Gardenia Iridoid Glucosides Protect Against α-Naphthalene Isothiocya-Nate-Induced Cholestatic Rats Through Activation of the FXR-SHP Signaling Pathway.

Introduction: Cholestasis is a common liver disorder that currently has limited treatment options. Gardenia Iridoid Glucosides (GIG) have been found to possess various physiological activities, such as cholagogic, hypoglycemic, antibacterial, and anti-inflammatory effects. The objective of this study was to investigate the effects of GIG on bile acid enterohepatic circulation and explore the underlying mechanism in cholestatic rats. Methods: In order to identify key pathways associated with cholestasis, we conducted Gene Ontology (GO) Enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. In vivo experiments were then performed on alpha-naphthylisothiocyanate (ANIT)-treated rats to assess the impact of GIG. We measured bile flow and various biomarkers including total bilirubin (TB), total bile acids (TBA), total cholesterol (TC), malondialdehyde (MDA), glutamic-pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and total superoxide dismutase (T-SOD) in the serum. We also examined the expression levels of bile salt export pump (BSEP), ATP-binding cassette subfamily B member 4 (ABCB4), far-nesoid X receptor (FXR), small heterodimer partner (SHP), cholesterol 7α-hydroxylase (CYP7A1), and sodium taurocholate cotransporting polypeptide (NTCP) in liver tissue. In vitro experiments were conducted on primary hepatocytes to further investigate the mechanism of action of GIG on the expression of SHP, CYP7A1, NTCP, and FXR. Results: Our in vivo experiments demonstrated that GIG significantly increased bile flow and reduced the levels of TB, TBA, TC, MDA, GPT, and GOT, while increasing T-SOD levels in ANIT-treated rats. Addi-tionally, GIG ameliorated liver tissue damage induced by ANIT, upregulated the expression of BSEP and ABCB4, and modulated the protein expression of FXR, SHP, CYP7A1, and NTCP in model rats. In vitro experiments further revealed that GIG inhibited the expression of SHP, CYP7A1, and NTCP by suppressing the expression of FXR. Conclusion: This study provides new insights into the therapeutic potential of GIG for the treatment of cholestasis. GIG demonstrated beneficial effects on bile acid enterohepatic circulation and liver biomarkers in cholestatic rats. The modulation of FXR and its downstream targets may contribute to the mechanism of action of GIG. These findings highlight the potential of GIG as a therapeutic intervention for cholangitis.

Integrating the atomically separated frontier molecular orbital distribution of two multiple resonance frameworks through a single bond for high-efficiency narrowband emission.

Atomically separated frontier molecular orbital (FMO) distribution plays a crucial role in achieving narrowband emissions for multiple resonance (MR)-type thermally activated delayed fluorescence emitters. Directly peripherally decorating a MR framework with donor or acceptor groups is a common strategy for developing MR emitters. However, this approach always induces bonding features and thus spectral broadening as a side effect. How direct donor/acceptor decoration enhances atomic FMO separation while avoiding bonding features has not been explored. For this aim, two MR derivatives are synthesized by integrating two MR frameworks at different sites. Following resonance alignment, DOBNA-m-CzBN avoids breaking nonbonding FMO features at the single connecting bond and shows enhanced MR characteristics, with a sharp emission at 491 nm and a full width at half maximum (FWHM) of 24 nm/118 meV. Conversely, DOBNA-p-CzBN emerges as a bonding feature due to its continuous π-conjugation extension, with a broadened FWHM of 26 nm/132 meV peaking at 497 nm. Impressively, both emitters exhibit outstanding external quantum efficiencies of 37.8-38.6% in organic light-emitting diodes (OLEDs), demonstrating improved performance with rigid acceptor decoration. Distinctly, the electroluminescence of DOBNA-m-CzBN shows a narrower FWHM than that of DOBNA-p-CzBN. This work for the first time reports the enhancement of atomic FMO separation for MR emitters via peripheral decoration through a single bond and provides a more comprehensive illustration for further development of MR emitters.

Autophagy and its therapeutic potential in diabetic nephropathy.

Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is the most significant microvascular complication of diabetes and poses a severe public health concern due to a lack of effective clinical treatments. Autophagy is a lysosomal process that degrades damaged proteins and organelles to preserve cellular homeostasis. Emerging studies have shown that disorder in autophagy results in the accumulation of damaged proteins and organelles in diabetic renal cells and promotes the development of DN. Autophagy is regulated by nutrient-sensing pathways including AMPK, mTOR, and Sirt1, and several intracellular stress signaling pathways such as oxidative stress and endoplasmic reticulum stress. An abnormal nutritional status and excess cellular stresses caused by diabetes-related metabolic disorders disturb the autophagic flux, leading to cellular dysfunction and DN. Here, we summarized the role of autophagy in DN focusing on signaling pathways to modulate autophagy and therapeutic interferences of autophagy in DN.

Nocardia cyriacigeorgica infection in a patient with repeated fever and CD4+ T cell deficiency: A case report.

BACKGROUND: Nocardia pneumonia shares similar imaging and clinical features with pulmonary tuberculosis and lung neoplasms, but the treatment and anti-infective medication are completely different. Here, we report a case of pulmonary nocardiosis caused by Nocardia cyriacigeorgica (N. cyriacigeorgica), which was misdiagnosed as community-acquired pneumonia (CAP) with repeated fever. CASE SUMMARY: A 55-year-old female was diagnosed with community-acquired pneumonia in the local hospital because of repeated fever and chest pain for two months. After the anti-infection treatment failed in the local hospital, the patient came to our hospital for further treatment. Enhanced computed tomography showed multiple patchy, nodular and strip-shaped high-density shadows in both lungs. A routine haematological examination was performed and showed abnormalities in CD19+ B cells and CD4+ T cells. Positive acid-fast bifurcating filaments and branching gram-positive rods were observed in the bronchoalveolar lavage fluid of the patient under an oil microscope, which was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry as N. cyriacigeorgica. The patient's condition quickly improved after taking 0.96 g compound sulfamethoxazole tablets three times a day. CONCLUSION: The antibiotic treatment of Nocardia pneumonia is different from that of common CAP. Attention should be given to the pathogenic examination results of patients with recurrent fever. Nocardia pneumonia is an opportunistic infection. Patients with CD4+ T-cell deficiency should be aware of Nocardia infection.

The protection of luteolin against diabetic cardiomyopathy in rats is related to reversing JNK-suppressed autophagy.

Increasing evidence has shown that impaired autophagy dramatically causes myocardial hypertrophy and fibrosis in the diabetic heart, ultimately leading to diabetic cardiomyopathy (DCM). Luteolin has been reported to effectively attenuate diabetic cardiovascular injury by inhibiting oxidative stress and alleviate sepsis-induced myocardial injury by enhancing autophagy. However, whether luteolin can reduce DCM through activating autophagy and the underlying mechanism remain unclear. Here, reversing the c-Jun N-terminal kinase (JNK)-suppressed autophagy pathway by which luteolin attenuates DCM was explored. Male Sprague-Dawley rats were injected with streptozotocin to induce diabetes. After 6 weeks of diabetes, rats were treated with luteolin (50, 100 and 200 mg kg-1, i.g.) for 4 weeks. Histological and functional alterations in the diabetic heart were determined using HE staining, Masson staining and echocardiography. The expressions of myocardial miR-221, JNK, and c-Jun and autophagic vesicles in diabetes were evaluated by quantitative PCR, Western blotting and electron microscopy. Luteolin significantly improved cardiac function and attenuated myocardial disorganization and fibrosis in the diabetic rat accompanying the dose-dependent down-regulation of JNK, c-Jun, miR-221 and p62, increase of LC3-II/I and autophagic vesicles, and decrease of mitochondrial swelling in the diabetic heart. These data suggest that the protection of luteolin against DCM, at least, is related to suppressing JNK/c-Jun-regulated miR-221 and the subsequent blockage of autophagy.

Quantitative and site-specific detection of inosine modification in RNA by acrylonitrile labeling-mediated elongation stalling.

