Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Sepsis-associated encephalopathy (SAE) is the most common neurological complication of sepsis, with an incidence of up to 70% in sepsis, and contributes to the increased mortality and disability in sepsis. To date, the exact pathogenesis of SAE is not clear. Most of current researches indicated that blood-brain barrier (BBB) dysfunction, active neuroinflammation, glial cell over activation as well as cerebral microcirculation dysfunction contributed to the pathophysiology of SAE. BBB, as a complex cellular structure between the central nervous system and the peripheral system, strictly controls the entrance and discharge of substances and plays an important role in maintaining the balance between biochemical system and immune system of central system. During the progress of sepsis, inflammatory cytokines and reactive oxygen species resulting from peripheral system directly or indirectly resulted in the damage to the integrity and structure of BBB, which helped above species easily enter into the central system. Above these damages caused glial cell activation (microglia and astrocyte), the imbalance of neurotransmitters, mitochondrial dysfunction and neural apoptosis, which also reversely contributed to the damage to the integrity and permeability of BBB via decreasing the expression of tight junctional protein between cells. Therefore, this review focuses on the structural and functional changes of BBB in SAE, and how these changes lead to the development of SAE, in order to seek a BBB-targeted therapy for SAE.

Objective:To explore the effect of core stability training on rehabilitation of patients after lumbar fusion.Methods:From June 2018 to December 2019, 90 patients with lumbar fusion admitted to Wuxi Second Hospital Affiliated to Nanjing Medical University were selected by convenience sampling. The patients were divided into control group and training group according to the method of random number table, with 45 cases in each group. The control group received routine postoperative rehabilitation nursing, while the training group carried out postoperative core stability training nursing. The rehabilitation effects of the two groups were observed.Results:The scores of Numerical Rating Scale (NRS) in the training group were lower than those in the control group at 2, 4, 12 and 24 weeks postoperatively, and the difference were statistical ( P<0.05) . The scores of Oswestry Disability Index (ODI) in the training group 12 and 24 weeks after operation were lower than those in the control group, with statistically significant differences ( P<0.05) . Conclusions:The core stability training nursing is helpful to improve the functional recovery after lumbar fusion, reduce the degree of postoperative pain, and then increase the rehabilitation effect of patients.

Objective: To observe the efficacy of electroacupuncture (EA) in treating dry eye syndromes (DES) and its regulatory effects on patient's quality of life (QOL), anxiety, and depression.Methods: By following a randomized controlled study design, eligible DES patients were allocated to an EA group (EAG) or an acupuncture group (AG). Patients in the AG were intervened by acupuncture alone, while in the EAG, electrical stimulation was applied to Cuanzhu (BL2) and Taiyang (EX-HN5) in addition to the same treatment in the AG. Changes in clinical manifestations, ocular surface disease index (OSDI), Schirmer tear test-1 (STT-1), tear-film break-up time (TF-BUT), cornea fluorescein staining (CFS), and corneal sensitivity (CS) were observed, as well as changes in the short-form 36-item health survey (SF-36) and hospital anxiety and depression scale (HADS) scores. Results: The scores of clinical symptoms, OSDI, and CFS decreased significantly in both EAG and AG when compared with the baseline values (P<0.05), respectively, while the TF-BUT and CS increased significantly (P<0.05), and the tear secretion of patients in the EAG increased (P<0.05). Compared with those before treatment, the scores of physical role functioning, general health perception, emotional role functioning, and mental health of patients in both EAG and AG showed significant increases after treatment (P<0.05), together with a marked decrease in the score of anxiety (P<0.05). Compared with the AG, the EAG obtained a more significant increase in STT-1 (P<0.05).Conclusion: DES patients respond well to both EA and acupuncture treatments, manifested by prolonged TF-BUT and improvement of CS. Meanwhile, the two approaches can improve QOL and reduce anxiety. Furthermore, EA appears more effective in increasing tear secretion than acupuncture alone.

