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Purpose The aim of this study was to analyze the effect of preoperative bicarbonate and lactate levels (LL) on the short-term outcomes and prognosis in elderly (≥ 65 years) patients with colorectal cancer (CRC). Methods We collected the information of CRC patients from Jan 2011 to Jan 2020 in a single clinical center. According to the results of preoperative blood gas analysis, we divided patients into the higher/lower bicarbonate group and the higher/lower lactate group, and compared their baseline information, surgery-related information, overall survival (OS) and disease-free survival (DFS). Results A total of 1473 patients were included in this study. Comparing the clinical data of the higher/lower bicarbonate group and the higher/lower lactate group, the lower group were older (p Conclusion Preoperative LL significantly affected postoperative OS and DFS of CRC patients, but bicarbonate might not affect the prognosis of CRC patients. Therefore, surgeons should actively focus on and adjust the LL of patients before surgery.

PurposeThe aim of this study was to evaluate the effect of carbon nanoparticles staining (CNS) on colorectal cancer (CRC) surgery, lymph node tracing and postoperative complications using propensity score matching (PSM).MethodPatients who were diagnosed with CRC and underwent surgery were retrospectively collected from a single clinical center from Jan 2011 to Dec 2021. Baseline characteristics, surgical information and postoperative information were compared between the CNS group and the non-CNS group. PSM was used to eliminate bias.ResultsA total of 6,886 patients were enrolled for retrospective analysis. There were 2,078 (30.2%) patients in the CNS group and 4,808 (69.8%) patients in the non-CNS group. After using 1: 1 ratio PSM to eliminate bias, there were 2,045 patients left in each group. Meanwhile, all of their baseline characteristics were well matched and there was no statistical significance between the two groups (P > 0.05). In terms of surgical information and short-term outcomes, the CNS group had less intraoperative blood loss (P P P P = 0.013), more total retrieved lymph nodes (P P = 0.011) and less postoperative overall complications (P P = 0.004), shorter postoperative hospital stay (P P P > 0.05).ConclusionPreoperative CNS could help the surgeons detect more lymph nodes, thus better determining the patient's N stage. Furthermore, it could reduce intraoperative blood loss and reduce the hospital stay.

In multiple types of cancer, decreased tumour cell apoptosis during chemotherapy is indicative of decreased chemosensitivity. Forkhead box K2 (FOXK2), which is essential for cell fate, regulates cancer cell apoptosis through several post‐translational modifications. However, FOXK2 acetylation has not been extensively studied. Here, we evaluated the effects of sirtiun 1 (SIRT1) on FOXK2 deacetylation. Our findings demonstrated that SIRT1 inhibition increased FOXK2‐induced chemosensitivity to cisplatin and that K223 in FOXK2 was acetylated. Furthermore, FOXK2 K223 deacetylation reduced chemosensitivity to cisplatin in vitro and in vivo. Mechanistically, FOXK2 was acetylated by the acetyltransferase cAMP response element binding protein and deacetylated by SIRT1. Furthermore, cisplatin attenuated the interaction between FOXK2 and SIRT1. Cisplatin or SIRT1 inhibition enhanced FOXK2 acetylation, thereby reducing the nuclear distribution of FOXK2. Additionally, FOXK2 K223 acetylation significantly affected the expression of cell cycle–related and apoptosis‐related genes in cisplatin‐stimulated cancer cells, and FOXK2 K223 hyperacetylation promoted mitotic catastrophe, which enhanced chemosensitivity to cisplatin. Overall, our results provided insights into the mechanisms of SIRT1‐mediated FOXK2 deacetylation, which was involved in chemosensitivity to cisplatin.

