Preliminary validation of Global Leadership Initiative on Malnutrition criteria in cancer patients:A cross-sectional study

Background:The Global Leadership Initiative on Malnutrition(GLIM)has been used in China since 2019.This study aimed to test the use of the GLIM criteria in Chinese cancer patients and to compare the diagnostic performance of the GLIM criteria with the Patient-Generated Subjective Global Assessment(PG-SGA)and modified PG-SGA(mPG-SGA). Methods:A total of 2,000 cancer patients were consecutively screened using the Nutritional Risk Screening 2002 instrument on ad-mission.Patients at nutritional risk(Nutritional Risk Screening 2002 score≥3)were enrolled to obtain the complete GLIM,PG-SGA,and mPG-SGA criteria.To evaluate the convergent validity,Spearman correlation analysis was used to compare the test-retest reliability of the GLIM criteria and its results with the scores of various nutritional tools and objective parameters.Kruskal-Wallis tests and χ2 tests were used to test the discriminant validity among groups with different nutritional status.We calculated the sensitivity,specificity,positive predictive value,and negative predictive value for the various tools. Results:There were 562 patients found to be at nutritional risk,accounting for 28.1%of all patients.One hundred seventy-four patients(8.7%)were diagnosed as moderately malnourished,and 333 patients(16.6%)were severely malnourished based on the PG-SGA.When assessed using the GLIM criteria,185 patients(9.3%)were diagnosed as moderately malnourished and 311 patients(15.5%)were severely malnourished.The content validity of the GLIM criteria was 95%,evaluated by 60 medical staff members.The test-retest reliability was good.For the diagnosis of malnutrition versus the PG-SGA,the sensitivity of the GLIM was"good"(90.5%;95%confidence interval[95%CI]=88.0%-93.1%),with a positive predictive value of 92.5%(95%CI=90.2%-94.9%),but the spec-ificity and negative predictive value were"poor."Similar results were obtained when the mPG-SGA was used as the criterion. Conclusions:Overall,this cross-sectional study suggests that the GLIM criteria comprise a valid and reliable tool to assess the nutri-tional status of Chinese cancer patients.

Long-term outcomes of combined hepatocellular-cholangiocarcinoma after hepatectomy or liver transplantation: A systematic review and meta-analysis

Background: Combined hepatocellular-cholangiocarcinoma(cHCC-CC) is a rare primary liver malignancy. We conducted a systematic review and meta-analysis to assess the evidence available on the long-term outcomes of cHCC-CC patients after either hepatectomy or liver transplantation(LT). Data Sources: Relevant studies published between January 2000 and January 2018 were identified by searching Pub Med and Embase and reviewed systematically. Data were pooled using a random-effects model. Results: A total of 42 observational studies involving 1691 patients(1390 for partial hepatectomy and 301 for LT) were included in the analysis. The median tumor recurrence and 5-year overall survival(OS) rates were 65%(range 38%–100%) and 29%(range 0–63%) after hepatectomy versus 54%(range 14%–93%) and 41%(range 16%–73%) after LT, respectively. Meta-analysis found no significant difference in OS and tumor recurrence between LT and hepatectomy groups. Conclusion: Hepatectomy rather than LT should be considered as the prior treatment option for cHCC-CC.

Survival after repeat hepatectomy for recurrent colorectal liver metastasis: A review and meta-analysis of prognostic factors

