Characteristics of pulmonary infarction in patients with acute pulmonary embolism in China: a single-center retrospective observational study.

Background: Pulmonary infarction (PI) is an uncommon complication of pulmonary embolism (PE). The risk factors of PI are still relatively unclear. Methods: This was a single-center retrospective review conducted on 500 patients with PE. After applying the inclusion and exclusion criteria, 386 patients diagnosed with PE were enrolled in our study. These patients were then categorized into the PI group (n=64) and the non-PI group (n=322). A comparison was conducted between the two groups regarding the clinical characteristics. Results: The occurrence of PI secondary to PE was 16.58%. In univariate analysis, recent trauma (21.9% vs. 9.9%, P=0.007), pleuritic chest pain (46.9% vs. 17.4%, P<0.001), hemoptysis (29.7% vs. 2.5%, P<0.001), fever (26.6% vs. 8.1%, P<0.001), lower limb edema/pain (37.5% vs. 14.0%, P<0.001), white blood cell (WBC) counts (37.5% vs. 24.5%, P=0.032), C-reactive protein (CRP) (65.6% vs. 41.3%, P<0.001), and pleural effusion (45.3% vs. 18.6%, P<0.001) were associated with an increased risk of PI. Multivariate analysis demonstrated that age [odds ratio (OR) 0.975, 95% confidence interval (CI): 0.951-0.999, P=0.045], pleuritic chest pain (OR 2.878, 95% CI: 1.424-5.814, P=0.003), hemoptysis (OR 10.592, 95% CI: 3.503-32.030, P<0.001), lower limb edema/pain (OR 2.778, 95% CI: 1.342-5.749, P=0.006) and pleural effusion (OR 3.127, 95% CI: 1.531-6.388, P=0.002) were independent factors of PI due to PE. No significant difference was recorded between the two groups in treatment and mortality. Conclusions: Young patients were found to be a higher risk of PI. Pleural effusion was found to be a factor for PI. PI should be considered when pleuritic chest pain, hemoptysis, or lower limb edema/pain are present with peripheral opacity.

Targeting proteasomal deubiquitinases USP14 and UCHL5 with b-AP15 reduces 5-fluorouracil resistance in colorectal cancer cells.

5-Fluorouracil (5-FU) is the first-line treatment for colorectal cancer (CRC) patients, but the development of acquired resistance to 5-FU remains a big challenge. Deubiquitinases play a key role in the protein degradation pathway, which is involved in cancer development and chemotherapy resistance. In this study, we investigated the effects of targeted inhibition of the proteasomal deubiquitinases USP14 and UCHL5 on the development of CRC and resistance to 5-FU. By analyzing GEO datasets, we found that the mRNA expression levels of USP14 and UCHL5 in CRC tissues were significantly increased, and negatively correlated with the survival of CRC patients. Knockdown of both USP14 and UCHL5 led to increased 5-FU sensitivity in 5-FU-resistant CRC cell lines (RKO-R and HCT-15R), whereas overexpression of USP14 and UCHL5 in 5-FU-sensitive CRC cells decreased 5-FU sensitivity. B-AP15, a specific inhibitor of USP14 and UCHL5, (1-5 µM) dose-dependently inhibited the viability of RKO, RKO-R, HCT-15, and HCT-15R cells. Furthermore, treatment with b-AP15 reduced the malignant phenotype of CRC cells including cell proliferation and migration, and induced cell death in both 5-FU-sensitive and 5-FU-resistant CRC cells by impairing proteasome function and increasing reactive oxygen species (ROS) production. In addition, b-AP15 inhibited the activation of NF-κB pathway, suppressing cell proliferation. In 5-FU-sensitive and 5-FU-resistant CRC xenografts nude mice, administration of b-AP15 (8 mg·kg-1·d-1, intraperitoneal injection) effectively suppressed the growth of both types of tumors. These results demonstrate that USP14 and UCHL5 play an important role in the development of CRC and resistance to 5-FU. Targeting USP14 and UCHL5 with b-AP15 may represent a promising therapeutic strategy for the treatment of CRC.

Ditangquan exercises based on safe-landing strategies prevent falls and injury among older individuals with sarcopenia.