Purpose The current study was to evaluate the effect of the preoperative serum lactate dehydrogenase-to-albumin ratio (LAR) on the short-term outcomes and overall survival (OS) of patients with gastric cancer (GC) who received surgery. Methods GC patients who underwent gastrectomy at a single clinical medical center were enrolled and were divided into the low and the high LAR groups by LAR cutoff (12.8). The baseline information, short-term outcomes, and OS were compared between the two groups. Cox regression analysis was performed to identify independent risk factors for OS. The Kaplan-Meier method was used to estimate the OS between the two groups in different tumor stages. Results A total of 570 patients were included for analysis. As for baseline information, we found that the high LAR group had older patients (PConclusion LAR was not an independent factor of OS. However, LAR might affect the prognosis of stage II GC.

Leptin receptor (LEPR) plays a vital role in obesity in humans and animals. The objective of this study is to assess LEPR functional variants for chicken adipose deposition by integration of association and in-silico analysis using a unique chicken population, the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF). Five online bioinformatics tools were used to predict the functionality of the single nucleotide polymorphisms (SNPs) in coding region. Further, the possible structure–function relationship of high confidence SNPs was determined by bioinformatics analyses, including the conservation and stability analysis based on amino acid residues, prediction of protein ligand-binding sites, and the superposition of protein tertiary structure. Meanwhile, we analyzed the association between abdominal fat traits and 20 polymorphisms of chicken LEPR gene. The integrated results showed that rs731962924 (N867I) and rs13684622 (C1002R) could lead to striking changes in the structure and function of proteins, of which rs13684622 (C1002R) was significantly associated with abdominal fat weight (AFW, P=0.0413) and abdominal fat percentage (AFP, P=0.0260) in chickens. Therefore, we are of the opinion that rs13684622 (C1002R) may be an essential functional SNP affecting chicken abdominal fat deposition, and potentially applied to improvement of broiler abdominal fat in molecular marker-assisted selection (MAS) program. Additionally, the coupling of association with computer electronic predictive analysis provides a new avenue to identify important molecular markers for breeders.

For a long time, the epidemic situation of hemorrhagic fever with renal syndrome (HFRS) caused by hantavirus (HV) in Yunnan Province of China has been relatively severe. The molecular epidemiology and host characteristics of HV in Yunnan Province are still not completely clear, and the systematic and long-term investigation of the epidemic area is very limited. In this study, a total of 488 murine-shaped animals were captured in the three regions of Mile City, Mangshi City and Lianghe County in Yunnan Province, and then the type of HV was identified by multiplex real-time RT-PCR and sequenced. The results indicate that 2.46% of the murine-shaped animal specimens were infected with HV. A new subtype of Seoul virus (SEOV) was found in the rare rat species Rattus nitidus in Lianghe County, and the two strains of this new subtype were named YNLH-K40 and YNLH-K53. Through the phylogenetic analysis of this new subtype, it is shown that this new subtype is very similar to the type S5 of SEOV, which is previously described as the main cause for the high incidence of HFRS in Longquan City, Zhejiang Province, China. This new subtype is highly likely to cause human infection and disease. Therefore, in addition to further promoting the improvement of the HV gene database and strengthening the discovery and monitoring of the host animals in Yunnan Province, more attention should be paid to the pathogenic potential of the newly discovered HV type.

Toads produce potent toxins, named bufadienolides, to defend against their predators. Pharmacological research has revealed that bufadienolides are potential anticancer drugs. In this research, we reported nine bufadienolides from the eggs of the toad Bufo bufo gargarizans, including two new compounds (1 and 3). The chemical structures of 1 and 3, as well as of one previously reported semisynthesized compound (2), were elucidated on the basis of extensive spectroscopic data interpretation, chemical methods, and X-ray diffraction analysis. Compound 1 is an unusual 19-norbufadienolide with rearranged A/B rings. A biological test revealed that compounds 2 and 4-8 showed potent cytotoxic activities toward human melanoma cell line SK-MEL-1 with IC50 values less than 1.0 μM. A preliminary mechanism investigation revealed that the most potent compound, 8, could induce apoptosis via PARP cleavage, while 5 and 6 significantly suppressed angiogenesis in zebrafish. Furthermore, an in vivo biological study showed that 5, 6, and 8 inhibit SK-MEL-1 cell growth significantly.

