Mechanism of EGFR inhibitor AG1478 combined with oxaliplatin in inhibiting PI3K/AKT pathway and promoting autophagy in HI 975 cells / 中国药理学通报

Aim To explore the effect of oxaliplatin combined with epidermal growth factor receptor tyrosine kinase inhibitor AG1478 on autophagy in non-small cell lung cancer H1975 cells. Methods H1975 cells were cultured in vitro using gradient concentrations of AG1478 (0, 5, 10, 15, 20, 25, 30, 35, 40 jjimol • IT

Evaluation of Animal Model of Autism Spectrum Disorders Based on Characteristics of Clinical Symptoms of Traditional Chinese and Western Medicine / 中国实验方剂学杂志

ObjectiveBased on the new method of animal model evaluation， this paper summarized and analyzed the characteristics of traditional Chinese medicine（TCM） and Western medicine syndromes in existing autism spectrum disorder（ASD） animal models， and put forward suggestions for improvement. MethodRelevant literature on ASD animal models in China National Knowledge Infrastructure（CNKI） and PubMed were searched. According to the diagnostic standards of traditional Chinese and western medicine， core symptoms and accompanying symptoms were assigned values， and the clinical consistency of the models was comprehensively evaluated. ResultMost ASD model experimental animals were rodents， and the modeling methods included genetic and non-genetic. Domestic research focused on biochemical induction， while foreign research used genetic models more commonly. Among all models， valproic acid induction had the highest clinical consistency， followed by the neuroligin 4（NLGN4） and contactin associated protein like 2（CNTNAP2） gene knockout models. Most modeling methods could meet the characteristics of surface validity and structural validity， but did not clearly distinguish TCM syndromes. Currently， there is no model that has a high degree of clinical agreement between TCM and western medicine at the same time. ConclusionThe existing ASD animal models are mostly constructed under the guidance of western medicine， which lacks the characteristics of TCM syndromes. And the selection of evaluation indicators of western medicine is relatively single， without specifying the types of TCM syndromes. It is recommended to apply TCM intervention factors during the process of model preparation， to improve the evaluation indicators of traditional Chinese and western medicine， and to emphasize the study of on non-human primates， so as to lay a solid foundation for future experiments.

Can the Blended Application of Controlled-Release and Common Urea Effectively Replace the Common Urea in a Wheat-Maize Rotation System? A Case Study Based on a Long-Term Experiment.

The one-time application of blended urea (BU), combining controlled-release urea (CRU) and uncoated urea, has proven to be a promising nitrogen (N) management strategy. However, the long-term sustainability of blending urea remains largely unexplored. To assess whether a single application of blended urea could effectively replace split uncoated urea applications, a long-term field experiment was conducted in the North China Plain (NCP). The results indicated that, when compared to common urea (CU) at the optimal N rate (180 kg N ha-1), BU achieved comparable grain yields, N uptake and NUE (61% vs. 62). BU exhibited a 12% higher 0-20 cm soil organic nitrogen stock and a 9% higher soil organic carbon (C) stock. Additionally, BU reduced life-cycle reactive N (Nr) losses and the N footprint by 10%, and lowered greenhouse gas (GHG) emissions and the C footprint by 7%. From an economic analysis perspective, BU demonstrated comparable private profitability and a 3% greater ecosystem economic benefit. Therefore, BU under the optimal N rate has the potential to substitute split applications of common urea in the long-term and can be regarded as a sustainable N management strategy for wheat and maize production in the NCP.

Canagliflozin alleviates high glucose-induced peritoneal fibrosis via HIF-1α inhibition.