Background: Sarcopenia is the age-related loss of skeletal muscle mass and function; it is a risk factor for falls among older individuals. Few studies have focused on training such individuals to adopt a safe-landing strategy that would protect them from fall-related injuries. Ditangquan is a traditional Chinese martial art comprising movements that conform to the principles of safe landing. This study aims to investigate the effectiveness of Ditangquan in preventing fall-related injuries among older individuals with sarcopenia. Methods: A total of 70 participants (21 males and 49 females with sarcopenia) between 60 and 80 years of age were recruited from three local communities and randomly assigned to the Ditangquan exercise group (DG) or the control group (CG) in a 1:1 ratio. Three times a week for 24 weeks, both the DG and CG received an hour of conventional exercise and an hour of Ditangquan exercise based on safe landing. Primary outcomes were the modified falls efficacy scale (MFES), the number of falls, and fall injuries; the secondary outcome was the Timed Up & Go (TUG) test. Results: The DG had significantly fewer falls (1 vs. 8, P = 0.028) and fall injuries (0 vs. 6, P = 0.025) than the CG. Furthermore, at the end of the study, the DG had a significantly improved MFES (mean difference: 32.17 scores; 95% CI: 21.32, 43.02; P <0.001) and TUGT (mean difference: -4.94 s; 95% CI: -7.95, -1.93; P = 0.002) as compared with the CG. Conclusion: Ditangquan exercise based on the safe-landing strategy effectively improves the functional mobility of the elderly, reduces the occurrence of falls and injuries, and increases the individual's confidence in preventing falls.

Establishment of a Systemic Inflammatory Response Syndrome Model and Evaluation of the Efficacy of Umbilical Cord Mesenchymal Stem Cell Transplantation.

Based on the characteristics of modern weapon injury, a repetitive model of traumatic systemic inflammatory response syndrome (SIRS) and an evaluation system were established. The models were treated with GFP-labeled tree shrew umbilical cord mesenchymal stem cells (UCMSCs). Forty out of 50 tree shrews were used to make a unilateral femoral comminuted fracture. Lipopolysaccharide was injected intravenously to create a traumatic SIRS model. The other 10 shrews were used as normal controls. After the model was established for 10 days, 20 tree shrews were injected intravenously with GFP-labeled UCMSCs, and 18 tree shrews were not injected as the model control group. The distribution of GFP-labeled cells in vivo was measured at 2 and 10 days after injection. Twenty days after treatment, the model group, the normal control group, and the treatment group were taken to observe the pathological changes in each tissue, and blood samples were taken for the changes in liver, renal, and heart function. Distribution of GFP-positive cells was observed in all tissues at 2 and 10 days after injection. After treatment, the HE staining results of the treatment group were close to those of the normal group, and the model group had a certain degree of lesions. The results of liver, renal, and heart function tests in the treatment group were returned to normal, and the results in the model group were abnormally increased. UCMSCs have a certain effect on the treatment of traumatic SIRS and provide a new technical solution for modern weapon trauma treatment.

Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials.

BACKGROUND: Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients. OBJECTIVE AND DESIGN: We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome. SUBJECTS AND METHODS: We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (<75 years [n = 7,079], 75-80 years [n = 1,034], 81-85 years [n = 803] and >85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay. RESULTS: Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of -1.99 (95% confidence interval [CI] -2.36 to -1.62), -1.98 (95% CI -2.94 to -1.02), -2.20 (95% CI -3.15 to -1.25) and - 2.10 (95% CI -3.29 to -0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05). CONCLUSIONS: This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.

Microarray Expression Profile and Analysis of Circular RNA Regulatory Network in Pulmonary Thromboembolism.

