Search

PURPOSE To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer. MATERIALS AND METHODS Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node–positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS). RESULTS Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P < .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group ( P < .001). CONCLUSION Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.

Academically gifted adolescent students (N = 213) at 10 junior high schools in Taoyuan, Taiwan, completed a survey to examine the socioaffective factors associated with their engagement in regular classes. Structural equation modeling was performed for inferential statistical analysis. The results show that the students' emotional intelligence was associated with their engagement in regular classes. In addition, teacher–student and peer relationships mediated the relationship between students' emotional intelligence and engagement. Therefore, emotional competencies and interpersonal relationships may play a crucial role in promoting academically gifted adolescent students' engagement in regular classes.

It's worth noting that detect effective methods for tracking ClO

Our study aimed to explore the intercorrelations of brachial‐ankle pulse wave velocity (baPWV), ankle‐brachial index (ABI), ambulatory arterial stiffness index (AASI), 24‐hour mean pulse pressure (24‐h PP), and augmentation index (AIx, AIx@75, the AIx standardized to a heart rate of 75) and compare the effectiveness of these markers for predicting renal outcomes. A total of 117 patients with chronic kidney disease (CKD) who received noninvasive arterial stiffness examinations were enrolled. We used correlation analysis and linear regression to explore the correlations between these five arterial stiffness markers and the Cox proportional hazards model and receiver operator characteristic (ROC) curve to assess the associations of markers with kidney disease outcomes. The median (interquartile range) of age and eGFR were 61 (49‐65) years and 50.5 (35.5‐84.1) ml/min/1.73 m2, respectively. In Pearson correlation analysis, baPWV was significantly associated with 24‐h PP (r = .531, p

AIM To investigate the possible associations between intrarenal arteriolosclerosis as determine by renal biopsy and endothelial function as well as arterial stiffness measured by peripheral arterial tonometry (EndoPAT). METHODS This was a cross-sectional study. Patients who underwent both renal biopsy and EndoPAT were recruited, and intrarenal arteriolosclerosis was graded according to the pathological slice. Endothelial function and arterial stiffness were both measured by EndoPAT and were expressed by the reactive hyperemia index (RHI) and augmentation index (AIx), respectively. AIx@75, representing the AIx standardized to a heart rate of 75 bpm was also determined. RESULTS In total, 113 patients were assessed, the mean age was 51 ± 13, and 68.1% were men. The natural logarithm RHI (LnRHI), AIx and AIx@75 were significantly different among different grades of intrarenal arteriolosclerosis (P = .030, P

Two α-amino-phosphonate derivatives (1 & 2) were synthesized and their compositions and structures were characterized by Elemental Analysis (EA), FT-IR Spectrascopy (FT-IR), Electrospray Ionization Mass Spectrometry (ESI-MS), Nuclear Magnetic Resonance (NMR, 1H, 13C and 31P) and X-ray crystallography. Compound 1 & 2 were crystallized in monoclinic system with the space group P2(1)/n and P2(1)/c, respectively. The interaction effects of two α-aminophosphonate derivatives (1 & 2) with BSA were investigated and the binding constants were 1.07 × 104 M-1, 1.68 × 104 M-1, respectively. Besides, the values of n were indicated that 1:1 complex was formed between BSA and 1&2.

Malaria, caused by protozoan parasites of the genus Plasmodium especially by the most prevalent parasite Plasmodium falciparum, represents one of the most devastating and common infectious disease globally. Nearly half of the world population is under the risk of being infected, and more than 200 million new clinical cases with around half a million deaths occur annually. Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance, so it's imperative to develop new antimalarials with great potency against both drug-susceptible and drug-resistant malaria. Triazoles, bearing a five-membered heterocyclic ring with three nitrogen atoms, exhibit promising in vitro antiplasmodial and in vivo antimalarial activities. Moreover, several triazole-based drugs have already used in clinics for the treatment of various diseases, demonstrating the excellent pharmaceutical profiles. Therefore, triazole derivatives have the potential for clinical deployment in the control and eradication of malaria. This review covers the recent advances of triazole derivatives especially triazole hybrids as potential antimalarials. The structure-activity relationship is also discussed to provide an insight for rational designs of more efficient antimalarial candidates.

