近年来红外光谱在临床医药学中的应用新进展

本文对近年来红外光谱在临床医药学应用中的新进展进行综述。叙述(1)微量样品红外光谱测定的前处理;(2)红外光谱在药品质量检测方面的应用。例如中药材的检测、西药及其制剂的检测;(3)红外光谱在临床疾病诊断方面的应用。例如冠心病、糖尿病、各种癌症的诊断;(4)红外光谱联用技术的应用。例如GC-FTIR、HPCL-FTIR、TCL-FTIR、HPTCL-FTIR等。为药物质量控制、临床诊断提供参考。

傅立叶变换红外光谱在临床医药学中的应用进展

本文对近年来傅立叶变换红外光谱(FTIR)在临床医药学中的应用进展进行了综述,主要包括FTIR在药品质量检测方面和临床疾病诊断方面以及FTIR联用技术的应用等,为药物质量控制、临床诊断提供参考。

临床研究中的知识产权问题

众所周知,知识产权在科学研究和社会发展中起着越来越重要的作用,它已成为衡量一个国家综合国力和国民素质的重要标志之一。同样,知识产权与医药学研究的各个方面也有着密切关系,或者说医药学研究也是知识产权研究和保护的重要领域,并且具有特殊性和复杂性。本文主要探讨临床医药学研究中所涉及的知识产权问题,与大家讨论。

Defensive medicine practices among gastroenterologists in Japan

AIM： To clarify the prevalence of defensive medicine and the specific defensive medicine practices among gastroenterologists in Japan. METHODS： A survey of gastroenterologists in Hiroshima, Japan, was conducted by mail in March 2006. The number of gastroenterologists reporting defensive medicine behaviors or changes in their scope of practice and the reported defensive medicine practices, i.e., assurance and avoidance behaviors, were examined. RESULTS： A total of 131 （77%） out of 171 gastroenterologists completed the survey. Three （2%） respondents were sued, and most respondents （96%） had liability insurance. Nearly all respondents （98%） reported practicing defensive medicine. Avoidance behaviors, such as avoiding certain procedures or interventions and avoiding caring for high-risk patients, were very common （96%）. Seventy-five percent of respondents reported often avoiding certain procedures or interventions. However, seasoned gastroenterologists （those in practice for more than 20 years） adopted avoidance behaviors significantly less often than those in practice for less than 10 years. Assurance behaviors, i.e., supplying additional services of marginal or no medical value, were also widespread （91%）. Sixty-eight percent of respondents reported that they sometimes or often referred patients to other specialists unnecessarily. CONCLUSION： Defensive medicine may be highly prevalent among gastroenterologists throughout 3apan, with potentially serious implications regarding costs, access, and both technical and interpersonal quality of care.

Question & Answer

Chinese insect drugs are drastic in nature, capable ofclearing channels and collaterals to promote a freeflow of qi and blood, and effective in someintractable and obstinate diseases due to long-termstagnation of phlegm and blood, which are hard to betreated by ordinary Chinese drugs. In clinic, properuse of insect drugs can often help raise thetherapeutic effects. Some commonly used pairs ofinsect drugs are introduced in the following.

Management of hypertensive crises in the elderly

Hypertensive crises are elevations of blood pressure higher than 180/120 mmHg. These can be urgent or emergent, depending on the presence of end organ damage. The clinical presentation of hypertensive crises is quite variable in elderly patients, and clinicians must be suspicious of non-specific symptoms. Managing hypertensive crises in elderly patients needs meticulous knowledge of the pathophysiological changes in them, pharmacological options, pharmacokinetics of the medications used, their side effects, and their interactions with other medications. Clevidipine, nicardipine, labetalol, esmolol, and fenoldopam are among the preferred choices in the elderly due to their efficacy and tolerability. Nitroprusside, hydralazine, and nifedipine should be avoided, unless there are no other options available, due to the high risk of complications and unpredictable responses.

