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PURPOSE P-glycoprotein, encoded by ABCB1 (or MDR1), may contribute to drug resistance in epilepsy by limiting gastrointestinal absorption and brain access to antiseizure medications (ASMs). The study aimed to evaluate the impact of ABCB1 polymorphisms on lacosamide (LCM) serum concentrations in Uygur pediatric epileptic patients. METHODS The serum concentrations of LCM were determined by ultra-performance liquid chromatography, and the ABCB1 polymorphism was analyzed via polymerase chain reaction-fluorescence staining in situ hybridization. The chi-squared test and Fisher's exact test were used to analyze the allelic and genotypic distributions of ABCB1 polymorphisms between the drug-resistant and drug-responsive patient groups. Differences in steady-state and dose-corrected LCM serum concentrations between different genotypes were analyzed using the One-Way Analysis of Variance (ANOVA) and Mann-Whitney test. RESULTS A total of 131 Uygur children with epilepsy were analyzed, and of them, 41 demonstrated drug resistance. The frequency of the GT genotype of ABCB1 G2677T/A was significantly higher in the drug-resistant group than that in the drug-responsive group (p < 0.05, OR = 1.966, 95% CI = 1.060-3.647). Patients with the G2677T/A- AT genotype had a statistically significantly lower concentration-to-dose (CD) value than patients with the G2677T/A-GG genotype (mean: 0.6 ± 0.2 vs 0.8 ± 0.5 μg/ml per mg/kg, p < 0.001). Significantly lower LCM serum concentrations were observed in ABCB1 C3435T CT and TT genotype carriers than those in the CC carriers (p = 0.008 and p = 0.002), and a significantly lower LCM CD value was observed in ABCB1 C3435T CT genotype carriers than that in the CC carriers (p = 0.042). CONCLUSION ABCB1 G2677T/A and C3435T polymorphisms may affect LCM serum concentrations and treatment efficacy in Uygur pediatric patients with epilepsy, leading to drug resistance in pediatric patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19), infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a severe outbreak throughout the world. The host immunity of COVID-19 patients is unknown. METHODS: The routine laboratory tests and host immunity in COVID-19 patients with different severity of illness were compared after patient admission. RESULTS: A total of 65 SARS-CoV-2–positive patients were classified as having mild (n = 30), severe (n = 20), and extremely severe (n = 15) illness. Many routine laboratory tests, such as ferritin, lactate dehydrogenase, and D-dimer, were increased in severe and extremely severe patients. The absolute numbers of CD4(+) T cells, CD8(+) T cells, and B cells were gradually decreased with increased severity of illness. The activation markers such as HLA-DR and CD45RO expressed on CD4(+) and CD8(+) T cells were increased in severe and extremely severe patients compared with mild patients. The costimulatory molecule CD28 had opposite results. The percentage of natural Tregs was decreased in extremely severe patients. The percentage of IFN-γ–producing CD8(+) T cells was increased in both severe and extremely severe patients compared with mild patients. The percentage of IFN-γ–producing CD4(+) T cells was increased in extremely severe patients. IL-2R, IL-6, and IL-10 were all increased in extremely severe patients. The activation of DC and B cells was decreased in extremely severe patients. CONCLUSION: The number and function of T cells are inconsistent in COVID-19 patients. The hyperfunction of CD4(+) and CD8(+) T cells is associated with the pathogenesis of extremely severe SARS-CoV-2 infection. FUNDING: This work was funded by the National Mega Project on Major Infectious Disease Prevention (2017ZX10103005-007) and the Fundamental Research Funds for the Central Universities (2019kfyRCPY098).

Background: Coronavirus Disease-2019 (COVID-19) has caused considerable morbidity and mortality. Hence, there is an urgency to find effective treatment. Tocilizumab, an inhibitor of IL-6, has been widely proposed as a treatment of severely ill patients without robust evidence supporting its use. Methods: In this multicentre, retrospective, cohort study, we included 5,235 adult patients who were admitted to 3 hospitals in Wuhan, China with confirmed COVID-19 from January 20 to March 18, 2020 . 65 patients in tocilizumab group and 130 patients in non-tocilizumab group were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities. Detailed demographic data, comorbidities, radiological and laboratory parameters, complications and treatments were compared between tocilizumab group and non-tocilizumab group. Furthermore, univariable and multivariable Logistic and Cox regression models were used to explore the risk of complications and in-hospital death associated with tocilizumab. Findings: During the follow-up, patients in non-tocilizumab group were more likely to develop into death (42 [32·31%] vs 14 [21·54%]). After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus the non-tocilizumab group (HR=0·47; 95% CI=0·25-0·90; p=0·023). In the multivariable logistic regression model, use of tocilizumab was associated with a lower risk of ARDS (OR=0 · 23; 95% CI=0·11-0·45; p

