Enhancing thromboprophylaxis after colorectal cancer surgery in China: Bridging the gap between evidence and implementation through pathway optimization.

BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.

Rational Design of 2D Metal Halide Perovskites with Low Congruent Melting Temperature and Large Melt-Processable Window.

Metal halide perovskites (MHPs) have garnered significant attention due to their distinctive optical and electronic properties, coupled with excellent processability. However, the thermal characteristics of these materials are often overlooked, which can be harnessed to cater to diverse application scenarios. We showcase the efficacy of lowering the congruent melting temperature (Tm) of layered 2D MHPs by employing a strategy that involves the modification of flexible alkylammonium through N-methylation and I-substitution. Structural-property analysis reveals that the N-methylation and I-substitution play pivotal roles in reducing hydrogen bond interactions between the organic components and inorganic parts, lowering the rotational symmetry number of the cation and restricting the residual motion of the cations. Additional I···I interactions enhance intermolecular interactions and lead to improved molten stability, as evidenced by a higher viscosity. The 2D MHPs discussed in this study exhibit low Tm and wide melt-processable windows, e.g., (DMIPA)2PbI4 showcasing a low Tm of 98 °C and large melt-processable window of 145 °C. The efficacy of the strategy was further validated when applied to bromine-substituted 2D MHPs. Lowering the Tm and enhancing the molten stability of the MHPs hold great promise for various applications, including glass formation, preparation of high-quality films for photodetection, and fabrication of flexible devices.

Room-Temperature Anisotropic Actuation Driven by a Synergistic Order-Disorder and Displacive Phase Transition in a Ferroelectric Crystal.

Actuating materials convert different forms of energy into mechanical responses. To satisfy various application scenarios, they are desired to have rich categories, novel functionalities, clear structure-property relationships, fast responses, and, in particular, giant and reversible shape changes. Herein, we report a phase transition-driven ferroelectric crystal, (rac-3-HOPD)PbI3 (3-HOPD = 3-hydroxypiperidine cation), showing intriguingly large and anisotropic room-temperature actuating behaviors. The crystal consists of rigid one-dimensional [PbI3] anionic chains running along the a-axis and discrete disk-like cations loosely wrapping around the chains, leaving room for anisotropic shape changes in both the b- and c-axes. The shape change is switched by a ferroelectric phase transition occurring at around room temperature (294 K), driven by the exceptionally synergistic order-disorder and displacive phase transition. The rotation of the cations exerts internal pressure on the stacking structure to trigger an exceptionally large displacement of the inorganic chains, corresponding to a crystal lattice transformation with length changes of +24.6% and -17.5% along the b- and c-axis, respectively. Single crystal-based prototype devices of circuit switches and elevators have been fabricated by exploiting the unconventional negative temperature-dependent actuating behaviors. This work provides a new model for the development of multifunctional mechanically responsive materials.

Tuning ferroelectric phase transition temperature by enantiomer fraction.

Tuning phase transition temperature is one of the central issues in phase transition materials. Herein, we report a case study of using enantiomer fraction engineering as a promising strategy to tune the Curie temperature (TC) and related properties of ferroelectrics. A series of metal-halide perovskite ferroelectrics (S-3AMP)x(R-3AMP)1-xPbBr4 was synthesized where 3AMP is the 3-(aminomethyl)piperidine divalent cation and enantiomer fraction x varies between 0 and 1 (0 and 1 = enantiomers; 0.5 = racemate). With the change of the enantiomer fraction, the TC, second-harmonic generation intensity, degree of circular polarization of photoluminescence, and photoluminescence intensity of the materials have been tuned. Particularly, when x = 0.70 - 1, a continuously linear tuning of the TC is achieved, showing a tunable temperature range of about 73 K. This strategy provides an effective means and insights for regulating the phase transition temperature and chiroptical properties of functional materials.

Unveiling Chiral Perovskite CD Signal Scaling: Discerning Authentic and Counterfeit Signals through Sample-State Analysis.