Giant duodenal ulcers

Giant duodenal ulcers （GDUs） are a subset of duodenal ulcers that have historically resulted in greater morbidity than usual duodenal ulcers. Until recently, few cases had been successfully treated with medical therapy. However, the widespread use of endoscopy, the introduction of H-2 receptor blockers and proton p^Jmp inhibitors, and the improvement in surgical techniques all have revolutionized the diagnosis, treatment and outcome of this condition. Nevertheless, GDUs are still associated with high rates of morbidity, mortality and complications. Thus, surgical evaluation of a patient with a GDU should remain an integral part of patient care. These giant variants, while usually benign, can frequently harbor malignancy. A careful review of the literature highlights the important differences when comparing GDUs to classical peptic ulcers and why they must be thought of differently than their more common counterpart.

Molecular mechanisms of coronavirus RNA capping and methylation

The 5′-cap structures of eukaryotic m RNAs are important for RNA stability, pre-m RNA splicing,m RNA export, and protein translation. Many viruses have evolved mechanisms for generating their own cap structures with methylation at the N7 position of the capped guanine and the ribose 2′-Oposition of the first nucleotide, which help viral RNAs escape recognition by the host innate immune system. The RNA genomes of coronavirus were identified to have 5′-caps in the early1980 s. However, for decades the RNA capping mechanisms of coronaviruses remained unknown.Since 2003, the outbreak of severe acute respiratory syndrome coronavirus has drawn increased attention and stimulated numerous studies on the molecular virology of coronaviruses. Here, we review the current understanding of the mechanisms adopted by coronaviruses to produce the 5′-cap structure and methylation modification of viral genomic RNAs.

Responses of the Toll-like receptor and melanoma differentiation-associated protein 5 signaling pathways to avian infectious bronchitis virus infection in chicks

Avian infectious bronchitis virus(IBV) is a Gammacoronavirus in the family Coronaviridae and causes highly contagious respiratory disease in chickens. Innate immunity plays significant roles in host defense against IBV. Here, we explored the interaction between IBV and the host innate immune system. Severe histopathological lesions were observed in the tracheal mucosa at 3–5days post inoculation(dpi) and in the kidney at 8 dpi, with heavy viral loads at 1–11 and 1–28 dpi,respectively. The expression of m RNAs encoding Toll-like receptor(TLR) 3 and TLR7 were upregulated at 3–8 dpi, and that of TIR-domain-containing adapter-inducing interferon(IFN) β(TRIF) was upregulated at 21 dpi in the trachea and kidney. Myeloid differentiation primary response protein 88(My D88) was upregulated in the trachea during early infection. Tumor necrosis factor receptor-associated factor(TRAF) 3 and TRAF6 were upregulated expression in both tissues.Moreover, melanoma differentiation-associated protein 5(MDA5), laboratory of genetics and physiology 2(LGP2), stimulator of IFN genes(STING), and mitochondrial antiviral signaling protein(MAVS), as well as TANK binding kinase 1(TBK1), inhibitor of kappa B kinase(IKK) ?, IKKα, IKKβ,IFN regulatory factor(IRF) 7, nuclear factor of kappa B(NF-κB), IFN-α, IFN-β, various interleukins(ILs), and macrophage inflammatory protein-1β(MIP-1β) were significantly upregulated in the trachea and downregulated in the kidney. These results suggested that the TLR and MDA5 signaling pathways and innate immune cytokine were induced after IBV infection. Additionally,consistent responses to IBV infection were observed during early infection, with differential and complicated responses in the kidney.

