Transcatheter arterial chemoembolisation combined with lenvatinib and cabozantinib in the treatment of advanced hepatocellular carcinoma.

OBJECTIVE: The objective of this study was to evaluate the effect and prognosis of transcatheter arterial chemoembolisation (TACE) combined with lenvatinib and cabozantinib in the treatment of advanced unresectable hepatocellular carcinoma (uHCC) and identify the predictors of prognosis related to cellular inflammation and body mass index (BMI). To the best of our knowledge, this is the first study to report the efficacy and prognosis of TACE combined with lenvatinib and cabozantinib in patients with uHCC and propose the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) as predictors of response and survival outcomes in this context. METHODS: The clinicopathologic data of 217 patients with advanced uHCC who underwent TACE combined with systemic therapy (lenvatinib mesylate + cabozantinib) in the Department of Hepatobiliary Surgery, Dazhou Central Hospital between October 2017 and February 2020 were collected retrospectively, and the relevant parameters were analysed and compared. RESULTS: Univariate and multivariate logistic regression analyses showed that BMI, NLR, PLR and prothrombin time were independent factors for the objective response rate (ORR) of transformed therapy for uHCC (OR = 0.812 vs 1,290.68 vs 1.067 vs 0.626, 95 % CI: 0.719-0.897 vs 108.081-11,541.137 vs 1.037-1.099 vs 0.414-0.946, respectively, p < 0.05). The results showed that BMI, NLR and PLR had certain predictive values for the ORR in patients with liver cancer undergoing translational therapy (p < 0.05); the combined predictive effect of the three was the best, and the area under the curve (AUC) of BMI + NLR + PLR for predicting the ORR in patients with liver cancer undergoing translational therapy was 0.951 (95 % CI: 0.921, 0.964). A total of 181 patients experienced adverse reactions at different grades, including 104 cases at grade 1, 50 cases at grade 2, 22 cases at grade 3 and 5 cases at grade 4. There was a significant difference in overall survival (OS) between low- and high-NLR groups, low- and high-PLR groups and low- and high-BMI groups (χ2 = 9.644, 8.313 and 10.314, respectively, p < 0.05). There was a significant difference in progression-free survival (PFS) between the low- and high-NLR groups, the low- and high-PLR groups and the low- and high-BMI groups (χ2 = 8.965, 9.783 and 6.343, respectively, p < 0.05). CONCLUSION: Transcatheter arterial chemoembolisation combined with lenvatinib and cabozantinib is safe and effective in the treatment of advanced uHCC, with controllable adverse reactions. High NLR and PLR and low BMI values before treatment were independent risk factors for the ORR. Body mass index, NLR and PLR predicted responses to triple switch therapy and survival outcomes in uHCC. Patients with pretreatment NLR ≥ 2.96 and PLR ≥ 184.41 had worse OS and PFS rates. Patients with pretreatment BMI ≥ 23 kg/m2 had improved OS and a reduced risk of death.

A Novel Autophagy-Related Marker for Improved Differential Diagnosis of Rheumatoid Arthritis and Osteoarthritis.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are two most common rheumatic diseases in the world. Although there are standard methods for the diagnosis of both RA and OA, the differentials in some cases are poor. With deepening research, the role of autophagy in maintaining cell homeostasis and thus enabling cells adapt to external environments has become increasingly prominent. Both RA and OA, two diseases with inherent differences in pathogenesis, gradually show differences in autophagy levels. Our study therefore aims to further understand differences in pathogenesis of RA and OA through in-depth studies of autophagy in RA and OA. We also define appropriate autophagy-related markers as recognition indicators. Differences in autophagy levels between RA and OA were found based on analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and single-sample gene set enrichment (ssGSEA). These differences were mainly caused by 134 differentially expressed genes (DEGs). In two autophagy-related genes, CXCR4 and SERPINA1, there existed significant statistical difference between RA and OA. An autophagy related index (ARI) was thus successfully constructed based on CXCR4 and SERPINA by binary logistic regression of the generalized linear regression (GLR) algorithm. Pearson analysis indicated that the expression of CXCR4, SERPINA1, and ARI were closely correlated with autophagy scores and immune infiltration. Moreover, ARI showed high disease identification through receiver operating characteristic (ROC) analysis (AUCtesting cohort = 0.956, AUCtraining cohort = 0.867). These results were then verified in GSE12021 independent cohort. In conclusion, ARI associated with autophagy and immune infiltration was successfully constructed for accurately identifying OA and RA. The index, thus, has great potential in clinical applications.