Ambulatory blood pressure monitoring (ABPM) can produce many variables, of which the lowest nocturnal systolic blood pressure (LNSBP) currently used in calculating morning surge is occasionally overlooked in recent kidney studies compared with other ABPM parameters. We explored the clinical effects of LNSBP in elderly patients with chronic kidney disease (CKD) in a multicenter, observational cohort study. A total of 356 elderly patients with CKD from 19 clinics were included in this analysis. We used multiple logistic regression and survival analyses to assess the associations between the lowest nocturnal systolic blood pressure and heavy proteinuria and kidney disease outcomes, respectively. The median age was 66 years, and 66.6% were men. The median eGFR was 49.2 ml/min/1.73 m2. Multivariate logistic regression analysis demonstrated that LNSBP (OR 1.24; 95% CI 1.10–1.39; P

The mass spectrum of hidden charm pentaquark states composed of two diquarks and an antiquark are calculated by use of an effective Hamiltonian which includes explicitly the spin, color, and flavor dependent interactions. The results show that the $P_c(4312)^+$ and $P_c(4440)^+$ states could be explained as hidden charm pentaquark states with isospin and spin-parity $IJ^P=1/2\left(3/2^-\right)$, the $P_c(4457)^+$ state could be explained as a hidden charm pentaquark state with $IJ^P=1/2\left(5/2^-\right)$, and the $P_{cs}(4459)^+$ state could be explained as a hidden charm pentaquark state with $IJ^P=0\left(1/2^-\right)$ or $0\left(3/2^-\right)$. Predications for the masses of other possible pentaquark states are also given, and the possible decay channels of these hidden charm pentaquark states are discussed., Comment: 9 pages

The purpose of the present study is to explore the mass spectrum of the hidden charm tetraquark states within a diquark model. Proposing that a tetraquark state is composed of a diquark and an antidiquark, the masses of all possible $[qc][\bar{q}\bar{c}]$, $[sc][\bar{s}\bar{c}]$, and $[qc][\bar{s}\bar{c}]$ $\left([sc][\bar{q}\bar{c}]\right)$ hidden charm tetraquark states are systematically calculated by use of an effective Hamiltonian, which contains color, spin, and flavor dependent interactions. Apart from the $X(3872)$, $Z(3900)$, $\chi_{c2}(3930)$, and $X(4350)$ which are taken as input to fix the model parameters, the calculated results support that the $\chi_{c0}(3860)$, $X(4020)$, $X(4050)$ are $[qc][\bar{q}\bar{c}]$ states with $I^GJ^{PC}=0^+0^{++}$, $1^+1^{+-}$, and $1^-2^{++}$, respectively, the $\chi_{c1}(4274)$ is an $[sc][\bar{s}\bar{c}]$ state with $I^GJ^{PC}=0^+1^{++}$, the $X(3940)$ is a $[qc][\bar{q}\bar{c}]$ state with $I^GJ^{PC}=1^-0^{++}$ or $1^-1^{++}$, the $Z_{cs}(3985)^-$ is an $[sc][\bar{q}\bar{c}]$ state with $J^{P}=0^{+}$ or $1^+$, and the $Z_{cs}(4000)^+$ and $Z_{cs}(4220)^+$ are $[qc][\bar{s}\bar{c}]$ states with $J^{P}=1^{+}$. Predictions for other possible tetraquark states are also given., Comment: 9 pages. Version published in Phys. Rev. D

