Risk factors for brain metastases in locally advanced non-small cell lung cancer patients treated with radical radiotherapy.

Background: Brain metastases (BM) happen frequently in lung cancer patients and lead to a poor prognosis as well as a lower quality of life. The aim of this study was to identify risk factors for BM in locally advanced non-small cell lung cancer (LA-NSCLC) patients receiving radical radiotherapy, which will be useful for selecting appropriate patient population for further intervention and future trial design. Methods: This was a retrospective cohort study. Patients with inoperable stage IIB-IIIC NSCLC were treated consecutively with definitive thoracic radiotherapy from January 2018 to December 2021, and were retrospectively reviewed and enrolled. Patients with various clinical variables were analyzed to clarify their impact on BM with competing risk models by Fine and Gray. Results: A total of 134 patients were enrolled in this study. The median follow-up for all patients was 37 months [95% confidence interval (CI): 30.5-43.5 months]. BM occurred in 25 patients at the time of analysis. The 1-year and 3-year cumulative BM incidence were 10.5% and 19.9%, respectively. Patients with BM had worse overall survival than those without BM [stratified hazard ratio (HR) for death: 2.83; 95% CI:1.31-6.11; P<0.001]. Based on univariate analyses, non-squamous cell carcinoma (non-SCC), biological effective dose (BED) and planning target volume (PTV) were used as input variables in multivariable analysis (P<0.01). According to multivariate analysis, non-SCC (P<0.001; HR: 6.08; 95% CI: 2.26-16.37), BED <72 Gy (P=0.017; HR: 2.81; 95% CI: 1.20-6.57), and PTV >157.73 cm3 (P=0.043; HR: 2.56; 95% CI: 1.03-6.35) were independent risk factors for BM. In subgroup analysis of adenocarcinoma with known epidermal growth factor receptor (EGFR) mutation status, PTV >157.73 cm3 and positive EGFR mutation were independent predictors for BM. Conclusions: In this retrospective study, we found that BED <72 Gy and PTV >157.73 cm3 were significantly associated with BM development and we validated that non-SCC and positive EGFR mutation were risk factors for BM. More research is required to screen the high-risk patient population.

The value of multiparametric MRI combined with clinical prognostic parameters in predicting the 5-year survival of stage IIIC1 cervical squamous cell carcinoma.

OBJECTIVES: To explore the value of multiparametric magnetic resonance imaging（MRI）in predicting the 5-year progression-free survival (PFS) and overall survival (OS) of cervical squamous cell carcinoma (CSCC) in 2018 FIGO stage IIIC1. METHODS: This retrospective study collected156 patients with CSCC from Dec. 2014 to Jul. 2018. Sixty-one patients underwent radical hysterectomy (RH), and 95 patients underwent concurrent chemoradiotherapy (CCRT). Clinical and MR parameters of primary tumours were analysed. A 1:1 ratio propensity score matching (PSM) was performed for the RH group and CCRT group according to T stage. The Cox proportional hazard model was used to evaluate the associations between imaging or clinical variables and PFS and OS. RESULTS: The 5-year PFS and OS rates were 72.6% and 78.3%, respectively. The analysis results show that the treatment method, ADCmin < 0.604 × 10-3 mm2/s, and Ktrans < 0.699 min-1 correlated with worse PFS, while SCC-Ag > 6.7 ng/L, ADCmin < 0.604 × 10-3 mm2/s, and Ktrans < 0.699 min-1 correlated with worse OS. After PSM, we confirmed that the treatment methods did not affect the long-term survival of patients with stage IIIC1 disease, and a low Ktrans value was an independent poor prognostic factor. CONCLUSION: Functional MRI parameters and SCC-Ag have potential predictive value for the 5-year survival of 2018 FIGOIIIC1 CSCC. There were no significant differences in survival between CCRT and RH + adjuvant therapy for IIIC1 stage CSCC if the T stage was earlier.

Diastereodivergent and Enantioselective Synthesis of Homoallylic Alcohols via Nickel-Catalyzed Borylative Coupling of 1,3-Dienes with Aldehydes.

We present the first enantioselective nickel-catalyzed borylative coupling of 1,3-dienes with aldehydes, providing an efficient route to highly valuable homoallylic alcohols in a single step. The reaction involves the 1,4-carboboration of dienes, leading to the formation of C-C and C-B bonds accompanied by the construction of two continuous stereogenic centers. Enabled by a chiral spiro phosphine-oxazoline nickel complex, this transformation yields products with exceptional diastereoselectivity, E-selectivity, and enantioselectivity. The diastereoselectivity of the reaction can be controlled by employing either (Z)-1,3-dienes or (E)-1,3-dienes.

