简介：AbstractThe low success rates in the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant TB (XDR-TB), which account for 55% and 34% respectively, led the WHO to conclude that MDR/XDR-TB is a serious public health crisis. However, the virulence of MDR/XDR-Mycobacterium Tuberculosis(Mtb) has not been analyzed in details, which could provide a specific guidance for the control and prevention. In this review, we discuss different aspects of MDR/XDR-Mtb virulence and its relationship to fitness cost by probing the following questions: (1) what mediates the virulence of MDR/XDR-Mtb? (What is the relationship between fitness and virulence of Mtb? (2) Is it possible that drug-resistant Mtb(DR Mtb) can show higher fitness? (3) What is the definite effect on fitness of each drug-resistant mutant? (4) What other important factors affecting fitness in the mutant strain? (5) How to study the virulence of a large number of DR Mtb?And what prevention and control measures will be taken in the future, especially for the high virulent DR Mtb? We therefore summarized the congruent relationship between drug resistance and fitness from the global response-related genes to antibiotic resistance-contributing mutation, provided methods to explore the virulence of DR Mtb. This review may offer some critical information and concise guide to creating strategies for the prevention and control of drug-resistant Mtb.

简介：AbstractIn recent years, the research of immune checkpoint inhibitors has made a great breakthrough in lung cancer treatment. Currently, a variety of immune checkpoint inhibitors have been applied into clinical practice, including antibodies targeting the programmed cell death-1, programmed cell death-ligand 1, and cytotoxic T-lymphocyte antigen 4, and so on. However, not all patients can benefit from the treatment. Abnormal antigen presentation, functional gene mutation, tumor microenvironment, and other factors can lead to primary or secondary resistance. In this paper, we reviewed the molecular mechanism of immune checkpoint inhibitor resistance and various combination strategies to overcome resistance, in order to expand the beneficial population and enable precision medicine.

简介：AbstractDrug resistance via drug-resistant mutations in the human immunodeficiency virus (HIV) genome is the primary cause of antiviral therapy failure. Consequently, HIV drug resistance genotyping has become a critical approach in HIV prevention and control. Compared to the Sanger sequencing technology, high-throughput sequencing (HTS) technology has superior sensitivity and timeliness, with strong detection capabilities for low-frequency mutations. With the continued advancement of HTS technologies, their prominence in HIV drug resistance detection techniques has increased accordingly. This article will review the latest developments in HTS technology and its applications in HIV drug resistance testing.

简介：AbstractBackground:After the scale-up of antiretroviral therapy (ART) for HIV infected people, increasing numbers of patients have pretreatment drug resistance (PDR). In this study, the prevalence of PDR was evaluated in adults initiating antiretroviral therapy in China.Methods:Blood samples were obtained from 1943 patients who initiated antiretroviral therapy (ART) in 2017 from 13 provinces or cities in China. Pol sequences were used to analyze drug resistance and construct transmission networks. Logistic regression model was used to estimate the potential factors associated with PDR.Results:In total, 1711 eligible patients (76.0% male; 87.8% aged ≥ 25 years) were included, of which 117 (6.8%) had PDR. The highest rates of PDR were 12.2% in Liangshan Prefecture of Sichuan and 9.3 and 8.9% in Dehong and Lincang Prefecture of Yunnan. A multivariate logistic regression analysis revealed that PDR was significantly higher among intravenous drug users (adjusted Odds Ratio (aOR) = 2.64, 95% CI: 1.57–4.44) and individuals from Liangshan, Dehong, and Lincang (aOR= 2.04, 95% CI: 1.26–3.30). In total, 754 sequences were used to generate 164 transmission networks. Five transmission networks had two or three sequences containing the same mutations, two networks contained subjects from Liangshan, and one network contained subjects from Dehong.Conclusions:Overall, the PDR prevalence was moderate, with a particularly high prevalence in areas with severe HIV epidemics. These results indicate the importance of continuous PDR monitoring in patients initiating antiretroviral therapy.

