Peripheral circulating free DNA (cfDNA) is DNA that is detected in plasma or serum fluid with a cell-free status. For cancer patients, cfDNA not only originates from apoptotic cells but also from necrotic tumor cells and disseminated tumor cells that have escaped into the blood during epithelial-mesenchymal transition. Additionally, cfDNA derived from tumors, also known as circulating tumor DNA (ctDNA), carries tumor-associated genetic and epigenetic changes in cancer patients, which makes ctDNA a potential biomarker for the early diagnosis of tumors, monitory and therapeutic evaluations, and prognostic assessments, among others, for various kinds of cancer. Moreover, analyses of cfDNA chromatin modifications can reflect the heterogeneity of tumors and have potential for predicting tumor drug resistance.

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In this study, we investigated the safety and efficacy in cancer patients of a single intra-tumor injection of recombinant adenovirus vector-mediated herpes simplex virus thymidine kinase gene (AdV/TK) followed by systemic administration of ganciclovir (GCV). In 18 patients with malignant tumors refractory to standard treatment, AdV/TK was injected on day 1 with dose escalation from 2.5 Â 10 11 to 1 Â 10 12 virus particles (VP), and GCV (5 mg kg À1 ) was delivered intravenously every 12 h from days 2 to 15. The most common treatment-related toxicities were transient fever (10/18) and local injection site reaction (10/18), and most adverse events were WHO grade I/II. Anti-adenovirus antibody levels increased continuously during treatment, but anti-HSV antibody levels remained stable. One patient had a PR at the injection site but PD was found in the primary site (lung cancer), one patient with fibrosarcoma of the neck had an MR, five patients had SD, and 10 patients had PD. In conclusion, AdV/TK followed by GCV can be administered safely to Chinese cancer patients, and achieved a local response with few environmental effects. Because the response was localized, single regional tumor relapse, especially after radiation, may be an indication for this suicide gene therapy.

Background. Criteria for antiretroviral treatment (ART) were adjusted to enable early HIV treatment for people living HIV/AIDS (PLHIV) in China in recent years. This study aims to determine how pretreatment waiting time after HIV confirmation affects subsequent adherence and outcomes over the course of treatment. Methods. A retrospective observational cohort study was conducted using treatment data from PLHIV in Yuxi, China, between January 2004 and December 2015. Results. Of 1,663 participants, 348 were delayed testers and mostly initiated treatment within 28 days. In comparison, 1,315 were nondelayed testers and the median pretreatment waiting time was 599 days, but it significantly declined over the study period. Pretreatment CD4 T-cell count drop (every 100 cells/mm3) contributed slowly in CD4 recovery after treatment initiation (8% less, P < 0.01) and increased the risk of poor treatment adherence by 15% (ARR = 1.15, 1.08–1.25). Every 100 days of extensive pretreatment waiting time increased rates of loss to follow-up by 20% (ARR = 1.20, 1.07–1.29) and mortality rate by 11% (ARR = 1.11, 1.06–1.21), based on multivariable Cox regression. Conclusion. Long pretreatment waiting time in PLHIV can lead to higher risk of poor treatment adherence and HIV-related mortality. Current treatment guidelines should be updated to provide ART promptly.

PurposeTo study the characteristic morphology and quantitatively evaluate the eye shape in different types of myopic maculopathy.MethodsA total of 103 eyes from 65 patients with high myopic maculopathy were examined by spectral-domain optical coherence tomography (SD-OCT) and three-dimensional magnetic resonance imaging (3D MRI). The participants were classified into two groups, namely myopic traction maculopathy (MTM) eyes and non-MTM eyes, with SD-OCT imaging. Volume renderings and morphology analysis of the 3D MRI of the eyeball were obtained. Quantitative analysis was achieved in the calculation of vitreous volume and the three-dimensional diameters of the eyeball in three cardinal axes. The eye shape distribution and the diameters of the eyeball were compared between the two groups. Eye shape distribution, vitreous volume, and eyeball diameter were compared between MTM and non-MTM eyes.ResultsThe MTM and non-MTM groups had a total of 68 and 35 eyes, respectively. A significant difference was found in the eye shape distribution (P<0.0001) between MTM and non-MTM eyes. Most of the MTM eyes had undergone a non-uniform expansion of the eyeball, whereas the non-MTM eyes had expanded uniformly. There was no significant difference (P>0.05) in either vitreous volume or other diameters between the two groups.ConclusionsNon-uniform globe expansion and staphyloma formation might play an important role in the pathogenesis of MTM.

ObjectiveTo compare the outcomes of routine provider-initiated HIV testing and counselling (PITC) and oral rapid HIV testing for dental clinic outpatients in a hospital.DesignWe employed a case–control study design and recruited dental outpatients into routine serum-based and oral rapid testing groups. We compared the acceptance, completion and result notification rate between groups.SettingA dental outpatient clinic in the Yuxi People's Hospital, Yunnan.ParticipantsA total of 758 and 816 dental outpatients were enrolled for routine and oral rapid testing, respectively.ResultsThe percentage of participants willing to receive routine HIV testing was 28.1% (95% CI 24.9% to 31.3%) and 96.1% (95% CI 94.8% to 97.4%, χ2=186.4, p<0.001) for the rapid testing. Among accepted participants, the percentage of participants who received HIV testing was 26.8% (95% CI 20.9% to 32.7%) in the routine testing group and 100.0% in the oral rapid HIV testing group (χ2=77.5, p<0.001). About 93.0% of routine testers returned for the test results on the next day, whereas all rapid testers received their test results on the same day (χ2=34.6, p<0.001). These correspond to an overall completion rate of 7.0% (95% CI 5.2% to 8.8%) and 96.1% (95% CI 94.8% to 97.4%, p<0.001), respectively. Among the 545 patients who declined routine serum-based HIV testing, the main reasons included, an unnecessary hassle (254/545, 46.6%), having been previously tested (124/545, 22.8%) and self-perceived low risk of HIV infection (103/545, 18.9%). In contrast, only 32 individuals declined oral rapid testing, and having received a previous test was the primary reason. Three patients in the rapid testing group were later confirmed HIV-positive, yielding an HIV prevalence of 0.38%.ConclusionOral rapid HIV testing is a feasible and efficient approach in a clinical setting.

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Database knob tuning is important to achieve high performance (e.g., high throughput and low latency). However, knob tuning is an NP-hard problem and existing methods have several limitations. First, DBAs cannot tune a lot of database instances on different environments (e.g., different database vendors). Second, traditional machine-learning methods either cannot find good configurations or rely on a lot of high-quality training examples which are rather hard to obtain. Third, they only support coarse-grained tuning (e.g., workload-level tuning) but cannot provide fine-grained tuning (e.g., query-level tuning). To address these problems, we propose a query-aware database tuning system QTune with a deep reinforcement learning (DRL) model, which can efficiently and effectively tune the database configurations. QTune first featurizes the SQL queries by considering rich features of the SQL queries. Then QTune feeds the query features into the DRL model to choose suitable configurations. We propose a Double-State Deep Deterministic Policy Gradient (DS-DDPG) model to enable query-aware database configuration tuning, which utilizes the actor-critic networks to tune the database configurations based on both the query vector and database states. QTune provides three database tuning granularities: query-level, workload-level, and cluster-level tuning. We deployed our techniques onto three real database systems, and experimental results show that QTune achieves high performance and outperforms the state-of-the-art tuning methods.