Background and purpose Altered drug pharmacokinetics is a significant concern in non-alcoholic steatohepatitis (NASH) patients. Although high-fat high-cholesterol (HFHC) diet-induced NASH (HFHC-NASH) rats could simulate the typical dysregulation of cholesterol in NASH patients, experimental investigation on the altered drug pharmacokinetics in this model are limited. Thus, the present study comprehensive investigates the nature of such altered pharmacokinetics using simvastatin as the model drug. Experimental approach Pharmacokinetic profiles of simvastatin and its active metabolite simvastatin acid together with compartmental pharmacokinetic modelling were used to identify the key factors involved in the altered pharmacokinetics of simvastatin in HFHC-NASH rats. Experimental investigations via in situ single-pass intestinal perfusion and intrahepatic injection of simvastatin were carried out. Histology, Ces1 activities and mRNA/protein levels of Oatp1b2/CYP2c11/P-gp in the small intestine/liver of healthy and HFHC-NASH rats were compared. Key results Reduced intestinal absorption and more extensive hepatic elimination in HFHC-NASH rats resulted in less systemic exposures of simvastatin/simvastatin acid. In the small intestine of HFHC-NASH rats, thicker intestinal wall with more collagen fibres, increased Ces1 activity and up-regulated P-gp protein decreased the permeability of simvastatin, accelerated the hydrolysis of simvastatin and promoted the efflux of simvastatin acid respectively. In the liver of HFHC-NASH rats, higher hepatic P-gp expression accelerated the hepatic elimination of simvastatin. Conclusion and implications Altered histology, Ces1 activity and P-gp expression in the small intestine/liver were identified to be the major contributing factors leading to less systemic exposure of drugs in HFHC-NASH rats, which may be applicable to NASH patients.

Five novel bisindole alkaloids, hunzeylanines A-E (1-5), with an unprecedented skeleton were isolated from the roots of Hunteria zeylanica. Compounds 1-5 represent the first examples of akuammine-pleioarpamine-type bisindole alkaloids fused with a dihydropyran unit. Their structures including absolute configurations were established through comprehensive spectroscopic data analyses and computational calculation methods. The plausible biogenetic pathway of 1 was also proposed. Alkaloids 1 and 2 displayed moderate cytotoxicity toward three human cancer cell lines (MDA-MB-231, AV3, and Huh7).

In traditional Chinese medicine herbs (TCM), including Radix Salviae Miltiorrhizae (Danshen), Radix Puerariae Lobatae (Gegen), Radix Angelicae Sinensis (Danggui), and Rhizoma Chuanxiong (Chuanxiong) are widely used for the prevention and treatment of cardiovascular diseases and also often co-administered with Western drugs as a part of integrative medicine practice. Carboxylesterase 1 (CES1) plays a pivotal role in the metabolisms of pro-drugs. Since (S)-2-(2-(6-dimethylamino)-benzothiazole)-4,5-dihydro-thiazole-4-carboxylate (NLMe) has recently been identified by us as a selective CES1 bioluminescent sensor, we developed a rapid method using this substrate for the direct measurement of CES1 activity in rats. This bioluminescence assay was applied to determine CES1 activity in rat tissues after a two-week oral administration of each of the four herbs noted above. The results demonstrated the presence of CES1 enzyme in rat blood and all tested tissues with much higher enzyme activity in the blood, liver, kidney and heart than that in the small intestine, spleen, lung, pancreas, brain and stomach. In addition, the four herbs showed tissue-specific effects on rat CES1 expression. Based on the CES1 biodistribution and its changes after treatment in rats, the possibility that Danshen, Gegen and Danggui might alter CES1 activities in human blood and kidney should be considered. In summary, a selective and sensitive bioluminescence assay was developed to rapidly evaluate CES1 activity and the effects of orally administered TCMs in rats., Graphical abstract Image 1, Highlights • A rapid bioluminescence assay to quantify CES1 activity was developed. • Profiles of CES1 activity in rat biomatrices were fully described for the first time. • Impacts of four traditional Chinese medicinal herbs on CES1 activity in rats were evaluated for the first time.

