Antibiotics are medicines used to prevent and treat bacterial infections. Antibiotic resistance occurs when bacteria change in response to the use of these medicines. Antibiotic resistance is rising to dangerously high levels in all parts of the world, leading to higher medical costs, prolonged hospital stays, and increased mortality. In the European Union alone, drug-resistant bacteria are estimated to cause 25,000 deaths and cost more than US$1.5 billion every year in healthcare expenses and productivity losses. The problems of antibiotic misuse and antibiotic resistance are quite serious in China. In 2015, results of a study by the State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences indicated that the total antibiotic usage in China in 2013 was approximately 162,000 tons, including human use (48%) and use in animals (52%). This amount accounted for about half of the antibiotic usage worldwide. The per-capita use of antibiotics in China is more than 5 times that in Europe and the United States. These data mean that China is one of the world's leading countries with serious problems in terms of antibiotic misuse and antibiotic resistance. The current article analyzes the current state and harms of antibiotic misuse and causes of antibiotic resistance in China. The Government needs to pay close attention to the issue of antibiotic resistance in China and formulate a strategy at the national level. Thus, the following suggestions are offered: i) The Chinese Government should implement policies that promote antibiotic research and development; ii) Medical facilities in China should create multidisciplinary teams (MDTs) and encourage early action by MDTs to control the spread of multi-drug-resistant bacteria (MDRB); iii) An intervention in the form of health education should target patients and accompanying family members (AFM) in China. In other words, antibiotic resistance is not a personal problem but an urgent public health problem. Without urgent action, China is heading for a post-antibiotic era in which common infections and minor injuries can once again kill. Therefore, the aforementioned proposals have been offered with the hope that policy suggestions help to limit the phenomenon of antibiotic misuse and antibiotic resistance in China.
Community-acquired pneumonia (CAP) is a world wide cause of morbidity and mortality. The etiology of CAP is different between countries and changes over time. With the increasing incidence, atypical pathogens are attracting more and more attention all over the world. In many countries, atypical pathogens are one of the main pathogens of CAP, and even could be the most prevalent etiology in China. Atypical pathogen infections can cause multi-system complications, which leads to a worse prognosis. Although still controversial, empirical antibiotic coverage of atypical pathogens in CAP may improve outcomes, shorten length of hospitalization, reduce mortality and lower total hospitalization costs. The macrolide resistance rate of atypical pathogens, especially Mycoplasma Pneumoniae (M. Pneumoniae) is high, so fluoroquinolones or tetracyclines should be considered as alternative therapy.
Nosocomial infection is a kind of infection, which is spread in various hospital environments, and leads to many serious diseases (e.g. pneumonia, urinary tract infection, gastroenteritis, and puerperal fever), and causes higher mortality than community-acquired infection. Bacteria are predominant among all the nosocomial infection-associated pathogens, thus a large number of antibiotics, such as aminoglycosides, penicillins, cephalosporins, and carbapenems, are adopted in clinical treatment. However, in recent years antibiotic resistance quickly spreads worldwide and causes a critical threat to public health. The predominant bacteria include Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. In these bacteria, resistance emerged from antibiotic resistant genes and many of those can be exchanged between bacteria. With technical advances, molecular mechanisms of resistance have been gradually unveiled. In this review, recent advances in knowledge about mechanisms by which (i) bacteria hydrolyze antibiotics (e.g. extended spectrum β-lactamases, (ii) AmpC β-lactamases, carbapenemases), (iii) avoid antibiotic targeting (e.g. mutated vanA and mecA genes), (iv) prevent antibiotic permeation (e.g. porin deficiency), or (v) excrete intracellular antibiotics (e.g. active efflux pump) are summarized.
Tokyo Guideline 2013 (TG13) is an international guideline for the diagnosis, classification and treatment of acute cholangitis. Progress and controversy for the two years after TG13 was summarized. Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) are both effective imaging tests for common bile duct (CBD) stones. More factors e.g. obesity may be involved in severity assessment. Initiation of broad-spectrum antibiotics addressing the typical Gram-negative enteric bacteria spectrum and early biliary drainage are the mainstay therapeutic options. Early laparoscopic exploration is also an option for stone-related nonsevere acute cholangitis besides endoscopic retrograde cholangial or percutaneous transhepatic cholangial drainage. Surgical biliary drainage should be avoided in severe cholangitis.
