Attention deficit hyperactivity disorder in children with epilepsy: a multicenter cross-sectional analysis in China.

BACKGROUND: The diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) comorbid with epilepsy have been insufficiently addressed in China. We conducted a study in China to investigate the current status, diagnosis, and treatment of ADHD in children to further our understanding of ADHD comorbid with epilepsy, strengthen its management, and improve patients' quality of life. METHODS: We carried out a multicenter cross-sectional survey of children with epilepsy across China between March 2022 and August 2022. We screened all patients for ADHD and compared various demographic and clinical factors between children with and without ADHD, including gender, age, age at epilepsy onset, duration of epilepsy, seizure types, seizure frequency, presence of epileptiform discharges, and treatment status. Our objective was to explore any possible associations between these characteristics and the prevalence of ADHD. RESULTS: Overall, 395 epilepsy patients aged 6-18 years were enrolled. The age at seizure onset and duration of epilepsy ranged from 0.1-18 to 0.5-15 years, respectively. Focal onset seizures were observed in 212 (53.6%) patients, while 293 (76.3%) patients had epileptiform interictal electroencephalogram (EEG) abnormalities. Among the 370 patients treated with anti-seizure medications, 200 (54.1%) had monotherapy. Although 189 (47.8%) patients had ADHD, only 31 received treatment for it, with the inattentive subtype being the most common. ADHD was more common in children undergoing polytherapy compared to those on monotherapy. Additionally, poor seizure control and the presence of epileptiform interictal EEG abnormalities may be associated with a higher prevalence of ADHD. CONCLUSIONS: While the prevalence of ADHD was higher in children with epilepsy than in normal children, the treatment rate was notably low. This highlights the need to give more importance to the diagnosis and treatment of ADHD in children with epilepsy.

Neurological autoantibody prevalence in chronic epilepsy: Clinical and neuropathologic findings.

BACKGROUND: We aimed to explore the prevalence of autoimmune antibodies (Abs) in a large consecutive series with "chronic" epilepsy and without symptoms of autoimmune encephalitis; and to compare the immunopathology of brain tissue from drug-resistant epilepsy (DRE) with and without Abs positivity. METHODS: Neuronal and glial antibodies were detected in the serum of patients who were admitted to the wards of West China Hospital from October 2016 to September 2019 and had epilepsy by cell-based assays and tissue-based assays. RESULTS: Twenty-one (6.8 %) of 328 patients had positive Ab findings for the following: dipeptidyl-peptidase-like protein-6 (n = 7), contactin-associated protein-like 2 (n = 5), glutamic acid decarboxylase 65 (n = 4), gamma aminobutyric acid beta receptor (n = 2), N-methyl-d-aspartate receptor (n = 2), and dopamine D2 receptor (n = 1). Antibodies were detected in 6.9 % (13/187) of epilepsy people with unknown etiology and 5.6 % (8/141) of patients with known etiology, respectively. Among 190 patients with DRE, 14 (7.3 %) patients were Abs-positive. There was no significant difference between individuals with seropositive and seronegative results in clinical manifestations, except that the history of febrile seizure was significantly more frequent in the seropositive group. Moreover, brain samples from 3 patients with Abs-positive DRE (with DPPX in 2 patients, and CASPR2 in 1 patient) and 18 patients with Abs-negative DRE were analyzed for immunopathology. We found higher expression of CD8-positive T-cells in the hippocampus of Abs-positive DRE group. CONCLUSIONS: Neuronal antibodies are potentially involved in the process of "chronic" epilepsy, and CD8-positive T-cells may play an important role in this process.

Cancer of unknown primary site in the mandibular region: A case report.

The diagnosis and treatment of cancer of unknown primary site (CUP) present with difficulties and produce a poor prognosis. The current study presents the case of a patient with CUP in the mandibular region was treated with docetaxel and lobaplatin chemotherapy, and vascular embolization of the tumor. The tumor size was markedly reduced and the patient's quality of life improved following radiotherapy. The present case report is accompanied by a discussion of the literature to contextualize the treatment regimen for patients with CUP. These findings will support current treatment practices, inform oncologists and benefit patients with cancer.