Endometrial cancer (EC) is the second most common gynecological malignancy worldwide. Tribbles pseudokinase 3 (TRIB3) is a scaffolding protein that regulates intracellular signal transduction, and its role in tumor development is controversial. Here, we investigated the biological function of TRIB3 in EC. We found that the messenger RNA (mRNA) expression level of TRIB3 was significantly and positively correlated with shorter overall survival of EC patients in The Cancer Genome Atlas database. The protein expression of TRIB3 was found to be significantly increased in EC cancer stem cells (CSCs) enriched by tumorsphere cultivation. Knockdown of TRIB3 in EC cells suppressed tumorsphere formation, the expression of cancer stemness genes, and the in vivo tumorigenesis. The expression of &beta, catenin at both the protein and the mRNA levels was downregulated upon TRIB3 silencing. TRIB3 was found to interact with E74 Like ETS transcription factor 4 (ELF4) in the nucleus and bound to ELF4 consensus sites within the catenin beta 1 (CTNNB1) promoter in EC cell lines. These data indicated that TRIB3 may regulate CTNNB1 transcription by enhancing the recruitment of ELF4 to the CTNNB1 promoter. In conclusion, our results suggest that TRIB3 plays an oncogenic role in EC and positively regulates the self-renewal and tumorigenicity of EC-CSCs. Targeting TRIB3 is considered as a potential therapeutic strategy in future EC therapy.

Background The cytotoxin-associated gene A protein (CagA), an effector protein of Helicobacter pylori (H. pylori), was the first identified bacterium oncoprotein. Based on its sequence characteristics, H. pylori has been classified into East Asian and Western strains. We hypothesized that the differences in structure of CagA and proteomic profiles between East Asian and Western H. pylori strains are the primary cause of the differential clinical outcomes of H. pylori infection. Results In this study, we isolated 27 H. pylori strains from gastric mucosa of Chinese patients with gastric diseases and revealed that the Western CagA has more variation in its EPIYA motifs than East Asian CagA. This result was further confirmed via analyzing the CagA sequences of 150 H. pylori strains from GenBank. More importantly, we detected the deletion or partial deletion of 13 amino acids in CagA in all East Asian strains but not in Western strains. iTRAQ -based proteomic analysis showed that the CagA protein related to cytotoxicity was highly expressed in Western strains, while urease-associated proteins UreA and UreH, flagellin related proteins FlaA, FlgE and FlhA, and cell division proteins FtsZ and FtsI were highly expressed in East Asian strains. These proteins were associated with the colonization, motility, and viability potential of H. pylori in the human stomach and were clustered into an interaction network. Conclusions This study provides significant, unreported differential sequences of CagA and proteomic profiles between East Asian and Western H. pylori, which maybe serves as promising new targets to ascertain the pathogenesis of H. pylori.

Both unitary chiral theories and lattice QCD simulations show that the DK interaction is attractive and can form a bound state, namely, $$D^*_{s0}(2317)$$ D s 0 ∗ ( 2317 ) . Assuming the validity of the heavy antiquark–diquark symmetry, the $$\Xi _{cc}{\bar{K}}$$ Ξ cc K ¯ interaction is the same as the DK interaction, which implies the existence of a $$\Xi _{cc}{\bar{K}}$$ Ξ cc K ¯ bound state with a binding energy of $$49-64$$ 49 - 64 MeV. In this work, we study whether a $$\Xi _{cc}\Xi _{cc}{\bar{K}}$$ Ξ cc Ξ cc K ¯ three-body system binds. The $$\Xi _{cc}\Xi _{cc}$$ Ξ cc Ξ cc interaction is described by exchanging $$\pi $$ π , $$\sigma $$ σ , $$\rho $$ ρ , and $$\omega $$ ω mesons, with the corresponding couplings related to those of the NN interaction via the quark model. We indeed find a $$\Xi _{cc}\Xi _{cc}{\bar{K}}$$ Ξ cc Ξ cc K ¯ bound state, with quantum numbers $$J^P=0^-$$ J P = 0 - , $$I=\frac{1}{2}$$ I = 1 2 , $$S=1$$ S = 1 and $$C=4$$ C = 4 , and a binding energy of 80–118 MeV. With the same formalism, we find that the $$\Xi _{cc}\bar{\Xi }_{cc}{\bar{K}}$$ Ξ cc Ξ ¯ cc K ¯ system also binds, yielding a $$I(J^P)=\frac{1}{2}(0^+)$$ I ( J P ) = 1 2 ( 0 + ) state and a $$\frac{1}{2}(1^+)$$ 1 2 ( 1 + ) state with binding energies of 56–68 MeV and 56–67 MeV respectively. As a byproduct, we show the existence of a $$NN{\bar{K}}$$ N N K ¯ state with a binding energy of 35–43 MeV, consistent with the results of other theoretical works and experimental data, which serves as a consistency check on the predicted $$\Xi _{cc}\Xi _{cc}{\bar{K}}$$ Ξ cc Ξ cc K ¯ bound state.