Circular dichroism (CD) spectroscopy is a well-known and powerful technique widely used for distinguishing chiral enantiomers based on their differential absorbance of the right and left circularly polarized light. With the increasing demand for solid-state chiral optics, CD spectroscopy has been extended to elucidate the chirality of solid-state samples beyond the traditional solution state. However, due to the sample preparation differential, the CD spectra of the same compound measured by different researchers may not be mutually consistent. In this study, we employ solution, powder, thin-film, and single-crystal samples to explore the challenges associated with CD measurements and distinguish between genuine and fake signals. Rational fabrication of the solid-state samples can effectively minimize the macroscopic anisotropic nature of the samples and thereby mitigate the influence of linear dichroism (LD) and linear birefringence (LB) effects, which arise from anisotropy-induced differences in the absorbances and refractive indices. The local anisotropic and overall isotropic features of the high-quality thin-film sample achieve an optically isotropic state, which exhibits superior CD signal repeatability at the front and back sides at different angles by rotating the sample along the light path. In addition, sample thickness-induced CD signal overload and absorption saturation pose more severe challenges than the LBLD-induced amplified CD signal but are rarely focused on. The CD signal overload in the deep UV region leads to the presence of fake signals, while absorption saturation results in a complete loss of the CD signal. These findings help obtain accurate CD signals by a well-fabricated optically isotropic sample to avoid LDLB and optimize the sample thickness to avoid fake signals and no signals.

Incidence, prevention, risk factors, and prediction of venous thromboembolism in Chinese patients after colorectal cancer surgery: a prospective, multicenter cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a common and serious complication after colorectal cancer (CRC) surgery. Few large-sample studies have reported VTE incidence and management status after CRC surgery in China. This study aimed to investigate the incidence and prevention of VTE in Chinese patients after CRC surgery, identify risk factors for developing VTE, and construct a new scoring system for clinical decision-making and care planning. METHODS: Participants were recruited from 46 centers in 17 provinces in China. Patients were followed up for 1 month postoperatively. The study period was from May 2021 to May 2022. The Caprini score risk stratification and VTE prevention and incidence were recorded. The predictors of the occurrence of VTE after surgery were identified by multivariate logistic regression analysis, and a prediction model (CRC-VTE score) was developed. RESULTS: A total of 1836 patients were analyzed. The postoperative Caprini scores ranged from 1 to 16 points, with a median of 6 points. Of these, 10.1% were classified as low risk (0-2 points), 7.4% as moderate risk (3-4 points), and 82.5% as high risk (≥5 points). Among these patients, 1210 (65.9%) received pharmacological prophylaxis, and 1061 (57.8%) received mechanical prophylaxis. The incidence of short-term VTE events after CRC surgery was 11.2% (95% CI 9.8-12.7), including deep venous thrombosis (DVT) (11.0%, 95% CI 9.6-12.5) and pulmonary embolism (PE) (0.2%, 95% CI 0-0.5). Multifactorial analysis showed that age (≥70 years), history of varicose veins in the lower extremities, cardiac insufficiency, female sex, preoperative bowel obstruction, preoperative bloody/tarry stool, and anesthesia time at least 180 min were independent risk factors for postoperative VTE. The CRC-VTE model was developed from these seven factors and had good VTE predictive performance ( C -statistic 0.72, 95% CI 0.68-0.76). CONCLUSIONS: This study provided a national perspective on the incidence and prevention of VTE after CRC surgery in China. The study offers guidance for VTE prevention in patients after CRC surgery. A practical CRC-VTE risk predictive model was proposed.

Structural Descriptors to Correlate Pb Ion Displacement and Broadband Emission in 2D Halide Perovskites.

2D hybrid lead halide perovskites exhibit versatile photoluminescent behaviors for narrowband to broadband emissions (BBEs) and have become attractive candidates for potential applications such as solid-state lighting. Establishing the relationship between the perovskite structural distortion and BBE is key but challenging in designing and optimizing the perovskite luminophores. Conventional attention is given to analyzing the intra-octahedron distortion of the [PbX6]4- (X = halide) unit that has not yet provided a clear structure-luminescence relationship. Herein, we introduce a descriptor, Pb displacement, to describe the inter-octahedron distortion to clarify the structure-emission relationship. The displacement of adjacent Pb centers represents the lattice distortion, which determines the broadband/narrowband emission instead of the octahedron distortion itself. We find a kite-type quadrilateral rule in (001) type 2D perovskites, that is, the degree to which the four octahedral central ions deviate from a square relates to the BBE. The kite-type arrangement of the Pb ions usually corresponds to the BBEs due to the large structure distortions. In contrast, the square-type arrangement of the Pb ions corresponds to the narrowband emissions because of the small distortions. The distortion descriptor magnifies the distortion scale, making it larger than the conventional one for the intra-octahedron distortion, which matches the general concept of excitons based on the scale of the crystal lattice. Therefore, the set of structural descriptors is better to correlate the perovskite structures and emission properties.