Development of an immune-related gene pairs index for the prognosis analysis of metastatic melanoma.

Melanoma is a skin cancer with great metastatic potential, which is responsible for the major deaths in skin cancer. Although the prognosis of melanoma patients has been improved with the comprehensive treatment, for patients with metastasis, the complexity and heterogeneity of diffuse diseases make prognosis prediction and systematic treatment difficult and ineffective. Therefore, we established a novel personalized immune-related gene pairs index (IRGPI) to predict the prognosis of patients with metastatic melanoma, which was conducive to provide new insights into clinical decision-making and prognostic monitoring for metastatic melanoma. Through complex analysis and filtering, we identified 24 immune-related gene pairs to build the model and obtained the optimal cut-off value from receiver operating characteristic curves, which divided the patients into high and low immune-risk groups. Meantime, the Kaplan-Meier analysis, Cox regression analysis and subgroup analysis showed that IRGPI had excellent prognostic value. Furthermore, IRGPI was shown that was closely associated with immune system in the subsequent tumor microenvironment analysis and gene set enrichment analysis. In addition, we broken through the data processing limitations of traditional researches in different platforms through the application of gene pairs, which would provide great credibility for our model. We believe that our research would provide a new perspective for clinical decision-making and prognostic monitoring in metastatic melanoma.

How to Accomplish a Square C(N)4 Substructure of the Planar Tetracoordinate Carbon.

Nitrogen-based groups are usually not used as ligands to coordinate to the ptC atom. However, here we reported only nitrogen-based ligands to accomplish a theoretically successful square planar C(N)4 substructure. The first difficulty in accomplishing a square ptC(N)4 substructure is to conquer the tremendous strain from the planar to tetrahedral arrangements, and the second is to restrict it in a suitable system with the right symmetry. We designed several neutral molecules with the square ptC(N)4 substructures, and the molecules were studied using the density functional theory method at the B3LYP/6-311++G(3df,3pd) and TPSSh/6-311++G(3df,3pd) level of theory. The results of this work show that the molecules are all real minima on the potential energy surface and successfully achieved the square ptC(N)4 substructure in the theoretical method. The group orbitals among the square ptC(N)4 arrangement in the D 2d symmetry have been discussed and used to investigate the bonding interactions among all atoms in the square ptC(N)4 substructure. Usually, the ptC systems have 18 valence electrons, but the present ptC systems mentioned in this work have 24 valence electrons, which is unusual for ptC.

The DFT study on neutral molecules with planar tetracoordinate oxygen surrounded by four carbon-based groups.

Oxygen usually forms two single bonds with other atoms. In contrast, here we reported the neutral molecules with the planar O(C)4-type tetracoordinate oxygen substructures. The molecules with planar tetracoordinate oxygen, as desirable targets for studying the nonclassical structures and unusual bonding features, remain an important challenge in only carbon-based groups as ligands. In this work, several neutral molecules with planar tetracoordinate oxygen atom surrounded by four carbon-based groups in the pagodane-like derivatives, have been designed out by using the "charge-compensation" and "mechanical" strategies, and studied at the B3LYP/6-311++G(3df,3pd) level of theory. The computational results show that they are all minima on the potential energy surfaces without any imaginary vibrational frequency, and unlike ptC delocalization of the oxygen 2pz lone pair in ptO(C)4 is no longer the principal reason for stabilizing a ptO substructure.