BACKGROUND: Pulmonary thromboembolism (PTE) is a common disease which may be a serious condition and has high mortality. Recently, it has been shown that circRNAs play an important role in the development of various diseases, including thromboembolic disease. However, circRNAs expression profiling is not clear in PTE, this study aims to identify the circRNAs expressed in PTE and to elucidate their possible role in pathophysiology of PTE. METHODS: A total of 5 patients with CTPA-confirmed PTE and 5 healthy controls were recruited for the present study. The circRNAs expression profile was analyzed by microarray. RESULTS: In total, 256 differentially expressed circRNAs (up 142, down114) and 1162 mRNA (up 446, down 716) were summarized by analyzing the circRNAs microarray data. The top 3 up-regulated and 3 down-regulated circRNAs were validated by Real-Time Polymerase Chain Reaction (qRT-PCR). Two differentially expressed circRNAs (hsa_circ_0000891, hsa_circ_0043506) were selected for further analysis. Finally, we construct a circRNA-miRNA-mRNA ceRNA network with a bioinformatic prediction tool. Pathway analysis shows that the enriched mRNAs targets take part in Protein processing in endoplasmic reticulum, Systemic lupus erythematosus, Endocytosis, Spliceosome, HTLV-I infection and Ubiquitin mediated proteolysis. CONCLUSION: Our findings indicated that aberrantly expressed circRNAs (hsa_circ_0000891, hsa_circ_0043506) may be involved in the development of PTE.

Co-optimization Learning Network for MRI Segmentation of Ischemic Penumbra Tissues.

Convolutional neural networks (CNNs) have brought hope for the medical image auxiliary diagnosis. However, the shortfall of labeled medical image data is the bottleneck that limits the performance improvement of supervised CNN methods. In addition, annotating a large number of labeled medical image data is often expensive and time-consuming. In this study, we propose a co-optimization learning network (COL-Net) for Magnetic Resonance Imaging (MRI) segmentation of ischemic penumbra tissues. COL-Net base on the limited labeled samples and consists of an unsupervised reconstruction network (R), a supervised segmentation network (S), and a transfer block (T). The reconstruction network extracts the robust features from reconstructing pseudo unlabeled samples, which is the auxiliary branch of the segmentation network. The segmentation network is used to segment the target lesions under the limited labeled samples and the auxiliary of the reconstruction network. The transfer block is used to co-optimization the feature maps between the bottlenecks of the reconstruction network and segmentation network. We propose a mix loss function to optimize COL-Net. COL-Net is verified on the public ischemic penumbra segmentation challenge (SPES) with two dozen labeled samples. Results demonstrate that COL-Net has high predictive accuracy and generalization with the Dice coefficient of 0.79. The extended experiment also shows COL-Net outperforms most supervised segmentation methods. COL-Net is a meaningful attempt to alleviate the limited labeled sample problem in medical image segmentation.

Obesity promotes gastric cancer metastasis via diacylglycerol acyltransferase 2-dependent lipid droplets accumulation and redox homeostasis.

Experimental and molecular epidemiological studies indicate important roles for adipose tissue or high-fat diet (HFD) in tumor growth and metastasis. Gastric cancer (GC) possesses a metastatic predilection for the adipocyte-rich peritoneum. However, the precise molecular relevance of HFD in the peritoneal metastasis of GC remains unclear. Here, we showed that HFD causes obvious fat accumulation and promotes peritoneal dissemination of GC in vivo. Peritoneum-derived adipocytes induces robust lipid droplet (LD) accumulation and fatty acid oxidation in GC cells through transcriptional upregulation of DGAT2 in a C/EBPα-dependent manner and prevents anoikis during peritoneal dissemination. Treatment of GC cells with FAs or coculture with adipocytes induces intracellular formation of LDs and production of NADPH to overcome oxidative stress in vitro. Importantly, overexpression of DGAT2 was identified as an independent predictor of poor survival that promotes lung and peritoneal metastasis of GC, and genetic or pharmacological inhibition of DGAT2, via disruption of lipid droplet formation in a lipid-rich environment, enhances the sensitivity of GC to anoikis in vitro and inhibits peritoneal metastasis in vivo. Overall, our findings highlight the notion that DGAT2 may be a promising therapeutic target in GC with peritoneal implantation and provide some evidence for uncovering the link between obesity and tumor metastasis.

Systemic inflammation and the effects of short-term antibiotic treatment for PPM positive patients with stable COPD.