Background:Frequent recurrent hepatic metastasis after hepatic metastasectomy is a major obstacle in the treatment of colorectal liver metastasis(CRLM).We performed the present systematic review to evaluate the short-and long-term outcomes after repeat hepatectomy for recurrent CRLM and determine factors associated with survival in these patients.Data sources:An electronic search of PubMed database was undertaken to identify all relevant peerreviewed papers published in English between January 20 0 0 and July 2018.Hazard ratios(HR)with 95%confidence interval(95%CI)were calculated for prognostic factors of overall survival(OS).Results:The search yielded 34 studies comprising 3039 patients,with a median overall morbidity of 23%(range 8%–71%),mortality of 0(range 0–6%),and 5-year OS of 42%(range 17%–73%).Pooled analysis showed that primary T3/T4 stage tumor(HR=1.94;95%CI:1.04–3.63),multiple tumors(HR=1.49;95%CI:1.10–2.01),largest liver lesion≥5 cm(HR=1.89;95%CI:1.11–3.23)and positive surgical margin(HR=1.80;95%CI:1.09–2.97)at initial hepatectomy,and high serum level of carcinoembryonic antigen(HR=1.87;95%CI:1.27–2.74),disease-free interval≤12 months(HR=1.34;95%CI:1.10–1.62),multiple tumors(HR=1.64;95%CI:1.32–2.02),largest liver lesion≥5 cm(HR=1.85;95%CI:1.34–2.56),positive surgical margin(HR=2.25;95%CI:1.39–3.65),presence of bilobar disease(HR=1.62;95%CI:1.19–2.20),and extrahepatic metastases(HR=1.60;95%CI:1.23–2.09)at repeat hepatectomy were significantly associated with poor OS.

Zircon U-Pb-Hf isotopic and geochemical characteristics of the Xierzi biotite monzogranite pluton,Linxi,Inner Mongolia and its tectonic implications

The opening, subduction and final closure of the Paleo-Asian Ocean led to the formation of the Central Asian Orogenic Belt. Controversy has long surrounded the timing of final closure of the Paleo-Asian Ocean. Here we present zircon U-Pb ages and petrological, geochemical and in situ Hf isotope data for the Xierzi biotite monzogranite pluton, Linxi, SE Inner Mongolia. U-Pb dating of zircon by LA-ICP-MS yields a middle Permian emplacement age(268.7 ± 2.3 Ma) for the Xierzi pluton that is dominated by biotite monzogranites with high SiO_2(71.2-72.8 wt.%),alkali(Na_2 O + K_2 O =8.05-8.44 wt.%), Al_2 O_3(14.4-15.2 wt.%) and Fe_2 O_3~T relative to low MgO contents, yielding Fe_2 O_3~T/MgO ratios of 2.87-3.44, and plotting within the high-K calc-alkaline field on a SiO_2 vs. K_2 O diagram. The aluminum saturation indexes(A/CNK) of the biotite monzogranites range from 1.06 to 1.19, corresponding to weakly to strongly peraluminous. They are enriched in rare earth elements(REE), high field strength elements(HFSEs; Zr,Hf). and large ion lithophile elements(LILEs; Rb, U, Th). The LREEs are enriched relative to the HREEs,with a distinct negative Eu anomaly in a chondrite-normalized REE diagram. Geochemically, the Xierzi biotite monzogranite is classified as an aluminous A-type granite, with all samples plotting within the A2-type granite field on a Y/Nb vs. Rb/Nb diagram. Zircon ε_(Hf)(t) values and two-stage modal ages of the zircons within the pluton range from +4.80 to +13.65 and from 983 to 418 Ma, respectively, indicating that the primary magma was generated through partial melting of felsic rocks from juvenile crust.Consequently, these results demonstrate that the Xierzi pluton formed under the post-orogenic extensional setting after arc-continent collision in the middle Permian.

Proposal of a new T-stage classification system for ampullary carcinoma based on Surveillance,Epidemiology and End Result(SEER)database