Bulk Mn2+ Doped 1D Hybrid Lead Halide Perovskite with Highly Efficient, Tunable and Stable Broadband Light Emissions.

Mn2+ doped colloidal three-dimensional (3D) lead halide perovskite nanocrystal (PNC) has attracted intensive research attention; however, the low exciton binding energy and fatal optical instability of 3D PNC seriously hinder the optoelectronic application. Therefore, it remains significant to explore new stable host perovskite with strongly bound exciton to realize more desirable luminescent property. In this work, we utilized bulk one-dimensional (1D) hybrid perovskite of [AEP]PbBr5 ⋅ H2 O (AEP=N-aminoethylpiperazine) as structural platform to rationally optimize the luminescent property by a controllable Mn2+ doping strategy. Significantly, the series of Mn2+ -doped 1D [AEP]PbBr5 ⋅ H2 O show enhanced energy transfer efficiency from the strongly bound excitons of host material to 3d electrons of Mn2+ ions, resulting in tunable broadband light emissions from weak yellow to strong red spectral range with highest photoluminescence quantum yield up to 28.41 %. More importantly, these Mn2+ -doped 1D perovskites display ultrahigh structural and optical stabilities in humid atmosphere, water and high temperature exceeding the conventional 3D PNC. Combined highly efficient, tunable and stable broadband light emissions enable Mn2+ -doped 1D perovskite as excellent down-converting phosphor showcasing the potential application in white light emitting diode. This work not only provides a profound understanding of low-dimensional perovskites but also opens a new way to rationally design high-performance broadband light emitting perovskites for solid-state lighting and displaying devices.

Improving Broadband White-Light Emission Performances of 2D Perovskites by Subtly Regulating Organic Cations.

Recently, 2D organic-inorganic hybrid lead halide perovskites have attracted intensive attention in solid-state luminescence fields such as single-component white-light emitters, and rational optimization of the photoluminescence (PL) performance through accurate structural-design strategies is still significant. Herein, by carefully choosing homologous aliphatic amines as templates, isotypical perovskites [DMEDA]PbCl4 (1, DMEDA=N,N-dimethylethylenediamine) and [DMPDA]PbCl4 (2, DMPDA=N,N-dimethyl-1,3-diaminopropane) having tunable and stable broadband bluish white emission properties were rationally designed. The subtle regulation of organic cations leads to a higher degree of distortion of the 2D [PbCl4 ]2- layers and enhanced photoluminescence quantum efficiencies (<1 % for 1 and 4.9 % for 2). The broadband light emissions could be ascribed to self-trapped excitons on the basis of structural characterization, time-resolved PL, temperature-dependent PL emission, and theoretical calculations. This work gives a new guidance to rationally optimize the PL properties of low-dimensional halide perovskites and affords a platform to probe the structure-property relationship.

A three-dimensional cuprous lead bromide framework with highly efficient and stable thermochromic luminescence properties.

Herein, by using a structural design strategy of incorporating hetrometallic halide blocks, we prepared the first 3D bimetallic halide of [H2DABCO]2Cu6PbBr12 with new topological network based on two types of 6-connected nodes. Remarkably, this 3D framework displays highly efficient thermochromic luminescence from broadband yellow to green light emissions with remarkable stability.

Fibroblast growth factor receptor-like-1: a new therapeutic target and unfavorable prognostic indicator for rectal adenocarcinoma.