Characterization of the protein expression and localization of hnRNP family members during murine spermatogenesis.

Mammalian testis exhibits remarkably high transcriptome complexity, and spermatogenesis undergoes two periods of transcriptional cessation. These make the RNA-binding proteins (RBPs) the utmost importance during male germ cell development. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a large family of RBPs implicated in many steps of RNA processing; however, their roles in spermatogenesis are largely unknown. Here, we investigated the expression pattern of 12 hnRNP family members in mouse testes and found that most detected members are highly expressed in the testis. Furthermore, we found that most of the detected hnRNP proteins (hnRNPD, hnRNPK, hnRNPQ, hnRNPU, and hnRNPUL1) display the highest signals in the nuclei of pachytene spermatocytes, round spermatids, and Sertoli cells, whereas hnRNPE1 exclusively concentrates in the manchette of elongating spermatids. The expression of these hnRNP proteins showed both similarities and specificity, suggesting their diverse roles in spermatogenesis.

Latent, Early or Late Human Herpes Virus-6B Expression in Adult Mesial Temporal Lobe Epilepsy: Association of Virus Life Cycle with Inflammatory Cytokines in Brain Tissue and Cerebral Spinal Fluid.

BACKGROUND: Human herpes virus-6B (HHV-6B) was suggested as an important etiologic factor of mesial temporal lobe epilepsy, while the mechanism is still unknown. Here, we aimed to analyze antigens representing latent, early and late HHV-6B infection and the association with inflammatory cytokines in brain tissue and cerebral spinal fluid (CSF) from MTLE patients with HHV-6B-positivity. METHODS: Nested polymerase chain reaction (nPCR), real-time PCR, immunohistochemistry (IHC) and suspension bead array for cytokines were performed. RESULTS: Nested polymerase chain reaction (nPCR) in brain tissue revealed HHV-6B DNA in 19 of 49 MTLE patients (39%) and 1 of 19 controls (5%) (P < 0.001), but not in CSF. ICH showed HHV-6B early antigen (P41) positivity in 3 patients (6%), late antigen (gp116/54/64) positivity in 5 patients (10%), latent antigen (U94) positivity in 8 patients (16%), and multiple antigen (early and late or/and latent) positivity in 9 patients (18%). None of these HHV-6B related proteins were found positive in control brain tissue. PCR revealed significant up-regulation of IL-1a, IL-2 and IL-7 mRNA levels in the brain tissue from MTLE patients expressing early antigens compared to those expressing late, latent, multiple antigens, negative antigens and the controls. Suspension bead array of the CSF confirmed significant up-regulation of IL-1a and IL-7 protein expression from MTLE patients expressing early antigens compared to the other groups. CONCLUSIONS: Our finding suggests HHV-6B is a common etiologic agent of MTLE. Different virus life cycle may play an important modifying role in inflammatory biology that warrants further investigation. Though virus DNA is difficult detected in CSF, up-regulation of IL-1a and IL-7 in CSF indicates the two cytokines may be taken as indirect biomarker of HHV-6B infection.

The detection of up-regulated anti-thyroid antibodies and autoimmune thyroid diseases in patients with autoimmune encephalitis: a retrospective study of 221 patients.