Background Whether hypokalemia can affect the short-term outcomes of CRC patients after radical surgery remains unclear. The purpose of this study was to investigate the impact of preoperative hypokalemia on the short-term outcomes for colorectal cancer (CRC) patients who underwent radical CRC surgery using propensity score matching (PSM). Methods We retrospectively enrolled consecutive CRC patients from Jan 2011 to Dec 2021 in a single-center hospital. Hypokalemia was defined as a serum potassium concentration Results A total of 6183 CRC patients who underwent radical surgery were included in this study, of whom 390 (6.3%) patients were diagnosed with hypokalemia before surgery. After 1:1 ratio PSM, there were 390 patients in the hypokalemia group and in the normal potassium group. No significant difference was found between the two groups after PSM in terms of baseline information (p > 0.05). Regarding short-term outcomes, the hypokalemia group had a longer hospital stay (p = 0.028), a higher proportion of overall complications (p = 0.048) and a higher incidence of postoperative pneumonia (p = 0.008) after PSM. Moreover, hypokalemia (p = 0.036, OR = 1.291, 95% CI = 1.017–1.639) was an independent risk factor for overall complications. Conclusion Preoperative hypokalemia could increase complications after CRC surgery and prolong the hospital stay. Moreover, preoperative hypokalemia was an independent risk factor for overall complications.

PurposeThe purpose of the current study was to analyze the effect of intraoperative blood loss (IBL) and intraoperative blood transfusion (IBT) on the short-term outcomes and prognosis for patients who underwent primary colorectal cancer (CRC) surgery.MethodsWe retrospectively collected the patients' information from the database of a teaching hospital from January 2011 to January 2020. IBL and IBT were collected and analyzed, and the propensity score matching (PSM) analysis was performed.ResultsA total of 4,250 patients with CRC were included in this study. There were 1,911 patients in the larger IBL group and 2,339 patients in the smaller IBL group. As for IBT, there were 82 patients in the IBT group and 4,168 patients in the non-IBT group. After 1:1 ratio PSM, there were 82 patients in the IBT group and 82 patients in the non-IBT group. The larger IBL group had longer operation time (p = 0.000 < 0.01), longer post-operative hospital stay (p = 0.000 < 0.01), smaller retrieved lymph nodes (p = 0.000 < 0.01), and higher overall complication (p = 0.000 < 0.01) than the smaller IBL group. The IBT group had longer operation time (p = 0.000 < 0.01), longer hospital stay (p = 0.016 < 0.05), and higher overall complications (p = 0.013 < 0.05) compared with the non-IBT group in terms of short-term outcomes. Larger IBL (p = 0.000, HR = 1.352, 95% CI = 1.142–1.601) and IBT (p = 0.044, HR = 1.487, 95% CI = 1.011–2.188) were independent predictive factors of overall survival (OS). Larger IBL (p = 0.000, HR = 1.338, 95% CI = 1.150–1.558) was an independent predictor of disease-free survival (DFS); however, IBT (p = 0.179, HR = 1.300, 95% CI = 0.886–1.908) was not an independent predictor of DFS.ConclusionBased on the short-term outcomes and prognosis of IBL and IBT, surgeons should be cautious during the operation and more careful and proficient surgical skills are required for surgeons.

The literature related to TMZ research in the Web of Science (WOS) database was analyzed using bibliometrics and visualization by Citespace and VOSviewer.The publication status (number of publications, institutions, and frequency of citations), collaborations, and research focus was analyzed to clarify the current situation of TMZ research. And the recent research on TMZ provides a detailed summary. Based on objective data analysis, this study provides a complete analysis portraying the progression of historical milestones in TMZ development and future research directions from various TMZ research domains.