Objective:To compare the clinical and imaging characteristics of patients with stage I coal worker's pneumoconiosis (CWP) .Methods:All 347 cases of coal workers' pneumoconiosis diagnosed in the Third Hospital of Peking University from January 2014 to December 2018 were included in the study. According to different working posts, the subjects were divided into three categories: mining, tunneling and mixing workers. Dust exposure duration, initial dust exposure age, diagnosis age, latency, small shadow shape and lung regions distribution in X-ray chest film of different categories of CWP patients were analyzed.Results:Among the 347 patients, 216 were mining workers (62.2%) , 77 were tunneling workers (22.2%) and 54 were mixing workers (15.6%) . The dust exposure duration of mining, tunneling and mixing workers were (14.5±7.0) , (16.3±8.2) and (19.0±8.8) years, respectively. There are statistically significant differences in dust exposure duration between different categories of workers ( P<0.05) . There were no significant difference in the age of diagnosis, initial dust exposure age and the latency between different categories of workers ( P>0.05) . The X-ray films of mining, tunneling and mixing workers showed small round shadow, accounting for 50.9% (110/216) , 96.1% (74/77) and 96.3% (52/54) respectively. 48.1% (104/216) of the mining workers and 38.9% (21/54) of mixing workers, the distribution of small shadow in chest X-ray films reached middle and lower lung regions, while in the 48.1% (37/77) of the tunneling workers, the distribution of small shadow in chest X-ray films reached lower lung regions. There were differences in above indicators among workers with different categories ( P<0.05) . Conclusion:The dust exposure duration, the shape and the distribution of lung area on chest X-ray films are different in stage I CWP patients of different occupational categories.

Objective:To explore the correlation between occupational gasoline exposure and metabolic syndrome (MS) .Methods:In September 2019, a total of 147 occupational gasoline exposure workers from a oil sales company in Beijing were selected as the observation group by using cluster sampling method, 158 people without gasoline exposure from the company were selected as the control group. Occupational health examination were performed to measure body mass, blood pressure and fasting plasma glucose (FPG) , triglycerides (TG) , high-density lipoprotein cholesterol (HDL-C) and other data. General demographic characteristics, occupational history, past medical history and personal history were analyzed either.Results:The levels of systolic blood pressure, diastolic blood pressure, FPG, TG and BMI in the observation group were all higher than those in the control group ( P<0.05) . The detection rates of MS, obesity and hypertension in the observation group were all higher than those in the control group ( P<0.05) . There were no significant differences in age, gender, working age, drinking, smoking, marital status, HDL-C level, detection rates of abnormal TG and HDL-C between the observation group and the control group ( P>0.05) . The odds ratio ( OR) of MS in the observation group was 1.988 times that in the control group ( P<0.05) . Conclusion:Occupational gasoline exposure is associated with the increasing detection rate of MS.

Objective:To compare the clinical and imaging characteristics of patients with stage I coal worker's pneumoconiosis (CWP) .Methods:All 347 cases of coal workers' pneumoconiosis diagnosed in the Third Hospital of Peking University from January 2014 to December 2018 were included in the study. According to different working posts, the subjects were divided into three categories: mining, tunneling and mixing workers. Dust exposure duration, initial dust exposure age, diagnosis age, latency, small shadow shape and lung regions distribution in X-ray chest film of different categories of CWP patients were analyzed.Results:Among the 347 patients, 216 were mining workers (62.2%) , 77 were tunneling workers (22.2%) and 54 were mixing workers (15.6%) . The dust exposure duration of mining, tunneling and mixing workers were (14.5±7.0) , (16.3±8.2) and (19.0±8.8) years, respectively. There are statistically significant differences in dust exposure duration between different categories of workers ( P<0.05) . There were no significant difference in the age of diagnosis, initial dust exposure age and the latency between different categories of workers ( P>0.05) . The X-ray films of mining, tunneling and mixing workers showed small round shadow, accounting for 50.9% (110/216) , 96.1% (74/77) and 96.3% (52/54) respectively. 48.1% (104/216) of the mining workers and 38.9% (21/54) of mixing workers, the distribution of small shadow in chest X-ray films reached middle and lower lung regions, while in the 48.1% (37/77) of the tunneling workers, the distribution of small shadow in chest X-ray films reached lower lung regions. There were differences in above indicators among workers with different categories ( P<0.05) . Conclusion:The dust exposure duration, the shape and the distribution of lung area on chest X-ray films are different in stage I CWP patients of different occupational categories.