RNA molecules contain diverse modifications that play crucial roles in a wide variety of biological processes. Inosine is one of the most prevalent modifications in RNA and dysregulation of inosine is correlated with many human diseases. Herein, we established an acrylonitrile labeling-mediated elongation stalling (ALES) method for quantitative and site-specific detection of inosine in RNA from biological samples. In ALES method, inosine is selectively cyanoethylated with acrylonitrile to form N1-cyanoethylinosine (ce1I) through a Michael addition reaction. The N1-cyanoethyl group of ce1I compromises the hydrogen bond between ce1I and other nucleobases, leading to the stalling of reverse transcription at original inosine site. This specific property of stalling at inosine site could be evaluated by subsequent real-time quantitative PCR (qPCR). With the proposed ALES method, we found the significantly increased level of inosine at position Chr1:63117284 of Ino80dos RNA of multiple tissues from sleep-deprived mice compared to the control mice. This is the first report on the investigation of inosine modification in sleep-deprived mice, which may open up new direction for deciphering insomnia from RNA modifications. In addition, we found the decreased level of inosine at GluA2 Q/R site (Chr4:157336723) in glioma tissues, indicating the decreased level of inosine at GluA2 Q/R site may serve as potential indicator for the diagnosis of glioma. Taken together, the proposed ALES method is capable of quantitative and site-specific detection of inosine in RNA, which provides a valuable tool to uncover the functions of inosine in human diseases.

Profile of crosstalk between glucose and lipid metabolic disturbance and diabetic cardiomyopathy: Inflammation and oxidative stress.

In recent years, the risk, such as hypertension, obesity and diabetes mellitus, of cardiovascular diseases has been increasing explosively with the development of living conditions and the expansion of social psychological pressure. The disturbance of glucose and lipid metabolism contributes to both collapse of myocardial structure and cardiac dysfunction, which ultimately leads to diabetic cardiomyopathy. The pathogenesis of diabetic cardiomyopathy is multifactorial, including inflammatory cascade activation, oxidative/nitrative stress, and the following impaired Ca2+ handling induced by insulin resistance/hyperinsulinemia, hyperglycemia, hyperlipidemia in diabetes. Some key alterations of cellular signaling network, such as translocation of CD36 to sarcolemma, activation of NLRP3 inflammasome, up-regulation of AGE/RAGE system, and disequilibrium of micro-RNA, mediate diabetic oxidative stress/inflammation related myocardial remodeling and ventricular dysfunction in the context of glucose and lipid metabolic disturbance. Here, we summarized the detailed oxidative stress/inflammation network by which the abnormality of glucose and lipid metabolism facilitates diabetic cardiomyopathy.

The Hepatoprotective Effect of Leonurine Hydrochloride Against Alcoholic Liver Disease Based on Transcriptomic and Metabolomic Analysis.

Excessive alcohol consumption can eventually progress to alcoholic liver disease (ALD). The underlying mechanism of ALD toxicity is primarily associated with oxidative damage. Many alkaloids have been reported to possess potential antioxidative efficacy, while the mechanism of their hepatoprotective activity against ALD is still not clear. In this study, eight alkaloids were selected from a monomer library of Traditional Chinese Medicine and evaluated for their antioxidant activity against ALD by the evaluation of Glutathione (GSH) and Malondialdehyde (MDA). The result suggested that Leonurine hydrochloride (LH) was a potent antioxidant that could reduce alcoholic liver damage. To further investigate the underlying mechanism of LH against ALD, the molecular pathway induced by LH was identified by RNA-seq analyses. Transcriptome data revealed the principal mechanism for the protective effect of LH against ALD might be attributed to the differentially expressed genes (DEGs) of PI3K-AKT, AMPK, and HIF-1 signaling pathways involved in the lipid metabolism. Given the hepatoprotective mechanism of LH is involved in lipid metabolism, the lipid metabolism induced by LH was further analyzed by UHPLC-MS/MS. Metabolome analysis indicated that LH significantly regulated glycerophospholipid metabolism including phosphatidylcholine, 1-acyl-sn-glycero-3-phosphocholine, phosphatidylethanolamine and 1-acyl-sn-glycero-3-phosphoethanolamine in the liver. Overall, this study revealed that the hepatoprotective mechanism of LH against alcoholic liver damage might be associated with the genes involved in glycerophospholipid metabolism.

