The novel probiotic preparation based on Lactobacillus spp. mixture on the intestinal bacterial community structure of Cherry Valley duck.

The development and utilization of probiotics have many environmental benefits when they are used to replace antibiotics in animal production. In this study, intestinal lactic acid bacteria were isolated from the intestines of Cherry Valley ducks. Probiotic lactic acid bacterial strains were screened for antibacterial activity and tolerance to produce a Lactobacillus spp. mixture. The effects of the compound on the growth performance and intestinal flora of Cherry Valley ducks were studied. Based on the results of the antibacterial activity and tolerance tests, the highly active strains Lactobacillus casei 1.2435, L. salivarius L621, and L. salivarius L4 from the intestines of Cherry Valley ducks were selected. The optimum ratio of L. casei 1.2435, L. salivarius L621, and L. salivarius L4 was 1:1:2, the amount of inoculum used was 1%, and the fermentation time was 14 h. In vivo experiments showed that compared with the control group, the relative abundances of intestinal Lactobacillus and Blautia were significantly increased in the experimental group fed the lactobacilli compound (P < 0.05); the relative abundances of Parabacteroides, [Ruminococcus]_torques_group, and Enterococcus were significantly reduced (P < 0.05), and the growth and development of the dominant intestinal flora were promoted in the Cherry Valley ducks. This study will provide more opportunities for Cherry Valley ducks to choose microecological agents for green and healthy breeding.

A Unique Approach: Biomimetic Graphdiyne-Based Nanoplatform to Treat Prostate Cancer by Combining Cuproptosis and Enhanced Chemodynamic Therapy.

Purpose: Current treatment approaches for Prostate cancer (PCa) often come with debilitating side effects and limited therapeutic outcomes. There is urgent need for an alternative effective and safe treatment for PCa. Methods: We developed a nanoplatform to target prostate cancer cells based on graphdiyne (GDY) and a copper-based metal-organic framework (GDY-CuMOF), that carries the chemotherapy drug doxorubicin (DOX) for cancer treatment. Moreover, to provide GDY-CuMOF@DOX with homotypic targeting capability, we coated the PCa cell membrane (DU145 cell membrane, DCM) onto the surface of GDY-CuMOF@DOX, thus obtaining a biomimetic nanoplatform (DCM@GDY-CuMOF@DOX). The nanoplatform was characterized by using transmission electron microscope, atomic force microscope, X-ray diffraction, etc. Drug release behavior, antitumor effects in vivo and in vitro, and biosafety of the nanoplatform were evaluated. Results: We found that GDY-CuMOF exhibited a remarkable capability to load DOX mainly through π-conjugation and pore adsorption, and it responsively released DOX and generated Cu+ in the presence of glutathione (GSH). In vivo experiments demonstrated that this nanoplatform exhibits remarkable cell-killing efficiency by generating lethal reactive oxygen species (ROS) and mediating cuproptosis. In addition, DCM@GDY-CuMOF@DOX effectively suppresses tumor growth in vivo without causing any apparent side effects. Conclusion: The constructed DCM@GDY-CuMOF@DOX nanoplatform integrates tumor targeting, drug-responsive release and combination with cuproptosis and chemodynamic therapy, offering insights for further biomedical research on efficient PCa treatment.

FKBP10 promotes clear cell renal cell carcinoma progression and regulates sensitivity to the HIF2α blockade by facilitating LDHA phosphorylation.

Renal cell carcinoma (RCC) is one of the three major malignant tumors of the urinary system and originates from proximal tubular epithelial cells. Clear cell renal cell carcinoma (ccRCC) accounts for approximately 80% of RCC cases and is recognized as a metabolic disease driven by genetic mutations and epigenetic alterations. Through bioinformatic analysis, we found that FK506 binding protein 10 (FKBP10) may play an essential role in hypoxia and glycolysis pathways in ccRCC progression. Functionally, FKBP10 promotes the proliferation and metastasis of ccRCC in vivo and in vitro depending on its peptidyl-prolyl cis-trans isomerase (PPIase) domains. Mechanistically, FKBP10 binds directly to lactate dehydrogenase A (LDHA) through its C-terminal region, the key regulator of glycolysis, and enhances the LDHA-Y10 phosphorylation, which results in a hyperactive Warburg effect and the accumulation of histone lactylation. Moreover, HIFα negatively regulates the expression of FKBP10, and inhibition of FKBP10 enhances the antitumor effect of the HIF2α inhibitor PT2385. Therefore, our study demonstrates that FKBP10 promotes clear cell renal cell carcinoma progression and regulates sensitivity to HIF2α blockade by facilitating LDHA phosphorylation, which may be exploited for anticancer therapy.