Fibroblast growth factor receptor-like-1 (FGFRL1) is important to cell motility and links with tumorigenic potential in various types of cancers. To investigate the biological function and underlying mechanism of FGFRL1 in rectal adenocarcinoma, we conducted this study. TCGA and Oncomine databases were used to analyze FGFRL1 expression and its association with clinical characteristics or overall survival (OS) in rectal adenocarcinoma patients. siRNA strategy was implemented to knockdown FGFRL1 expression in rectal adenocarcinoma cells. CCK8, colony formation, wound healing, and transwell assays were implemented to measure cell behaviors. qRT-PCR and western blot were utilized to identify mRNA and protein expression levels. FGFRL1 was significantly increased in rectal adenocarcinoma tissue samples, either colon or rectum. High-regulation of FGFRL1 expression induced poorer outcome of rectal adenocarcinoma patients. Downregulation of FGFRL1 inhibited the proliferation, colony formation, migration, and invasion of SW837 cells. The MAPK pathway-related proteins, phosphorylation of MEK and ERK, were also decreased after si-FGFRL1 transfection. These findings demonstrated that FGFRL1, acting as a potential inducator, may promote the progression of rectal adenocarcinoma via activating the MAPK signaling pathway.

Usefulness of large-section cytokeratin 20 in the detection of intestinal wall infiltration and mesangial metastasis in patients with middle and lower rectal cancer.

OBJECTIVE: The objective of the study was to evaluate the usefulness of large-section cytokeratin 20 (CK20) staining technique in the detection of infiltration on the distal wall and mesangial metastasis in patients with middle and lower rectal cancer. MATERIALS AND METHODS: A total of 62 patients with rectal cancer in the middle and lower segment were studied on large slices stained with CK20. Logistic regression was used to analyze the clinicopathologic factors related to distal low and middle rectal cancer metastasis to the mesorectum and rectal wall. RESULTS: Two types of distal metastasis of the tumor were observed in the rectal wall in 18% (11/62) of the patients: submucosal invasion and muscularis propria invasion. The extent of distal metastasis to the rectal wall was around 0.5-1.0 cm. Four types of distal metastasis occurred in the mesorectum: lymph node invasion, blood and lymphatic vessel invasion, perineural invasion, and isolated neoplastic microfoci. Distal metastasis to the mesorectum was observed in 24% (15/62) of the patients. The extent of metastasis to the mesorectum was around 0.5-4.0 cm. Another three patients with microcapillary invasion in the distal mesorectum were observed by immunohistochemistry, as it was difficult to determine the spread by conventional hematoxylin and eosin staining. CONCLUSION: The large-section CK20 staining technique is useful for the detection of infiltration on the distal wall and mesangial metastasis in patients with middle and lower rectal cancer.

Semaphorin 4D and hypoxia-inducible factor-1α overexpression is related to prognosis in colorectal carcinoma.

AIM: To investigate semaphorin 4D (Sema4D) and hypoxia-inducible factor-1α (HIF-1α) expression in colorectal carcinoma and evaluate their clinicopathological and prognostic significance. METHODS: Eighty-six curatively resected colorectal carcinoma patients at different stages of disease were randomly selected from the group of patients who underwent surgery, and none of them received preoperative radiochemotherapy. Normal proximal adjacent bowel tissue, which served as an internal control, was obtained from 52 randomly selected patients. Immunohistochemistry was performed to analyze the expression of Sema4D and the tumor angiogenesis-related protein HIF-1α in normal colorectal tissues and colorectal carcinoma tissues. The relationships between the expression and clinical characters and prognosis were analyzed. RESULTS: HIF-1α and Sema4D were positively expressed in 58% and 60% of colorectal carcinoma tissues, respectively. Significantly lower expression levels were observed in normal mucosa (8% and 12%, respectively). HIF-1α and Sema4D expression was closely correlated with histological tumor type, tumor-node-metastasis (TNM) stage, and lymphatic metastasis (P<0.05), but not with age or tumor size (P>0.05). HIF-1α and Sema4D protein expression was significantly correlated with prognosis of colorectal carcinoma, as determined by Spearman rank correlation analysis (r=0.567; P<0.01). Multivariate Cox analysis revealed that only Sema4D expression played a significant role in predicting patient prognosis (P<0.05). CONCLUSION: These findings suggest that HIF-1α and Sema4D expression correlates with histological tumor type, TNM stage, and lymphatic metastasis in colorectal carcinoma and that Sema4D is a prognostic indicator of colorectal carcinoma.

