Study of HIV-1 Drug Resistance in Patients Receiving Free Antiretroviral Therapy in China

To investigate the prevalence of drug-resistance mutations,resistance to antiretroviral drugs,and the subsequent virological response to therapy in treatment-naive and antiretroviral-treated patients infected with HIV/AIDS in Henan,China,a total of 431 plasma samples were collected in Queshan county between 2003 and 2004,from patients undergoing the antiretroviral regimen Zidovudine Didanosine Nevirapine(Azt Ddi Nvp).Personal information was collected by face to face interview.Viral load and genotypic drug resistance were tested.Drug resistance mutation data were obtained by analyzing patient-derived sequences through the HIVdb Program(http://hivdb.stanford.edu).Overall,38.5% of treatment-naive patients had undetectable plasma viral load(VL),the rate significantly increased to 61.9% in 0 to 6 months treatment patients(mean 3 months)(P<0.005)but again significantly decrease to 38.6% in 6 to 12 months treatment patients(mean 9 months)(P<0.001)and 40.0% in patients receiving more than 12 months treatment(mean 16 months)(P<0.005).The prevalence of drug resistance in patients who had a detectable VL and available sequences were 7.0%,48.6%,70.8%,72.3% in treatment-na?ve,0 to 6 months treatment,6 to 12 months treatment,and treatment for greater than 12 months patients,respectively.No mutation associated with resistance to Protease inhibitor(PI)was detected in this study.Nucleoside RT inhibitor(NRTI)mutations always emerged after non-nucleoside RT inhibitor(NNRTI)mutations,and were only found in patients treated for more than 6 months,with a frequency less than 5%,with the exception of mutation T215Y(12.8%,6/47)which occurred in patients treated for more than 12 months.NNRTI mutations emerged quickly after therapy begun,and increased significantly in patients treated for more than 6 months(P<0.005),and the most frequent mutations were K103N,V106A,Y181C,G190A.There had been optimal viral suppression in patients undergoing treatment for less than 6 months in Queshan,Henan.The drug resistance strains were highly prevalent in antiretroviral-treated patients,and increased with the continuation of therapy,with many patients encountering virological failure after 6 months therapy.     

抗利福平结核分枝杆菌的多药耐药性调查

The correlation between rifampin resistance and multiple drug resistance in 236 clinical isolates of Mycobacterium tuberculosis was investigated in this thesis. It has found that 99.4% of the strains with rifampin resistance were multidrug-resistant strains and 89% of the multidrug-resistant strains were resistant to rifampin. This result showed that the rifampin resistance of Tuberculosis baccilli could be used as the marker of multidrug resistance of Mycobacterium tuberculosis.     

Vimentin a potential biomarker for therapeutic efficiency of HAART

Human immunodeficiency virus （HIV） is recognized to be one of the most destructive pandemics in recorded history. By 2011, approximately 34 million people had been infected globally. There were 2.5 million new HIV infections just in 2011 alone according to the Joint United Nations Programme on HIV/AIDS （UNAIDS）Report （2012）. With the use of highly active antiretroviral therapy （HAART）, the replication of HIV virus and the progression of HIV disease can be suppressed. However, during the life-long treatment of AIDS, HIV resistance and adverse drug reactions have become serious problems.     

Care of HIV-infected patients in China

Compared with high infection areas of the world, the total HIV infection rate in China is relatively low. Nonetheless, because of China＇s vast territory and large population, the potential infection risk must be taken seriously. In the next few years, needle sharing among injection drug users will remain the most common route of transmission for the HIV/AIDS epidemic in China. Unprotected sex is gradually becoming a major route of transmission. China began to implement HAART in 1999 according to international standards. Prior to 2003, there were only about 150 HIV/AIDS patients were treated with HAART in some clinical trials and about 100 HIV/AIDS patients were treated by private sources. Results of those treatments are the scientific basis for development of the therapeutic strategies in China. In March of 2003, the Chinese government initiated China CARES program. In November of 2003, the Chinese Ministry of Health announced a national policy of free ARV treatment to all HIV＋ Chinese citizens who were in poverty and required ARV therapy. There are total of 19,456 HIV/AIDS patients received free ARV drugs to date in 159 regions and 441 towns. Current challenges are how to follow-up and evaluate those patients in the clinical settings. The longer the therapy is postponed, the more side effects and the higher probability of drug resistance are going to occur. It remains unclear, therefore, when HAART regimen should be started in the HIV/AIDS population in China.     