Appraisal of guidelines for managing contrast medium in patients with metformin: consensuses, controversies, and gaps.

OBJECTIVES: The current guidelines contain substantial inconsistency regarding the use of metformin concomitantly with contrast media. The objective of this study is to appraise the guidelines and summarize the agreements and differences among recommendations. METHODS: Our search focused on English language guidelines published between 2018 and 2021. Guidelines for the management of contrast media in patients with continuous metformin were included. Guidelines were assessed using the Appraisal of Guidelines for Research and Evaluation II instrument. RESULTS: Six guidelines out of 1134 fulfilled the inclusion criteria with an AGREE II score of 79.2% (IQR 72.7 to 85.1%). There was good overall quality of the guidelines, with six considered "strongly recommended." CPGs scored poorly in "Clarity of Presentation" and "Applicability," with scores of 75.9% and 76.4%, respectively. The intraclass correlation coefficients were excellent in each domain. There are some guidelines (33.3%) that recommend discontinuation of metformin in patients with an eGFR of < 30 mL/min/1.73 m2, while some guidelines (16.7%) suggest the threshold of renal function should be eGFR < 40 mL/min/1.73 m2. CONCLUSIONS: Most guidelines recommend withdrawing metformin before using contrast agents in diabetic patients with severely impaired kidney function but disagree on the renal function thresholds. Furthermore, the gaps regarding discontinuing metformin with moderate renal impairment (30 mL/min/1.73 m2 < eGFR < 60 mL/min/1.73 m2) must be considered in future studies. KEY POINTS: • Guidelines involving metformin and contrast agents are reliable and optimal. • Most guidelines advocate discontinuing metformin before using contrast agents in diabetic patients with advanced renal failure, but there are controversial suggestions regarding kidney function thresholds. • The gaps regarding the time of discontinuation of the metformin with moderate renal impairment (30 mL/min/1.73 m2 < eGFR < 60 mL/min/1.73 m2) must be considered in the extensive RCT studies.

Molecular predictors of metastasis in patients with prostate cancer.

INTRODUCTION: Prostate cancer is a serious threat to the health of older adults worldwide. The quality of life and survival time of patients sharply decline once metastasis occurs. Thus, early screening for prostate cancer is very advanced in developed countries. The detection methods used include Prostate-specific antigen (PSA) detection and digital rectal examination. However, the lack of universal access to early screening in some developing countries has resulted in an increased number of patients presenting with metastatic prostate cancer. In addition, the treatment methods for metastatic and localized prostate cancer are considerably different. In many patients, early-stage prostate cancer cells often metastasize due to delayed observation, negative PSA results, and delay in treatment time. Therefore, the identification of patients who are prone to metastasis is important for future clinical studies. AREAS COVERED: this review introduced a large number of predictive molecules related to prostate cancer metastasis. These molecules involve the mutation and regulation of tumor cell genes, changes in the tumor microenvironment, and the liquid biopsy. EXPERT OPINION: In next decade, PSMA PET/CT and liquid biopsy will be the excellent predicting tools, while 177 Lu- PSMA-RLT will be showed excellent anti-tumor efficacy in mPCa patients.

Intestinal Microbiota of Anser fabalis Wintering in Two Lakes in the Middle and Lower Yangtze River Floodplain.