OBJECTIVE: To investigate the potential detection rate of anti-thyroid antibodies' (ATAbs) positivity, thyroid dysfunctions, and autoimmune thyroid diseases (AITDs) in autoimmune encephalitis (AE) and to analyze whether thyroid autoimmunity/dysfunction can affect the clinical course of AE. METHODS: Two hundred twenty-one AE patients and 229 age- and sex-matched controls were included in this study. We measured the levels of ATAbs (anti-thyroglobulin antibodies [TgAb], anti-thyroid peroxidase anti-bodies [TPOAb]) and thyroid hormones in all the individuals. In addition, the association of thyroid autoimmunity/dysfunctions with functional outcomes of AE was identified by using logistic regression and Kaplan-Meier analyses. RESULTS: The prevalence of TPOAb-positive and TgAb-positive was significantly higher in AE patients (16.3% and 16.7%, respectively) as compared with controls (9.6% and 7.4%, respectively; P = 0.034 and P = 0.002, respectively). In addition, the free triiodothyronine (fT3) level was significantly lower in AE patients as compared to the controls (P < 0.001). However, the frequency of AITDs (Hashimoto's thyroiditis and Graves' disease) did not significantly differ between AE patients and control subjects. Importantly, low fT3 was found to be associated with poor functional outcomes at the 3-month follow-up in AE. Adjustment of potential confounders did not change the association. However, the presence of ATAbs did not significantly alert the disease course of AE. CONCLUSIONS: ATAbs-positive and/or AITD patients with symptomatic encephalopathy should undergo proper surveillance for AE. Moreover, low fT3 could serve as a possible predictor of poor short-term outcome in AE, thereby suggesting that monitoring of thyroid function in AE may be necessary.

ALDH2, ADCY3 and BCMO1 polymorphisms and lifestyle-induced traits are jointly associated with CAD risk in Chinese Han people.

BACKGROUNDS: To investigate associations of genetic and environmental factors with coronary artery disease (CAD), we collected medical reports, lifestyle details, and blood samples of 2113 individuals, and then used the polymerase chain reaction (PCR)-ligase detection reaction (LDR) to genotype the targeted 102 SNPs. METHODS: We adopted elastic net algorithm to build an association model that considered simultaneously genetic and lifestyle/clinical factors associated with CAD in Chinese Han population. RESULTS: In this study, we developed an all covariates-based model to explain the risk of CAD, which incorporated 8 lifestyle/clinical factors and a gene-score variable calculated from 3 significant SNPs (rs671, rs6751537 and rs11641677), attaining an area under the curve (AUC) value of 0.71. It was found that, in terms of genetic variants, the AA genotype of rs671 in the additive (adjusted odds ratio (OR) = 2.51, p = 0.008) and recessive (adjusted OR = 2.12, p = 0.021) models, the GG genotype of rs6751537 in the additive (adjusted OR = 3.36, p = 0.001) and recessive (adjusted OR = 3.47, p = 0.001) models were associated with increased risk of CAD, while GG genotype of rs11641677 in additive model (adjusted OR = 0.39, p = 0.044) was associated with decreased risk of CAD. In terms of lifestyle/clinical factors, the history of hypertension (unadjusted OR = 2.37, p < 0.001) and dyslipidemia (unadjusted OR = 1.82, p = 0.007), age (unadjusted OR = 1.07, p < 0.001) and waist circumference (unadjusted OR = 1.02, p = 0.05) would significantly increase the risk of CAD, while height (unadjusted OR = 0.97, p = 0.006) and regular intake of chicken (unadjusted OR = 0.78, p = 0.008) reduced the risk of CAD. A significantinteraction was foundbetween rs671 and dyslipidemia (the relative excess risk due to interaction (RERI) = 3.36, p = 0.05). CONCLUSION: In this study, we constructed an association model and identified a set of SNPs and lifestyle/clinical risk factors of CAD in Chinese Han population. By considering both genetic and non-genetic risk factors, the built model may provide implications for CAD pathogenesis and clues for screening tool development in Chinese Han population.

Challenges of patients with epilepsy and measures for improving epilepsy care in western China: A qualitative study.