Factors Affecting the Risk of Brain Metastasis in Limited-Stage Small Cell Lung Cancer After Prophylactic Cranial Irradiation.

Background: Prophylactic cranial irradiation (PCI) can reduce the risk of brain metastases (BM) and improve overall survival (OS) in patients with limited-stage small cell lung cancer (LS-SCLC) after partial or complete response to primary therapy. However, some SCLC patients still develop BM after PCI. This study aimed to evaluate the risk factors of BM in patients with LS-SCLC after PCI and identify characteristics of patients who may not benefit from PCI. Methods and Materials: We identified 550 patients with LS-SCLC who received chemoradiotherapy at Zhejiang Cancer Hospital between 2002 and 2017. All patients received PCI. Kaplan-Meier analyses and Cox regression analyses were used to identify factors affecting OS and brain metastasis-free survival (BMFS). Results: For this patient population, the median survival time was 27.9 months, and the 5-year OS rate was 31%. The median survival time was 24.9 months (95% CI: 22.6-27.2 months), and 30.2 months (95% CI: 24.2-36.3 months) in patients with or without BM (P = 0.000). The overall BM rate was 15.6% (86/550). The frequency of BM in patients with pathologic stages I, II, and III were 9.3% (4/43), 13.4% (7/52), and 16.5% (75/455). The patients with tumors ≥5 cm had an increased risk of BM (HR: 1.781, 95% CI: 1.044-3.039, P = 0.034) but not death (HR: 1.126, 95% CI: 0.925-1.663, P = 0.182). The median survival time among patients <60 years was significantly longer than patients ≥60 years (34.9 months vs 24.6 months, P = 0.001); however, the difference in the BM risk between the two groups was not statistically significant. Conclusion: PCI remains the standard of care for LS-SCLC patients who achieve complete or partial response after completion of chemoradiotherapy. However, patients with tumors ≥5 cm may have a higher risk of developing BM after PCI.

First report of powdery mildew caused by Erysiphe euonymicola on wintercreeper (Euonymus fortunei) in China.

Wintercreeper (Euonymus fortunei) is an evergreen shrub, a semi climbing plants with very strong vitality. It can tolerate a broad range of environmental conditions varying from full sun to deep shade. So, wintercreeper is a good groundcover plants and tree species of vertical greening. It is widely used in urban greening in China. In May 2021, severe powdery mildew signs were found on wintercreeper plant in a garden of Luohe cities of Henan province, China. Approximately 40% of leaves on a plant were symptomatic, and about 60% of the plants were infected. Powdery mildew colonies appeared as white spots on the upper surface of the leaf and stem of the plants in the initial stage. Later, mycelial growth was amphigenous, thick, forming irregular white patches, effused to cover the entire leaf surface. At last, leaves turned yellow and senescence. One representative voucher specimen was deposited at the herbarium of Shangqiu Normal University (SQNU), Shangqiu, China, under the accession number of EF02. Conidiophores arising terminally from the mother cell, mostly central, erect, straight, 40.7 to 67.7µm (average 49.1µm) 6.1 to 8.5µm (average 7.5µm) (n=30) composed of 3 to 4 cells and produced conidia singly. Conidia were obovoid-ellipsoid, apex rounded, base subtruncate, ends truncate or subtruncate, long 26.1 to 36.4µm (average 30.7µm) and width 9.9 to 16.0µm (average 11.8µm) (n=30). No chasmothecia were observed. The morphological characteristics and measurements were consistent with those of Erysiphe euonymicola (Braun and Cook 2012). The internal transcribed spacer regions of EF02 were amplified using primers ITS1/ITS4, and sequences directly. The obtained sequence of 648 bp was deposited in GenBank (accession no. OM304857). The isolate (EF02) was 99.83% similarity with E. euonymicola on E. fortunei var. radicans (KM361621 from Korea) (Lee et al. 2015), 99.23% with E. euonymicola on E. fortunei (MT510003 from USA), 99.23% with E. euonymicola on E. japonicus (LC270841and LC270834 from Azerbaijan, AB250228 from Japan ). The domains D1 and D2 of the 28S rDNA obtained 619 bp sequences from the powdery mildew of isolate EF02 with primer NL1/NL4, deposited in GenBank (OM302187). A NCBI BLAST search of the EF02 isolate showed 100% similarity with 28S rDNA sequence of E. euonymicola on E. japonicus (AB250230 from Japan) (Limkaisang et al. 2006), and 28S phylogenetic tree analysis EF02 isolate is located in the same branch as E. euonymicola. The pathogenicity was confirmed by gently pressing the infected leaves onto five healthy plants. Five uninoculated plants served as controls. Ten inoculated and non-inoculated plants were placed in different growth chambers with 14-h photoperiod at 22±2°C and 60% of relative humidity. After 11 to 13 days, powdery mildew colonies developed on inoculated plants. Non-inoculated control plants did not show powdery mildew symptoms. The fungus on inoculated leaves was morphologically identical to that first observed in the field. Although E. euonymi-japonici (synonym E. euonymicola) has been recorded on E. japonicus in China (Li et al. 2011), this is the first report of powdery mildew caused by E. euonymicola on E. fortunei in China. It could become a threat to the widespread planting of wintercreeper, Similar report has been in Korea (Lee, C. K., et al. 2015).