The intestinal microbiota of migratory birds participate in the life activities of the host and are affected by external environmental factors. The difference in habitat environment provides diversity in external environmental selection pressure for the same overwintering waterfowl, which may be reflected in their intestinal microbiota. Caizi lake and Shengjin Lake in the Middle and Lower Yangtze River Floodplain are the main habitats for migratory waterfowl in winter, especially the Anser fabalis (A. fabalis). It is important to explore the changes in intestinal microbiota composition and function of A. fabalis in the early overwintering period to clarify the effect of habitat size and protection status on intestinal microbiota. In this study, the composition and structural characteristics of the intestinal microbiota of A. fabalis in Shengjin Lake (SL) and Caizi Lake (CL) were preliminarily explored in order to obtain data for the migratory birds. In both SL and CL groups, 16S rRNA amplicon sequencing analysis showed that Firmicutes was the dominant bacterial phylum, but the relative abundance showed significant differences. Lactobacillus was the most abundant genus in both SL and CL groups. At the species level, the abundance of L. aviaries was the highest, with a relative abundance in both SL and CL groups of more than 34%. When comparing the average relative abundance of the 15 most abundant genera, it was found that Subdoligranulum, Exiguobacterium, and Terrisporobacter had higher abundances in the intestinal microbiota of CL A. fabalis, while Streptococcus and Rothia had higher abundances in the intestinal microbiota of SL A. fabalis. There was only a positive correlation between Bacteroidota and Proteobacteria in the intestinal microbiota flora of SL A. fabalis, and the species were closely related. At the same time, there were positive and negative correlations between Firmicutes and Actinomycetes. However, CL is mainly associated with a positive correlation between Firmicutes and Actinomycetes, and there are also a small number of connections between Firmicutes. PICRUSt1 prediction analysis revealed that the Clusters of Orthologous Groups (COG) functions of SL and CL involve energy production and transformation, amino acid transport and metabolism, carbohydrate transport and metabolism, and transcription. Understanding the changes in intestinal microbiota in Aves during the overwintering period is of great importance to explore the adaptation mechanism of migratory Aves to the overwintering environment. This work provides basic data for an A. fabalis intestinal microbiota study.

Ferrocene-Based Polymeric Nanoparticles Carrying Doxorubicin for Oncotherapeutic Combination of Chemotherapy and Ferroptosis.

Mono-chemotherapy has significant side effects and unsatisfactory efficacy, limiting its clinical application. Therefore, a combination of multiple treatments is becoming more common in oncotherapy. Chemotherapy combined with the induction of ferroptosis is a potential new oncotherapy. Furthermore, polymeric nanoparticles (NPs) can improve the antitumor efficacy and decrease the toxicity of drugs. Herein, a polymeric NP, mPEG-b-PPLGFc@Dox, is synthesized to decrease the toxicity of doxorubicin (Dox) and enhance the efficacy of chemotherapy by combining it with the induction of ferroptosis. First, mPEG-b-PPLGFc@Dox is oxidized by endogenous H2 O2 and releases Dox, which leads to an increase of H2 O2 by breaking the redox balance. The Fe(II) group of ferrocene converts H2 O2 into ·OH, inducing subsequent ferroptosis. Furthermore, glutathione peroxidase 4, a biomarker of ferroptosis, is suppressed and the lipid peroxidation level is elevated in cells incubated with mPEG-b-PPLGFc@Dox compared to those treated with Dox alone, indicating ferroptosis induction by mPEG-b-PPLGFc@Dox. In vivo, the antitumor efficacy of mPEG-b-PPLGFc@Dox is higher than that of free Dox. Moreover, the loss of body weight in mice treated mPEG-b-PPLGFc@Dox is lower than in those treated with free Dox, indicating that mPEG-b-PPLGFc@Dox is less toxic than free Dox. In conclusion, mPEG-b-PPLGFc@Dox not only has higher antitumor efficacy but it reduces the damage to normal tissue.

Identification and experimental validation of a tumor-infiltrating lymphocytes-related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common aggressive malignant tumor of the urinary system. Given the heterogeneity of the tumor microenvironment, immunotherapy may not fully exert its role in the treatment of advanced patients. Long noncoding RNA (lncRNA) has been reported to be critically associated with the differentiation and maturation of tumor-infiltrating lymphocytes (TILs), which work against tumor cells. In this study, we identified 10 TIL-related lncRNAs (AL590094.1, LINC02027, LINC00460, AC147651.1, AC026401.3, LINC00944, LINC01615, AP000439.2, AL162586.1, and AC084876.1) by Pearson correlation, univariate Cox regression, Lasso regression, and multivariate Cox regression based on The Cancer Genome Atlas (TCGA) database. A risk score model was established based on these lncRNAs. Next, a nomogram was constructed to predict the overall survival. By employing differentially expressed genes (DEGs) between groups with high and low risk scores, gene ontology (GO) enrichment analysis was performed to identify the major biological processes (BP) related to immune DEGs. We analyzed the mutation data of the groups and demonstrated that SETD2 and BAP1 had the highest mutation frequency in the high-risk group. The "CIBERSORT" R package was used to detect the abundance of TILs in the groups. The expression of lymphocyte markers was compared. We also determined the expression of two lncRNAs (AC084876.1 and AC026401.3) and their relationship with lymphocyte markers in the kidney tissue of ccRCC patients and showed that there was a positive correlation between AC084876.1 and FoxP3. Proliferation, migration, and invasion of AC084876.1-downregulated ccRCC cell lines were inhibited, and the expression of PD-L1 and TGF-ß secretion decreased. To our knowledge, this is the first bioinformatics study to establish a prognostic model for ccRCC using TIL-related lncRNAs. These lncRNAs were associated with T-cell activities and may serve as biomarkers of disease prognosis.