OBJECTIVE: The aim of this qualitative study was to explore the challenges that patients with epilepsy (PWEs) face and the opportunities or areas where changes in nursing care may improve epilepsy care in western China. METHODS: Semi-structured interviews with open-ended questions based on a review of the literature were conducted at the epilepsy center of a tertiary hospital in western China. A total of 18 PWEs, 18 caregivers and 11 neurology nurses were interviewed by using purposive sampling. The data were transcribed verbatim, and a content analysis was used to conduct the framework analysis. RESULTS: Three key themes were identified, namely, the impact of epilepsy, barriers to epilepsy management, and measures in nursing care for improving epilepsy care. Psychological stress, the side effects of drugs and accidental injury related to seizures were reported to be the main negative impacts on patients. Limited knowledge about epilepsy, poor adherence to therapy, and a lack of effective communication between patients and medical staff were the major barriers to epilepsy management. Strengthening health education, assessing the frequency and type of seizures, screening for psychological disorders and mental intervention, and maintaining continuity of care were identified as crucial measures for nurses to improve epilepsy care. CONCLUSIONS: This study highlights the challenges among PWEs and opportunities for improving the quality of epilepsy care in western China. Limited knowledge and poor drug adherence are the main barriers to epilepsy management, which might be improved by more health education and continuing care provided by nurses. Assessing seizures, screening for psychological disorders and providing appropriate psychological care would help improve epilepsy care.

Gansui-Banxia Decoction extraction inhibits MDSCs accumulation via AKT /STAT3/ERK signaling pathways to regulate antitumor immunity in C57bl/6 mice.

BACKGROUND: Gansui-Banxia Decoction (GSBXD) is a classic formula of traditional Chinese medical (TCM) sage Zhang Zhongjing to treat stagnation of evil heat and obstruction of qi. At present GSBXD is wildly used to treat cancerous ascites, pleural effusion, peritoneal effusion, pericardial effusion, cranial cavity effusion and several types of cancers, such as hepatocellular carcinoma (HCC) and esophageal cancer. Myeloid-derived suppressor cells (MDSCs) are a kind of immature and heterogeneous cells which can suppress lymphocytes activation by forming a suppressive environment. MDSCs accumulation in peripheral blood and tumors are closely related to the cancer stage and low survival rate of clinical patients. The antitumor immune effect of GSBXD has not received widespread attention. PURPOSE: To investigate the effects of GSBXD on MDSCs accumulation and the mediators including AKT/STAT3/ERK signaling pathways. METHODS: The chemical components of GSBXD were analyzed by UHPLC-MS, and the putative pathways of GSBXD based on Network pharmacology were predicted. Mice were vaccinated with Hepatoma 22 (H22) to establish tumor growth model, which were then administrated with GSBXD ethanol extraction (0.49 mg/kg/day, 1.75 mg/kg/day), sorafenib (60 mg/kg) or saline for 14 days. The cell morphology was evaluated by hematoxylin and eosin (H&E) staining, and immunity cells were determined through flowcytometry analysis. The levels of cytokines production in blood were evaluated by using ELISA kits. STAT3, ERK and AKT/mTOR signaling transduction associated proteins were determined by Western blot. RESULTS: GSBXD could inhibit tumor growth and splenomegaly in H22 tumor model mice. Importantly, GSBXD reduced MDSCs accumulation and differentiation, and inhibited proliferation of F4/80+ CD11b+ macrophages and apoptosis of T cells and B cells, and increased the percentage of CD 3- NK1.1+ NK cells. To better understand the active component of GSBXD, the ethanol-extraction powdered GSBXD was prepared and analyzed by UHPLC-MS. Combined with these main chemical compounds, we predicted that the anti-tumor effect of GSBXD mainly mediated PI3K-AKT and RAS-MAPK signal pathways based on Network Pharmacology. Western blot analysis of tumor tissues and MDSCs cells demonstrated that phosphorylation of AKT, ERK and STAT3 were significantly reduced, specially the activation of ERK. The levels of IL-1ß and IFN-γ were significantly decreased by ELISA analysis. CONCLUSION: GSBXD exhibited antitumor immune activity by reducing the accumulation of MDSCs in vivo, which is possible via down-regulation of AKT/STAT3/ERK signaling pathway and suppression of IL-1ß and IFN-γ.

