Hydrothermal Growth of an Al-Doped α-Ga2O3 Nanorod Array and Its Application in Self-Powered Solar-Blind UV Photodetection Based on a Photoelectrochemical Cell.

Herein, we successfully fabricated an Al-doped α-Ga2O3 nanorod array on FTO using the hydrothermal and post-annealing processes. To the best of our knowledge, it is the first time that an Al-doped α-Ga2O3 nanorod array on FTO has been realized via a much simpler and cheaper way than that based on metal-organic chemical vapor deposition, magnetron sputtering, molecular beam epitaxy, and pulsed laser deposition. And, a self-powered Al-doped α-Ga2O3 nanorod array/FTO photodetector was also realized as a photoanode at 0 V (vs. Ag/AgCl) in a photoelectrochemical (PEC) cell, showing a peak responsivity of 1.46 mA/W at 260 nm. The response speed of the Al-doped device was 0.421 s for rise time, and 0.139 s for decay time under solar-blind UV (260 nm) illumination. Compared with the undoped device, the responsivity of the Al-doped device was ~5.84 times larger, and the response speed was relatively faster. When increasing the biases from 0 V to 1 V, the responsivity, quantum efficiency, and detectivity of the Al-doped device were enhanced from 1.46 mA/W to 2.02 mA/W, from ~0.7% to ~0.96%, and from ~6 × 109 Jones to ~1 × 1010 Jones, respectively, due to the enlarged depletion region. Therefore, Al doping may provide a route to enhance the self-powered photodetection performance of α-Ga2O3 nanorod arrays.

Systematic evaluation of the prevalence of cognitive impairment in elderly patients with diabetes in China.

OBJECTIVE: To systematically evaluate the prevalence of cognitive impairment in elderly patients with diabetes in China. METHODS: Computerized searches of the Chinese Biomedical, WanFang, Vip, Chinese National Knowledge Infrastructure, PubMed, Embase, and the Cochrane Library databases were used to collect research literature on cognitive impairment in older Chinese patients with diabetes from the time of database creation to May 5, 2021. A meta-analysis was performed using the Stata v14.0 software after two investigators independently screened the literature, extracted the information, and evaluated the bias risk of the included studies. RESULTS: A total of 17 studies containing the records of 4380 elderly patients with diabetes were included. The meta-analysis results showed that the incidence of cognitive impairment in elderly patients with diabetes was 48% (95% confidence interval [0.40-0.55]). The results of the subgroup analysis showed that the incidence of cognitive impairment was higher in the elderly population with diabetes who were female, older, with a lower education level, no spouse, living alone, and with a monthly income of less than 2000 yuan. CONCLUSION: Current evidence showed that the incidence of cognitive impairment in elderly patients with diabetes in China was 48%, with a higher incidence in the elderly population who were female, older, with a lower education level, a low income, no spouse, and living alone.

A novel cervix carcinoma biomarker: Pathological-epigenomics, integrated analysis of MethylMix algorithm and pathology for predicting response to cancer immunotherapy.

Herein, A non-invasive pathomics approach was developed to reveal the methylation status in patients with cervical squamous cell carcinoma and predict clinical outcomes and treatment response. Using the MethylMix algorithm, 14 methylation-driven genes were selected for further analysis. We confirmed that methylation-driven genes were differentially expressed in immune, stromal, and tumor cells. In addition, we constructed a methylation-driven model and explored the alterations in immunocyte infiltration between the different models. The methylation-driven subtypes identified in our investigation could effectively predict the clinical outcomes of cervical cancer. To further evaluate the level of methylation-driven patterns, we constructed a risk model with four genes. Significant correlations were observed between the score and immune response markers, including PD1 and CTLA4. Multiple immune infiltration algorithms evaluated the level of immunocyte infiltration between the high- and low-risk groups, while the components of anti-tumor immunocytes in the low-risk group were significantly increased. Subsequently, a total of 205 acquired whole-slide imaging (WSI) images were processed to capture image signatures, and the pathological algorithm was employed to construct an image prediction model based on the risk score classification. The model achieved an area under the curve (AUC) of 0.737 and 0.582 for the training and test datasets, respectively. Moreover, we conducted vitro assays for validation of hub risk gene. The proposed prediction model is a non-invasive method that combines pathomics features and genomic profiles and shows satisfactory performance in predicting patient survival and treatment response. More interdisciplinary fields combining medicine and electronics should be explored in the future.