Novel dual methylation of cytidines in the RNA of mammals.

RNA modifications play critical roles in regulating a variety of physiological processes. Methylation is the most prevalent modification occurring in RNA. Three isomeric cytidine methylation modifications have been reported in RNA, including 3-methylcytidine (m3C), N4-methylcytidine (m4C), and 5-methylcytidine (m5C), in mammals. Aside from the single methylation on the nucleobase of cytidines, dual methylation modifications occurring in both the 2' hydroxyl of ribose and the nucleobase of cytidines also have been reported, including N4,2'-O-dimethylcytidine (m4Cm) and 5,2'-O-dimethylcytidine (m5Cm). m4Cm has been found in the 16S rRNA of E. coli, while m5Cm has been found in the tRNA of terminal thermophilic archaea and mammals. However, unlike m4Cm and m5Cm, the presumed dual methylation of 3,2'-O-dimethylcytidine (m3Cm) has never been discovered in living organisms. Thus, the presence of m3Cm in RNA remains an open question. In the current study, we synthesized m3Cm and established a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method to determine the dimethylation of cytidines, m3Cm, m4Cm and m5Cm. Under optimized analytical conditions, m3Cm, m4Cm and m5Cm can be clearly distinguished. Using the method, we discovered the existence of m3Cm in the RNA of mammals. The identified m3Cm is a novel modification that hasn't been reported in the three-domain system, including archaea, bacteria, and eukaryotes. We confirmed that m3Cm mainly existed in the small RNA (<200 nt) of mammals. In addition, we identified, for the first time, the presence of m4Cm in the 18S rRNA of mammalian cells. The stable isotope tracing monitored by mass spectrometry demonstrated that S-adenosyl-l-methionine was a methyl donor for all three dimethylations of cytidines in RNA. The discovery of m3Cm broadens the diversity of RNA modifications in living organisms. In addition, the discovery of m3Cm and m4Cm in mammals opens new directions in understanding RNA modification-mediated RNA processing and gene expression regulation.

Enhancement of photo-driven biomethanation under visible light by nano-engineering of Rhodopseudomonas palustris.

Biomethanation is of great interest as it can transform CO2 to methane under ambient conditions. In particular, genetically engineered bacterium of Rhodopseudomonas palustris showed great promise for one-step biomethanation powered by solar energy, which is attractive for CO2 fixation as well as solar energy storage. However, biomethanation with R. palustris under visible light is inefficient due to its poor visible light response. In this study, CdS quantum dots with excellent visible light response were prepared and R. palustris/CdS hybrid cells were constructed. Interestingly, this bio-nano-hybrid cells showed high cell viability without significant cell damage, and the biomethanation performance of was enhanced about ~ 79% compared to that of the bare R. palustris cells. Moreover, the effects of different parameters on the methane production of this bio-nano-hybrid cells were determined, and the methane production rate was further improved by parameter optimization. This work demonstrated an efficient approach to reinforce the biomethanation of bacteria under unfavorable light wavelength, which would be helpful to extend the light spectra for photo-driven biomethanation.