Ketone α-alkylation at the more-hindered site.

Control of the regioselectivity of α-alkylation of carbonyl compounds is a longstanding topic of research in organic chemistry. By using stoichiometric bulky strong bases and carefully adjusting the reaction conditions, selective alkylation of unsymmetrical ketones at less-hindered α-sites has been achieved. In contrast, selective alkylation of such ketones at more-hindered α-sites remains a persistent challenge. Here we report a nickel-catalysed alkylation of unsymmetrical ketones at the more-hindered α-sites with allylic alcohols. Our results indicate that the space-constrained nickel catalyst bearing a bulky biphenyl diphosphine ligand enables the preferential alkylation of the more-substituted enolate over the less-substituted enolate and reverses the conventional regioselectivity of ketone α-alkylation. The reactions proceed under neutral conditions in the absence of additives, and water is the only byproduct. The method has a broad substrate scope and permits late-stage modification of ketone-containing natural products and bioactive compounds.

Antibacterial Metabolites from Kiwi Endophytic Fungus Fusarium tricinctum, a Potential Biocontrol Strain for Kiwi Canker Disease.

Pseudomonas syringae pv. actinidiae (Psa) is a Gram-negative bacterium causing the kiwifruit canker disease, resulting in serious economic losses to the kiwifruit industry. This study investigated the use of an endophytic fungus, Fusarium tricinctum, obtained from the kiwi plant (Actinidia chinesis) as a potential biocontrol strain against the Psa. F. tricinctum showed an inhibition rate of 59.5% in vitro against Psa. Bioassay-guided isolation was conducted on the cultural broth of F. tricinctum and seven new imidazole alkaloids, (±)-fusaritricine J ((±)-1) and fusaritricines K-P (2-7), and four enniatins (8-11) were identified. Their absolute configurations were established through extensive spectroscopic methods, quantum chemical calculations, and X-ray single crystal diffraction. Compounds 1, 4, 5, and 8-11 showed comparable anti-bacterial activities against Psa as positive control, with MIC values of 25-50 µg/mL. Further cell membrane permeability assay suggested that the most active compound 4 could destroy the bacterial cell wall structure. Hence, F. tricinctum metabolites could be applied as potential anti-Psa agents, and F. tricinctum could be considered a biocontrol strain for the control of the kiwifruit canker disease.

Chemical constituents from mushroom Geoglossum fallax and their bioactive activities.

Chemical investigation on the fruiting bodies of the mushroom Geoglossum fallax led to the isolation of two carboxamides, geoglamides A and B (1 and 2), one meroterpenoid, geoglol A (3), together with seven known metabolites (4-10). Their structures were identified by spectroscopic analyses as well as ECD calculations. Compounds 1 and 2 are rare long chain fatty amides containing a 4-oxo-1,4-dihydropyridine moiety, while compound 3 is a rare C6-C5 type meroterpenoid. Compound 1 displayed cytotoxic activity against human MCF-7 cells with an IC50 value of 25.9 ± 0.51 µM. compounds 2 and 8 showed weak pancreatic lipase inhibition activity. To our best knowledge, this is the first report of the chemical constituents in the genera Geoglossum and their bioactive activity.

The Impact of Chemosensitivity on the Outcome of Brain Metastases in Small-Cell Lung Cancer: A Retrospective Analysis.

PURPOSE: The purpose of this study was to investigate the prognostic differences between patients with small-cell lung cancer (SCLC) with different chemosensitivity to first-line chemotherapy who developed brain metastasis (BM) as the first site of progression. METHODS: Patients with a BM after first-line treatment in the Tianjin Cancer Hospital were retrospectively analyzed. According to the time-free interval (TFI) between the completion of first-line chemotherapy and the onset of the BM, the patients were divided into the chemo-sensitive group (TFI ≥ 90 days, n = 145) and the chemo-resistant group (TFI < 90 days, n = 97). The survival time, which was calculated from the diagnosis of the BM, was analyzed after the onset of brain metastasis (BM-OS). Survival curves were plotted using the Kaplan-Meier method, and differences between groups were compared using the log-rank test. RESULTS: In total, the median BM-OS was 8.4 months. The median BM-OS in the chemo-sensitive group was 8.8 months, and it was 8.0 months in the chemo-resistant group (p = 0.538). In patients without extracranial progression (n = 193), the median BM-OSes in the chemo-sensitive and chemo-resistant groups were 9.4 months and 9.7 months, respectively (p = 0.947). In patients with extracranial progression (n = 49), the median BM-OSes in the chemo-sensitive and chemo-resistant groups were 5.4 months and 4.2 months, respectively (p = 0.161). Conclusions: After the development of a BM as the first site of progression following chemotherapy in patients with SCLC, the prognosis of chemo-sensitive patients was not necessarily superior to chemo-resistant patients, especially in patients without extracranial progression.