Evaluation of Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio on Predicting Responsiveness to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Patients.

Objective: Neutrophil-lymphocyte ratio (NLR) and Platelet-lymphocyte ratio (PLR) have been proposed as prognostic biomarkers in multiple cancers. However, the implications of NLR and PLR in the responsiveness to neoadjuvant chemoradiotherapy (nCRT) remain to be clarified in locally advanced rectal cancer (LARC) patients. This retrospective study investigated the prognostic value of NLR and PLR in nCRT responsiveness of LARC patients. Methods: A total number of 86 patients diagnosed with LARC and treated with nCRT and total mesorectal excision were retrospectively followed from 2013 to 2016. Receiver operating characteristic (ROC) curve was used to determine the cutoff values of NLR and PLR, and the patients were divided into NLR elevation and NLR decrease groups, or PLR elevation and PLR decrease groups. The correlation between NLR and PLR changes, and clinicopathological factors were analyzed. The relationship between NLR and PLR changes and the curative responsiveness towards nCRT were further evaluated. Results: NLR and PLR changes after nCRT were significantly correlated with the distance of tumors to the anus and BMI (body mass index) (P < 0.05). The clinical remission rate of patients with NLR reduction was 72.09% (31/43), which was significantly higher than that in patients with NLR increment (22/43, 51.16%). There was no significant difference in the clinic remission rate between the patients with PLR reduction and those with PLR increment (P > 0.05). However, the pathological responsiveness rate was significantly higher in patients with PLR reduction (21/43, 48.84%) when compared to the ones with PLR increment (9/43, 20.9%) (P = 0.036). Conclusion: Our data indicate that in LARC patients with nCRT, the reduction of NLR and the reduction of PLR could serves as predictors for the clinic remission rate and pathological responsiveness rate, respectively. The combination of NLR and PLR changes may be employed as a simple and effective prognostic parameter to predict the treatment outcome of nCRT in LARC.

Untargeted metabolomics reveals alterations in the metabolic reprogramming of prostate cancer cells by double-stranded DNA-modified gold nanoparticles.

Metabolic reprogramming plays an important role in the development of prostate cancer (PCa). However, there are few reports on the effects of nanomaterials as vectors on cancer metabolic reprogramming. Herein, a type of nanoparticle with good biocompatibility was synthesized by modifying the double-stranded of DNA containing a sulfhydryl group on the surface of gold nanoparticles (AuNPs-dsDNA) through salt-aging conjugation methods. The resultant AuNPs-dsDNA complexes possessed low toxicity to PC3 and DU145 cells in vitro. There was also no obvious hepatorenal toxicity after intravenous injection of AuNPs-dsDNA complexes in vivo, which indicated that these nanoparticles had good biological compatibilities. We investigated their biological functions using prostate cancer cells. Seahorse assay showed that AuNPs-dsDNA complexes could increase glycolysis and glycolysis capacity both in PC3 and DU145 cells. We further detected the expression of glycolysis-related genes by qPCR assay, and found that PKM2, PDHA, and LDHA were significantly upregulated. Furthermore, untargeted metabolomics revealed that PC (18:2(9Z,12Z)/18:2(9Z,12Z)) and PC (18:0/18:2 (9Z,12Z)) levels were decreased and inosinic acid level was increased in PC3 cells. Whereas (3S,6E,10E)-1,6,10,14-Phytatetraen-3-ol, Plasmenyl-PE 36:5 and Cer (d18:2/18:2) were decreased, PE 21:3 and 1-pyrrolidinecarboxaldehyde were increased in DU145 cells after co-culturing with AuNPs-dsDNA. In summary, we found that AuNPs and AuNPs-dsDNA complexes possibly regulate the metabolic reprogramming of cancer cells mainly through the lipid metabolic pathways, which could compensate for the previously mentioned phenomenon of enhanced glycolysis and glycolysis capacity. This will provide an important theoretical basis for our future research on the characteristic targeted design of nanomaterials for cancer metabolism.