Background: Multiple organ damage and abnormal inflammation caused by COVID-19 have previously been reported in hospitalized patients. It remains unclear whether these patients can return to a healthy individual three months after discharge and whether there are related sequelae. Methods: We followed up 95 severe/critical patients and 51 mild/moderate ones who recovered from COVID-19 and were discharged from hospital for 3 months. For comparison, 28 asymptomatic COVID-19 recovered individuals and 42 uninfected healthy donors (HDs) were included. At the visit, patients were interviewed and subjected to quality-of-life evaluation (St. George respiratory questionnaire [SGRQ]), pulmonary function tests, chest CT imaging, laboratory examination, detection of immune cells, and cytokine profiling. Findings: At three months, all recovered patients tested negative for nucleic acid of SARS-CoV-2, and most were positive for serum SARS-COV-2 IgG, but few were still positive for serum IgM. The SGRQ scores for the quality-of-life were higher in recovered patients, especially those who had had severe/critical disease. Laboratory test revealed that CRP, LDH and D-dimer, three prevalent risk factors for COVID-19 prognosis in the acute phase, did not recover to the level of uninfected HDs in the convalescence. Immune cells virtually returned to normal levels in patients who recovered from COVID-19, but some pro-inflammatory cytokines, especially chemokines and factors related to vascular injury and angiogenesis, did not return to the level of HDs, and this was especially true of severe/critical recovered patients. CT of the lungs showed that ground-glass opacity (GGO) still lingered as the main manifestation, followed by strip-like fibrosis. Artificial intelligence (AI) analysis indicated that the lesions were most prominent in the lower lobe of right lung, and were mainly found in recovered severe/critical individuals. Abnormal lung function was mainly manifested as restrictive ventilation dysfunction and lowered diffusion capacity, which was more pronounced in severe/critical COVID-19 recovered patients. Overall, the recovery status of the patients varied with the severity of the disease. Interpretation: Decreased physical quality of life, respiratory sequelae (restrictive ventilatory dysfunction, diffusion capacity disorder, and chest CT abnormalities), vascular injury and aberrant cytokine profiles still existed three months after discharge, and were more frequent and conspicuous in severe/critical COVID-19 rehabilitation patients compared to their mild/moderate and asymptomatic counterparts. Trial Registration: This project was registered on the Clinical Trials website (No. NCT04456101) Funding: This study was supported in part by the National Natural Science Special Foundation of China (82041018, 81800094), National Major Science and Technology Projects of China (CN):2019ZX09301001, Ministry of Science and Technology of the People's Republic of China (CN):2020YFC0844300, and the Fundamental Research Funds for the Central Universities, HUST: 2020kfyXGYJ011. Declaration of Interests: The authors have no conflict of interest or financial relationships to disclose. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Ethics Approval Statement: The protocol used in this project has been reviewed and approved by the institutional review boards of Medical Ethics Committee of Wuhan Union Hospital (NO.0271-01). All participants or their surrogates signed informed consent.

Following acute infection, individuals COVID-19 may still shed SARS-CoV-2 RNA. However, limited information is available regarding the active shedding period or whether infectious virus is also shed. Here, we monitored the clinical characteristics and virological features of 38 patients with COVID-19 (long-term carriers) who recovered from the acute disease, but still shed viral RNA for over 3 months. The median carrying history of the long-term carriers was 92 days after the first admission, and the longest carrying history was 118 days. Negative-positive viral RNA-shedding fluctuations were observed. Long-term carriers were mostly elderly people with a history of mild infection. Infectious SARS-CoV-2 was isolated from the sputum, where high level viral RNA was found. All nine full-length genomes of samples obtained in March–April 2020 matched early viral clades circulating in January–February 2020, suggesting that these patients persistently carried SARS-CoV-2 and were not re-infected. IgM and IgG antibodies and neutralizing-antibody profiles were similar between long-term carriers and recovered patients with similar disease courses. In summary, although patients with COVID-19 generated neutralizing antibodies, they may still shed infectious SARS-CoV-2 for over 3 months. These data imply that patients should be monitored after discharge to control future outbreaks.