The cardioprotective effects of sodium-glucose cotransporter type 2 (SGLT2) inhibitors have been demonstrated in many studies. However, their benefits for end-stage kidney disease patients, particularly those on peritoneal dialysis, remain unclear. SGLT2 inhibition has shown peritoneal protective effects in some studies, but the mechanisms are still unknown. Herein, we investigated the peritoneal protective mechanisms of Canagliflozin in vitro by simulating hypoxia with CoCl2 in human peritoneal mesothelial cells (HPMCs) and rats by intraperitoneal injection of 4.25% peritoneal dialysate simulating chronic high glucose exposure. CoCl2 hypoxic intervention significantly increased HIF-1α abundance in HPMCs, activated TGF-ß/p-Smad3 signaling, and promoted the production of fibrotic proteins (Fibronectin, COL1A2, and α-SMA). Meanwhile, Canagliflozin significantly improved the hypoxia of HPMCs, decreased HIF-1α abundance, inhibited TGF-ß/p-Smad3 signaling, and decreased the expression of fibrotic proteins. Five-week intraperitoneal injection of 4.25% peritoneal dialysate remarkably increased peritoneal HIF-1α/TGF-ß/p-Smad3 signaling and promoted peritoneal fibrosis and peritoneal thickening. At the same time, Canagliflozin significantly inhibited the HIF-1α/TGF-ß/p-Smad3 signaling, prevented peritoneal fibrosis and peritoneal thickening, and improved peritoneal transportation and ultrafiltration. High glucose peritoneal dialysate increased the expression of peritoneal GLUT1, GLUT3 and SGLT2, all of which were inhibited by Canagliflozin. In conclusion, we showed that Canagliflozin could improve peritoneal fibrosis and function by ameliorating peritoneal hypoxia and inhibiting the HIF-1α/TGF-ß/p-Smad3 signaling pathway, providing theoretical support for the clinical use of SGLT2 inhibitors in patients on peritoneal dialysis.

Arenobufagin-loaded PEG-PLA nanoparticles for reducing toxicity and enhancing cancer therapy.

Arenobufagin (ArBu) is a natural anticancer drug with good anti-tumor effects, but its clinical applications and drug development potential are limited due to its toxicity. The purpose of this study is to reduce the toxic side effects of ArBu and improve the efficacy of tumor treatment by incorporating it into poly(ethylene glycol)-b-poly (lactide) co-polymer (PEG-PLA). ArBu@PEG-PLA micelles were prepared by a thin film hydration method. The optimized micelles were characterized by size, stability, drug loading, encapsulation rate, and drug release. The tumor-inhibition efficacy of the micelles was evaluated on A549 cells and tumor-bearing mice. The ArBu@PEG-PLA micelles have good drug-loading capacity, release performance, and stability. They can accumulate at the tumor site through the EPR effect. The micelles induce apoptosis through a mitochondrial apoptosis pathway. Compared with the free ArBu, the ArBu@PEG-PLA micelles had lower toxicity and higher safety in the acute toxicity evaluation experiment. The in vivo anti-tumor experiment with tumor-bearing mice showed that the tumor-inhibition rate of ArBu@PEG-PLA micelles was 72.9%, which was 1.28-fold higher than that of free ArBu (57.1%), thus showing a good tumor treatment effect. This study indicates that ArBu@PEG-PLA polymeric micelles can significantly improve the toxicity and therapeutic efficacy of ArBu. These can lead to a new therapeutic strategy to reduce the toxicity of ArBu and enhance tumor treatment.

Advances in conditioning regimens for allogeneic hematopoietic stem cell transplantation in elderly patients with acute myeloid leukemia / 中华器官移植杂志

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a sole viable treatment for acute myeloid leukemia (AML). As the median age of AML is approaching 68 years and the global population is aging, allo-HSCT for is becoming more vital for elderly AML patients (60 years and over). Conditioning regimen is important in determining the clinical outcomes of post-allo-HSCT patients.This review summarized the classic and latest conditioning regimens and evaluated their respective clinical outcomes.Clinicians may appreciate the advantages of each conditioning regimen and formulate optimal options for elderly AML patients.