mFOLFOX4 with or without radiation in neoadjuvant treatment of locally advanced middle and low rectal cancer.

Context: Neoadjuvant therapy can reduce the recurrence rate of locally advanced middle and low rectal cancer. Radiation therapy can not only bring benefits but also produce acute and late toxicity, which will affect the quality of life and organ function of patients; the application of neoadjuvant chemotherapy can avoid the toxicity of radiotherapy. Aims: To investigate the efficiency and side effects of preoperative modified FOLFOX4 (mFOLFOX4) chemotherapy with or without radiotherapy for locally advanced middle and low rectal cancer (LAMLRC). Methods and Material: This study included 431 patients with LAMLRC receiving mFOLFOX4 chemotherapy independently or combined with radiotherapy before operation. The basic information, efficacy indicators, and adverse reactions of the two groups were recorded in detail. Side effects were evaluated using the Common Terminology Criteria for Adverse Events v. 3.0. Statistical Analysis Used: Statistical analyses were conducted using SPSS (Statistical Package for Social Science, IBM SPSS Statistics, Version 22). Mann-Whitney test and Chi-square test were used for comparative analysis. Statistical significance was defined as P < 0.05. Results: Of 128 patients who met the inclusion criteria, 52 received neoadjuvant chemotherapy (NCT), and 76 received neoadjuvant chemoradiotherapy (NCRT). The average operation time in the NCT group was 2.71 h, and that in the NCRT group was 3.35 h (P = 0.005). The pathological complete remission rates in the NCT and NCRT groups were 1.9% and 17.1%, respectively (P = 0.007). There was no significant difference in the T-stage decline rate and lymph node positive rate between the two groups. There were higher rates of leukopenia (32.7% vs. 57.9%; P < 0.05) and diarrhea (0% vs. 9.2%; P < 0.05) in the NCRT group. The 3-year overall survival rates in the NCT and NCRT groups were 80.3% and 82.8% (P = 0.715), respectively, and the respective 3-year disease-free survival rates were 68.8% and 70.5% (P = 0.966). Conclusions: NCT with mFOLFOX4 independently resulted in a lower pathological complete remission rate, with less toxicity and shorter operation time. NCT with mFOLFOX4 has certain clinical usefulness.

The prognostic roles of CYP19A1 expression in bladder cancer patients of different genders.

BACKGROUND: The incidence of bladder cancer (BCa) in male is approximately three to four times higher than in female, but the oncological outcomes in female patients with BCa are significantly worse than in male patients. Although many biomarkers have been identified in recent decades to predict the prognosis of BCa patients, few of them are able to distinguish the prognosis of BCa patients with gender difference. Aromatase encoded by the CYP19A1 gene catalyzes the conversion of androgens to estrogens. In this study, we investigate the prognosis significance of CYP19A1 expression considering the gender difference in BCa patients from four available public databases. METHODS: Four available public databases of BCa, including GSE13507, TCGA-BLCA, E-MTAB-4321, and E-MTAB-1803, were utilized in this analysis. The overall survival (OS) and progression-free survival (PFS) in different stages and genders were evaluated using the Kaplan-Meier analysis based on the optimal cut-off values of CYP19A1 expression. Then, Gene Set Enrichment Analysis (GSEA) were further performed to explore the potential biologic pathways by altering CYP19A1 expression in BCa patients. RESULTS: The results showed that patients with high CYP19A1 expression had a poorer outcome compared with those with low expression in both BCa cohorts in general. Higher CYP19A1 expression in male patients were significantly associated with shorter survival for either non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC). However, female NMIBC patients with high CYP19A1 expression were identified to have a better prognosis, whereas high CYP19A1 expression in female MIBC patients were significantly associated with poorer survival. The result of the GSEA showed that different outcomes in female and male patients with NMIBC were related to the interaction of CYP19A1 and the cell-cycle-related pathways. CONCLUSIONS: These findings demonstrated that CYP19A1 expression might have a potential role in distinguishing the prognosis of female BCa patients dependent on tumor stage. Our results provide new insights for aromatase-mediated BCa therapy.