Direct economic burden of patients with tuberculous meningitis in western China.

OBJECTIVE: To estimate the direct economic burden of tuberculous meningitis (TBM) in China for the first time. METHODS: Patients who were first diagnosed with TBM from December 2015 to December 2018 in Western China Hospital were enrolled. We retrospectively collected data on demographic and clinical features, resource utilization, costs, and long-term outcomes. The patients were followed up for 15-53 months. We performed a cost-of-illness study and analyzed the cost contributors with a generalized linear model. RESULTS: In total, the cases of 154 TBM patients (95 males, 59 females, aged 14-82 years) were reviewed. The average total direct cost per person was USD (United States dollars) 9,484 (range 1,822-67,285), with a mean direct medical cost of USD 8,901 (range 1,189-67,049). The average inpatient cost and drug cost after discharge were USD 6,837 (range 845-52,921) and USD 1,967 (range 0-60,423), respectively. The mean direct nonmedical cost was USD 583 (range 33-3,817), which accounted for 6.2% of the total direct cost. The average length of stay (LOS) in hospital was 25.0 days (range 6-152). A total of 117 of the patients (76.0%) had good outcomes (mRS = 0-2). There was no significant difference in the costs, LOS, or outcomes between rural and urban patients. Contributors to total direct cost were definite TBM, fever, coma, seizures, multidrug resistance, hydrocephalus, and poor long-term outcome. CONCLUSIONS: Although the accessibility of medical resources in remote and rural regions has significantly improved in China, the cost of TBM imposes a catastrophic burden on patients.

Universal colorful staining of cancer tissues and normal tissues for histological diagnosis.

The versatility of multicolor imaging of human tissues based on staining with perylene monoimide-mannose conjugates PMI-Man and co-staining with PMI-Man and eosin (P&E) was investigated for human cancer and normal tissues. Staining with PMI-Man or co-staining with PMI-Man and eosin showed a perfect histological morphology both in confocal fluorescence microscopy and light microscopy. This approach provided a universal colorful staining method for cancer tissues and normal tissues.

Selective sensing of DNA and live/dead cells and histological imaging based on a perylene derivative.

A mannose-modified perylene monoimide derivative PMI-Man was developed, which shows highly selective binding to double-stranded DNA molecules, potent live/dead cell imaging, and histological imaging via both confocal and light microscopies. This approach can be used to develop a universal colorful staining method for human tissues for both confocal and light microscopies.

Co-expression of NMDA-receptor subunits NR1, NR2A, and NR2B in dysplastic neurons of teratomas in patients with paraneoplastic NMDA-receptor-encephalitis: a retrospective clinico-pathology study of 159 patients.

OBJECTIVE: To comprehensively describe the pathological features of neurons in patients with ovarian teratomas and paraneoplastic anti-NMDAR encephalitis (anti-NMDARE), emphasizing on NMDA-receptor expression and infiltrating lymphocytes. METHODS: A retrospective study was performed in a large series of 159 patients from the West China Hospital. We retrospectively identified 12 patients with paraneoplastic anti-NMDARE (11 case with ovarian teratomas and 1 case with mixed germ cell tumor), which were compared to 35 patients with teratomas and no encephalitis and to 147 patients with anti-NMDARE and no evidence for tumors. Patient history and outcome were reviewed from the clinical charts and compared between all three groups. Histopathological examination, including double-immunofluorescence of NMDAR subunits and IgG was performed in all teratoma tissues. Magnetic Luminex Assay Human Premixed Multi-Analyte Kit was performed to investigate cytokines profile of CSF. RESULTS: Patients with paraneoplastic anti-NMDARE had a more severe clinical presentation, i.e. they required more mechanical ventilation and intensive care (p < 0.001). Though immunotherapy was initiated earlier in this group, repeated intravenous immunoglobulin administration (IVIG) was more common (p = 0.002) and with higher cerebrospinal fluid (CSF) antibody titres (p = 0.004). Following tumor resection, the outcome did not differ between groups. A peculiar population of floating-frog like dysplastic neurons were observed only in teratomas of patients with paraneoplastic anti-NMDARE, co-expressing NR1, NR2A, NR2B subunits and IgG. Also, CD20 positive B-cells were more common in anti-NMDARE teratomas. In CSF of paraneoplastic anti-NMDARE patients, TNF-α, IL-10 and GM-CSF concentrations were higher than in negative symptom control and VEGF-A and IL-1a were lower than in anti-NMDARE patients (0.25 < p < 0.05). CONCLUSIONS: Patients with teratomas and paraneoplastic anti-NMDARE revealed a cellular population of dysplastic neurons co-expressing NMDAR subunits, which were the potential source of autoantigens triggering anti-NMDARE. Some inflammatory cytokines may be involved in pathogenesis of paraneoplastic anti-NMDARE.