The high-precision differential cross-section data for the reaction $\ensuremath{\gamma}p\ensuremath{\rightarrow}{K}^{*+}\mathrm{\ensuremath{\Lambda}}$ are reanalyzed within a Regge-inspired effective Lagrangian approach. The model adopts Regge phenomenology to constrain the $t$-channel contributions from the $\ensuremath{\kappa}$, $K$, and ${K}^{*}$ exchanges. A minimal number of resonances in the $s$ channel are introduced in constructing the reaction amplitudes in order to describe the data. It is shown that the differential cross-section data for $\ensuremath{\gamma}p\ensuremath{\rightarrow}{K}^{*+}\mathrm{\ensuremath{\Lambda}}$ can be satisfactorily described by introducing the only $N(2060){5/2}^{\ensuremath{-}}$ resonance in the $s$ channel, which is quite different from our earlier work performed in an effective Lagrangian approach [A. C. Wang et al., Phys. Rev. C 96, 035206 (2017)], where the amplitudes are computed by evaluating Feynman diagrams and it is found that introducing at least one additional resonance apart from the $N(2060){5/2}^{\ensuremath{-}}$ is indispensable for reproducing the data. The roles of individual contributions from meson and baryon exchanges on the angular distributions are found to be highly model dependent. The extracted mass of $N(2060){5/2}^{\ensuremath{-}}$ turns out to be well determined, independent of how the $t$-channel amplitudes are constructed, whereas the width does not.

The photoproduction of γp→K+Σ0(1385) is investigated based on an effective Lagrangian approach using the tree-level Born approximation, with the purpose of understanding the reaction mechanisms and resonance contents and their associated parameters in this reaction. In addition to the t-channel K and K*(892) exchanges, s-channel nucleon (N) exchange, u-channel Λ exchange, and generalized contact term, the exchanges of a minimum number of N and Δ resonances in the s channel are taken into account in constructing the reaction amplitudes to describe the experimental data. It is found that the most recent differential cross-section data from the CLAS Collaboration can be well reproduced by including one of the N(1895)1/2-, Δ(1900)1/2-, and Δ(1930)5/2- resonances. The reaction mechanisms of γp→K+Σ0(1385) are discussed in detail, and the predictions of the beam and target asymmetries for this reaction are given. The cross sections of γp→K0Σ+(1385) are shown to be able to further constrain the theoretical models and pin down the resonance contents for γp→K+Σ0(1385).

The authors proposed a positive discipline, well-being and teaching effectiveness model that suggested that teachers’ positive discipline would facilitate students’ well-being and effective teachin...

Purpose of the study The incidence of acute kidney injury (AKI) with a poor prognosis in the elderly has been increasing each year. This study aimed to investigate the clinical characteristics of and risk factors for death from AKI in the elderly and help improve prognosis. Study design This study was a retrospective cohort study based on data from adult patients (≥18 years old) admitted to 15 hospitals in China between 1 January 2009 and 31 December 2011. The characteristics of AKI in the elderly were compared with those in younger patients. Results In elderly patients with AKI, rates of hypertension, cardiovascular disease and multiple organ dysfunction syndrome (MODS) were higher than in younger patients (44.2% vs 31.2%, 16.1% vs 4.6% and 20.9% vs 16.9%, respectively), the length of ICU stay was longer (3.8 days vs 2.7 days, P=0.019) and renal biopsy (1.0% vs 7.13%, P Conclusions HA-AKI and pre-renal AKI were more common in the elderly. Age, cardiovascular disease, cancer, MODS and mechanical ventilation were independent risk factors for death in the elderly with AKI.