Abdominopelvic leiomyoma with large ascites: A case report and review of the literature.

BACKGROUND: Leiomyoma of the uterus is relatively common, but uterine leiomyoma of the greater omentum is rare. CASE SUMMARY: Here, we report the case of a 22-year-old woman who presented with a 3 mo history of progressive abdominal distension and a hypervascular abdominopelvic mass. Due to a high serum concentration of CA125, the preoperative diagnosis was unclear. During surgery, 5 L of ascites was removed. An 18.8 cm solid mass, which was pedunculated from the uterine fundus and exhibited complex adhesion to the greater omentum, was removed. The CA125 level was reduced postoperatively, and a pathologic study confirmed that the mass was a leiomyoma that originated in the uterus. CONCLUSION: Uterine leiomyoma can share vessels with the greater omentum. This case highlights the difficulty of diagnosing pseudo-Meigs syndrome and the importance of imaging and laboratory examinations.

Gene mutations of esophageal squamous cell carcinoma based on next-generation sequencing.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers without effective therapy. To explore potential molecular targets in ESCC, we quantified the mutation spectrum and explored the relationship between gene mutation and clinicopathological characteristics and programmed death-ligand 1 (PD-L1) expression. METHODS: Between 2015 and 2019, 29 surgically resected ESCC tissues and adjacent normal tissues from the Fourth Hospital of Hebei Medical University were subjected to targeted next-generation sequencing. The expression levels of PD-L1 were detected by immunohistochemistry. Mutational signatures were extracted from the mutation count matrix by using non-negative matrix factorization. The relationship between detected genomic alterations and clinicopathological characteristics and PD-L1 expression was estimated by Spearman rank correlation analysis. RESULTS: The most frequently mutated gene was TP53 (96.6%, 28/29), followed by NOTCH1 (27.6%, 8/29), EP300 (17.2%, 5/29), and KMT2C (17.2%, 5/29). The most frequently copy number amplified and deleted genes were CCND1/FGF3/FGF4/FGF19 (41.4%, 12/29) and CDKN2A/2B (10.3%, 3/29). By quantifying the contribution of the mutational signatures to the mutation spectrum, we found that the contribution of signature 1, signature 2, signature 10, signature 12, signature 13, and signature 17 was relatively high. Further analysis revealed genetic variants associated with cell cycle, chromatin modification, Notch, and Janus kinase-signal transducer and activator of transcription signaling pathways, which may be key pathways in the development and progression of ESCC. Evaluation of PD-L1 expression in samples showed that 13.8% (4/29) of samples had tumor proportion score ≥1%. 17.2% (5/29) of patients had tumor mutation burden (TMB) above 10 mut/Mb. All samples exhibited microsatellite stability. TMB was significantly associated with lymph node metastasis (r = 0.468, P = 0.010), but not significantly associated with PD-L1 expression (r = 0.246, P = 0.198). There was no significant correlation between PD-L1 expression and detected gene mutations (all P > 0.05). CONCLUSION: Our research initially constructed gene mutation profile related to surgically resected ESCC in high-incidence areas to explore the mechanism underlying ESCC development and potential therapeutic targets.

HPV-16/18 E6-induced APOBEC3B expression associates with proliferation of cervical cancer cells and hypomethylation of Cyclin D1.