Theoretical Study on Neutral Molecules with Square Planar Tetracoordinate Oxygen O(B)4 Arrangements.

As we know, oxygen usually forms two single bonds with other atoms, whereas in this work, we reported the neutral molecules with square planar O(B)4-type tetracoordinate oxygen substructures. The difficulty to achieve a square planar O(B)4-type arrangement is not only to overcome the strain from the planar to tetrahedral configuration but also to constrain it in a right system with the proper symmetry. Several neutral molecules with square planar O(B)4-type arrangements have been studied using the DFT method at the B3LYP/6-311++G(3df,3pd) level of theory. The computational results show that they are all real minima on potential energy hypersurfaces. Thus, it has been shown theoretically that the square planar O(B)4-type arrangement is achieved. The molecular orbitals among the square planar O(B)4-type substructure at D 2d symmetry have been suggested. Using the molecular orbitals, it has been explained that the oxygen 2p z -π electrons in the square planar O(B)4-type arrangement are no longer the lone-pair electrons.

(C=C=C=C)@C60: A Bonding C60-Endohedral Molecular Allotrope of Carbon.

The allotropes of carbon have been the focus of attention in recent years. In this work, we reported a molecular allotrope of carbon, C60-endohedral: (C=C=C=C)@C60. The smallest vibrational frequency is 226.0 cm-1, which confirms that (C=C=C=C)@C60 is a minimum on the potential energy hypersurface. Its geometry, NMR diagram, IR spectrum, heat of formation, and bonding interactions have been predicted using the density functional theory (DFT) method at the B3LYP/6-311G(d) level of theory. Since there must be a large family of the fullerene-endohedral allotropes of carbon, the research studies on these allotropes of carbon will open an avenue for allotropes of carbon.

[Fabrication of a Biomass-Based Hydrous Zirconium Oxide Nanocomposite for Advanced Phosphate Removal].

Wheat straws were modified by 3-chloro-2-hydroxypropyl trimethylammonium chloride (CTA) to obtain aminated wheat straw St-N'. The optimum synthetic conditions were determined to be NaOH with 30% mass fraction, CTA of 100 mL, reaction temperature of 80℃, and reaction time of 3 h, which was verified by orthogonal experiments. Nano-sized hydrous zirconium oxides (HZO) were immobilized into St-N' by an in situ precipitation method to obtain the nanocomposite St-N'-Zr. The SEM, TEM, XRD, and BET results indicated that the nano-sized HZO with 50-100 nm sizes were uniformly loaded onto the inner surface of the biomass-based carrier St-N' that was amorphous in nature. A Langmuir adsorption isotherm fitted the adsorption process well, and the maximum adsorption amount was calculated to be 33.90 mg·g-1. The optimal pH range was 1.8-6.0, displaying good removal capacity of phosphate in acidic waters. In the presence of high levels of competing anions, the phosphate adsorption still retained more than 70% of the original amount, showing the higher preference of St-N'-Zr towards phosphate than towards the commercial anion exchanger D-201. After 10 cycles of adsorption-desorption, the removal efficiency remained stable, confirming the good regeneration ability and potential application of St-N'-Zr.

[Characteristics and sources apportionment of OC and EC in PM1.1 from Nanjing].