简介：AbstractBackground:Rapid and accurate detection of drug resistance in Mycobacterium tuberculosis is critical for effective control of tuberculosis (TB). Herein, we established a novel, low cost strategy having high accuracy and speed for the detection of M. tuberculosis drug resistance, using gene splicing by overlap extension PCR (SOE PCR).Methods:The SOE PCR assay and Sanger sequencing are designed and constructed to detect mutations of rpoB, embB, katG, and inhA promoter, which have been considered as the major contributors to rifampicin (RFP), isoniazid (INH), and ethambutol (EMB) resistance in M. tuberculosis. One hundred and eight M. tuberculosis isolates came from mycobacterial cultures of TB cases at Chongqing Public Health Medical Center in China from December 2018 to April 2019, of which 56 isolates were tested with the GeneXpert MTB/RIF assay. Performance evaluation of the SOE PCR technique was compared with traditional mycobacterial culture and drug susceptibility testing (DST) or GeneXpert MTB/RIF among these isolates. Kappa identity test was used to analyze the consistency of the different diagnostic methods.Results:We found that the mutations of S531L, S315T and M306V were most prevalent for RFP, INH and EMB resistance, respectively, in the 108 M. tuberculosis isolates. Compared with phenotypic DST, the sensitivity and specificity of the SOE PCR assay for resistance detection were 100.00% and 88.00% for RFP, 94.64% and 94.23% for INH, and 68.97% and 79.75% for EMB, respectively. Compared with the GeneXpert MTB/RIF, the SOE PCR method was completely consistent with results of the GeneXpert MTB/RIF, with a concordance of 100% for resistance to RFP.Conclusions:In present study, a novel SOE PCR diagnostic method was successfully developed for the accurate detection of M. tuberculosis drug resistance. Our results using this method have a high consistency with that of traditional phenotypic DST or GeneXpert MTB/RIF, and SOE PCR testing in clinical isolates can also be conducted rapidly and simultaneously for detection of drug resistance to RFP, EMB, and INH.

简介：AbstractBackground:Human immunodeficiency virus (HIV) prevalence among student men who have sex with men (MSM) in college is more than 5.0% and keeps on increasing in China. This study aims to clarify the proportion of HIV recent infection, its propeller and the source among college student MSM.Methods:We conducted a multicenter cross-sectional study in seven major Chinese cities during 2012-2013. HIV recent infections (≤168 days) and incidence was measured and estimated by BED HIV-1 capture enzyme immunoassay (BED-CEIA) testing strategy. HIV-related behaviors and transmitted drug resistance (TDR) were investigated and compared between the college student MSM, < 25-year-old non-student youth MSM (NSYM), and ≥25-year-old non-student non-youth MSM (NSNYM), using structured survey, and analyses of drug resistance.Results:Overall, 4496 (4496/4526, 99.3%) were eligible for enrollment, comprising 565 college student MSM, 1094 NSYM, and 2837 NSNYM. The proportion of HIV recent infection were 70.3% (26/37), 50.8% (65/128) and 35.1% (95/271), the HIV incidence rate were 10.0 (95% CI: 6.2-13.9)/100 person-year (PY), 12.9 (95% CI: 9.8-16.1 )/100PY, 6.8 (95% CI: 5.4-8.2)/100 PY, and TDR prevalences were 7.4% (2/27), 2.0%, (2/98) and 4.9% (11/226), among student MSM, NSYM, and NSNYM, respectively. Among HIV positive student MSM with age <21 years, the proportion of HIV recent infection is 90.9% (10/11). Factors independently associated with HIV recent infection in student MSM was usage of recreational drug in the past 6 months (adjusted odds ratio [aOR]: 2.5; 95% CI: 1.0-5.8).Conclusions:College student MSM had higher proportion of HIV recent infection and TDR than the youth and older MSM in China during 2012-2013. The HIV infections were more likely to happen during the early year of college life among student MSM.