Background:Tumor size is still considered a useful prognostic factor in currently available tumor-nodemetastasis(TNM)classification staging systems for most solid tumors,but the significance of tumor size on the prognosis of ampullary carcinoma remains controversial.The aim of the current study was to propose a new T-stage classification system for ampullary carcinoma to address the impact of tumor size on the prognostic outcome.Methods:Using the Surveillance,Epidemiology,and End Results(SEER)database,we identified 1080 patients with ampullary carcinoma who underwent radical surgical resection between 2004 and 2015.Based on the results obtained from analysis of various clinicopathologic factors,a new T-stage classification system was proposed.Results:Among the 1080 patients,618 were men and 462 were women,with a median tumor size of 2.3(range 0.1–12)cm.Using the 7 th edition of the American Joint Committee on Cancer(AJCC)staging manual,we noticed significant differences in overall survival(OS)between T2 vs.T3 tumors(P<0.001)and T3 vs.T4 tumors(P=0.002),but failed to observe significant differences between T1 vs.T2 tumors(P=0.498)in our pair-wise comparison.Using the newly developed T-stage classification system,we were able to differentiate significant differences in OS between T1 vs.T2 tumors(P=0.032),T2 vs.T3 tumors(P<0.001)and T3 vs.T4 tumor(P=0.003)in all pair-wise comparisons.The c-index of the new staging system was 0.653(95%CI:0.629–0.677),showing a better discriminatory power than the 0.636 of the 7 th AJCC staging system(95%CI:0.612–0.660).Conclusions:The new T-stage classification system described herein can better differentiate prognostic outcomes after radical resection in patients with ampullary carcinoma by incorporating tumor size and depth of tumor infiltration.

Earlier onset and multiple primaries in familial as opposed to sporadic esophageal cancer

AIM: To study the differences in onset age and multiple primary cancers between familial and sporadic esophageal squamous cell carcinoma(ESCC).METHODS: The differences in onset age and multiple primary cancers were analyzed between ESCC patients with(n = 766) and without(n = 1776) a family history of the cancer. The cases analyzed constituted all consecutive patients who had undergone cure-intent surgery at the Department of Thoracic Surgery of the 4th Hospital of Hebei Medical University from January 1 1975 to December 31 1989. Because we also originally aimed to examine the difference in survival time, only older subjects with a long follow-up period were selected.RESULTS: Overall, patients with ESCC and a positive family history of the cancer had a significantly younger age at onset and more multiple primary cancers than those without a positive family history(51.83 ± 8.39 vs 53.49 ± 8.23 years old, P = 0.000; 5.50% vs 1.70%, P = 0.000). Both of these differences were evident in subgroup analyses, however, no correlations were observed. While age at onset differed significantly by family history in males, smokers, and drinkers, the difference in multiple primary cancers by family history was significant in nonsmoking, nondrinking, and younger onset patients. In multivariate analysis, age over 50 years, tobacco smoking, and multiple primary cancers were found to be significant predictors of familial cancer: the corresponding OR(95%CI) and P-value were 0.974(0.963-0.985) and 0.000; 1.271(1.053-1.535) and 0.012; and 4.265(2.535-7.176) and 0.000, respectively.CONCLUSION: Patients with ESCC and a positive family history of the cancer had a significantly younger onset age and more multiple primary cancers than those without a positive family history. Sub-group analyses indicated that younger onset age may be due to the interaction of genetic predisposition and environmental hazards, and multiple primary cancers may only be due to genetic predisposition.

An Organic Small Molecule as a Solid Additive in Non-Fullerene Organic Solar Cells with Improved Efficiency and Operational Stability

The use of additive is an effective approach to optimize the active layer morphology and improve the power conversion efficiency(PCE)of organic solar cells(OSCs).However,residual solvent additives always lead to undesirably compromise the stability of OSCs.In this work,an organic small molecule BBT-Cl was designed and used as a novel solid additive to partly replace solvent additive to fabricate highperformance OSCs.The synergistic effect of the dual additives on the optical property,morphology and photovoltaic characteristics of the PM6:Y6 based non-fullerene OSCs have been systematically characterized.The introduction of BBT-Cl could effectively enhance the crystallinity of the blend and promote charge extraction and transport.Consequently,the OSCs processed by the dual additives exhibit a high PCE of 17.73%,which is obviously higher than OSCs with CN additive(16.48%).Meanwhile,BBT-Cl based dual additives treatment has also been successfully introduced into another two non-fullerene OSCs to verify its general applicability.Furthermore,20%PCE aging is significantly prolonged from 720 min to 2880 min for the devices proceeded with the dual additives.This work highlights the great potential of solid additive in the fabrication of efficient OSCs with excellent stability.