Better understanding of the role of vegetation and soil on hydraulic resistance of overland flow requires quantitative partition of their interaction. In this paper, a total of 144 hydraulic flume experiments were carried out to investigate the hydraulic characteristics of overland flow. Results show that hydraulic resistance is negatively correlated with Reynolds number on non-simulated vegetated slopes, while positively on vegetated slopes. The law of composite resistance agrees with the dominant resistance, depending on simulated vegetation stem, surface roughness, and discharge. Surface roughness has greater influence on overland flow resistance than vegetation stem when unit discharge is lower than the low-limited critical discharge, while vegetation has a more obvious influence when unit discharge is higher than the upper-limited critical discharge. Combined effects of simulated vegetation and surface roughness are unequal to the sum of the individual effects through t-test, implying the limitation of using linear superposition principle in calculating overland flow resistances under combined effect of roughness elements.

Objective Programmed death-1 (PD-1), an important immunosuppressive molecule, plays a key role in tumor-cell-mediated immune escape. In the present study, we evaluated the effect of PD-1 gene polymorphisms on the risk of developing epithelial ovarian cancer (EOC) and patients' outcomes. Methods A case–control study was performed in 620 EOC patients and 620 control women. Survival data were available for 258 patients who received platinum-based chemotherapy after cytoreductive surgery. Results There were significant differences in the genotype and allele distribution frequencies of the PD-1.1 A/G between cases and controls (P=0.028 and P=0.02, respectively). Compared with the AA genotype, AG and GG genotypes may significantly decrease the risk of developing EOC (OR=0.71, 95%CI=0.54–0.94; OR=0.68, 95%CI=0.50–0.94, respectively). We did not find a significant difference in the genotype distribution frequency of the PD-1.5 C/T between cases and controls (P=0.096), but the frequency of T alleles was significantly lower in the EOC cases than that in the controls (P=0.033). Compared to the carriers with C alleles, the carriers with T alleles were at a significantly decreased risk of developing EOC (OR=0.82, 95%CI=0.69–0.98). Survival analysis showed that the two polymorphisms were not associated with patients' outcomes. Conclusions PD-1 gene polymorphisms may be involved in the development of EOC, but not associated with its clinical outcome in EOC patients among northern Chinese women.

The purpose of this descriptive study was to survey and compare. A sample of 32 people who have a developmental disability were asked to complete five questionnaires (i.e., demographics, sexual orientation, sexual history, recalled childhood gender identity and adult gender identity). Comparisons were made regarding their sexual orientation and gender identity, as well as differences based on their diagnosis that may not have been related to their developmental disability. One case study was presented to aid in better understanding of a transgendered individual. Research results showed that most subjects perceived themselves as heterosexual (87%), followed by those that saw themselves as bisexual or questioning (9.7%) and lastly those that reported that they were interested in same sex partners (3.2%). No differences were found for diagnostic category. Four subjects scored within the range to indicate that they had gender identity dysphoria (GID). Again, no differences were found for diagnostic category. Interesting findings resulted when comparisons were made to other measures and to other studies. It is proposed that it is good practice for professionals to rule out the possibility of ambivalence about gender and sexual issues caused by social and life experiences, especially regarding abuse and the lack of information/education. However, their identities, gender identity and/or sexual identity, must be honored as we do with the general population.

This exploratory study examines the ethical justification that cancer care and dementia care nurses gave for active voluntary euthanasia. A convenient sample of 319 nurses working in seven countries was interviewed using a structured interview guide. The great majority of the nurses could not ethically justify active voluntary euthanasia. Even if the law changed, only 96 of the total sample viewed active voluntary euthanasia as ethical. For those nurses who could ethically justify active voluntary euthanasia, the majority did so because of the patients' suffering.

Superficial burns of the hand leave hardly any deformity after healing, but deep burns, especially those that have not been properly treated or just left to heal without skin grafting, will result in deformities with marked functional disturbances owing to scar contraction. Therefore, proper postburn reconstruction for these deformed hands is urgent and paramount. Since 1955, a total of 416 cases with postburn hand deformity has been admitted into our hospital for reconstruction; 317 patients were male and 99 female; 336 patients were adults and 80 children. Of the total patients, 40% (167 cases) were between 20 and 30 years old. In this chapter, we discuss the principles of treatment and methods adopted in our hospital.