Oncogenic high-risk human papillomavirus (HR-HPV) infection causes a majority of cases of cervical cancer and pre-cancerous cervical lesions. However, the mechanisms underlying the direct evolution from HPV-16/18-infected epithelium to cervical intraepithelial neoplasia (CIN) III, which can progress to cervical cancer, remain poorly identified. Here, we performed RNA-seq after laser capture microdissection, and found that APOBEC3B was highly expressed in cervical cancer specimens compared with CIN III with HPV-16/18 infection. Furthermore, immunohistochemical analysis confirmed that high levels of APOBEC3B were correlated with lymph node metastasis in cervical cancer. Subsequent experiments revealed that HPV-16 E6 could upregulate APOBEC3B through direct binding to the promoter of APOBEC3B in cervical cancer cells. Silencing of APOBEC3B by stable short hairpin RNA-mediated knockdown reduced the proliferative capacity of Caski and HeLa cells in vitro and in vivo, but had only a small effect on the migration and invasion of two cervical cancer cell lines. Finally, we identified the changes in gene expression following APOBEC3B silencing in Caski cells by microarray, demonstrating a biological link between APOBEC3B and CCND1 in cervical cancer cells. Importantly, through methyl-capture sequencing and pyrosequencing, APOBEC3B was found to affect the levels of the downstream protein Cyclin D1 (which is encoded by the CCND1 gene) through hypomethylation of the CCND1 promoter. In conclusion, our study supports HPV-16 E6-induced APOBEC3B expression associates with proliferation of cervical cancer cells and hypomethylation of Cyclin D1. Thus, APOBEC3B may be a potential therapeutic target in human cervical cancer.

Could saline irrigation clear all residual common bile duct stones after lithotripsy? A self-controlled prospective cohort study.

BACKGROUND: A previous study showed that irrigation with 100 mL saline reduced residual common bile duct (CBD) stones, which potentially cause recurrent stones after endoscopic retrograde cholangiopancreatography. AIM: To determine whether saline irrigation can improve CBD clearance after lithotripsy. METHODS: This prospective self-controlled study enrolled patients receiving mechanical lithotripsy for large (> 1.2 cm) CBD stones. After occlusion cholangiography confirmed CBD stone clearance, peroral cholangioscopy (POC) was performed to determine clearance scores based on the number of residual stones. The amounts of residual stones spotted via POC were graded on a 5-point scale (score 1, worst; score 5, best). Scores were documented after only stone removal (control) and after irrigation with 50 mL and 100 mL saline, respectively. The stone composition was analyzed using infrared spectroscopy. RESULTS: Between October 2018 and January 2020, 47 patients had CBD clearance scores of 2.4 ± 1.1 without saline irrigation, 3.5 ± 0.7 with 50 mL irrigation, and 4.6 ± 0.6 with 100 mL irrigation (P < 0.001). Multivariate analysis showed that CBD diameter > 15 mm [odds ratio (OR) = 0.08, 95% confidence interval (CI): 0.01-0.49; P = 0.007] and periampullary diverticula (PAD) (OR = 6.51, 95%CI: 1.08-39.21; P = 0.041) were independent risk factors for residual stones. Bilirubin pigment stones constituted the main residual stones found in patients with PAD (P = 0.004). CONCLUSION: Irrigation with 100 mL of saline may not clear all residual CBD stones after lithotripsy, especially in patients with PAD and/or a dilated (> 15 mm) CBD. Pigment residual stones are soft and commonly found in patients with PAD. Additional saline irrigation may be required to remove retained stones.

Clinical characteristics and treatment outcome of COVID-19 patients with stroke in China: A multicenter retrospective study.

OBJECTIVE: Previous studies mainly reported the clinical characteristics of novel coronavirus 2019 (COVID-19) infections, but the research on clinical characteristics and treatment outcomes of COVID-19 patients with stroke is still rare. METHODS: A multi-center retrospective study was conducted at 11 hospitals in 4 provinces of China, and COVID-19 patients with stroke were enrolled from February 24 to May 4, 2020. We analyzed epidemiological, demographic, and clinical characteristics of cases as well as the laboratory test results, treatment regimens and outcomes, and the clinical characteristics and therapeutic outcomes were compared between severe and nonsevere patients, and by age group, respectively. RESULTS: A total of 27 patients [mean age: 66.41 (SD 12.1) years] were enrolled. Among them, 9 (33.3%) were severe patients and 18 (66.7%) were nonsevere patients; 17 (63.0%) were female; 19 (70.4%) were aged 60 years and above. The most common symptoms were fever [19 (70.4%)], fatigue [12 (44.4%)] and cough [11 (40.7%)], respectively. Abnormal laboratory findings of COVID-19 patients with stroke included high levels of C-reactive protein [19 (73.1%)], D-dimer [14 (58.3%)], blood glucose [14 (53.8%)], fibrinogen [13 (50.0%)], and decreased lymphocytes [12 (44.4%)]. Comparing to nonsevere cases with stroke, severe patients with stroke were likely to be older, susceptible to receiving oxygen inhalation, and had more complications (p < 0.05). In addition, there were significant differences in lymphocytes, neutrophils, lactate dehydrogenase, C-reactive protein, creatine kinase between the severe cases and nonsevere cases (p < 0.05). The older patients had a decreased platelet count and elevated fibrinogen, compared with the younger (p < 0.05). All patients (100%) received antiviral treatment, 12 (44.4%) received antibiotics treatment, 26 (96.3%) received Traditional Chinese Medicine (Lung cleansing & detoxifying decoction), and oxygen inhalation was in 18 (66.7%). The median duration of hospitalization was 16 days. By May 4, 2020, a total of 26 (96.3%) patients were cured and discharged, and 1 (3.7%) patients died. CONCLUSION: COVID-19 patients with stroke had poor indicators of coagulation system, and severe and older patients might have a higher risk of complications and unfavorable coagulation system. However, the overall treatment outcome is favorable.