Cadinane sesquiterpenoids from the fungus Antrodiella albocinnamomea and their inhibitory activity against nitric oxide production.

Seven previously undescribed cadinane sesquiterpenoids, albocinnamins A‒G, were isolated from the fungus Antrodiella albocinnamomea. Their structures with absolute configurations were elucidated on the basis of extensive spectroscopic methods, as well as single crystal X-ray diffraction. Cadinane sesquiterpenoids were reported from A. albocinnamomea for the first time. All of these sesquiterpenoids possess an unusual ether ring with minor modifications. Albocinnamins D and G showed certain inhibitory activities against nitric oxide production in LPS-activated RAW264.7 macrophages with IC50 values of 26.1 and 19.2 µM, respectively.

Synthesis of superparamagnetic MnFe2O4/mSiO2 nanomaterial for degradation of perfluorooctanoic acid by activated persulfate.

In this paper, magnetic MnFe2O4/mSiO2 nanocomposites were successfully synthesized, and the activation performance of the materials for persulfate was evaluated by the degradation efficiency of perfluorooctanoic acid. The structure of the catalyst was proved to be a core-shell structure by several characterization methods. The mesoporous silicon coating can effectively avoid the agglomeration of MnFe2O4 and at the same time increase the contact area with the reactants. A comparison of different catalyst addition conditions demonstrates that MnFe2O4/mSiO2 can effectively activate the persulfate. The optimal reaction conditions were investigated by several key influencing factors. It was experimentally demonstrated that about 90% of PFOA (10 mg·L-1) could be decomposed under the conditions of 0.4 g·L-1 MnFe2O4/mSiO2 and PS, pH 5.68, and 25 °C within 4 h; the defluorination rate reached 58.33%. In addition, the cyclability and stability tests demonstrated that MnFe2O4/mSiO2 is a stable material that can be recycled. Furthermore, XPS characterization and radical scavenging experiments demonstrated that sulfate radicals (SO4·-) and hydroxyl radicals (OH) play a major role in the reaction of MnFe2O4/mSiO2 activated PS. Subsequently, the degradation products were detected by high-performance liquid chromatography tandem triple quadrupole mass spectrometry, indicating that the degradation of PFOA is a gradual process of defluorination and decarbonization in the presence of free radicals. Finally, the metal leaching rate is tested to prove that the material meets environmental requirements while reacting efficiently. In conclusion, this study shows that MnFe2O4/mSiO2 is an easily recoverable and highly efficient and stable material that has great potential for PS activation to treat organic pollutants in water.

Natural imidazole alkaloids as antibacterial agents against Pseudomonas syringae pv. actinidiae isolated from kiwi endophytic fungus Fusarium tricinctum.

Kiwi (Actinidia chinensis) plants are severely destroyed by canker disease which is caused by the bacterium Pseudomonas syringae pv. actinidiae (Psa). This program tries to find anti-Psa agents among secondary metabolites of endophytic fungi from kiwi plant itself. The chemical investigation on one kiwi endophytic fungi, Fusarium tricinctum, resulted in the isolation of nine new imidazole alkaloids, fusaritricines A-I (1-9) together with seven known analogues (10-16). The structures of new compounds were established by extensive spectroscopic methods. Compounds 2, 3, 9, and 13 showed good antibacterial activity against Psa with MIC values between 25 and 50 µg/mL. It is suggested that imidazole alkaloids should be potential anti-Psa agents.

Estimating survival and clinical outcome in advanced non-small cell lung cancer with bone-only metastasis using molecular markers.