The concentrations of OC and EC in PM1.1 collected from Nanshi (NS) and Nanhua (NH) in 2011 were analyzed using DRI Model 2001A Thermal Optical Carbon Analyzer. In addition, source apportionment was simultaneously evaluated. The results showed that the annual average concentrations of OC and EC in PM1.1 were 10. 10 µg x m(-3) and 2.52 µg x m(-3) in NS area, and 11.22 µg x m(-3) and 3.12 µg x m(-3) in NH area, respectively. This result indicated that OC and EC pollution in NH was more serious than that in NS area. Meanwhile, the concentrations of OC and EC in winter and spring were obviously higher compared to those in summer in these two sampling sites, which was mainly ascribed to the increased coal combustion and the unfavorable emission condition of air pollutants in summer and spring. We noted that the SOC/TOC value was the highest in summer and the lowest in winter. In addition, the SOC concentration was observed to show a positive correlation with ozone concentrations, which indicated that the photochemical reaction was a main way of SOC formation in autumn.

Geldanamycin mediates the apoptosis of gastric carcinoma cells through inhibition of EphA2 protein expression.

The aim of the present study was to investigate the role of EphA2 in the carcinogenesis and progression of gastric carcinoma. Moreover, we aimed to determine the effect of geldanamycin (GA), an inhibitor of Hsp90, on the proliferation and apoptosis of human gastric carcinoma cells. Gastric carcinoma tissues, paired adjacent mucosa and paired normal mucosa were obtained from resected surgical specimens of gastric carcinoma, and EphA2 mRNA and protein levels were assessed by RT-PCR, immunohistochemistry and western blot analysis. FCM was used to detect cell cycle distribution and apoptosis. MGC803 cell proliferation and apoptosis were assessed by MTT and FCM, respectively. We found that EphA2 protein was increased in the carcinogenesis of gastric epithelial cells. Proliferation index (PI) was significantly upregulated following an increase in EphA2 expression in gastric carcinoma compared with dysplasia and normal samples, and was notably correlated with grade and lymph node metastasis. Knockdown of EphA2 increased the apoptosis rate and decreased the PI of MGC803 cells, which overexpressed the EphA2 protein. GA inhibited the cell proliferation of MGC803 cells in a dose- and time-dependent manner and induced cell apoptosis. In addition, GA decreased the EphA2 protein expression in MGC803 cells. Overexpression of EphA2 inhibited cell growth, blocked cells in the G0/G1 stage and increased cell apoptosis induced by GA in MGC803 cells. However, knockdown of EphA2 in MGC803 cells increased the apoptosis ratio induced by GA. In conclusion, EphA2 overexpression is an important characteristic in the carcinogenesis of gastric epithelial cells, followed by an increase in apoptosis and cell cycle arrest. Knockdown of EphA2 blocked MGC803 cell proliferation and induced cell apoptosis. In conclusion GA inhibits MGC803 cell proliferation and induces cell apoptosis by upregulating expression of EphA2.

[Size distributions of organic carbon and elemental carbon in Nanjing aerosol particles].

The concentrations and size distributions of organic carbon (OC) and elemental carbon (EC) in particles collected in Nanjing Normal University representing urban area and in Nanjing College of Chemical Technology standing for industrial area were analyzed using Model 2001A Thermal Optical Carbon Analyzer. The mass concentrations were the highest with the size below 0.43 microm in urban and industrial area. OC accounted for 20.9%, 21.9%, 29.6%, 27.9% respectively and those were 24.0%, 23.5%, 31.4%, 22.6% respectively for EC in the four seasons in urban area. In the industrial area, OC accounted for 18.6%, 45.8%, 26.6%, 25.9% respectively and the proportions of EC were 16.7%, 60.9%, 26.3%, 24.3% respectively. Overall, OC and EC were enriched in fine particles below 2.1 microm and they accounted for the highest proportion in summer in urban area while it did not show significant seasonal variation for industrial area. SOC in fine particles achieved high values in summer while the unobvious seasonal variation in coarse particles might be attributed to the contribution of different pollution sources and meteorological factors. Correlations and OC/EC ratio method implied that OC and EC mainly came from vehicles exhaust and coal combustion in fine particles while they were also related to biomass combustion and cooking in coarse particles.

[Stable carbon isotopic composition in PM 2.1 in Nanjing Region].