Correction to: Timing of thoracic radiotherapy is more important than dose intensification in patients with limited-stage small cell lung cancer: a parallel comparison of two prospective studies.

Correction to: Strahlenther Onkol 2019 https://doi.org/10.1007/s00066-019-01539-1 The original version of this article unfortunately contained a mistake. The correct version of the funding information are given ….

Quantification and Single-Base Resolution Analysis of N1-Methyladenosine in mRNA by Ligation-Assisted Differentiation.

RNA modification, such as N1-methyladenosine (m1A), affects the secondary structure of RNA and its ability to recognize specific reader proteins. Methods for detecting site-specific m1A are in demand. We report here a ligation-assisted differentiation approach for quantitative detection of m1A in mRNA with single-base resolution. The methyl group in m1A disrupts the Watson-Crick base pairing with uridine, resulting in a lower ligation efficiency of certain ligases and lower amounts of ligation products. Detection of the ligation products using quantitative real-time PCR provided site-specific evaluation of m1A. We first screened appropriate ligase and found that T3 DNA ligase offered the best discrimination between m1A and adenosine. We successfully detected and quantified m1A at position 1674 of bromodomain containing 2 (BRD2) mRNA from HEK293T cells. In lung carcinoma tissues, the level of m1A at position 1674 of BRD2 mRNA was significantly decreased compared to the tumor-adjacent normal tissues, suggesting that site-specific m1A may be involved in carcinogenesis.

Timing of thoracic radiotherapy is more important than dose intensification in patients with limited-stage small cell lung cancer: a parallel comparison of two prospective studies.

PURPOSE: The optimal radiotherapy dose/fraction for limited-stage small cell lung cancer (SCLC) is undefined. Our objectives were to compare efficacy between hyperfractionated thoracic radiotherapy (TRT; 1.5 Gy 2 times per day [bid] in 30 fractions) and hypofractionated TRT (2.5 Gy once per day [qd] in 22 fractions), and to explore prognostic factors influencing the prognosis, such as the timing of TRT. METHODS: Patients enrolled in two independent prospective studies were combined and analyzed. The primary endpoint was local/regional control (LRC). The prognosis was analyzed using the Cox proportional hazards regression model. RESULTS: Ninety-two and 96 patients were treated with hyperfractionated TRT and hypofractionated TRT, respectively. The 1­ and 2­year LRC rates of the two arms were 82.1 and 60.7%, and 84.9 and 68.8% (P = 0.27), respectively. The median overall survival (OS) times (months) were 28.3 (95% confidence interval, CI 16.4-40.1) and 22.0 (95% CI 16.4-27.5), while the 1­year, 3­year, and 5­year OS rates were 85.2, 40.8, and 27.1%, and 76.9, 34.3, and 26.8% (P = 0.37), respectively. Using a multivariate Cox regression study, time (days) from the initiation of chemotherapy to TRT (TCT) ≤43 was associated with improved LRC (hazard radio, HR 0.39, 95% CI 0.20-0.76; P = 0.005). Time (days) from the start of chemotherapy to the end of TRT (SER) ≤63 (HR 0.50, 95% CI 0.32-0.80; P = 0.003) and prophylactic cranial irradiation (HR 0.43; 95% CI 0.29-0.63; P = 0.000) were favorably related to OS. Grade 2/3 acute radiation esophagitis was observed in 37.0 and 17.7% of patients in the hyperfractionated and hypofractionated arms, respectively (P = 0.003). CONCLUSION: Both hyperfractionated and hypofractionated TRT schedules achieved good LRC and OS for patients with limited-stage SCLC in this study. Keeping TCT ≤43 and SER ≤63 resulted in a better prognosis. The incidence of acute esophagitis was significantly higher in the hyperfractionated arm.