OBJECTIVES: This retrospective study investigated prognostic factors in advanced non-small cell lung cancer (NSCLC) with bone-only metastasis, and developed a graded prognostic assessment (GPA) model to estimate patient survival. METHODS: The primary endpoint was overall survival. We investigated the patients with advanced NSCLC with bone-only metastasis at the initial diagnosis and diagnosed between 2013 and 2019 in our hospital. A log-rank test and Cox proportional hazards model were used to examine factors. A GPA model was developed in the training set based on the factors that were determined significant according to their hazard ratios and verified by the validation set. RESULTS: We finally included 220 patients for analysis. These patients were divided into two groups, 147 cases for the training cohort and 73 for the validation cohort. The following were significant independent prognostic factors, and were included in the GPA model: smoking; EGFR (epidermal growth factor receptor) sensitive/ALK (anaplastic lymphoma kinase) mutations; loss of weight; hypoalbuminemia; and primary site treated by surgery or radiotherapy. GPA score of nil was assigned to smoking, without sensitive mutations, loss of weight, hypoalbuminemia, and without local treatment of primary site; the corresponding superior alternatives were scored 1.5, 2.0, 1.5, 1.5, and 1.5, respectively. The median survival times of patients with GPA scores of nil to 3.0, 3.5 to 6.0, and 6.5 to 8.0 were 14.2, 29.5, and 56.6 months in the training set (P < 0.001) and 15.2, 31.2, and 54.0 months in the validation set (P < 0.001). CONCLUSION: The survival time of patients with NSCLC with bone-only metastasis was dramatically influenced by the presence of the determined prognostic factors. The GPA model developed in this study may be a useful clinical tool to estimate the life expectancy of these patients, and guide treatment.

Advances in Research on Chemical Constituents and Their Biological Activities of the Genus Actinidia.

Kiwi, a fruit from plants of the genus Actinidia, is one of the famous fruits with thousand years of edible history. In the past twenty years, a great deal of research has been done on the chemical constituents of the Actinidia species. A large number of secondary metabolites including triterpenoids, flavonoids, phenols, etc. have been identified from differents parts of Actinidia plants, which exhibited significant in vitro and in vivo pharmacological activities including anticancer, anti-inflammatory, neuroprotective, anti-oxidative, anti-bacterial, and anti-diabetic activities. In order to fully understand the chemical components and biological activities of Actinidia plants, and to improve their further research, development and utilization, this review summarizes the compounds extracted from different parts of Actinidia plants since 1959 to 2020, classifies the types of constituents, reports on the pharmacological activities of relative compounds and medicinal potentials.

Pardinumones A-D: Antibacterial Polyketide-Amino Acid Derivatives from the Mushroom Tricholoma pardinum.

Four polyketide-amino acid derivatives, pardinumones A-D (1-4), were isolated from the wild mushroom Tricholoma pardinum. Their structures together with absolute configurations were characterized by means of spectroscopic data analyses, as well as calculated electronic circular dichroism (ECD) and NMR with sorted training set (STS) protocol analysis. Compounds 1-4 exhibited antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli with MIC values in the range of 6.25-50 µg/mL.

Combined dynamic contrast enhanced MRI parameter with clinical factors predict the survival of concurrent chemo-radiotherapy in patients with 2018 FIGO IIICr stage cervical cancer.

PURPOSE: Combined clinical prognostic factors and magnetic resonance imaging (MRI) parameters on predicting the prognosis after concurrent chemo-radiotherapy (CCRT)in patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) IIICr stage patients. METHODS: A total of 117 patients with cervical cancer (2018 FIGO stage IIICr) who underwent CCRT were enrolled from Dec.2014 to Jul.2017. 47 patients developed outcome events, including 32 recurrences and 15 deaths. Clinical and MR parameters of primary tumors were analyzed, including apparent diffusion coefficient (ADC) values (ADCmean, ADCmin, and ADCmax) and dynamic contrast-enhanced MRI (DCE-MRI) parameters (Ktrans, Kep, Ve) were recorded. The short diameters of visible lymph nodes in the MRI and enhanced computed tomography (CT) images were measured. Progression-free survival (PFS) was compared by Kaplan-Meier analysis and independent predictors were identified using cox regression analysis. RESULTS: The median PFS was 35 months (6-68 month). The 1-year and 3-year PFS rates were was 90.4 %, 74.4 %, respectively. Multivariate analysis showed that 2018 FIGOIIIC2r stage (HR 2.701,95 %CI1.259to. 5.797; p = 0.011), Ktrans(HR 0.353;95 %CI 0.189 to 0.659; p = 0.001) and ADCmin (HR0.423,95 %CI0.229to0.783; p = 0.006) were highly correlated with poor PFS. CONCLUSION: In conclusion, we have identified IIIC2r stage, Ktrans value and ADCmin value as the most important factors in evaluating the survival rate and prognosis of patients with stage IIICr cervical cancer. For stage IIIC1r subgroup, Ktrans, ADCmin value and site of positive lymph node >2 were independent prognostic factors.

Does the Low-Carbon City Pilot Policy Promote Green Technology Innovation? Based on Green Patent Data of Chinese A-Share Listed Companies.