Up-regulation of T-lymphoma and metastasis gene 1 in gastric cancer and its involvement in cell invasion and migration.

BACKGROUND: T-lymphoma and metastasis gene 1 (Tiam1) produces a guanine nucleotide exchange factor (GNEF) that regulates guanosine triphosphatase, which transforms guanosine diphosphate to guanosine triphosphate. Recently published data indicate that Tiam1 was associated with gastric cancer. The aim of this study was to investigate biological effects and potential mechanisms of Tiam1 in gastric carcinoma. METHODS: We analyzed the expression of Tiam1 in 114 pair-matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time PCR. We investigated Tiam1 expression and its prognostic value for gastric cancer. Furthermore, the functions of Tiam1 over-expression were analyzed with stable-expression Tiam1 plasmid in human gastric cancer cell lines. RESULTS: Tiam1 expression was significantly associated with cell differentiation and lymphatic metastasis; expression of Tiam1 mRNA was up-regulated in gastric cancer compared to pair-matched adjacent non-tumor tissues. Analyses of surgical tissue samples and 5-year survival of gastric cancer patients showed that those with strong Tiam1 expression had significantly shorter overall survival time than those with negative Tiam1 expression. Ectopic expression of Tiam1 promoted cell growth, migration and invasion of gastric cancer cells in vitro. CONCLUSIONS: In gastric cancer cells, Tiam1 affects multiple properties associated with acquisition of the metastatic phenotype, and may be a marker of gastric cancer progression and metastasis in a subset of cancer.

[Effects of RNA interference and nolatrexed on thymidylate synthase expression and cell proliferation of human colorectal carcinoma LOVO cells].

OBJECTIVE: To investigate the effect of the RNAi and the chemotherapy drugs nolatrxed on the expression of thymidylate synthase(TS) and the growth of the colorectal carcinoma LOVO cells. METHODS: The siRNA was constructed targeting the human TS gene, and then transfected into the human colorectal cancer LOVO cells. RT-PCR and Western blot technique were used to observe the TS gene and protein expression levels, and MTT was used to detect cell proliferation after silencing the TS gene. In addition, siRNA and nolatrxed were applied to the LOVO cells to observe the TS protein expression and cell growth. RESULTS: TS siRNA significantly reduced the expression of TS gene and protein in LOVO cells, and inhibited cell growth. The IC50 value of LOVO cells was (1.46±0.25) µmol/L in TS siRNA combined with nolatrexed group, (6.81±0.31) µmol/L in the negative control group, and (6.47±0.43) µmol/L in the single nolatrexed group. After treatment of TS siRNA combined with nolatrexed on LOVO cells for 36 hours, the apoptosis index was higher than that in single TS siRNA and nolatrexed[(62.12±0.89)% vs.(21.56±0.67)% and(40.51±0.83)%, both P<0.05]. CONCLUSION: TS siRNA can partly suppress the expression of TS gene in LOVO cells, inhibit cell proliferation, promote cell apoptosis and enhance cell sensitivity to apoptosis induced by nolatrexd.

Down-regulation of miR-622 in gastric cancer promotes cellular invasion and tumor metastasis by targeting ING1 gene.

AIM: To evaluate the biological and clinical characteristics of miR-622 in gastric cancer. METHODS: We analyzed the expression of miR-622 in 57 pair matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time polymerase chain reaction. Functional analysis of miR-622 expression was assessed in vitro in gastric cancer cell lines with miR-622 precursor and inhibitor. The roles of miR-622 in tumorigenesis and tumor metastasis were analyzed using a stable miR-622 expression plasmid in nude mice. A luciferase reporter assay was used to assess the effect of miR-622 on inhibitor of growth family, member 1 (ING1) expression. RESULTS: Expression of miR-622 was down-regulated in gastric cancer. MiR-622 was found involved in differentiation and lymphatic metastasis in human gastric cancer. Ectopic expression of miR-622 promoted invasion, tumorigenesis and metastasis of gastric cancer cells both in vitro and in vivo. ING1 is a direct target of miR-622. CONCLUSION: These findings help clarify the molecular mechanisms involved in gastric cancer metastasis and indicate that miR-622 modulation may be a bona fide treatment of gastric cancer.