Wen-Ling Wang,1,2 Shuang Liang,1 Fang-Lei Zhu,1 Jie-Qiong Liu,1 Si-Yang Wang,1 Xiang-Mei Chen,1 Guang-Yan Cai1On behalf of the C-OPTION study group1Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease, Beijing, People’s Republic of China; 2General Internal Medicine Department, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaPurpose: The prevalence of depression and the relationship between depression and kidney function and health-related quality of life (HRQOL) are not well understood in elderly patients with predialysis chronic kidney disease (CKD). This study aimed to evaluate the prevalence of depression and the association between depression and kidney function and HRQOL.Patients and methods: In this cross-sectional study, 1079 elderly participants with CKD were recruited at 32 clinical centers located within 26 cities throughout 24 provinces in China. Demographic information and laboratory analyses were collected. Symptoms of depression were assessed using the 15-item Geriatric Depression Scale (GDS-15). HRQOL was evaluated using the Kidney Disease Quality of Life-36 (KDQOL-36) instrument.Results: The prevalence of depression was 23.0%. The estimated glomerular filtration rate (eGFR) was negatively correlated with the GDS score whether it was treated as a categorical variable (r=−0.097, P=0.001) or as a continuous variable (r=−0.100, P=0.001). Marital status, education level, history of CVD and diabetes, CKD stage and proteinuria confirmed to be independent and significant predictors of depression in patients with CKD. Compared with CKD 1–2 patients, we observed an increase of 0.541 and 4.171 in the odds for developing depression in patients CKD 4 (odds ratio [OR] =1.541; P=0.031) and CKD 5 (odds ratio [OR] =5.171; P

The purpose of the present study was to explore the possibility of accommodating the $$d^*(2380)$$ and its flavor SU(3) partners in a diquark model. Proposing that $$d^*(2380)$$ is composed of three vector diquarks, its mass is calculated by use of an effective Hamiltonian approach and its decay width is estimated by considering the effects of quark tunneling from one diquark to the others and the decays of the subsequent two-baryon bound state. Both the obtained mass and decay width of $$d^*(2380)$$ are in agreement with the experimental data, with the unexpected narrow decay width being naturally explained by the large tunneling suppression of a quark between a pair of diquarks. The masses and decay widths of the flavor SU(3) partners of $$d^*(2380)$$ are also predicated within the same diquark scenario.

The two-channel photoproductions of $\ensuremath{\gamma}p\ensuremath{\rightarrow}{K}^{*+}{\mathrm{\ensuremath{\Sigma}}}^{0}$ and $\ensuremath{\gamma}p\ensuremath{\rightarrow}{K}^{*0}{\mathrm{\ensuremath{\Sigma}}}^{+}$ are investigated based on an effective Lagrangian approach at the tree-level Born approximation. In addition to the $t$-channel $K, \ensuremath{\kappa}, {K}^{*}$ exchanges, the $s$-channel nucleon ($N$) and $\mathrm{\ensuremath{\Delta}}$ exchanges, the $u$-channel $\mathrm{\ensuremath{\Lambda}}, \mathrm{\ensuremath{\Sigma}}, {\mathrm{\ensuremath{\Sigma}}}^{*}$ exchanges, and the generalized contact term, we try to take into account the minimum number of baryon resonances in constructing the reaction amplitudes to describe the experimental data. It is found that by including the $\mathrm{\ensuremath{\Delta}}(1905)5/{2}^{+}$ resonance with its mass, width, and helicity amplitudes taken from the Review of Particle Physics [Particle Data Group, C. Patrignani et al., Chin. Phys. C 40, 100001 (2016)], the calculated differential and total cross sections for these two reactions are in good agreement with the experimental data. An analysis of the reaction mechanisms shows that the cross sections of $\ensuremath{\gamma}p\ensuremath{\rightarrow}{K}^{*+}{\mathrm{\ensuremath{\Sigma}}}^{0}$ are dominated by the $s$-channel $\mathrm{\ensuremath{\Delta}}(1905)5/{2}^{+}$ exchange at low energies and $t$-channel ${K}^{*}$ exchange at high energies, with the $s$-channel $\mathrm{\ensuremath{\Delta}}$ exchange providing significant contributions in the near-threshold region. For $\ensuremath{\gamma}p\ensuremath{\rightarrow}{K}^{*0}{\mathrm{\ensuremath{\Sigma}}}^{+}$, the angular dependences are dominated by the $t$-channel $K$ exchange at forward angles and the $u$-channel ${\mathrm{\ensuremath{\Sigma}}}^{*}$ exchange at backward angles, with the $s$-channel $\mathrm{\ensuremath{\Delta}}$ and $\mathrm{\ensuremath{\Delta}}(1905)5/{2}^{+}$ exchanges making considerable contributions at low energies. Predictions are given for the beam, target, and recoil asymmetries for both reactions.