The purpose of this study is to determine the prevalence of burnout among different grade hospitals and to examine if a relation exists between burnout and medical mistakes. A multi-center cross-sectional survey was conducted. Physicians were interviewed in hospitals from 10 provinces in China. Burnout was measured using the Chinese version of the Maslach Burnout Inventory-General Survey. Overall, 1,537 physicians were included in this study. Of these, 76.9% reported some burnout symptoms or serious burnout symptoms and 54.8% reported committing medical mistakes during the last year. 39.6%, 50.0%, and 59.5% of the respondents in primary, secondary, and tertiary hospitals respectively reported having made mistakes over the course of the previous year. Multivariate analysis demonstrated that being female was protective against medical mistakes (OR = 0.72, 95% CI: 0.58-0.89), whereas physician-reported 60 or more work hours per week (OR = 1.65, 95% CI: 1.22-2.22), and physicians who reported serious burnout (OR = 2.28, 95% CI: 1.63-3.17) were independently associated with higher incidence of medical mistakes. In conclusion, Chinese physicians reported high workloads, high rates of burnout and high medical mistakes. Physicians in tertiary hospitals were especially overworked and suffered the most serious burnout. Longer work hours per week, and burnout were the independent risk factors for medical mistakes.
In preeclampsia and gestational diabetes, the sympathetic nerves are activated, leading to disrupted sleep. Melatonin, which transmits information to regulate the sleep-wake rhythm and other such biorhythms, has been implicated in insulin resistance, antioxidant behaviors, and metabolic syndrome. In addition, its reduced secretion increases the risk of hypertension and diabetes. The aim of this study was to elucidate the features of melatonin secretion, sleep quality, and sleep-wake rhythms in pregnant women with complications. Fifty-eight pregnant women with pregnancy complications (hypertensive or glucose metabolic disorders) and 40 healthy pregnant women completed questionnaires, including sleep logs and the Pittsburgh Sleep Quality Index (PSQI), during the second to third trimesters. Their salivary melatonin levels were also measured. Pregnant women with complications had significantly lower morning (p < 0.001), daytime (p < 0.01), evening (p < 0.001), night (p < 0.01), daily mean (p < 0.001), peak (p < 0.001), and bottom (p < 0.01) melatonin values than healthy pregnant women. Pregnant women with complications also had significantly smaller melatonin amplitudes than healthy pregnant women (p < 0.001). Among pregnant women with complications, the duration (p < 0.05) and frequency (p < 0.01) of wake after sleep-onset were significantly greater in the poor sleep group than in the favorable sleep group which was divided by PSQI cutoff value. Pregnant women with hypertensive or glucose metabolic disorder complications had smaller circadian variation in salivary melatonin secretion, and their values were lower throughout the day than healthy pregnant women.
When treating HIV-infected patients with hemophilia, adverse drug reactions and interactions and the effect of treatment on bleeding disorders must be considered. Raltegravir is the first HIV integrase inhibitor, but its use in patients with hemophilia is rarely reported. Nine HIV-positive patients with hemophilia were retrospectively studied with a focus on the virological response, changes in the CD4 count, the tendency to bleed, and the response to replacement therapy before and after raltegravir-based antiretroviral therapy (ART). The nine patients were highly treatment-experienced patients and they received raltegravir-based ART for at least nine months. The patients had their own reasons for changing to raltegravir-based ART. During treatment, the CD4 count increased progressively in four patients, with a median absolute increase of 233 cells/mm3, while the count stabilized in the remaining five patients. Two previous recipients of lopinavir/ritonavir (LPV/r) who failed to respond to lamivudine (3TC) + zidovudine (ZDV) + efavirenz (EFV) had a viral rebound. Genotyping indicated multidrug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). A pattern of resistance to raltegravir was evident, including the primary mutation N155H and the secondary mutation T97A. In the two patients, the tendency to bleed decreased markedly and monthly usage of clotting factor VIII decreased significantly decreased. In the remaining seven patients, the viral load remained < 40 copies/mL, there was no evidence of an increased tendency to bleed, and no evidence of changes in the response to replacement therapy. All of the patients had a stable condition with no signs of disease progression and no serious adverse reactions. Results indicated that Raltegravir-based therapy offered a safe and well-tolerated option for HIV-positive patients with hemophilia.
Allograft inflammatory factor-1 (AIF-1) is a protein expressed by macrophages infiltrating the area around the coronary arteries of rats with an ectopic cardiac allograft. Some studies have shown that expression of AIF-1 increased in a mouse model of trinitrobenzene sulfonic acid-induced acute colitis and in acute cellular rejection of human cardiac allografts. These results suggest that AIF-1 is related to acute inflammation. The current study used bleomycin-induced acute lung injury to analyze the expression of AIF-1 and to examine its function in acute lung injury. Results showed that AIF-1 was significantly expressed in lung macrophages and increased in bronchoalveolar lavage fluid from mice with bleomycin-induced acute lung injury in comparison to control mice. Recombinant AIF-1 increased the production of IL-6 and TNF-α from RAW264.7 (a mouse macrophage cell line) and primary lung fibroblasts, and it also increased the production of KC (CXCL1) from lung fibroblasts. These results suggest that AIF-1 plays an important role in the mechanism underlying acute lung injury.