Objective: To evaluate patients with stable COPD for the presence of potentially pathogenic microorganisms (PPM), systemic inflammation and the effects of short-term antibiotic therapy in PPM positive patients. Methods: From January 2016 to June 2017, we enrolled 96 stable COPD patients. Bacterial cultures from sputum collections were quantitated, along with markers for systemic inflammation including serum C-reactive protein (CRP), interleukin-8 (IL-8) and plasma fibrinogen (FIB) in all patients. All enrolled patients were followed for 12 months. Forty patients were identified as PPM positive and were randomly divided into an antibiotic group and a control group. The antibiotic group was treated with moxifloxacin orally for 6 days. Lung function and markers for systemic inflammation were repeatedly measured at 30 days and 6 months in PPM positive subjects. Results: Binary logistic regression analysis showed that risk factors for PPM positive are bronchiectasis (OR 4.18, 95% CI 1.20-14.59; P=0.025), COPD assessment test (CAT) ≥20 (OR 17.55, 95% CI 2.82-109.18; P=0.002), spontaneous sputum (OR 15.09, 95% CI 1.36-168.02; P=0.027) and sputum purulence (OR 38.43, 95% CI 5.39-274.21; P=0.000). CRP and IL-8 were higher in PPM positive group than those in PPM negative group (P=0.001, P=0.007, respectively), but there were no differences of FIB between the two groups (P=0.086). Compared to the PPM negative group, the rate of acute exacerbation of COPD was higher (P=0.029) and time to next acute exacerbation was shorter (P=0.030) in PPM positive group. There were no differences in lung function and systemic inflammatory markers either in the control group or the antibiotic group at different time points of follow-up. Conclusion: PPM exists in stable COPD patients and can cause systemic inflammation and is associated with acute exacerbation of COPD. Short-term antibiotic therapy had no effect on systemic inflammation nor on acute exacerbation of COPD.China Clinical Trials Registry: ChiCTR-IOR-15006769.

Efficacy and mechanisms underlying the effects of allogeneic umbilical cord mesenchymal stem cell transplantation on acute radiation injury in tree shrews.

Umbilical cord mesenchymal stem cells (UC-MSCs) exert strong immunomodulatory effects and can repair organs. However, their roles in radiation injury remain unclear. We show that in tree shrews with acute radiation injury, injected UC-MSCs significantly improved survival rates, reduced lung inflammation and apoptosis, prevented pulmonary fibrotic processes, recovered hematopoiesis, and increased blood counts. A protein microarray analysis showed that serum levels of the anti-inflammatory cytokines IL-10 and IL-13 and the growth factors BMP-5, BMP-7, HGF, insulin, NT-4, VEGFR3, and SCF were significantly higher, while those of the inflammatory cytokines IL-2, TIMP-2, TNF-α, IFN-γ, IL-1ra, and IL-8 and the fibrosis-related factors PDGF-BB, PDGF-AA, TGF-ß1, IGFBP-2, and IGFBP-4 were significantly lower in UC-MSC-injected animals. A transcriptome analysis of PBMCs showed that the mRNA expression of C1q was upregulated, while that of HLA-DP was downregulated after UC-MSC injection. These results confirm the immunohistochemistry results. eGFP-labeled UC-MSCs were traced in vivo and found in the heart, liver, spleen, lungs, kidneys, thymus, small intestine and bone marrow. Our findings suggest that UC-MSC transplantation may be a novel therapeutic approach for treating acute radiation injury.

Evaluating Production of Cyclopentyl Tetraethers by Marine Group II Euryarchaeota in the Pearl River Estuary and Coastal South China Sea: Potential Impact on the TEX86 Paleothermometer.