The title compound was readily prepared from 2, 3, 4, 5-tetramethoxytoluene via the Blanc reaction, oxidation, and alkylation. The described method provides a good yield of the heterocyclic substitute at the C-5 position of the Coenzyme Q homologue and is suitable for the synthesis of other homologues.

Radiation therapy is a staple approach for cancer treatment, whereas radioresistance of cancer cells remains a substantial clinical problem. In response to ionizing radiation (IR) induced DNA-damage, cancer cells can sustain/activate pro-survival signaling pathways, leading to apoptotic resistance and induction of cell cycle checkpoint/DNA repair. Previous studies show that Rac1 GTPase is overexpressed/hyperactivated in breast cancer cells and is associated with poor prognosis. Studies from our laboratory reveal that Rac1 activity is necessary for G2/M checkpoint activation and cell survival in response to IR exposure of breast and pancreatic cancer cells. In the present study, we investigated the effect of Rac1 on the survival of breast cancer cells treated with hyper-fractionated radiation (HFR), which is used clinically for cancer treatment. Results in this report indicate that Rac1 protein expression is increased in the breast cancer cells that survived HFR compared to parental cells. Furthermore, this increase of Rac1 is associated with enhanced activities of ERK1/2 and NF-κB signaling pathways and increased levels of anti-apoptotic protein Bcl-xL and Mcl-1, which are downstream targets of ERK1/2 and NF-κB signaling pathways. Using Rac1 specific inhibitor and dominant negative mutant N17Rac1, here we demonstrate that Rac1 inhibition decreases the phosphorylation of ERK1/2 and IκBα, as well as the levels of Bcl-xL and Mcl-1 protein in the HFR-selected breast cancer cells. Moreover, inhibition of Rac1 using either small molecule inhibitor or dominant negative N17Rac1 abrogates clonogenic survival of HFR-selected breast cancer cells and decreases the level of intact PARP, which is indicative of apoptosis induction. Collectively, results in this report suggest that Rac1 signaling is essential for the survival of breast cancer cells subjected to HFR and implicate Rac1 in radioresistance of breast cancer cells. These studies also provide the basis to explore Rac1 as a therapeutic target for radioresistant breast cancer cells.

Jie-qiong Liu,1,2 Guang-yan Cai,1 Si-yang Wang,1 Yu-huan Song,1 Yuan-yuan Xia,1 Shuang Liang,1 Wen-ling Wang,1 Sa-sa Nie,1 Zhe Feng,1 Xiang-mei Chen1 1Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Disease, Beijing, China; 2Department of Nephrology, Chinese PLA 401 Hospital, Qingdao, China Objectives: The most serious adverse reaction of cisplatin is acute kidney injury (AKI). Cisplatin-induced acute kidney injury (CIA) has no specific preventive measures. This study aims to explore the characteristics and risk factors for CIA in the elderly and to identify potential methods to reduce CIA. Materials and methods: Patients ≥18 years old, with primary tumors, who received initial cisplatin chemotherapy and whose serum creatinine (SCr) values were measured within 2 weeks pre- and postcisplatin treatment and who had complete medical records, were selected from a single center from January 1, 2013 to December 31, 2015. The exclusion criteria included radiotherapy or surgery, recurrent tumors, previous cisplatin treatment, lack of any SCr values before or after cisplatin therapy, and incomplete medical records. Results: Out of a total of 527 patients, 349 were elderly. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) use (9.2%) was more prevalent in the elderly than in younger patients (2.8%, p = 0.007). The dosage of cisplatin treatment was lower in the elderly, but the incidence of CIA (9.46%) was higher in the elderly than in younger patients (3.37%). There were significant differences in the SCr levels, estimated glomerular filtration rate, ACEI/ARB use, and whether a single application of cisplatin was administered, between the elderly AKI group and the non-AKI group. Multivariable analysis showed that administration of a single application of cisplatin (OR 2.853, 95% CI: 1.229, 6.621, p = 0.015) and ACEI/ARB use (OR 3.398, 95% CI: 1.352, 8.545, p = 0.009) were predictive factors for developing CIA in the elderly. Conclusion: The incidence of CIA in the elderly was higher than in younger patients. ACEI/ARB usage and administration of a single application of cisplatin were independent risk factors for CIA in the elderly. Keywords: cisplatin-induced acute kidney injury, elderly, clinical characteristics, risk factors