Apolipoprotein E (ApoE) regulated bone metabolism in mice might mediate uptake of lipid particles into target cells such as osteoblasts via receptor-mediated endocytosis by apoE receptors, which includes the low-density lipoprotein receptor (LDLR) family and heparan sulfate proteoglycans (HSPGs). There is no report regarding the expression of ApoE receptors mRNA induced by estrogen during osteoblast differentiation in vitro. Primary osteoblasts were collected from the calvaria of newborn mice and were subjected to osteoblast mineralization culture with serial concentrations of 17-β-estradiol (E2) in vitro. RNA was isolated at days 0, 5 and 25 of differentiation. Real-time PCR was conducted to analyze apoE receptors mRNA levels. We found that most LDLR family members genes were induced during osteoblast differentiation in vitro. The effect of E2 on apoE receptors gene expression during osteoblast differentiation was multifarious. The most noted members of the LDLR family involved in the maintenance of bone metabolism were LRP5, LRP6, LRP4, and Apoer2. LRP6 was up-regulated, while LRP5, LRP4, and Apoer2 were down-regulated by E2. Given that LRP6 is required for early stages of differentiation, we speculate E2 promotes osteoblast differentiation mainly in the early stage.
Centrosomal protein 55 (CEP55), as a microtubule-bundling protein, plays an important role in cell cycle regulation. CEP55 has been recognized recently in several human cancers. In this study, we first observed that the mRNA level of CEP55 is commonly up-regulated in breast cancer compared with their normal counterparts as demonstrated by data derived from Oncomine database. To further evaluate the functional role of CEP55 in breast cancer cells. Expression of CEP55 was efficiently knocked down using lentivirus-mediated RNA interference in human breast cancer cell line ZR-75-30, as evidenced by quantitative real-time PCR (qRT-PCR) and Western blot analysis. Further investigations revealed that CEP55 knockdown significantly inhibited cell proliferation and colony formation. Moreover, flow cytometer analysis indicated knockdown of CEP55 induced cell cycle arrested at G0/G1 phase and cell apoptosis. These findings suggest that CEP55 plays a crucial role in promoting breast cancer cell proliferation and it might be a potential therapeutic target in breast cancer.
This study sought to investigate the broad-spectrum antibacterial action of an alternative medicine, Shufeng Jiedu capsules (SFJDC). Antibacterial testing was performed to determine whether SFJDC had broad-spectrum antibacterial action in vitro, and testing was performed to verify whether SFJDC prevented death due to a Streptococcus or Staphylococcus aureus infection in mice. Results of antibacterial testing suggested that SFJDC are a broad-spectrum antibacterial and that SFJDC are superior to Lianhua Qingwen capsules as a broad-spectrum antibacterial. Results of testing revealed that SFJDC lowered the mortality rate, it reduced mortality, it increased average survival time, and it increased the lifespan of mice dying due to a Staphylococcus aureus or Streptococcus infection. Thus, SFJDC could become a complement to broad-spectrum antimicrobials in clinical settings.
Mitochondrial aspartate aminotransferase (mAspAT) was recognized as a moonlighting enzyme because it has not only aminotransferase activity but also a high-affinity long-chain fatty acids (LCFA) binding site. This enzyme plays a key role in amino acid metabolism, biosynthesis of kynurenic acid and transport of the LCFA. Therefore, it is important to study the structure-function relationships of human mAspAT protein. In this work, the mature form of human mAspAT was expressed to a high level in Escherichia coli periplasmic space using pET-22b vector, purified by a combination of immobilized metal-affinity chromatography and cation exchange chromatography. Optimal activity of the enzyme occurred at a temperature of 47.5ºC and a pH of 8.5. Crystals of human mAspAT were grown using the hanging-drop vapour diffusion method at 277K with 0.1 M HEPES pH 6.8 and 25%(v/v) Jeffamine® ED-2001 pH 6.8. The crystals diffracted to 2.99 Å and belonged to the space group P1 with the unit-cell parameters a =56.7, b = 76.1, c = 94.2 Å, α =78.0, β =85.6, γ = 78.4º. Elucidation of mAspAT structure can provide a molecular basis towards understanding catalysis mechanism and substrate binding site of enzyme.