Mosaic variants resulting from postzygotic mutations are prevalent in the human genome and play important roles in human diseases. However, except for cancer-related variants, there is no collection of postzygotic mosaic variants in noncancer disease-related and healthy individuals. Here, we present MosaicBase, a comprehensive database that includes 6698 mosaic variants related to 266 noncancer diseases and 27,991 mosaic variants identified in 422 healthy individuals. Genomic and phenotypic information of each variant was manually extracted and curated from 383 publications. MosaicBase supports the query of variants with Online Mendelian Inheritance in Man (OMIM) entries, genomic coordinates, gene symbols, or Entrez IDs. We also provide an integrated genome browser for users to easily access mosaic variants and their related annotations for any genomic region. By analyzing the variants collected in MosaicBase, we find that mosaic variants that directlycontribute to disease phenotype show features distinct from those of variants in individuals with mild or no phenotypes, in terms of their genomic distribution, mutation signatures, and fraction of mutant cells. MosaicBase will not only assist clinicians in genetic counseling and diagnosis but also provide a useful resource to understand the genomic baseline of postzygotic mutations in the general human population. MosaicBase is publicly available at http://mosaicbase.com/ or http://49.4.21.8:8000.

Objective:To explore the correlation between occupational gasoline exposure and metabolic syndrome (MS) .Methods:In September 2019, a total of 147 occupational gasoline exposure workers from a oil sales company in Beijing were selected as the observation group by using cluster sampling method, 158 people without gasoline exposure from the company were selected as the control group. Occupational health examination were performed to measure body mass, blood pressure and fasting plasma glucose (FPG) , triglycerides (TG) , high-density lipoprotein cholesterol (HDL-C) and other data. General demographic characteristics, occupational history, past medical history and personal history were analyzed either.Results:The levels of systolic blood pressure, diastolic blood pressure, FPG, TG and BMI in the observation group were all higher than those in the control group ( P<0.05) . The detection rates of MS, obesity and hypertension in the observation group were all higher than those in the control group ( P<0.05) . There were no significant differences in age, gender, working age, drinking, smoking, marital status, HDL-C level, detection rates of abnormal TG and HDL-C between the observation group and the control group ( P>0.05) . The odds ratio ( OR) of MS in the observation group was 1.988 times that in the control group ( P<0.05) . Conclusion:Occupational gasoline exposure is associated with the increasing detection rate of MS.

Objective To evaluate the efficacy and safety of nemonoxacin as a combination drug in the treatment of patients with adult community acquired pneumonia (CAP) in the Department of Respiratory. Methods The data of patients with CAP treated with nemonoxacin as an agent in a combined therapy and admitted to Department of Respiratory of Shengjing Hospital of China Medical University from July to October 2018 were retrospectively analyzed. The patients' symptoms, curative effects and adverse reactions were recorded. Results Totally 48 patients with CAP were treated with combined nemonoxacin, including 6 patients with severe pneumonia. All the patients were treated with intravenous drip of β-lactams combined with oral nemonoxacin 500 mg, once a day. After 3 days of treatment, the improvement rate of symptoms was 47.92% (23/48), and 89.58% (43/48) of the patients were cured or improved after (9.83±3.49) days of treatment, no adverse reactions occurred during the period of oral administration;91.67% (44/48) of the patients were satisfied with the effect of medication. Compared with 178 CAP patients who were hospitalized in Department of Respiratory in the same period in 2017, the patients' length of stay in hospital in the present study was shorter (days: 12.52±4.45 vs. 14.53±6.73, P < 0.05). Conclusion As a combination drug, nemonoxacin is a safe and effective treatment for CAP patients admitted to Department of Respiratory, it can better control symptoms, shorten hospitalization time, induce less adverse reactions and its patients' tolerance is good.