sepsis group, while the transaminase/bilirubin abnormality was similar to that in non-sepsis group (P>0.05). A wide variety of pathogens were detected in the blood, respiratory tract secretions, and skin secretions of 21 patients in sepsis group, and 14 patients were infected with drug-resistant bacteria; among the 9 strains cultured from the blood samples, 8 were drug-resistant bacteria and 6 were Gram-positive bacteria. In non-sepsis group, pathogens were detected in blood, respiratory tract secretions, and skin secretions of 8 patients, with fewer species, and 6 patients were infected with drug-resistant bacteria. The gender, age, lesion area, blood microbial culture positivity, hormone use, and gamma globulin use of patients in sepsis group were similar to those in non-sepsis group (P>0.05). The proportion of patients combined with underlying diseases (χ2=4.493, P<0.05) and the proportion of patients with SCORTEN system score of 4-6 points (P<0.01) of patients in sepsis group were significantly higher than those in non-sepsis group. The gender, combined underlying diseases, lesion area, blood microbial culture positivity, hormone use, and gamma globulin use of patients were similar between survival group and death group (P>0.05). The proportion of patients with age≥60 years and the proportion of patients with SCORTEN system score of 4-6 points of patients in death group were significantly higher than those in survival group (χ2=4.412, 11.627, P<0.05 or P<0.01). The SCORTEN system score was an independent risk factor affecting sepsis and death in TEN patients (odds ratio=3.025, 2.757, 95% confidence interval=1.352-6.769, 1.244-6.110, P<0.05 or P<0.01). Conclusions: The diagnosis of TEN is difficult on admission. Male population is susceptible to TEN, and allopurinol is the common pathogenic agent. The proportion of patients combined with underlying diseases is high in TEN patients complicated with sepsis, with mainly drug-resistant bacteria and mostly Gram-positive bacteria in blood-borne infections. The deceased patients are older than the survived, and the main cause of death is sepsis. The SCORTEN system score is an independent risk factor affecting sepsis and death in TEN patients.

HLA-DR4-IE chimeric class II transgenic, murine class II-deficient mice are susceptible to experimental allergic encephalomyelitis.

To investigate the development of HLA-DR-associated autoimmune diseases, we generated transgenic (Tg) mice with HLA-DRA-IE alpha and HLA-DRB1*0401-IE beta chimeric genes. The transgene-encoded proteins consisted of antigen-binding domains from HLA-DRA and HLA-DRB1*0401 molecules and the remaining domains from the IE(d)-alpha and IE(d)-beta chains. The chimeric molecules showed the same antigen-binding specificity as HLA-DRB1*0401 molecules, and were functional in presenting antigens to T cells. The Tg mice were backcrossed to MHC class II-deficient (IA beta-, IE alpha-) mice to eliminate any effect of endogenous MHC class II genes on the development of autoimmune diseases. As expected, IA alpha beta or IE alpha beta molecules were not expressed in Tg mice. Moreover, cell-surface expression of endogenous IE beta associated with HLA-DRA-IE alpha was not detectable in several Tg mouse lines by flow cytometric analysis. The HLA-DRA-IE alpha/HLA-DRB1*0401-IE beta molecules rescued the development of CD4+ T cells in MHC class II-deficient mice, but T cells expressing V beta 5, V beta 11, and V beta 12 were specifically deleted. Tg mice were immunized with peptides, myelin basic protein (MBP) 87-106 and proteolipid protein (PLP) 175-192, that are considered to be immunodominant epitopes in HLA-DR4 individuals. PLP175-192 provoked a strong proliferative response of lymph node T cells from Tg mice, and caused inflammatory lesions in white matter of the CNS and symptoms of experimental allergic encephalomyelitis (EAE). Immunization with MBP87-106 elicited a very weak proliferative T cell response and caused mild EAE. Non-Tg mice immunized with either PLP175-192 or MBP87-106 did not develop EAE. These results demonstrated that a human MHC class II binding site alone can confer susceptibility to an experimentally induced murine autoimmune disease.

The effect of single nucleotide polymorphisms of STAT3 on epilepsy in children.

OBJECTIVE: To investigate the effect of single nucleotide polymorphisms (SNPs) of signal transducer and activator of transcription 3 (STAT3) on epilepsy in children. PATIENTS AND METHODS: A total of 169 children suffering from epilepsy admitted in No. 1 People's Hospital of Jining from July 2015 to December 2016 were enrolled as the research subjects. Immunohistochemistry and real time-PCR were used for analysis of the expression of STAT3 and p-STAT3 in epilepsy patients. The genotypes and alleles of rs1053005 and re744166 were analyzed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical analysis was conducted to explore the correlation between the polymorphism of STAT3 and the incidence of epilepsy in children, and the polymorphism of STAT3 in the drug-resistant and non-resistant patients was compared. RESULTS: Both the STAT3 and p-STAT3 were over-expressed in epilepsy patients. The GG genotype of rs1053005 was significantly lower in epilepsy patients than that of health control, p<0.05. By contrast, no significant difference was found in genotypes of rs744166 between epilepsy and healthy children. When comparing the genotypes of drug-resistant patients and that of non-resistant patients, the distribution of rs1053005 genotypes in the two groups showed a significant difference, p<0.05. No statistical difference was observed in rs744166 genotypes. CONCLUSIONS: STAT3 polymorphism was associated with the risk of epilepsy and drug resistance to epilepsy. This study may provide a better understanding of STAT3 in epilepsy patients and provide new targets for the treatment of epilepsy patients.