Identification and Validation of a PPP1R12A-Related Five-Gene Signature Associated With Metabolism to Predict the Prognosis of Patients With Prostate Cancer.

BACKGROUND: Prostate cancer (PCa) is the most common malignant male neoplasm in the American male population. Our prior studies have demonstrated that protein phosphatase 1 regulatory subunit 12A (PPP1R12A) could be an efficient prognostic factor in patients with PCa, promoting further investigation. The present study attempted to construct a gene signature based on PPP1R12A and metabolism-related genes to predict the prognosis of PCa patients. METHODS: The mRNA expression profiles of 499 tumor and 52 normal tissues were extracted from The Cancer Genome Atlas (TCGA) database. We selected differentially expressed PPP1R12A-related genes among these mRNAs. Tandem affinity purification-mass spectrometry was used to identify the proteins that directly interact with PPP1R12A. Gene set enrichment analysis (GSEA) was used to extract metabolism-related genes. Univariate Cox regression analysis and a random survival forest algorithm were used to confirm optimal genes to build a prognostic risk model. RESULTS: We identified a five-gene signature (PPP1R12A, PTGS2, GGCT, AOX1, and NT5E) that was associated with PPP1R12A and metabolism in PCa, which effectively predicted disease-free survival (DFS) and biochemical relapse-free survival (BRFS). Moreover, the signature was validated by two internal datasets from TCGA and one external dataset from the Gene Expression Omnibus (GEO). CONCLUSION: The five-gene signature is an effective potential factor to predict the prognosis of PCa, classifying PCa patients into high- and low-risk groups, which might provide potential novel treatment strategies for these patients.

Down-regulation of ACACA suppresses the malignant progression of Prostate Cancer through inhibiting mitochondrial potential.

Background and aim: Silencing the expression of ACACA inhibits cell proliferation and induces apoptosis in prostate cancer LNCaP cells. However, the role of ACACA in other prostate cancer cells is not fully understood. Also, the effect of knocking down ACACA gene on mitochondria remains unclear. This study aimed to discover the specific role of ACACA gene in prostate cancer (PCa) DU145 and PC3 cells as well as its effects on mitochondrial potential. Methods: The expression of ACACA gene was detected in human prostate cancer tissue microarrays and assessed in different clinical stages. Then, prostate cancer cell lines with low expression of ACACA were constructed to evaluate the changes in their cell cycle, proliferation, and metabolites. The effect of ACACA on tumor formation in vivo was analyzed. Also, mito-ATP production, mitochondrial staining, and mtDNA, nicotinamide adenine dinucleotide (NAD+/NADH), and reactive oxygen species (ROS) levels were detected. Results: ACACA was expressed more strongly in prostate cancer tissues. The expression level of ACACA was higher in patients with advanced PCa than in patients with lower grades. The proliferation ability reduced in ACACA-knockdown cells. In in vivo tests, the tumor volume and weight were lower in the experimental group than in the control group. Mito-ATP production decreased significantly after ACACA suppression, mtDNA levels and MitoTracker staining decreased in the experimental group. The ratio of NAD+/NADH and ROS levels were upregulated in the experimental group. Conclusion: Targeting ACACA gene and mitochondria might serve as a novel therapy for prostate cancer treatment.

Stepwise neoadjuvant chemoradiotherapy in the management of mid-low locally advanced rectal cancer.