Care of HIV-infected patients in China

Compared with high infection areas of the world, the total HIV infection rate in China is relatively low. Nonetheless,because of China‘s vast territory and large population, the potential infection risk must be taken seriously. In the next few years, needle sharing among injection drug users will remain the most common route of transmission for the HIV/AIDS epidemic in China. Unprotected sex is gradually becoming a major route of transmission. China began to implement HAART in 1999 according to international standards. Prior to 2003, there were only about 150 HIV/AIDS patients were treated with HAART in some clinical trials and about 100 HIV/AIDS patients were treated by private sources.Results of those treatments are the scientific basis for development of the therapeutic strategies in China. In March of 2003, the Chinese government initiated China CARES program. In November of 2003, the Chinese Ministry of Health announced a national policy of free ARV treatment to all HIV Chinese citizens who were in poverty and required ARV therapy. There are total of 19,456 HIV/AIDS patients received free ARV drugs to date in 159 regions and 441 towns.Current challenges are how to follow-up and evaluate those patients in the clinical settings. The longer the therapy is postponed, the more side effects and the higher probability of drug resistance are going to occur. It remains unclear,therefore, when HAART regimen should be started in the HIV/AIDS population in China.     

Change in drug resistance of staphylococcus aureus

Objective To analyze the change in drug resistance of staphylococcus aureus （SAU） in the PLA general hospital from January 2008 to December 2012, and to provide solid evidence to support the rational use of antibiotics for clinical applications. Methods The SAU strains isolated from clinical samples in the hospital were collected and subjected to the Kirby-Bauer disk diffusion test. The results were assessed based on the 2002 American National Committee for Clinical Laboratory Standards （NCCLS） guidelines. Results SAU strains were mainly isolated from sputum, urine, blood and wound excreta and distributed in penology, neurology wards, orthopedics and surgery ICU wards. Except for glycopeptide drugs, methicillin- resistant staphylococcus aureus （MRSA） had a higher drug resistance rate than those of the other drugs and had significantly more resistance than methicillin-sensitive staphylococcus aureus （MSSA） （P〈0.05）. In the dynamic observation of drug resistance, we discovered a gradual increase in drug resistance to fourteen test drugs during the last five years. Conclusion Drug resistance rate of SAU stayed at a higher level over the last five years; moreover, the detection ratio of MRSA keeps rising year by year. It is crucial for physicians to use antibiotics rationally and monitor the change in drug resistance in a dynamic way.     

Drug resistance in the sexually transmitted protozoan Trichomonas vaginalis

Trichomoniasis is the most common, sexually transmitted infection.It is caused by the flagellated protozoan parasite Trichomonas vagina/is. Symptoms include vaginitis and infections have been associatedwith preterm delivery, low birth weight and increased infant mortality, as well as predisposing to HIV/AIDSand cervical cancer. Trichomoniasis has the highest prevalence and incidence of any sexually transmitted infection. The 5-nitroimidazole drugs, of which metronidazole is the most prescribed, are the only approved,effective drugs to treat trichomoniasis. Resistance against metronidazole is frequently reported and cross-resistance among the family of 5-nitroimidazole drugs is common, leaving no alternative for treatment, withsome cases remaining unresolved. The mechanism of metronidazole resistance in T. Vagina/is from treatment failures is not well understood, unlike resistance which is developed in the laboratory under increasingmet ronidazole pressure. In the latter situation, hydrog enosomal function which is involved in activationof the prodrug, metronidazole, is down-regulated. Reversion to sensitivity is incomplete after removal ofdrug pressure in the highly resistant parasites while clinically resistant strains, so far analysed, maintaintheir resistance levels in the absence of drug pressure. Although anaerobic resistance has been regarded asa laboratory induced phenomenon, it clearly has been demonstrated in clinical isolates. Pursuit of both approaches will allow dissection of the underlying mechanisms. Many alternative drugs and treatments have been tested in vivo in cases of refractory trichomoniasis, as well as in vitro with some successes including the broad spectrum anti-parasitic drug nitazoxanide. Drug resistance incidence in T. Vagina/is appears to be on the increase and improved surveillance of treatment failures is urged.     