Features of intervertebral disc degeneration in rat's aging process

Objective:The age-related change is important part of degenerative disc disease. However,no appropriate animal model or objective evaluation index is available. This study aimed to investigate the features of intervertebral disc degeneration in aging process of rats. Methods:22-month-old Sprague-Dawley(SD) rats were used as spontaneously occurring intervertebral disc degeneration models and 6-month-old rats as young controls. Expression of collagen types II and X was measured by immunohistochemistry. Degenerations of intervertebral discs were scored according to Miyamoto's method. Numbers and areas of afferent vascular buds were measured. The thicknesses of non-calcified and calcified layers were measured and statistically analyzed. Results:There were less collagen type II expression and more collagen type X expression in the calcified layer of the cartilage endplates and nucleus pulposus in the rats of the aged group than in the young control. There were fewer and smaller afferent vascular buds in the rats of the aged group than in the young control group. The ratio of the non-calcified to the calcified layers in the rats of the aged group significantly decreased,compared with that of the young control group(P<0.01) . Conclusion:Rats can spontaneously establish intervertebral disc age-related degeneration. The expression of collagen types II and X,numbers and areas of afferent vascular buds,the ratio of the non-calcified to the calcified layers,and water and glycosaminoglycan contents in the nucleus pulposus are sensitive indexes of intervertebral disc degeneration.

CD 147 receptor is essential for TFF3-mediated signaling regulating colorectal cancer progression

Major gaps in understanding the molecular mechanisms of colorectal cancer(CRC)progression and intestinal mucosal repair have hampered therapeutic development for gastrointestinal disorders.Trefoil factor 3(TFF3)has been reported to be involved in CRC progression and intestinal mucosal repair;however,how TFF3 drives tumors to become more aggressive or metastatic and how TFF3 promotes intestinal mucosal repair are still poorly understood.Here,we found that the upregulated TFF3 in CRC predicted a worse overall survival rate.TFF3 deficiency impaired mucosal restitution and adenocarcinogenesis.CD147,a membrane protein,was identified as a binding partner for TFF3.Via binding to CD147,TFF3 enhanced CD147-CD44s interaction,resulting in signal transducer and activator of transcription 3(STAT3)activation and prostaglandin G/H synthase 2(PTGS2)expression,which were indispensable for TFF3-induced migration,proliferation,and invasion.PTGS2-derived PGE2 bound to prostaglandin E2 receptor EP4 subtype(PTGER4)and contributed to TFF3-stimulated CRC progression.Solution NMR studies of the TFF3-CD147 interaction revealed the key residues critical for TFF3 binding and the induction of PTGS2 expression.The ability of TFF3 to enhance mucosal restitution was weakened by a PTGS2 inhibitor.Blockade of TFF3-CD147 signaling using competitive inhibitory antibodies or a PTGS2 inhibitor reduced CRC lung metastasis in mice.Our findings bring strong evidence that CD147 is a novel receptor for TFF3 and PTGS2 signaling is critical for TFF3-induced mucosal restitution and CRC progression,which widens and deepens the understanding of the molecular function of trefoil factors.

The Finite-time Ruin Probability of a Discrete-time Risk Model with Subexponential and Dependent Insurance and Financial Risks

Consider a discrete-time risk model with insurance and financial risks in a stochastic economic environment. Assume that the insurance and financial risks form a sequence of independent and identically distributed random vectors with a generic random vector following a wide type of dependence structure. An asymptotic formula for the finite-time ruin probability with subexponential insurance risks is derived. In doing so, the subexponentiality of the product of two dependent random variables is investigated simultaneously.