简介：AbstractChoosing the appropriate antibiotics to treat bacterial infections has grown more challenging as a result of the emergence of antibiotic-resistant bacteria. Aminoglycosides, as broad-spectrum antibiotics, are increasingly being used clinically; however, for most effective employment of aminoglycosides, a comprehensive understanding of aminoglycoside resistance genes’ prevalence and dissemination is required. Therefore, to better understand the global resistance status of aminoglycoside antibiotics and the prevalence of antibiotic-resistance genes (ARGs) in various bacterial species, this systematic review gathered relevant data from multiple studies. Two primary resistance mechanisms—aminoglycoside enzymatic modification and 16S rRNA methylation—were assessed, and the prevalence of the corresponding ARGs was described. The coexistence of aminoglycoside ARGs with other ARGs was also demonstrated, as was the relationship between aminoglycoside ARGs and resistant phenotypes. The lack of effective therapeutic agents to combat resistant pathogens presents a real threat to public health. The combination of aminoglycosides with other antibiotics may provide a novel treatment strategy.

简介：AbstractChronic subdural hematoma (CSDH) is a chronic space-occupying lesion formed by blood accumulation between arachnoid and dura mater, which is usually formed in the third week after traumatic brain injury. Surgical treatment is usually the first choice for patients with CSDH having a significant space-occupying effect. Most of the patients showed good results of surgical treatment, but still some patients had a postoperative recurrence (the recurrence rate was up to 33%). Because CSDH is often seen in the elderly, patients are weak and have many basic diseases. The risk of surgical treatment is high; serious complications and even death (the death rate is up to 32%) can often occur. The overall good prognosis rate of patients aged more than 90 years is 24%. The drug treatment can provide a safe and effective treatment for elderly patients who are weak, intolerable to surgery, or failed in surgery. Low-dose and long-term use of atorvastatin (20mg/d) is suggested for continuous treatment for at least 8 weeks, while low-dose and short-term use of dexamethasone can improve the therapeutic effect of atorvastatin on CSDH. Patients should undergo CT or MRI scanning at least one time within 2 weeks after the start of drug treatment.

简介：AbstractThe wide use and abuse of antibiotics could make antimicrobial resistance (AMR) an increasingly serious issue that threatens global health and imposes an enormous burden on society and the economy. To avoid the crisis of AMR, we have to fundamentally change our approach. Artificial intelligence (AI) represents a new paradigm to combat AMR. Thus, various AI approaches to this problem have sprung up, some of which may be considered successful cases of domain-specific AI applications in AMR. However, to the best of our knowledge, there is no systematic review illustrating the use of these AI-based applications for AMR. Therefore, this review briefly introduces how to employ AI technology against AMR by using the predictive AMR model, the rational use of antibiotics, antimicrobial peptides (AMPs) and antibiotic combinations, as well as future research directions.

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简介：AbstractThe field of drug-induced sleep endoscopy (DISE) has grown considerably over the last 10~15 years, to now include its use in pediatric patients. In this review article, we outline our approach to the use of this technology in Children with Airway Obstruction, most specifically in the management of children with airway obstruction and known or suspected adenotonsillar enlargement.

简介：AbstractBackground:Despite free diagnosis and treatment for tuberculosis (TB), the costs during treatment impose a significant financial burden on patients and their households. The study sought to identify the determinants for cata-strophic costs among patients with drug-sensitive TB (DSTB) and their households in Kenya.Methods:The data was collected during the 2017 Kenya national patient cost survey from a nationally representative sample (n= 1071). Treatment related costs and productivity losses were estimated. Total costs exceeding 20% of household income were defined as catastrophic and used as the outcome. Multivariable Poisson regression analysis was performed to measure the association between selected individual, household and disease characteristics and occurrence of catastrophic costs. A deterministic sensitivity analysis was carried using different thresholds and the significant predictors were explored.Results:The proportion of catastrophic costs among DSTB patients was 27% (n = 294). Patients with catastrophic costs had higher median productivity losses, 39 h [interquartile range (IQR): 20-104], and total median costs of USD 567 (IQR: 299-1144). The incidence of catastrophic costs had a dose response with household expenditure. The poorest quintile was 6.2 times [95% confidence intervals (CI): 4.0-9.7] more likely to incur catastrophic costs compared to the richest. The prevalence of catastrophic costs decreased with increasing household expenditure quintiles (proportion of catastrophic costs: 59.7%, 32.9%, 23.6%, 15.9%, and 9.5%) from the lowest quintile (Q1) to the highest quintile (Q5). Other determinants included hospitalization: prevalence ratio (PR)= 2.8 (95% CI: 1.8-4.5) and delayed treatment: PR = 1.5 (95% CI: 1.3-1.7). Protective factors included receiving care at a public health facility: PR = 0.8 (95% CI: 0.6-1.0), and a higher body mass index (BMI): PR= 0.97 (95% CI: 0.96-0.98). Pre TB expenditure, hospitalization and BMI were significant predictors in all sensitivity analysis scenarios.Conclusions:There are significant inequities in the occurrence of catastrophic costs. Social protection interventions in addition to existing medical and public health interventions are important to implement for patients most at risk of incurring catastrophic costs.