BACKGROUND: This study aimed to compare the treatment response, complications and prognosis in mid-low locally advanced rectal cancer (LARC) patients who underwent stepwise neoadjuvant chemoradiotherapy (SCRT) or traditional neoadjuvant chemoradiotherapy (CRT). METHODS: The medical records of patients with mid-low rectal cancer who underwent SCRT or CRT were retrospectively analyzed. Differences in the treatment response, pathologic complete response (pCR), R0 resection, local recurrence, anastomotic leakage, presacral infection, anal preservation, defunctioning stoma, treatment-emergent adverse events (TEAEs), overall survival (OS) and disease-free survival (DFS) between patients who underwent SCRT and CRT were compared. RESULTS: A total of 430 medical records were investigated, including 194 patients in the SCRT group and 236 patients in the CRT group. There was no significant difference in the rates of treatment response, pCR, R0 resection, local recurrence, anastomotic leakage, presacral infection, anal preservation or TEAEs between the two groups. However, the rate of defunctioning stoma in the SCRT group was significantly lower than that in the CRT group (20.1% vs. 44.1%, respectively, P < 0.01). Moreover, the median OS time of the SCRT and CRT groups was 44.0 and 50.5 months, respectively (P = 0.17). The median DFS time of the SCRT and CRT groups was 41.0 and 46.8 months, respectively (P = 0.32). CONCLUSION: Compared with the CRT group, the SCRT group had a similar treatment response, local control and long-term prognosis, and more importantly, a portion of the patients in the SCRT group were exempted from excessive radiation.

Lactate dehydrogenase and serum tumor markers for predicting metastatic status in geriatric patients with lung adenocarcinoma.

BACKGROUND: No tumor biomarker (TM) is available for de novo metastatic lung adenocarcinoma. OBJECTIVE: To examine the serum levels of carcinoembryonic antigen (CEA), cytokeratin-19 fragments (CYFRA21-1), neuron-specific enolase (NSE), carbohydrate antigen (CA) 19-9, CA125, tissue polypeptide antigen (TPA), tissue polypeptide specific antigen (TPS), and lactate dehydrogenase (LDH) to predict de novo metastatic lung adenocarcinoma. METHODS: This was a retrospective study of geriatric (⩾ 60 years of age) patients with lung cancer diagnosed at Shanxi Cancer Hospital from 02/2012 to 12/2017. CEA, CYFRA21-1, CA199, NSE, CA125, TPA, and TPS were detected by ELISA and LDH was detected by LDH kit. Their predictive value was assessed using receiver operating characteristic (ROC) curves and multivariable logistic regression. RESULTS: The positive rates of LDH and TMs were higher in the metastatic group (all P< 0.05). The best single TMs were CYFRA21-1 (70.5% sensitivity) and CA199 (92.0% specificity). When using any two, the best were CYFRA21-1+TPA (77.1% sensitivity) and CA199+TPA or NSE (both 84.1% specificity). High LDH and CA125 statuses were each independently associated with brain, bone, liver, and lung metastases (all P< 0.05). CONCLUSIONS: Abnormal level of LDH and TMs, alone or in combination, had predictive value for metastasis in geriatric patients with lung adenocarcinoma; these indicators were also associated with the metastatic site.

[Relationship between CD4⁺CD25(High)CD127(low) regularly T cells in the peripheral blood and tumor regression after neoadjuvant therapy in patients with rectal cancer].

OBJECTIVE: To observe the proportion change of immune cells in the peripheral blood of patients with rectal cancer after neoadjuvant therapy and to explore the relationship between tumor regression and CD4⁺CD25(High)CD127(low) regularly T cells(Treg cells). METHODS: Patients with rectal cancer who underwent the neoadjuvant therapy before surgery at the Shanxi Cancer Hospital Colorectal Surgery Department from January to December 2013 were prospectively enrolled. These patients were divided into down-staging group and non-down-staging group according to the change of staging in accordance with TNM classification for rectal cancer after neoadjuvant therapy. Flow cytometry was used to analyze the proportions of Treg cells, CD4+T cells, CD8+T cells, NK cells, B cells, and CD4+/CD8+ ratio in the peripheral blood from these patients before and after neoadjuvant therapy. RESULTS: A total of 108 patients were enrolled, including 76 cases in the down staging group and 32 cases in the non-down-staging group. Differences of immune cells proportions between two groups before neoadjuvant therapy were not statistically significant(all P>0.05). In the down-staging group, the proportions of Treg cells, B cells and CD4+/CD8+ ratio were decreased while the proportion of NK cells did not change obviously after the neoadjuvant therapy. Interestingly, in the non-down-staging group, the proportions of B cells and CD4+/CD8+ ratio were decreased while the proportions of Treg cells and NK cells did not change obviously after the neoadjuvant therapy. In addition, after neoadjunvat therapy, the proportion of Treg cells in down-staging group was significantly lower than that in non-down-staging group [(4.4 ± 1.7)% vs. (6.2 ± 1.9)%, P=0.001]. CONCLUSION: For patients in the down-staging group after neoadjuvant therapy, the proportion of Treg cells in peripheral blood decreases, suggesting that Treg cells may be a valuable biomarker for assessing tumor regression.