Bevacizumab for non-small cell lung cancer patients with brain metastasis: A meta-analysis.

This study evaluates the efficacy and safety of bevacizumab (BEV) in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (BM) by performing meta-analyses of response and survival indices. Seventeen studies were included. BEV treatment was associated with a lower new BM incidence (hazard ratio: 0.30 [95% confidence interval (CI): 0.14, 0.46]) during follow-up. Disease control rate (DCR) of BEV-treated patients with BM was 91% [95% CI: 85, 95]. However, intracranial DCR was relatively higher (94% [95% CI: 87, 98]) than extracranial DCR (86% [95% CI: 74, 96]). DCR of NSCLC patients with BM was significantly better with BEV than with control therapies (odds ratio: 2.71 [95% CI: 1.26, 5.86], P = 0.01). Progression-free survival (PFS) of BEV-treated patients with and without BM was 7.1 months [95% CI: 6.2, 8.0] and 7.4 months [95% CI: 6.3, 8.4], respectively. Intracranial PFS of BEV-treated patients with BM was 8.0 months [95% CI: 6.0, 10.0]. Overall survival of BEV-treated NSCLC patients with and without BM was 13.5 months [95% CI: 11.4, 15.6] and 12.5 months [95% CI: 10.2, 14.8], respectively. The incidence of bleeding/hemorrhage in the central nervous system was 1% with BEV treatment.

The efficacy and safety of Apatinib mesylate in the treatment of metastatic osteosarcoma patients who progressed after standard therapy and the VEGFR2 gene polymorphism analysis.

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of Apatinib mesylate in the treatment of metastatic osteosarcoma patients who progressed after standard therapy and the VEGFR2 gene polymorphism analysis. METHODS: Designed as a retrospective study, a total of 105 metastatic osteosarcoma patients who progressed after standard therapy were included in this study. The metastatic osteosarcoma patients received 500-750 mg Apatinib mesylate according to body surface area until disease progression or unacceptable toxicity with 28 days one cycle. Overall response was evaluated after two cycles Apatinib treatment, then progression-free survival (PFS) and overall survival (OS) were evaluated, and safety data were recorded. Additionally. peripheral blood and peripheral blood mononuclear cell (PBMC) specimens in the osteosarcoma patients were collected for the genotyping of VEGFR2 genetic variation and mRNA expression, respectively. Analysis on the association between genotype and baseline characteristics and VEGFR2 gene mRNA expression was analyzed. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate analysis was adjusted by Cox regression analysis. RESULTS: The objective response rate (ORR) of the 105 metastatic osteosarcoma patients was 37.14%, disease control rate (DCR) was 77.14%, median PFS was 4.1 months, and median OS was 9.0 months. Regarding the VEGFR2 gene polymorphisms analysis, only - 906 T > C was of clinical significance. The prevalence of - 906 T > C in VEGFR2 among the study population was as follows: TT genotype 62 cases (59.05%), TC genotype 36 cases (34.29%) and CC genotype 7 cases (6.66%), minor allele frequency of - 906 T > C was 0.24. Compared with patients with TC/CC genotype, patients with TT genotype showed longer median PFS (5.0 versus 3.1 months, P = 0.011) and median OS (9.8 versus 7.6 months, P = 0.032). There was no correlation between the polymorphism and adverse reactions. Additionally, the mRNA expression in 69 randomly selected sample indicated that the mRNA expression of VEGFR2 of the patients with CC/TC genotypes were significantly higher than those of the TT genotype patients (P < 0.001). CONCLUSION: Apatinib was safe and effective in the treatment of metastatic osteosarcoma patients who progressed after standard therapy. The clinical outcomes of Apatinib may be influenced by the polymorphism - 906 T > C of VEGFR2 through mediating the mRNA expression of VEGFR2.