简介：AbstractMost of the medical and nonmedical research labs, all around the world, are racing against time to produce an effective vaccine or an antiviral medicine for coronavirus disease 2019 (COVID-19). Conventional medicines and novel nano-materials including chemical and herbal-based compounds are all into positive trials toward coronaviruses and other pandemic infections. Among them, natural immune boosters have attracted physicians because of their longevity and reliability for fewer side effects. This is a review article with a detailed picture of an unexplored antiviral source with maximum potency in curing viral infections. Cyanobacteriae have been known for centuries and are rich in secondary metabolites of proteins, biopeptides, and polysaccharides for prominent antiviral action against chest infections. But detailed exploratory research is required to purify, scale-up, and commercialize the pharmacologically active agents from these drug reserves.

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简介：AbstractDue to the coronavirus disease 2019 (COVID-19) pandemic, the development of antiviral drugs has attracted increasing attention. Clinical antiviral drugs show weak solubility, low bioavailability, adverse side effects, or only limited targets. With the advancement of nanotechnology and material science, biosafety nanomaterials have been constructed for drug delivery systems of antiviral disease therapy, such as liposomes, polymers, gold nanoparticles, and graphene. These nanodrug systems can either deliver synthesized antiviral drugs siRNA/miRNA and small molecular compounds, deliver bioactive large molecular drug proteins and mRNA, or show antiviral activity by themselves. Nanodelivery systems could effectively enhance the efficiency of antiviral drugs by increasing drug loading and host cell uptake with a small size and high specific surface area. This review focused on the biosafety nanomaterials used for antiviral therapy and discussed the options for the design of antiviral drugs in the future.

简介：AbstractAntibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.

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简介：AbstractObjective:To determine anatomic relationships and variation of the round window membrane to bony surgical landmarks on computed tomography.Study design:Retrospective imaging review.Methods:100 temporal bone images were evaluated. Direct measurements were obtained for membrane position. Vector distances and angulation from umbo and bony annulus were calculated from image viewer software coordinates.Results:The angle of round window membrane at junction with cochlear basal turn was (42.1 ± 8.6)°. The membrane’s position relative to plane of the facial nerve through facial recess was (14.7 ± 5.2)° posterior from a reference line drawn through facial recess to carotid canal. Regarding transtympanic drug delivery, the round window membrane was directed 4.1 mm superiorly from the inferior annulus and 5.4 mm anteriorly from the posterior annulus. The round window membrane on average was angled superiorly from the inferior annulus (77.1 ± 27.9)° and slightly anteriorly from the posterior annulus (19.1 ± 11.1°). The mean distance of round window membrane from umbo was 4 mm and posteriorly rotated 30° clockwise from a perpendicular drawn from umbo to inferior annulus towards posterior annulus. Together, these measurements approximate the round window membrane in the tympanic membrane’s posteroinferior quadrant.Conclusions:These radiologic measurements demonstrate normal variations seen in round window anatomy relative to facial recess approach and bony tympanic annulus, providing a baseline to assess round window insertion for cochlear implantation and outlines anatomic factors affecting transtympanic drug delivery.

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简介：AbstractThe emergence of mobile Tigecycline-resistant tet(X3) and tet(X4) is believed to be a global threat to public health. Here, we investigated the prevalence of tet(X3) and tet(X4) in our metagenomic data of migratory birds. While tet (X4) was not identified in our samples, tet(X3) was found in two gut microbiomes of bird fecal samples, with 100% amino acid identity of sites 150–387. These results suggest that tet(X3) has been spreading into the environment for a long period of time and that there is an urgent need to control its further transmission.