Phase synchronization analysis of prefrontal tissue oxyhemoglobin oscillations in elderly subjects with cerebral infarction.

PURPOSE: This study aims to assess the phase relationship of prefrontal tissue oxyhemoglobin oscillations using wavelet phase coherence analysis of cerebral Delta [HbO2] signals in cerebral infarction (CI) patients during the resting state. METHODS: Continuous recordings of near-infrared spectroscopy signals were obtained from the left and right prefrontal lobes in 21 subjects with CI (Group CI, age: 76.6 ± 8.5 yr) and 21 healthy elderly subjects (Group Healthy, age: 69.0 ± 7.4 yr) during the resting state. The Group CI was further divide into two groups: CI with hypertension and CI without hypertension. The phase synchronization between left and right prefrontal Delta [HbO2] oscillations in four frequency intervals (I, 0.6-2 Hz; II, 0.145-0.6 Hz; III, 0.052-0.145 Hz; and IV, 0.021-0.052 Hz) was analyzed using wavelet phase coherence method. RESULTS: The phase coherences in intervals III and IV were significantly lower in CI with hypertension than in healthy elderly subjects (F = 12.974, p = 0.001 for III and F = 10.073, p = 0.004 for interval IV). The phase coherence of CI without hypertension in interval III was significantly lower than in healthy elderly subjects (F = 9.909, p = 0.004). Also, the phase coherence in interval IV was significantly lower in CI with hypertension than in CI without hypertension (F = 5.665, p = 0.028). Also, the phase agreement in interval IV showed evident difference between Group CI with hypertension and without hypertension. CONCLUSIONS: The difference in phase characteristics of prefrontal tissue oxyhemoglobin oscillations between the CI patients and healthy elderly indicates altered phase synchronization. Moreover, the CI combined with hypertension would aggravate this process. This study provides new insight into the phase dynamics of cerebral oxygenation and may be useful in assessing the risk for stroke.

Preparation of an isocyano-beta-diketone via its metal complexes, by use of metal ions as protecting groups.

A ligand containing isocyanide and beta-diketone functional groups, 3-(4-isocyanophenyl)-2,4-pentanedione (HacphNC), and several of its metal complexes have been prepared. The free isocyano-beta-diketone could not be prepared by dehydration of the analogous formamide, HacphNHCHO, because of the reactivity of its beta-diketone moiety. Instead, the metal complexes Al(acphNC)(3), Fe(acphNC)(3), Cu(acphNC)(2), and Zn(acphNC)(2) were synthesized by dehydration of the formamido-beta-diketonate complexes Al(acphNHCHO)(3), Fe(acphNHCHO)(3), Cu(acphNHCHO)(2), and Zn(acphNHCHO)(2). The free isocyano-beta-diketone, HacphNC, can be liberated from its Al and Fe complexes by treatment with oxalate (C(2)O(4)(2-)) and HC(2)O(4)(-). In addition to these O-bound complexes, C(N)-bound complexes can be prepared by the reaction of either Al(acphNC)(3) or HacphNC with Au(I). X-ray analyses of HacphNC, Al(acphNC)(3), (HacphNC)AuCl, Cu(acphNHCHO)(2), trans-Zn(acphNHCHO)(2)(H(2)O)(2), and two other intermediates are also reported.

Thyroid carcinoma metastasis to the choroid plexus of the lateral ventricle.

We present a rare case of a lateral ventricle choroid plexus metastasis arising from thyroid carcinoma in a 62-year-old man. The patient underwent subtotal excision of the intracranial tumour followed by total thyroidectomy with good outcome. We review previous reports of intracranial thyroid metastases and discuss the role of surgical resection, radiosurgery, whole brain radiotherapy and radioactive iodine therapy. There is no consensus regarding treatment in the literature due to small numbers of patients reported. We recommend surgical resection for single accessible lesions.