Stable carbon isotopes (delta13C) in aerosol fine particles (PM2.1) collected in Nanjing Normal University representing urban area, and in Nanjing College of Chemical Technology standing for suburban industrial area, were analyzed using EA-IRMS. Besides, sources of carbonaceous contents were studied and the pollution characteristics of total carbon (TC) were evaluated. The annual average concentrations of TC in urban area and suburban industrial area were 15.94 microg.m-3 and 17.17 microg.m-3, respectively. The proportions for TC in PM2.1 were 17.18% and 16. 40% , indicating that carbonaceous pollution was more serious and the pollutants were more complex in suburban industrial area. The average delta13C for winter, spring, summer and autumn were -24. 42 per thousand +/- 1. 12 per thousand, -25. 19 per thousand +/- 1. 92% per thousand, - 25.79 per thousand +/- 0.45 per thousand and - 25.58 per thousand + 0. 65 per thousand, respectively in urban area and - 25.34 per thousand +/- 1. 18 per thousand, -25. 55 per thousand +/- 1. 50 per thousand, -25. 31 per thousand +/- 0. 55%o and -25. 38 per thousand +/- 0. 82 per thousand, respectively in suburban area. Correlation analysis and isotopic signatures of potential sources suggested that carbonaceous contents mainly came from gasoline vehicles exhaust in urban area, and might be attributed to the vehicle exhaust emissions and industrial emissions in suburban area. In addition, coal combustion,biomass burning and geological sources might have important contribution to aerosols in winter and spring. Back trajectory analysis implied that the long-range transport had considerable contribution to the carbonaceous aerosol in winter and spring. However, the major sources might be attributed to local emissions in the other two seasons.

Expression and mechanism of PinX1 and telomerase activity in the carcinogenesis of esophageal epithelial cells.

Esophageal tissues were collected from an esophageal carcinoma high-risk area of China and were used to detect the telomere length and the expression of human telomerase reverse transcriptase (hTERT) by immuhistochemistry and fluorescence in situ hybridization; esophageal carcinoma tissues, paired-adjacent mucosa and paired normal mucosa were obtained from resected surgical specimens of esophageal squamous cell carcinoma in order to determine telomerase activity and expression of hTERT and Pin2/TRF1 interacting protein X1 (PinX1) by telomeric repeat amplification protocol-silver staining, RT-PCR and flow cytometry (FCM). The cell proliferation and apoptosis of Eca109 cells were analyzed by FCM and MTT assay. We found that the length of telomere DNA decreased and hTERT protein expression increased in the carcinogenesis of esophageal epithelial cells; telomerase activity was significantly upregulated followed by a decrease of PinX1 expression in esophageal carcinoma compared with dysplasia and normal patients, which notably correlated with grade and lymph node metastasis. Overexpression of PinX1 inhibited cell growth, arrested cells at the G0/G1 stage and induced cell apoptosis in Eca109 cells. In addition, PinX1 overexpression significantly inhibited telomerase activity. In conclusion, the length shortening of telomere was an important characteristic in the carcinogenesis of esophageal epithelial cells, followed by increase of telomerase activity and downregulation of PinX1. Overexpression of PinX1 blocked Eca109 cell proliferation and induced cell apoptosis by downregulating telomerase activity.

Defective activities, but not secretions, resulting from gene point mutations of human mannan-binding lectin.

Human mannan-binding lectin (MBL) plays a pivotal role in innate immunity. Substantial literature supports the belief that three point mutations, CGT52TGT, GGC54GAC and GGA57GAA, in the collagen-like region (CLR) of the human MBL gene, are associated with increased susceptibility to infection, autoimmunity and carcinogenesis. To investigate the mechanisms of MBL deficiency, human wild-type and three variant MBL genes were expressed in COS-7 and Chinese hamster ovary (CHO) cells. Results showed that no apparent differences were found among the levels of gene transcription and protein secretion of four forms of MBL. However, the degree of oligomerization of variant forms of MBL was found to be much lower than that of recombinant human wild-type MBL. The ability of variant MBL proteins to bind mannan was much weaker than that of the wild-type MBL protein, and the MBL variants failed to effectively activate the complement lectin pathway. These data suggested that a lower order oligomer, but not decreased plasma levels of MBL, may be the main result of MBL gene mutations and may be associated with immunodeficiency.