Association of Genetic and Environmental Factors with Non-Alcoholic Fatty Liver Disease in a Chinese Han Population.

Lifestyle choices such as the intake of sweets, history of diseases, and genetic variants seem to play a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). To explore which genetic and environmental factors are associated with NAFLD in a Chinese Han population, we conducted this study. We collected the medical reports, lifestyle details, and blood samples of individuals and used the polymerase chain reaction-ligase detection reaction method to genotype the single-nucleotide polymorphism (SNPs) from the 2113 eligible people. The GG genotype of the additive model of rs7493 in the PON2, the CC genotype of the additive and recessive models of rs7593130 in the ADCY3, together with dyslipidemia, regular intake of egg and sweets and hypertension, increased the risk of NAFLD (adjusted OR > 1, p < 0.05). The TT genotype of the additive and dominant models of rs11583680 in the PCSK9, together with the regular intake of vegetable, reduced the risk of NAFLD (adjusted OR < 1, p < 0.05). In addition, interactions between some variables were found. Eventually, we identified three SNPs and six environmental factors associated with NAFLD. These results provide the theoretical basis for gene and other risk factors screening to prevent NAFLD.

Antitumour properties based on the self-assembly of camptothecin and carbamoylmannose conjugates.

Camptothecin (CPT) and its analogues show potent antitumour activity. However, poor water solubility and severe side effects have restricted their applications in clinical practice. In this paper, a novel self-assembly based on camptothecin and carbamoylmannose conjugates (CPT-Man) was constructed. The self-assembly increased the water solubility of camptothecin to 0.64 mg/ml and antitumour activity. Moreover, CPT-Man could induce obvious cancer cell apoptosis. This work provides a new approach for exploring carbohydrate-modified antitumour properties by self-assembled CPT drugs.

Hydrocephalus in Guillain barre syndrome: A case report and review of the literature.

RATIONALE: Guillian-Barré syndrome (GBS) is a devastating autoimmune disorder characterized by progressive ascending weakness, areflexia with or without autonomic and sensory disturbances. Hydrocephalus is a rare but well-documented complication in patients with GBS. However, due to the rarity of this condition, no treatment guideline for GBS with hydrocephalus is currently available. PATIENT CONCERNS: We describe a 23-year old woman with a history of bilateral limbs pain followed by dysarthria, dysphagia, severe quadriplegia 0/5, areflexia, loss of consciousness and dysautonomia. Neuroimaging studies revealed enlarged lateral ventricles; while Electromyography demonstrated demyelination and nerve injury. Lumbar puncture results showed elevated protein level 2.6 g/L; normal glucose and cell count. DIAGNOSIS: GBS with hydrocephalus. INTERVENTIONS: The patient was started on intravenous immunoglobulin for 5 consecutive days followed by endotracheal intubation and supportive therapy including osmotherapy and CSF drainage. OUTCOMES: At 2 months after admission, the patient stopped choking and had a significant improvement in muscles' strength (grade 4) and pain; then was discharged. On 1 year post-discharge follow-up, CT has revealed a significant improvement of hydrocephalus, and the patient has completely returned to the normal baseline. LESSONS: Respiratory failure is the strongest predictor of concurrent hydrocephalus in patients with GBS. The prognosis of hydrocephalus in patients with GBS is usually good, and it can be medically treated; thereby shunt surgery is rarely required.