Final report of a prospective randomized study on thoracic radiotherapy target volume for limited-stage small cell lung cancer with radiation dosimetric analyses.

BACKGROUND: The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented. METHODS: After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded. RESULTS: The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy. CONCLUSIONS: TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC.

Comparison Of Long Term Results Between Matched Chemoradiotherapy And Surgery For Limited Stage Small Cell Lung Cancer.

PURPOSE: To compare the efficacy of chemoradiotherapy or surgery for limited-stage small cell lung cancer (SCLC). PATIENTS AND METHODS: A retrospective analysis was performed on 138 patients with limited-stage SCLC who received surgery (69 patients) or chemoradiotherapy (69 patients) between January 2000 and September 2016 in Zhejiang Cancer Hospital. Patients of the chemoradiotherapy group were selected by using "pair-matched case-control" methodology from a cohort of 503 patients who received chemoradiotherapy. RESULTS: The major prognostic factors, including T, N stage, treatment duration, age, gender, and whether or not they received prophylactic cranial irradiation were well balanced between two groups. The median overall survival (OS) time and 5-year OS rate were 37.1 months and 45.0% in the surgical group vs 45.0 months and 45.0% in the chemoradiotherapy group (P=0.846). The median progression-free survival (PFS) time and 5-year PFS rate were 27.1 months and 37.8% vs 36.2 months and 40.0%, respectively, in the two groups (P=0.610). The 5-year OS rate (62.3% vs 40.1%, P=0.038) and 5-year PFS rate (80.1% vs 40.1%, P=0.048) in the surgical group were significantly higher than those of the chemoradiotherapy group in patients with stage I disease. The 5-year OS rate (41.2% vs 50.6%, P=0.946) and 5-year PFS rate (64.7% vs 42.1%, P=0.280) of surgery for stage II SCLC were comparable to chemoradiotherapy. As for stage III SCLC, compared with the surgical group, the chemoradiotherapy group had a better 5-year OS trend (25.1% vs 47.6%, P=0.220), but the difference did not reach statistical significance. CONCLUSION: Surgery could confer survival benefits in patients with p-stage I disease, but not in patients with p-stage II and III disease.

The impact of prophylactic cranial irradiation for post-operative patients with limited stage small cell lung cancer.

To evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients who received definitive surgery for surgically resected small cell lung cancer (SCLC).A retrospective analysis was performed on post-operative SCLC patients treated in Zhejiang Cancer Hospital from January 2003 to December 2015. According to the treatment modality, patients were allocated to PCI group and non-PCI group. Univariate survival analysis was performed by the Kaplan-Meier method. Multivariate survival analysis was performed by a Cox proportional hazards model.A total of 52 patients were included for analysis, among which, 19 patients were in PCI group and 33 were in non-PCI group. Multivariate analysis revealed that PCI (HR = .330; P = .041) was an independently favorable prognostic factor for the overall survival. The median overall survival (OS) time was 32.9 months in PCI group, and 20.4 months in non-PCI group. The 2-year OS rates were 78.0% and 38.0% in PCI and non-PCI group respectively (P = .023). The brain metastasis-free survival (BMFS) rate at 2-year in PCI group was significantly higher than those of non-PCI group (89.0% vs 53.0%, respectively, P = .026).In conclusion, PCI might be suggested for limited SCLC patients who received definitive surgery.

Nickel-tungsten carbide catalysts for the production of 2,5-dimethylfuran from biomass-derived molecules.

The development of new catalytic systems for the conversion of biomass-derived molecules into liquid fuels has attracted much attention. We propose a non-noble bimetallic catalyst based on nickel-tungsten carbide for the conversion of the platform molecules 5-(hydroxymethyl)furfural into the liquid-fuel molecule 2,5-dimethylfuran (DMF). Different catalysts, metal ratios and reaction conditions have been tested and give rise to a 96% yield of DMF. The catalysts have been characterized and are discussed. The reaction mechanism is also explored through capture of reaction intermediates. The analysis of the reaction mixture over different catalysts is presented and helps to understand the role of nickel and tungsten carbide during the reaction.