A six-year descriptive epidemiological study of human coronavirus infections in hospitalized patients in Hong Kong

We conducted a six-year epidemiological study on human coronaviruses（HCoVs） circulating in Hong Kong, using 8275 nasopharyngeal samples from patients with acute respiratory tract infections. HCoVs were detected in 77（0.93%） of the samples by a pan-HCoV RT-PCR assay. The most frequently detected HCoV species was HCoV-OC43（0.58%）, followed by HCoV-229E（0.15%）,HCoV-HKU1（0.13%） and HCoV-NL63（0.07%）. HCoVs were detected throughout the study period（September 2008–August 2014）, with the highest detection rate from September 2010 to August2011（22/1500, 1.47%）. Different seasonal patterns of each HCoV species in Hong Kong were noted.HCoV-OC43 was predominant in the fall and winter, whereas HCoV-HKU1 showed peak activity in winter, with a few cases occurred in spring and summer. HCoV-229 E mainly occurred in winter and spring, while HCoV-NL63 was predominant in summer and autumn. HCoVs most commonly infect the elderly and young children, with median age of 79.5 years（range, 22 days to 95 years）.Intriguingly, the detection rate of HCoV-OC43 in the age group of ＆gt; 80 years（26/2380, 1.09%） was significantly higher than that in the age group of 0–10 years（12/2529, 0.47%）（P 〈 0.05）. These data provides new insight into the epidemiology of coronaviruses.

A molecular arms race between host innate antiviral response and emerging human coronaviruses

Coronaviruses have been closely related with mankind for thousands of years. Communityacquired human coronaviruses have long been recognized to cause common cold. However,zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome(SARS) and Middle East respiratory syndrome(MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived.

Detection and characterization of diverse alpha-and betacoronaviruses from bats in China

Bats have been implicated as important reservoir hosts of alpha- and betacoronaviruses. In this study, diverse coronaviruses(CoVs) were detected in 50 of 951(positive rate 5.3%) intestinal specimens of eight bat species collected in four provinces and the Tibet Autonomous Region of China by pan-coronavirus RT-PCR screening. Based on 400-nt RNA-dependent RNA polymerase(Rd RP) sequence analysis, eight belonged to genus Alphacoronavirus and 42 to Betacoronavirus.Among the 50 positive specimens, thirteen gave rise to CoV full-length Rd RP gene amplification for further sequence comparison, of which three divergent sequences(two from a unreported province) were subjected to full genome sequencing. Two complete genomes of betacoronaviruses(JTMC15 and JPDB144) and one nearly-complete genome of alphacoronavirus(JTAC2) were sequenced and their genomic organization predicted. The present study has identified additional numbers of genetically diverse bat-borne coronaviruses with a wide distribution in China. Two new species of bat CoV, identified through sequence comparison and phylogenetic analysis, are proposed.

Risk factors for severity and mortality in patients with MERS-CoV:Analysis of publicly available data from Saudi Arabia

Dear Editor,Middle East respiratory syndrome coronavirus(MERS-CoV)has affected over 1600 people across four continents;it has a fatality rate of about 36%(WHO,2015).Approximately 75%of MERS-CoV patients have a preexisting medical condition(Zumla et al.,2015).MERS-CoV is especially severe in patients with comorbidities.

Two-tube multiplex real-time reverse transcription PCR to detect six human coronaviruses

Dear Editor,Coronaviruses are enveloped positive-strand RNA viruses with 27–33 kb genomes.These viruses are classified into four genera,namely Alphacoronavirus,Betacoronavirus,Gammacoronavirus,

Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft

Since the 2002–2003 severe acute respiratory syndrome(SARS) outbreak prompted a search for the natural reservoir of the SARS coronavirus, numerous alpha- and betacoronaviruses have been discovered in bats around the world. Bats are likely the natural reservoir of alpha- and betacoronaviruses, and due to the rich diversity and global distribution of bats, the number of bat coronaviruses will likely increase. We conducted a surveillance of coronaviruses in bats in an abandoned mineshaft in Mojiang County, Yunnan Province, China, from 2012–2013. Six bat species were frequently detected in the cave: Rhinolophus sinicus, Rhinolophus affinis, Hipposideros pomona, Miniopterus schreibersii, Miniopterus fuliginosus, and Miniopterus fuscus. By sequencing PCR products of the coronavirus RNA-dependent RNA polymerase gene(Rd Rp), we found a high frequency of infection by a diverse group of coronaviruses in different bat species in the mineshaft. Sequenced partial Rd Rp fragments had 80%–99% nucleic acid sequence identity with well-characterized Alphacoronavirus species, including Bt CoV HKU2, Bt CoV HKU8, and Bt CoV1,and unassigned species Bt CoV HKU7 and Bt CoV HKU10. Additionally, the surveillance identified two unclassified betacoronaviruses, one new strain of SARS-like coronavirus, and one potentially new betacoronavirus species. Furthermore, coronavirus co-infection was detected in all six bat species, a phenomenon that fosters recombination and promotes the emergence of novel virus strains. Our findings highlight the importance of bats as natural reservoirs of coronaviruses and the potentially zoonotic source of viral pathogens.