2,2',4,4'-tetrabrominated diphenyl ether (BDE-47) is one of the most widely distributed PBDEs. BDE-47 is also the most abundant in organisms and the most toxic to humans and animals. Herein, we have studied the pathway of BDE-47 degradation and gene involvement in Acinetobacter pittii GB-2. This degradation is dominated by hydroxylation, resulting in hydroxylated products 6-OH-BDE-47, 5-OH-BDE-47 and 2'-OH-BDE-28, and bromophenol products 2,4-DBP and 4-BP. Transcriptome sequencing results showed 359 differentially expressed genes (DEGs) induced by BDE-47, of which 159 were up-regulated and 200 were down-regulated. The up-regulated ones were mainly related to substance transport, degradation and cell stress. From these results, we suggest that 1,2-dioxygenase, phenol hydroxylase and monooxygenase are involved in BDE-47 degradation. The function of AntA gene was identified by constructing a prokaryotic expression vector. Our study contributes to understanding how the metabolism of strain GB-2 changes under BDE-47 stress conditions, and sheds light on the mechanism of BDE-47 degradation.

Background: Using a classification network to generate class activation mapping (CAM) is a mainstream method for weakly supervised semantic segmentation. However, for brain tumor images, CAM cannot fit the boundary of the tumor well. Objective: To improve the performance of brain tumor CAM, we propose a weakly supervised learning strategy based on a multi-level sub-category and membership matrix. Methods: Firstly, a multi-level sub-category strategy is used to intensively classify the data set. It allows the convolutional network to learn the in-depth characteristics of the input for enhancing CAM. Secondly, the idea of fuzzy clustering is introduced into model learning. The membership matrix is combined with CAM to construct the loss function. Results: Exhaustive experiments on the brain tumor dataset BraTS2019 demonstrate that the proposed method can effectively improve the performance of CAM. Compared with the baseline method, our approach significantly improved by 17.1% using the common dice similarity coefficient evaluation approach, and compared with the recent study, our score also improved by almost 9%. Conclusion: The proposed methods train the network under image-level labels and help the convolutional network mine the target boundary information. They can help CAM fit the target border more accurately.

Purpose. The purpose of the current study is to analyze whether preoperative hyponatremia affected the short-term outcomes of colorectal cancer (CRC) surgery. Methods. This retrospective study was conducted in a single clinical center where we enrolled patients who underwent primary CRC surgery from January 2011 to December 2021. The short-term outcomes were compared between the hyponatremia group and the normal sodium group using propensity score matching (PSM) analysis. Results. A total of 6730 cases of patients who received CRC surgery were finally included in this study. There were 184 patients in the hyponatremia group and 6546 patients in the normal sodium group. After 1 : 1 ratio PSM, 184 patients in the normal sodium group were matched to 184 patients in the hyponatremia group. No significant difference was found in baseline information after PSM ( P > 0.05 ). After PSM, the hyponatremia group had higher patients with overall complications ( P = 0.013 ). Univariate and multivariate logistic regression analysis were conducted to find predictors of complications, and we found that older age ( P = 0.032 , OR = 1.023 , 95 % CI = 1.002 − 1.044 ), open surgery (P =0.001, OR = 2.300 , 95 % CI = 1.420 − 3.727 ), blood loss ( P = 0.015 , OR = 1.002 , 95 % CI = 1.000 − 1.003 ), and hyponatremia ( P = 0.012 , OR = 1.856 , 95 % CI = 1.148 − 3.001 ) were independent predictors of patients with overall complications. Conclusion. Hyponatremia was an independent predictor of patients with overall complications after CRC surgery, therefore, the adequate preparation of the patients for surgery remained fundamental.

Three novel monoterpenoid indole alkaloids gardflorine A (1), gardflorine B (2), and gardflorine C (3) were isolated from the leaves of Gardneria multiflora. Their structures, including absolute configurations, were established on the basis of spectroscopic methods (MS, UV, IR, 1D and 2D NMR) and circular dichroism experiments. All the compounds were evaluated for their vasorelaxant and acetylcholinesterase (AChE) inhibitory activities. Compound 1 exhibited potent vasorelaxant activity, with an EC50 value of 8.7 μM, and compounds 2 and 3 showed moderate acetylcholinesterase (AChE) inhibitory activities, with IC50 values of 26.8 and 29.2 μM, respectively.