DRG Neurons Promote Perineural Invasion of Endometrial Cancer via GluR2.

Background: Perineural invasion (PNI) is correlated with negative prognosis in multiple cancers, but its role in endometrial cancer (EC) is still largely unknown; thus, targeted treatment for nerve infiltration is lacking as well. Methods: The interaction between nerve and EC cells were investigated by in vitro neural invasion assay and transwell coculture system. Then the nerve-related receptor gene glutamate ionotropic receptor AMPA type subunit 2 (GRIA2) was detected in EC tissues and cells using PCR array, western blotting, and immunohistochemistry. The role of GluR2 (gene name GRIA2) on EC proliferation, migration and invasion was evaluated by a GluR2 antagonist and shRNA. At the same time, the neurotransmitter effect on GluR2 (glutamate) from the cocultured conditional medium was measured using high-performance liquid chromatography (HPLC). Results: EC cell line Ishikawa (ISK) showed the ability to migrate along neurites in vitro and the numbers of migrated/invaded EC cells in the DRG neuron coculture group were significantly increased. The expression of GluR2 in EC tissue was found to be higher than that in para-carcinoma tissue. After GluR2 antagonist and GluR2 shRNA treatment, the proliferation, migration and invasion of ISK cells was markedly inhibited. Moreover, the ability of DRG neurons to promote the migration and invasion of ISK cells could also be attenuated by downregulation of GluR2, and the concentration of the neurotransmitter glutamate was notably increased in the coculture conditional medium compared to that in the DRG neuron or ISK cells alone. Conclusions: DRG neurons promote metastasis of EC cells via GluR2, which might be a risk factor for PNI in EC. Moreover, the perineural system may promote tumor invasion and metastasis under certain circumstances.

Clinical Outcomes and Safety of Apatinib Mesylate in the Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer in Patients Who Progressed After Standard Therapy and Analysis of the KDR Gene Polymorphism.

PURPOSE: This study investigated the clinical outcomes and safety of apatinib mesylate in the treatment of advanced non-squamous non-small cell lung cancer (NSCLC) in patients who progressed after standard therapy, and analyzed the kinase insert domain receptor (KDR) gene polymorphism. METHODS: A total of 135 patients with advanced non-squamous NSCLC who received apatinib mesylate were included. Objective response rates were evaluated. Subsequently, progression-free survival (PFS) and overall survival (OS) were assessed and safety data were recorded. Additionally, peripheral blood and biopsy cancer tissue specimens were collected from the patients with NSCLC for the genotyping of the genetic polymorphism and mRNA expression of the KDR gene, respectively. Analysis on the association between genotypes and prognosis was conducted. RESULTS: The objective response rate of the 135 patients with NSCLC was 18.52%, disease control rate was 65.19%, median PFS was 3.95 months, and median OS was 10.05 months. Regarding the KDR gene polymorphism analysis, the distribution of the 4397T>C polymorphism genotypes was in accordance with the Hardy-Weinberg Equilibrium (P=0.868). Moreover, the prognosis analysis indicated that the median PFS of patients with the CC/TC and TT genotypes was 2.80 and 4.80 months, respectively (P=0.002). Furthermore, the median OS of patients with the two genotypes was 9.10 and 10.56 months, respectively (P=0.041). The multivariate Cox regression analysis showed that the TC/CC genotypes were an independent factor for PFS (odds ratio: 1.72, P=0.009). There was no correlation between the polymorphism and adverse reactions. Additionally, the mRNA expression analysis suggested that the mRNA levels of KDR in cancer tissues were significantly different between the TT and TC/CC genotypes (P<0.001). CONCLUSION: The clinical outcomes of treatment with apatinib mesylate for advanced non-squamous NSCLC in patients who progressed after standard therapy may be influenced by the KDR 4397T>C polymorphism through mediation of the mRNA expression of KDR.

Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China.

OBJECTIVE: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. METHODS: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( OR) and 95% confidence interval (95% CI) of the associations between comorbidities (cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19. RESULTS: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. CONCLUSION: Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.

[Down-regulation of HDAC6 Expression Promotes Apoptosis of Human Leukemia K562 Cells].

OBJECTIVE: To study the promoting-apoptosis effect of HDAC6 on the human leukemia cells and its mechanism. METHODS: The siRNA interference technology was used to inhibit the expression of HDAC6 gene, the RT-PCR and Western blot were used to detect the expression of HDAC6 and related signal pathway proteins respectively, the flow cytometry and Hoechest staining were used to detect the apoptosis and morphology changes of K562 cells. RESULTS: Compared with the periphal blood monocyte and bone marrow stromal cells of healthy volunteers, the expression level of HDAC6 in leukemia cell lines was up-regulated significantly(P<0.05); the flow cytometry and Hoechest staining showed that after interference of HDAC6 gene, the apoptosis of K562 cells increased, moreover the cell morphology was changed; the Western blot detection showed that the interfering HDAC6 increased BAX/BCL-2 ratio and cleaved caspase 3 expression, and activated the MAPK, ATK, ERK signaling pathway. CONCLUSION: The interferance of HDAC6 can promote the K562 cell apoptosis, its mechanism may relate with activation of MAPK signaling pathway.

Superior stability of a bifunctional oxygen electrode for primary, rechargeable and flexible Zn-air batteries.

Central to commercializing metal-air batteries is the development of highly efficient and stable catalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). In this study, a composite catalyst with a unique interpenetrating network (denoted as NiCo2O4@MnO2-CNTs-3) was synthesized and exhibited better bifunctional activity (ΔE = 0.87 V) and durability than both Pt/C and Ir/C catalysts. The improved performance arises from three factors: (i) MnO2 promotes the ORR while NiCo2O4 facilitates the OER; (ii) carbon nanotubes improve the electronic conductivity; and (iii) the highly porous structure enables the adsorption-desorption of O2 and enhances the structural stability. As a result, the primary and rechargeable Zn-air battery affords a high power density and specific capacity (722 mA h g-1), an outstanding discharge stability (255 mW cm-2 after 1000 cycles) and a high cycling stability (over 2280 cycles). Electron microscopy and electrochemical analysis revealed that the degradation of the rechargeable Zn-air battery performance resulted from the damage of the air electrode and the hydrogen evolution reaction on the zinc electrode. A flexible Zn-air battery employing a solid-state electrolyte showed an exciting stability (540 cycles) and high power density (85.9 mW cm-2), suggesting that the anion exchange membrane effectively prevents the migration of Zn2+ ions and the deposition of carbonates.

Limited Role of Promoter Methylation of MGMT and C13ORF18 in Triage of Low-Grade Squamous Intraepithelial Lesion.

BACKGROUND: Promoter methylation of MGMT and C13ORF18 has been confirmed as a potential biomarker for early diagnosis of cervical cancer. The aim of this study was to evaluate the performance of MGMT and C13ORF18 promoter methylation for triage of cytology screening samples and explore the potential mechanism. METHODS: Methylation-sensitive high-resolution melting was used to detect promoter methylation of MGMT and C13ORF18 in 124 cervical samples. High-risk human papillomavirus (HR-HPV) was detected by the Digene Hybrid Capture 2®. Gene methylation frequencies in relation to cervical intraepithelial neoplasia (CIN) were analyzed. Frequencies were compared by Chi-square tests. The expression of gene biomarkers and methylation regulators was analyzed by immunohistochemical staining, real-time fluorescence quantitative polymerase chain reaction, and Western blot. RESULTS: For triage of low-grade squamous intraepithelial lesion (LSIL), gene methylation increased specificity from 4.0% of HR-HPV detection to 30.8% of MGMT (χ2 = 9.873, P = 0.002) and to 50.0% of C13ORF18 (χ2 = 21.814, P = 0.001). For triage of atypical squamous cells of undetermined significance, HR-HPV detection had higher positive predictive value of 54.8%. Either MGMT or C13ORF18 methylation combined with HR-HPV increased the negative predictive value to 100.0% (χ2 = 9.757, P = 0.002). There was no relationship between MGMT and C13ORF18 expression and DNA methylation (χ2 = 0.776, P = 0.379 and χ2 = 1.411, P = 0.235, respectively). MBD2 protein level in cervical cancer was relatively lower than normal cervical tissue (t = 4.11, P = 0.006). CONCLUSIONS: HR-HPV detection is the cornerstone for triage setting of CIN. Promoter methylation of MGMT and C13ORF18 plays a limited role in triage of LSIL. Promoter methylation of both genes may not be the causes of gene silence.