Recent progress in the discovery of inhibitors targeting coronavirus proteases

Coronaviruses(CoVs) can cause highly prevalent diseases in humans and animals. The fatal outbreak of severe acute respiratory syndrome(SARS) and Middle East respiratory syndrome(MERS) highlights the threat posed by this unique virus subfamily. However, no specific drugs have been approved to treat CoV-associated diseases to date. The CoV proteases, which play pivotal roles in viral gene expression and replication through a highly complex cascade involving the proteolytic processing of replicase polyproteins, are attractive targets for drug design. This review summarizes the recent advances in biological and structural studies, together with the development of inhibitors targeting CoV proteases, particularly main proteases(M^(pro)s), which could help develop effective treatments to prevent CoV infection.

Longitudinal surveillance of SARS-like coronaviruses in bats by quantitative real-time PCR

Dear Editor,The 2002–2003 severe acute respiratory syndrome coronavirus（SARS-CoV）（Drosten et al.,2003）caused human pandemics that began in China and spread globally.Subsequently,

Comparison of lentiviruses pseudotyped with S proteins from coronaviruses and cell tropisms of porcine coronaviruses

The surface glycoproteins of coronaviruses play an important role in receptor binding and cell entry. Different coronaviruses interact with their specific receptors to enter host cells. Lentiviruses pseudotyped with their spike proteins(S) were compared to analyze the entry efficiency of various coronaviruses. Our results indicated that S proteins from different coronaviruses displayed varied abilities to mediate pseudotyped virus infection. Furthermore, the cell tropisms of porcine epidemic diarrhea virus(PEDV) and transmissible gastroenteritis virus(TGEV) have been characterized by live and pseudotyped viruses. Both live and pseudoviruses could infected VeroCCL-81(monkey kidney), Huh-7(human liver), and PK-15(pig kidney) cells efficiently. CCL94(cat kidney) cells could be infected efficiently by TGEV but not PEDV. Overall, our study provides new insights into the mechanisms of viral entry and forms a basis for antiviral drug screening.

New direction for clinical pharmacy in China: adopting a “form follows function” approach to improve future healthcare outcomes

Clinical pharmacy is an important development in modern pharmacy practice. In China, the recent recognition of clinical pharmacists by the Ministry of Health is an important step that can lead to a successful change in the functional role of the pharmacists to directly improve the health care outcomes. To optimize this role change, we propose that a ＂form follows function＂ structure be implemented. We believe that a ＂form＂ consisting of three components is highly desirable and should be established with careful coordination：（1） a formal education/training curriculum;（2） a professional organization to lead the clinical improvements in practice/research; and（3） an accrediting body for quality education/training and practice. By incorporating the clinical pharmacy experiences in USA and other countries as well as adopting this ＂form follows function＂ approach, we predict a bright future for the clinical pharmacists in China as valuable members of health care team to positively impact the health care outcomes.

The prevalence,origin,and prevention of six human coronaviruses

CORONAVIRUSES Coronaviruses（CoVs）are a large group of viruses found in many species of animals around the world,particularly bats and wild birds.CoVs result in various clinical manifestations ranging from asymptomatic respiratory,hepatic,