TEX86 [TetraEther indeX of glycerol dialkyl glycerol tetraethers (GDGTs) with 86 carbon atoms] has been widely applied to reconstruct (paleo-) sea surface temperature. Marine Group I (MG-I) Thaumarchaeota were thought to be the primary source of GDGTs constituting the TEX86 formula; however, recent research has suggested that Marine Group II (MG-II) Euryarchaeota may also contribute significantly to the GDGT pool in the ocean. Little is known regarding the potential impact of MG-II Euryarchaeota-derived GDGTs on TEX86 values recorded in marine sediments. In this study, we assessed the relationship between distributions of GDGTs and MG-II Euryarchaeota and evaluated its potential effect on the TEX86 proxy. Lipid and DNA analyses were performed on suspended particulate matter and surface sediments collected along a salinity gradient from the lower Pearl River (river water) and its estuary (mixing water) to the coastal South China Sea (SCS, seawater). TEX86-derived temperatures from the water column and surface sediments were significantly correlated and both were lower than satellite-based temperatures. The ring index (RI) values in these environments were higher than predicted from the calculated TEX86-RI correlation, indicating that the GDGT pool in the water column of the PR estuary and coastal SCS comprises relatively more cyclopentane rings, which thereby altered TEX86 values. Furthermore, the abundance of MG-II Euryarchaeota 16S rRNA gene in the mixing water was two to three orders of magnitude higher than those observed in the river or seawater. Significant linear correlations were observed between the gene abundance ratio of MG-II Euryarchaeota to total archaea and the fractional abundance of GDGTs with cyclopentane rings. Collectively, these results suggest that MG-II Euryarchaeota likely produce a large proportion of GDGTs with 1-4 cyclopentane moieties, which may bias TEX86 values in the water column and sediments. As such, valid interpretation of TEX86 values in the sediment record, particularly in coastal oceans, should consider the contribution from MG-II Euryarchaeota.

Umbilical cord mesenchymal stem cells are able to undergo differentiation into functional islet-like cells in type 2 diabetic tree shrews.

Islet transplantation is arguably one of the most promising strategies to treat patients suffering with diabetes mellitus. However, a combination of a lack of donors and chronic immune rejection limit clinical applications. Here, we evaluated the efficacy of cell therapy using islet-like cells differentiated from umbilical cord mesenchymal stem cells (UC-MSCs) of tree shrews for the treatment of type 2 diabetes. Enhanced green fluorescent protein (eGFP) labeled UC-MSCs were directly injected into type 2 diabetic tree shrews, where UC-MSC differentiated into functional islet-like cells and alleviated disease severity, as evidenced by improved biochemical features and reduced concentrations of inflammatory cytokines. We also demonstrated that in vitro culture of UC-MSCs for six days in a high-glucose environment (40 mmol/L or 60 mmol/L glucose) resulted in significant gene methylation. The potency of UC-MSCs differentiated into insulin-secreting cells was attributed to the activation of Notch signal pathways. This study provides evidence that cell therapy of islet-like cells differentiated from UC-MSCs is a feasible, simple and inexpensive approach in the treatment of type 2 diabetes.

Influence of Growth Phase, pH, and Temperature on the Abundance and Composition of Tetraether Lipids in the Thermoacidophile Picrophilus torridus.

The abundance and composition of glycerol dibiphytanyl glycerol tetraether (GDGT) and glycerol tribiphytanyl glycerol tetraether (GTGT) lipids were determined as a function of growth phase as a proxy for nutrient availability, the pH of growth medium, and incubation temperature in cultures of the thermoacidophile Picrophilus torridus. Regardless of the cultivation condition, the abundance of GDGTs and GTGTs was greater in the polar than core fraction, with a marked decrease in core GDGTs in cultures harvested during log phase growth. These data are consistent with previous suggestions indicating that core GDGTs are re-functionalized during polar lipid synthesis. Under all conditions examined, polar lipids were enriched in a GDGT with 2 cyclopentyl rings (GDGT-2), indicating GDGT-2 is the preferred lipid in this taxon. However, lag or stationary phase grown cells or cells subjected to pH or thermal stress were enriched in GDGTs with 4, 5, or 6 rings and depleted in GDGTs with 1, 2, 3, rings relative to log phase cells grown under optimal conditions. Variation in the composition of polar GDGT lipids in cells harvested during various growth phases tended to be greater than in cells cultivated over a pH range of 0.3-1.1 and a temperature range of 53-63°C. These results suggest that the growth phase, the pH of growth medium, and incubation temperature are all important factors that shape the composition of tetraether lipids in Picrophilus. The similarity in enrichment of GDGTs with more rings in cultures undergoing nutrient, pH, and thermal stress points to GDGT cyclization as a generalized physiological response to stress in this taxon.