Modular synthesis of α-aryl ß-perfluoroalkyl ketones via N-heterocyclic carbene catalysis.

A new general de novo synthesis of pharmaceutically important α-aryl ß-perfluoroalkyl ketones has been disclosed. Compared with trifluoromethylation-initiated radical 1,2-aryl migration of α,α-diaryl allylic alcohols, this protocol employs a new strategy of biomimetic carbene catalysis to assemble alkene, aldehyde and perfluoroalkyl reagents, providing access to products with excellent flexibility of the aryl unit and perfluoroalkyl group. This method also demonstrates excellent functional group compatibility, including some Grignard reagent sensitive groups.

Polymorphisms in arsenic (+ 3 oxidation state) methyltransferase (AS3MT) predict the occurrence of hyperleukocytosis and arsenic metabolism in APL patients treated with As2O3.

Polymorphisms in arsenic (+ 3 oxidation state) methyltransferase (AS3MT) have been shown to be related to interindividual variations in arsenic metabolism and to influence adverse health effects in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (As2O3). The occurrence of hyperleukocytosis with As2O3 treatment seriously affects the early survival rate of APL patients, but no definite explanation for such a complication has been clearly established. To clarify the causes of this situation, AS3MT polymorphisms 14215 (rs3740390), 14458 (rs11191439), 27215 (rs11191446), and 35991 (rs10748835) and profiles of plasma arsenic metabolites were evaluated in a group of 54 newly diagnosed APL patients treated with single-agent As2O3. High-performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) was used to determine the concentrations of plasma arsenic metabolites. Plasma arsenic methylation metabolism capacity was evaluated by the percentage of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), primary methylation index (PMI, MMA/iAs), and secondary methylation index (SMI, DMA/MMA). The results showed that APL patients who developed hyperleukocytosis had a higher plasma iAs%, but a lower MMA% and PMI than those who did not develop hyperleukocytosis during As2O3 treatment. In addition, patients with the AS3MT 14215 (rs3740390) CC genotype had significantly higher plasma iAs% and incidence of hyperleukocytosis, but lower PMI than patients with the CT + TT genotype. Conversely, we did not observe statistically significant associations between the occurrence of hyperleukocytosis and AS3MT 14458 (rs11191439), 27215 (rs11191446), and 35991 (rs10748835) polymorphisms in our study subjects. These results indicated that AS3MT 14215 (rs3740390) might be used as an indicator for predicting the occurrence of hyperleukocytosis in APL patients treated with As2O3.

Effective Renal Clearance and Photothermal Therapy of a Cyclodextrin-Modified Quaterrylene Derivative.

Metabolic clearance of drugs from the body is a key element for future clinical applications. Compared with the liver-bile metabolic route, the renal-urinary route is the most desirable and efficient clearance pathway for practical use in clinical trials and can effectively decrease the long-term risk of unpredictable intracellular catabolism and the potential toxicity to normal organs. However, renal clearable photothermal therapy (PTT) agents were limited. In this paper, a permethyl-ß-cyclodextrin-modified quaterrylene bisimide derivative (QDI-CD) was developed. QDI-CD as a biocompatible molecule could effectively be cleared with the renal clearance efficiency of (67.00 ± 2.37)% at 24 h by the renal-urinary route when administered by tail vein injection. Importantly, the structure of QDI-CD in urine after metabolism does not change. Furthermore, QDI-CD, as a potent photoacoustic and photothermal agent, could effectively be enriched in tumor tissue after 4 h of injection and showed the effective PTT in mice. This work developed a potent organic PTT agent with good renal clearance from the body and with promise for future clinical applications.