To cope with climate change and achieve sustainable development, low-carbon city pilot policies have been implemented. An objective assessment of the performance of these policies facilitates not only the implementation of relevant work in pilot areas, but also the further promotion of these policies. This study uses A-share listed enterprises from 2005 to 2019 and creates a multi-period difference-in-differences model to explore the impact of low-carbon city pilot policies on corporate green technology innovation from multiple dimensions. Results show that (1) low-carbon city pilot policies stimulates the green technological innovation of enterprises as manifested in their application of green invention patents; (2) the introduction of pilot policies is highly conducive to green technological innovation in eastern cities and enterprises in high-carbon emission industries; and (3) tax incentives and government subsidies are important fiscal and taxation tools that play the role of pilot policies in low-carbon cities. By alleviating corporate financing constraints, these policies effectively promote the green technological innovation of enterprises. This study expands the research on the performance of low-carbon city pilot policies and provides data support for a follow-up implementation and promotion of policies from the micro perspective at the enterprise level.

N-Heterocyclic Carbene/Palladium Cascade Catalysis: Construction of 2,2-Disubstitiuted Benzofuranones from the Reaction of 3-(2-Formylphenoxy)propenoates with Allylic Esters.

The cascade catalysis involving N-heterocyclic carbene (NHC) and palladium/ligand was demonstrated. In the presence of a triazolium salt, palladium catalyst, and base, the reaction of 3-(2-formylphenoxy)propenoates and allylic esters proceeded efficiently under mild conditions to afford 2-allylbenzofuran-3-one-2-acetates in moderated to good yields. An asymmetric cascade catalysis was achieved when (R)-BINAP was employed as a chiral ligand, producing enantiomerically enriched 2,2-disubstitiuted benzofuran-3-one derivatives with an ee up to 81%.

Correlation of expression of WWOX and JNK with clinicopathologic features in human breast carcinoma.

The aim of our study was to compare the expression levels of c-Jun N-terminal kinase (JNK) and WW domain-containing oxidoreductase (WWOX) in human breast carcinoma, to analyze the correlation between the expression of WWOX and JNK with the clinicopathologic features of human breast carcinoma, and to explore the potential mechanism of their antitumor effects. The mRNA and protein levels of WWOX and JNK in forty paired breast carcinoma tissues and the adjacent normal tissues were detected by real-time quantitative polymerase chain reaction (RT-PCR) and Western blot analysis. Protein expression was further confirmed by immunohistochemistry (IHC). The mRNA expression levels of both JNK and WWOX were downregulated in carcinoma tissues relative to those in the adjacent normal tissues, as determined by Western blot analysis and IHC (P<0.01). JNK expression was positively correlated with WWOX expression (r=0.47, P=0.002). Both WWOX and JNK play important roles in breast cancer. Therefore, the antitumor ability of WWOX and JNK could supply significant information for therapeutic strategy.

[FSH, LH, PRL, E2 and T in 8-17 year old males: investigation and analysis].

OBJECTIVE: To investigate the changes of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol (E2) and testosterone (T) in male adolescents of different ages by determining their levels in 8-17 years old boys. METHODS: We included in this study 627 male adolescents aged 8-17 years and qualified through physical examinations. All the subjects underwent determination of FSH, LH, PRL, E2 and T with an automatic ACCESS microparticle chemiluminescence immunoassay analyzer and detection of liquid quality control by immunoassay. RESULTS: FSH remained at a low level in the 8-10 years old male adolescents and increased at 11 years; the levels of LH and T were low before the age of 12 years and began to increase at 13 years; and that of E2 was low before the age of 13 years and began to rise after that, all with statistically significant differences (P < 0.01). CONCLUSION: In the male adolescents, FSH, LH and T significantly increased at 11, 12 and 13 years old, respectively, which marked the beginning of sexual development.

[Effect of Zhenyangjian on the penile hemodynamics of the patients with arterial erectile dysfunction].

OBJECTIVE: To explore an efficacious therapy for arterial erectile dysfunction (ED) by observing the effect of the Chinese traditional medicine Zhenyangjian on the penile hemodynamics of the patient. METHODS: Forty-seven patients with arterial ED, aged from 40 to 49 years, were treated with Zhenyangjian for 1 month. Intracavernous injection of papaverine and phentolamine (30 mg/l mg) was given and multifunctional color Doppler ultrasound was used to measure the peak systolic velocity(PSV) of the corpus cavernous arteries before and after Zhenyangjian administration. RESULTS: The PSV of the penis corpus cavernous arteries was obviously ameliorated in all the patients (P < 0.05). CONCLUSION: The Chinese traditional medicine Zhenyangjian can promote penile erection effectively.