Twelve-week ribavirin-free direct-acting antivirals for treatment-experienced Chinese with HCV genotype 1b infection including cirrhotic patients.

BACKGROUND: Treatment-experienced chronic hepatitis C (CHC) genotype (GT) 1b represents a major medical burden in China. We evaluate the efficacy, safety and cost-effectiveness of ribavirin (RBV)-free pan-oral direct-acting antivirals (DAAs) in treatment-experienced Chinese with GT1b CHC, including patients with cirrhosis. METHODS: One hundred forty treatment-experienced GT1b CHC Chinese with and without cirrhosis were included in this study. Ninety-four patients were treated with either daclatasvir (DCV, 60 mg)-sofosbuvir (SOF, 400 mg) (group 1, n = 46) or ledipasvir (LDV, 90 mg)-SOF (400 mg) (group 2, n = 48) for 12 weeks. Forty-six patients treated with pegylated interferon and RBV therapy for 72 weeks were enrolled as the control group (group 3). Patients were followed at 4-weekly intervals till 24 weeks after the end of treatment. RESULTS: All patients in group 1 (46/46, 100 %) and 2 (48/48, 100 %) had achieved sustained virologic response at 24 weeks after the end of treatment (SVR 24), which was significantly higher than that of group 3 (13/46, 28.3 %) (p < 0.001). The SVR 24 rates of cirrhotic patients in group 1 (27/27, 100 %) and 2 (27/27, 100 %) were also significantly higher than that of group 3 (3/25, 12 %) (p < 0.001). Twelve weeks of RBV-free LDV-SOF and DCV-SOF was either cost-saving or cost-effective. Adverse events were significantly lower in group 1 and 2 compared with group 3 (p < 0.001). CONCLUSION: Compared with standard therapies, 12 weeks of RBV-free DAA therapies is highly effective, well tolerated and cost-effective in treatment-experienced Chinese with GT1b CHC including patients with cirrhosis.

Directing Group in Decarboxylative Cross-Coupling: Copper-Catalyzed Site-Selective C-N Bond Formation from Nonactivated Aliphatic Carboxylic Acids.

Copper-catalyzed directed decarboxylative amination of nonactivated aliphatic carboxylic acids is described. This intramolecular C-N bond formation reaction provides efficient access to the synthesis of pyrrolidine and piperidine derivatives as well as the modification of complex natural products. Moreover, this reaction presents excellent site-selectivity in the C-N bond formation step through the use of directing group. Our work can be considered as a big step toward controllable radical decarboxylative carbon-heteroatom cross-coupling.

Will Sofosbuvir/Ledipasvir (Harvoni) Be Cost-Effective and Affordable for Chinese Patients Infected with Hepatitis C Virus? An Economic Analysis Using Real-World Data.

BACKGROUND: Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions. METHODS: A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable. RESULTS: Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US$21,612. It varied by economic regions. The probability of cost-effectiveness was 18% and 47% for treatment-naive and experienced patients, and it ranged from 15% in treatment-naïve patients in Central-China to 64% in treatment-experienced patients in Eastern-China. The price of 12-week sofosbuvir/ledipasvir treatment needs to be reduced by at least 81% to US$18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US$105 to make the regimen affordable in average patients in China. CONCLUSION: Sofosbuvir/ledipasvir regimen is not cost-effective in most Chinese patients with genotype 1b HCV infection. The results vary by economic regions. Drug price of sofosbuvir/ledipasvir needs to be substantially reduced when entering the market in China to ensure the widest accessibility.