IntroductionThe proportion of elderly people is steadily rising worldwide, especially in low-income and middle-income countries, including China. Chronic kidney disease (CKD) is a common disorder in older people. However, little is known about the epidemiology of CKD and its consequences among the elderly. Improvements on clinical guidelines and healthcare policies for this population are required. This study aims to examine the risk factors for progression of CKD among the elderly and develop models to identify subgroups who are at high risk.Methods and analysisThis is a prospective, multicentre, cohort study. The study population comprises ~3000 patients with predialysis CKD, aged ≥65 years, recruited between March 2016 and December 2017. After the baseline assessments, these patients will be followed for 5 years or until the occurrence of primary outcomes. Assessments that include anthropomorphic measures, laboratory tests, questionnaires, and blood and urine specimen collection will be performed at baseline and at follow-ups. Data on demographic information, cognitive function, depression, risk of malnutrition, physical activity and quality of life will be collected. The primary outcomes are incidence of end-stage renal disease, loss of renal function (≥40% decline in glomerular filtration rate from baseline), and death. The secondary outcomes are acute coronary syndrome, hospitalisation for heart failure or unstable angina, cerebrovascular events, and peripheral arterial disease.Ethics and disseminationThis study protocol has been approved by the ethics committees of the Chinese People’s Liberation Army General Hospital and the participating centres. All the participants gave written informed consent before data collection. The findings of the study will be published in peer-reviewed journals and will be presented at national or international conferences.Trial registration numberNCT03246204; Pre-results.

Non-inherited syndromes of dermatological interest are classified together in this chapter: Ascher syndrome, Baboon syndrome, blue rubber bleb nevus syndrome, Cronkhite-Canada syndrome, Favre-Racouchot syndrome associated with eyelid papilloma, Gorham syndrome, vulvovaginal-gingival lichen planus, Laugier-Hunziker syndrome, Parry-Romberg syndrome with subclinical cerebral involvement, and Marshall-white syndrome.

Acute myeloid leukemia is the majority type presented in leukemia patients. Forcing malignant cells to undergo differentiation is 1 strategy for acute myeloid leukemia therapy. However, the failure of acute myeloid leukemia patients to achieve remission as a result of drug resistance remains a challenge. In this study, we found that the abundances of the proinflammatory cytokine IL-18 and its receptor (IL-18R) correlated with the occurrence of drug resistance in AML patients during standard treatment. Cyclooxygenase 2 (COX-2) has been suggested to have an antiapoptotic role in chemoresistant cancer cells. IL-18 treatment resulted in an increase in COX-2 expression through the post-transcriptional regulation of COX-2 mRNA in differentiated U937 cells and showed antiapoptotic activity in U937 and THP-1 cells. Two RNA-binding proteins, human antigen R and insulin-like growth factor mRNA-binding protein 3, mediated the stabilization of COX-2 mRNA. IL-18 induced the shuttling of human antigen R and insulin-like growth factor mRNA-binding protein 3 from the nucleus to the cytoplasm and facilitated their interaction; subsequently, this complex bound to the 3′ untranslated region of COX-2 mRNA and affected its stability. We demonstrated further that JNK and/or ERK1/2 regulated human antigen R nucleocytoplasmic shuttling, mediating IL-18 stabilization of cyclooxygenase 2 mRNA.