Rabies Outbreaks and Vaccination in Domestic Camels and Cattle in Northwest China.

In contrast to many countries where rabies has been well controlled in humans and livestock, even in wildlife, rabies is still endemic in almost regions of China. In Northwest China, rabies transmitted by stray dogs and wild foxes has caused heavy economic losses to local herdsmen, as well as causing numbers of human cases. In this study, as part of an investigation of ways to prevent rabies epidemics in livestock, we report an analysis of domestic cattle and camel rabies cases in Ningxia Hui (NHAR) and Inner Mongolia Autonomous Region (IMAR) and the immune efficacy of canine inactivated rabies vaccines in these animals. We found that rabies viruses from these animals are closely related to dog-hosted China I and fox-associated China III lineages, respectively, indicating that the infections originated from two different sources (dogs and wild foxes). As well as the previously reported Arctic and Arctic-related China IV lineage in IMAR, at least three separate phylogenetic groups of rabies virus consistently exist and spread throughout Northwest China. Since there is no licensed oral vaccine for wild foxes and no inactivated vaccine for large livestock, local canine inactivated vaccine products were used for emergency immunization of beef and milk cattle and bactrian (two-humped) camels in local farms. Compared with a single injection with one (low-efficacy) or three doses (high-cost), a single injection of a double dose of canine vaccine provided low-price and convenience for local veterinarians while inducing levels of virus neutralizing antibodies indicative of protection against rabies for at least 1 year in the cattle and camels. However, licensed vaccines for wildlife and large domestic animals are still needed in China.

Electroclinical aspects and therapy of Han patients with juvenile myoclonic epilepsy in northern China.

OBJECTIVE: The objective of this study was to assess the electroclinical aspects and treatment of Han patients with juvenile myoclonic epilepsy (JME) in northern China. METHODS: One hundred fifty-six outpatients with JME from six epilepsy centers, between January 2011 and June 2012, were followed up for at least two years. They underwent twenty-four-hour video-EEG recording. Brain imaging was performed using magnetic resonance imaging (MRI). Clinical aspects, electroencephalographic (EEG) features, and antiepileptic drugs (AEDs) received were reviewed. RESULTS: Generalized tonic-clonic seizures (GTCS) were found in 150/156 patients. Delay of diagnosis was 4.60±9.92years. Photosensitivity was more common in eye closure condition during IPS in patients with JME; in addition, patients with JME with myoclonic seizures (MS) and GTCS as seizure types were likely to present photoparoxysmal responses (PPRs). The 82 nontreated patients showed a median latency to first interictal or ictal generalized spike-wave discharge (GSWD) of 50min (IQR: 22-102min). The first GSWDs were recorded in 63%, 76%, 90%, and 98% patients within one, two, three, and 4h, respectively; only 2% of patients had first GSWDs after 4h. One hundred eleven patients (111/156) chose extended-release valproate (VPA) at daily doses ≤1000mg. The percentages of seizure-free patients among MS, GTCS, and absence seizure (AS) groups were 88.3%, 99.0%, and 94.9%, respectively. CONCLUSION: Photoparoxysmal responses were more common in patients with JME with MS and GTCS and rare in patients with JME with MS and AS in northern Chinese Han patients. Most patients with JME in northern China chose VPA as first therapeutic choice, and low dose (500 to 1000mg daily) of extended-release VPA may be an optimal choice for them. Video-EEG monitoring for at least 4h may be helpful in detecting the first interictal or ictal GSWD in patients with potential JME. Moreover, video-EEG monitoring performed at about 9 o'clock in the morning with patients in the awake state might be useful to find the first GSWD. For JME diagnosis, Class II criteria are more helpful than Class I counterparts, the latter yielding more missed diagnoses.

Acute exacerbations of chronic obstructive pulmonary disease with low serum procalcitonin values do not benefit from antibiotic treatment: a prospective randomized controlled trial.