Current progress of China‘s free ART program

China‘s Free ART Program was initiated in 2002 as an emergency response to save and improve the lives of AIDS patients living mainly in impoverished rural regions of central China. With little experience in HIV/AIDS treatment and care and resource limitations, China‘s efforts to provide widespread access to free antiretroviral therapy has been a process fraught with difficulty. However, the Free ART Program is progressing from an emergency response to a standardized treatment and care system. The development of national guidelines, training programs, a laboratory support network, a national patient database, programs for special populations such as children and patients living with coinfections, and operational research has improved the scope and quality of the free treatment program. As of June 30,2005, a total of 19,456 patients in 28 provinces, autonomous regions, and special municipalities had received free ART.Challenges stemming from the nature of China‘s health system and patient population persist, but with strong government support and a diverse set of resources, China has the capacity to overcome these challenges and to provide nationwide access to high quality treatment and care.     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Enterovirus 71 3C proteolytically processes the histone H3 N-terminal tail during infection

Highlights
1. The N-terminal tail of histone H3 is specifically cleaved during EV71 infection.
2. Viral protease 3C is identified as a protease responsible for proteolytically processing the N-terminal H3 tail.
3. Our finding reveals a new epigenetic regulatory mechanism for Enterovirus 71 in virus-host interactions.     

Detection of EBV and HHV6 in the Brain Tissue of Patients with Rasmussen’s Encephalitis

Rasmussen’s encephalitis (RE) is a rare pediatric neurological disorder, and the exact etiology is not clear. Viral infection may be involved in the pathogenesis of RE, but conflicting results have reported. In this study, we evaluated the expression of both Epstein-Barr virus (EBV) and human herpes virus (HHV) 6 antigens in brain sections from 30 patients with RE and 16 control individuals by immunohistochemistry. In the RE group, EBV and HHV6 antigens were detected in 56.7% (17/30) and 50% (15/30) of individuals, respectively. In contrast, no detectable EBV and HHV6 antigen expression was found in brain tissues of the control group. The co-expression of EBV and HHV6 was detected in 20.0% (6/30) of individuals. In particular, a 4-year-old boy had a typical clinical course, including a medical history of viral encephalitis, intractable epilepsy, and hemispheric atrophy. The co-expression of EBV and HHV6 was detected in neurons and astrocytes in the brain tissue, accompanied by a high frequency of CD8⁺ T cells. Our results suggest that EBV and HHV6 infection and the activation of CD8⁺ T cells are involved in the pathogenesis of RE.     

Perinatal Vertical Transmission of Chikungunya Virus in Ruili,a Town on the Border between China and Myanmar

正Dear Editor,Chikungunya virus (CHIKV), an arbovirus in the family of Togaviridae, genus Alphavirus, is transmitted by the A.aegyptii or A. albopictus mosquito, and causes disease in humans characterized by fever, rash, and arthralgia (Silva and Dermody 2017; Suhrbier 2019). It was first reported in 1953 in Tanzania, and caused only a few outbreaks and sporadic cases in Africa and Asia in last century. However, in the epidemic in 2004, CHIKV acquired mutations that conferred enhanced transmission by the A. albopictus mosquito(Schuffenecker et al. 2006). Since then, it has successively caused outbreaks in Africa, the Indian Ocean, South East Asia, the South America, and Europe (Zeller et al. 2016).     

Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2

In conclusion, the novel visual RT-LAMP assay is a simple, rapid, and sensitive approach for detection of SARS-CoV-2, and it is ready for application in primary care and community hospitals or health care centers, and even patients' own houses in response to the current SARS-CoV-2 epidemic because the assay does not require sophisticated equipment and skilled personnel. Furthermore, it is also ready to be used in fields for screening samples from wild animals and environments to facilitate the identification of potential intermediate hosts that mediate the cross-species transmission of SARS-CoV-2 from bats to humans.