Clinical observation of Yinzhihuang Oral Liquid on prevention of the premature infantile jaundice.

OBJECTIVE: To observe the clinical efficacy of Yinzhihuang Oral Liquid (YOL) to prevent the premature infantile jaundice. METHODS: After excluded hemolytic, suffocation, infection, and the very low birth weight, 242 cases of premature infants were randomly assigned to two groups, the treatment group and the control group. Both groups were taken conventional procedures, such as warmth, feeding, and blood glucose monitoring, and the treated group was administered YOL 5 mL each time, twice daily additionally, and the control group without any treatment. The percutaneous bilirubin and blood cells were observed every day. RESULTS: Compared the two groups, the jaundice indices were more significantly different at 24-48 h, 48-72 h, and more than 72 h (P<0.05), but not statistically different at 0-24 h (P>0.05). Hemoglobin, reticulocyte, platelets, and leucocyte were not significantly different between the two groups (P>0.05). CONCLUSION: YOL as an early intervention has positive significance to decrease the incidence of pathological jaundice in the premature infants, and no significant impact on the blood cells.

Structural, electronic, and magnetic properties of heterofullerene C(58)Si with odd number of atoms and a near planar tetracoordinate Si atom.

Density functional calculations and minimization techniques have been employed to characterize the structural and electronic properties of [5,6]-heterofullerene-C(58)Si-C(2v). Since it has odd number of atoms and a near planar tetracoordinate Si atom on the skeleton of the cage, it has odd number of atoms assembling a cage and is a novel molecule. Vibrational frequencies of the molecule have been calculated at the B3LYP/6-31G* level of theory. The absence of imaginary vibrational frequency confirms that the molecule corresponds to a true minimum on the potential energy hypersurface. Sixteen (13)C nuclear magnetic resonance (NMR) spectral signals of C(58)Si are characterized, and its heat of formation was estimated in this work.

DFT study of structural, electronic, vibrational, and magnetic properties of the chirality cage-like molecule C24O12.

Bonding, vibrational and magnetic properties of the cage-like molecule C24O12 are studied by DFT calculations. Infrared- and Raman-active vibrational frequencies of the cage-like molecule C24O12 are assigned. Two 13C and one 17O nuclear magnetic resonance (NMR) spectral signals of the cage-like molecule C24O12 are characterized. Heat of formation of the cage-like molecule C24O12 is estimated. Compared to C60 and the cage-like molecule C24O12, only from the thermodynamic points of view, C24O12 is more stable than C60. Thus we believe that the cage-like molecule C24O12 has sufficient stability to allow its experimental preparation. We proposed that it could be synthesized by using the condensation of molecules C6(OH)6 and C12Cl12. Since the symmetry of C24O12 is D6, it is a chiral molecule.

Structural, electronic, and magnetic properties of two isomers of C40 O10 with cage-like structure.

Bonding, vibrational and magnetic properties of two isomers of cage-like molecule C40 O10 are studied by using hybrid DFT calculations at the B3LYP/6-31G* level of theory. Infrared- and Raman-active vibrational frequencies of two isomers of C40 O10 are assigned. Three 13C and one 17O nuclear magnetic resonance (NMR) spectral signals of each isomer are characterized. Heat of formation of each isomer is estimated. Compared the stability of the two isomers of C40 O10 with that of C60, only from the thermodynamic points of view, they are more stable than C60. Thus, we believe that they have sufficient stability to allow their experimental preparation. We proposed their synthesized route in this paper.