OBJECTIVE: The majority of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have low serum procalcitonin (PCT) values. The aim of this study was to determine whether these patients may benefit from antibiotic treatment. METHODS: A total of 457 patients with AECOPD were screened; 194 patients with AECOPD and PCT <0.1 ng/ml were assigned randomly to an antibiotic group or a control group. In the per-protocol (PP) population, the antibiotic group subjects were required to have used antibiotics for at least 3 days, and the control group subjects were required not to have used antibiotics within the 10 days after admission. The intention-to-treat (ITT) population was defined as the patients who were randomized. The primary outcome was the treatment success rate on day 10 after admission. Secondary outcomes were symptoms assessed on a visual analog scale (VAS), length of hospitalization, mortality, exacerbation rate, and re-hospitalization within 30 days of follow-up (study registered at chictr.org.cn: ChiCTR-TRC-14004726). RESULTS: 95 patients in the antibiotic group and 96 patients in the control group completed the study. In the ITT population, the overall treatment success rate in the control group (95.8%) was similar to that in the antibiotic group (93.7%), with no significant difference (p=0.732). Five patients in the antibiotic group died, either in hospital or within 30 days of discharge. In the control group, two died within 30 days of discharge. Antibiotic use in the control group was 17.7% (17/96), and age ≥75 years was a predictive risk factor for requiring antibiotic therapy in the control group (odds ratio 4.055, 95% confidence interval 1.297-12.678; p=0.012). According to the PP analysis, the treatment success rate on day 10 after admission was 98.7% (78/79) in the control group and 93.7% (89/95) in the antibiotic group, also with no significant difference (p=0.193). No secondary outcome was significantly different between the two groups. CONCLUSION: Antibiotic treatment is no better than placebo in AECOPD with a PCT level <0.1 ng/ml.

[Therapeutic Effect of Combined Cytokines on Nonhuman Primate Model of Severe Haemopoietic Acute Radiation Sickness].

OBJECTIVE: To evaluate the therapeutic effects of combined administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-2 (rhIL-2) on radiation-induced severe haemopoietic acute radiation sickness (ARS) in rhesus monkeys, so as to provide experimental evidences for the effective clinical treatment. METHODS: Seventeen rhesus monkeys were exposed to 7.0 Gy (60)Co γ-ray total body irradiation (TBI) to establish severe haemopoietic ARS model, and were randomly divided into supportive care group, rhG-CSF+rhTPO treatment group and rhG-CSF+rhTPO+rhIL-2 treatment group. Survival time, general signs such as bleeding and infections, and peripheral blood cell counts in each group were monitored. Bone marrow cells were cultivated to examine the colony formation ability. The histomorphology changes of bone marrow were observed at 45 d post irradiation. RESULTS: After 7.0 Gy (60)Co γ-ray TBI, monkeys of supportive care group underwent tarry stool and emesis, then died in 12~18 d. The overall survival rate in this group was 16.7%. Gastrointestinal reactions of monkeys in two combined-cytokines treatment groups were inapparent. Combined-cytokines treatment induced 100% survival. Complete blood cells declined sharply after irradiation in each group, but two combined-cytokines treatment schemes could elevate the nadir of all blood cells, shorten the duration of pancytopenia and accelerate the recovery of hemogram. Compared with rhG-CSF+ rhTPO treatment, rhG-CSF+ rhTPO+ rhIL-2 treatment could increase the counts of lymphocytes and monocytes. The colony-formation rate of haemopoietic stem/progenitor cells in bone marrow dropped markedly at 2 d after irradiation. Combined-cytokines treatment promoted the ability of colony formation on day 29. Hematopoietic cells mostly disappeared in bone marrow of animals in supportive care group, but hematopoietic functions were recovered after cytokines were administrated. CONCLUSION: rhG-CSF+ rhTPO and rhG-CSF+ rhTPO+ rhIL-2 treatment can significantly promote hematopoiesis recovery, improve the quantity of life, simplify the supportive therapy, and enhance the survival rate of rhesus monkeys with severe haemopoietic ARS induced by 7.0 Gy (60)Co γ-ray exposure. Especially the application of rhIL-2 can accelerate the recovery of lymphocytes and monocytes and restore the immunological function. Thus, combination of rhG-CSF, rhTPO and rhIL-2 on the basis of supportive care is an efficient strategy to treat severe haemopoietic ARS.