In situ cosmogenic ^(10)Be, ^(26)Al, and ^(21)Ne dating in sediments from the Guizhou Plateau, southwest China

Landscape evolution is modulated by the regional tectonic uplift,climate change,and river dynamics.However,how to distinguish these mechanisms through the research of surface exhumation and fluvial incision remains controversial.In this study,cosmogenic ^(10)Be,^(26)Al,and ^(21)Ne concentrations in quartz from cave deposits,modern river sediments,and bedrocks were measured to constrain the applicability of cosmogenic ^(21)Ne and discuss Quaternary landscape evolution history in the Guizhou Plateau,southeast China.Using the ^(26)Al-^(10)Be and ^(21)Ne-^(10)Be pairs to distinguish the cosmogenic ^(21)Ne concentration from the excess ^(21)Ne,we found that the nucleogenic ^(21)Ne produced by the U and Th decay in quartz is significant in the samples although there is the possibility of inherited cosmogenic ^(21)Ne.Combining with previous studies,we suggest that the precise approach for applying the cosmogenic ^(21)Ne could be reached by(1)estimating the contribution from nucleogenic ^(21)Ne,(2)avoiding samples with complex burial histories to exclude inherited cosmogenic ^(21)Ne,and(3)combining the ^(10)Be-^(26)Al-^(21)Ne nuclides method for the Quaternary samples.In addition,both pre-burial basin denudation rates and burial ages derived from the ^(26)Al-^(10)Be pair were used to determine the different timescale surface denudation rate and fluvial incision rate in relation to previous work.The consistency of the different timescales pre-burial basin denudation rate,^(36)Cl surface denudation rate,and modern basin denudation rate indicates that the landscape-scale surface denudation has been likely stabilized since the Quaternary in the Guizhou Plateau area.The slightly higher river incision rates than the local surface denudation rate show that the river dynamics may not have reached a steady-state due to the regional tectonic uplift in the Guizhou Plateau.

PDGFA-associated protein 1 is a novel target of c-Myc and contributes to colorectal cancer initiation and progression

Background:The mechanism underlying colorectal cancer(CRC)initiation and progression remains elusive,and overall survival is far from satisfactory.Previous studies have shown that PDGFA-associated protein 1(PDAP1)is upregulated in several cancers including CRC.Here,we aimed to identify the cause and consequence of PDAP1 dysregulation in CRC and evaluate its role as a potential therapeutic target.Methods:Multi-omics data analysis was performed to identify potential key players in CRC initiation and progression.Immunohistochemistry(IHC)staining was applied to determine the expression pattern of PDAP1 in CRC tissues.Pdap1 conditional knockout mice were used to establish colitis and CRC mouse models.RNA sequencing,a phosphoprotein antibody array,western blotting,histological analysis,5-bromo-2′-deoxyuridine(BrdU)incorporation assay,and interactome analysis were applied to identify the underlying mechanisms of PDAP1.A human patient-derived xenograft(PDX)model was used to assess the potential of PDAP1 as a therapeutic target.Results:PDAP1 was identified as a potential key player in CRC development using multi-omics data analysis.PDAP1 was overexpressed in CRC cells and correlated with reduced overall survival.Further investigation showed that PDAP1 was critical for the regulation of cell proliferation,migration,invasion,and metastasis.Significantly,depletion of Pdap1in intestinal epithelial cells impaired mucosal restitution in dextran sulfate sodium salt-induced colitis and inhibited tumor initiation and growth in colitis-associated cancers.Mechanistic studies showed that c-Myc directly transactivated PDAP1,which contributed to the high PDAP1 expression in CRC cells.PDAP1 interacted with the juxtamembrane domain of epidermal growth factor receptor(EGFR)and facilitated EGFRmitogen-activated protein kinase(MAPK)signaling activation,which resulted in FOS-related antigen 1(FRA-1)expression,thereby facilitating CRC progression.Notably,silencing of PDAP1 could hinder the growth of patient-derived xenografts that sustain high PDAP1 levels.Conclusions:PDAP1 facilitates mucosal restitution and carcinogenesis in colitis-associated cancer.c-Myc-driven upregulation of PDAP1 promotes proliferation,migration,invasion,and metastasis of CRC cells via the EGFRMAPK-FRA-1 signaling axis.These findings indicated that PDAP1 inhibition is warranted for CRC patients with PDAP1 overexpression.