Four new iboga-type alkaloids, ervaoffines H K (1–4), along with five known compounds were obtained from the aerial parts of Ervatamia officinalis. The absolute configurations of 1–4 were confirmed by X-ray diffraction and electronic circular dichroism (ECD) analyses. The isolates were tested for their anti-inflammatory activity. Compounds 1, 5, 6, and 9 showed potential inhibitory effect of NO production in LPS-stimulated BV2 and RAW264.7 cells.

This study provided baseline data for oral public health though epidemiological survey to investigate the prevalence of malocclusion and the relationship with caries in Kazak junior school students in Xinjiang Aletai district, China.Using stratified and cluster random sampling, 1 022 Kazak junior school students in Aletai district were chosen. According to the standard of Angle's classification and individual normal occlusion, a full clinical examination was carried out. The results were statistically analyzed by SAS JMP 10.0.Of all 1 022 subjects, the prevalence of malocclusion was 43.64%. Among them there were 215 males (43.97%) and 231 females (43.34%). The composition ratios of Class I, Class II and Class III malocclusion were 30.92%，3.42% and 9.30%, respectively. The malocclusion prevalence in urban was 44.56%, and 43.06% in rural areas. There was no significant difference between them. Among children with malocclusion, crowding of dentition was the majority, and the others in turn were abnormal space of anterior teeth, deep overjet, deep overbite, cross jet, and open bite. The prevalence of caries was 59.49%, and DMFT was 1.382. Students who had caries with malocclusion was 1.54 times more than those who did not have caries.Compared with other studies, the prevalence of malocclusion in Xinjiang Aletai district is not high. The incidence of malocclusion is closely related to caries.

Composite materials include various components with different structures, which cooperatively increase their properties and extend their application. In this study, the graphitic carbon nitride (g-C3N4) guest material was assembled into the porous of the SiO2 aerogel, which was prepared during the gel process. By this way, the g-C3N4 could be absolutely encapsulated into the porous of the disordered porous SiO2 aerogel. The prepared g-C3N4/SiO2 composite had a loose porous structure and exhibited the much higher photocatalytic activity to the photodegradation of rhodamine B (RhB) under visible light. The disordered porous structure enhanced photocatalytic activity, and the degradation rate reached to 96.42% in 90 min under the irradiation of visible light, which could be attributed to its high surface area and effective electron–hole separation rate. The catalyst had the much higher stability and could be easily recycled utilization. The prepared composites could be applied to degrade organic pollutants in wastewater.

Atmospheric aerosols,气溶胶作为悬浮分散在大气中的固态或液态微小颗粒物,对人体健康具有巨大影响,探索区域大气气溶胶变化特征和规律,对监测评估大气环境质量(尤其是人口聚集的城市地区)具有重要意义。本研究以东南亚、南亚和西亚“21世纪海上丝绸之路”沿线9个典型支点城市为例,基于MCD19A2 550 nm AOD产品,结合气象因素、土地利用数据和夜间灯光数据等,探讨亚洲发达城市区域带气溶胶的时空分布、变化特征、影响因素和成因驱动。结果表明: 2013—2018年间,9个城市气溶胶光学厚度(AOD)年平均值从高到低依次为卡拉奇、多哈、吉大港、曼谷、科伦坡、胡志明市、新加坡、瓜达尔和仰光。受区域气候系统和气溶胶类型的影响,各地区年、季和月AOD时序特征差异显著。大多数城市AOD高值区主要分布在城市中心区域或社会经济(如工农业)快速发展的地区。不同气象因素对各地区AOD的影响略有差异:降雨量、相对湿度和风速对东南亚4个城市(胡志明市、曼谷、新加坡和仰光)的影响较大,温度、相对湿度和风速与南亚4个城市(吉大港、科伦坡、卡拉奇和瓜达尔)和西亚多哈的AOD相关性较大。城市区域AOD受社会经济、城市化发展以及气象因素耦合协同作用的综合影响,其中,卡拉奇表现得最显著。.