Clinical Analysis of Colistin Sulfate in the Treatment of Hematonosis Infected by Multidrug-Resistant Gram-Negative Bacteria / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of colistin sulfate in the treatment of hematonosis patients infected by multidrug-resistant (MDR) gram-negative bacteria (GNB), and discuss the possible factors that affect the efficacy of colistin sulfate.@*METHODS@#The clinical data of 85 hematologic patients infected with MDR GNB in the Soochow Hopes Hematonosis Hospital from April 2022 to November 2022 were collected and divided into clinically effective group with 71 cases and ineffective group with 14 cases according to the therapeutic efficacy of colistin sulfate. The age, gender, type of hematologic disease, status of hematopoietic stem cell transplantation, infection sites, type of pathogen, timing of administration, daily dose and duration of colistin sulfate, and combination with other antibacterial agents of patients in two groups were compared. Logistic regression was used to analyze on the meaningful variables to study the influencing factors of colistin sulfate. The adverse reactions of colistin sulfate were also evaluated.@*RESULTS@#There were no significant differences in age, gender, type of hematologic disease, hematopoietic stem cell transplantation status, infection sites and pathogen type between the effective group and the ineffective group (P>0.05). Compared with the medication time more than 7 days, meropenem used within 7 days in the clinical effective group, and timely replacement with colistin sulfate could obtain better efficacy, the difference was statistically significant (P=0.018). The duration of tigacycline before colistin sulfate did not affect the efficacy, and there was no significant difference in efficacy between the effective and ineffective groups. The therapeutic effect of colistin sulfate at daily dose of 500 000 U q8h was better than that of 500 000 U q12h, the difference was statistically significant (P=0.035). The time of colistin sulfate use in the clinically effective group was longer than that in the ineffective group, which had a statistical difference (P=0.003). Compared with the clinical ineffective group, the efficacy of combination regimens with colistin sulfate was better than that of colistin sulfate monotherapy, and the difference was statistically significant (P=0.013). Multivariate logistic regression analysis was performed on the indicators with statistical differences in the two groups of patients, which suggested that the use time of colistin sulfate (B: 2.358; OR: 10.573; CI: 1.567-71.361; P=0.015) and the combination of colistin sulfate (B: 1.720; OR: 5.586; CI: 1.210-25.787; P=0.028) were influential factors in the efficacy of colistin sulfate. During the treatment, the incidence of nephrotoxicity, hepatotoxicity and peripheral neurotoxicity were 5.9%, 1.2% and 1.2%, respectively.@*CONCLUSION@#The use of colistin sulfate improves the clinical efficacy of MDR GNB infections in hematological patients, and the timing of colistin sulfate administration and the combination of drugs are independent factors affecting its clinical efficacy, and the safety during treatment is high.

Constructed "ashi point" / 中国针灸

Ashi point is one of the three major categories of acupoint in acupuncture-moxibustion theory nowadays. It is originally recorded in Beiji Qianjin Yaofang (Important Formulas Worth a Thousand Gold Pieces for Emergency) as one of the effective folk methods. The theoretic development of ashi point goes through the innovation period of contemporary and modern acupuncture-moxibustion theory, specifically in three aspects, definition, property and status. Through the analysis of historical data, it is found that the bias of ashi point theory results from the misunderstanding of connotation, the distortion of application techniques, the misinterpretation of semantics and the gradual promotion of status. All of these are generally caused by the reform of acupuncture-moxibustion theory in Japan, which covers the essence of ashi point, limits its connotation and clouds the concept of acupoint. It is necessary to re-understand the literal sense and theoretic construction of ashi point and timely update the knowledge system of acupuncture-moxibustion in association with the results of theoretical researches.

Effect of down-regulation of let-7c/g on triggering a double-negative feedback loop and promoting restenosis / 中华医学杂志(英文版)

BACKGROUND@#Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) are the main causes of restenosis (RS) in diabetic lower extremity arterial disease (LEAD). However, the relevant pathogenic mechanisms are poorly understood.@*METHODS@#In this study, we introduced a "two-step injury protocol" rat RS model, which started with the induction of atherosclerosis (AS) and was followed by percutaneous transluminal angioplasty (PTA). Hematoxylin-eosin (HE) staining and immunohistochemistry staining were used to verify the form of RS. Two-step transfection was performed, with the first transfection of Lin28a followed by a second transfection of let-7c and let-7g, to explore the possible mechanism by which Lin28a exerted effects. 5-ethynyl-2΄-deoxyuridine (EdU) and Transwell assay were performed to evaluate the ability of proliferation and migration of VSMCs. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the expression of Lin28a protein and let-7 family members.@*RESULTS@#Using a combination of in vitro and in vivo experiments, we discovered that let-7c, let-7g, and microRNA98 (miR98) were downstream targets of Lin28a. More importantly, decreased expression of let-7c/let-7g increased Lin28a, leading to further inhibition of let-7c/let-7g. We also found an increased level of let-7d in the RS pathological condition, suggesting that it may function as a protective regulator of the Lin28a/let-7 loop by inhibiting the proliferation and migration of VSMCs.@*CONCLUSION@#These findings indicated the presence of a double-negative feedback loop consisting of Lin28a and let-7c/let-7g, which may be responsible for the vicious behavior of VSMCs in RS.

Scientific, transparent and applicable rankings of Chinese guidelines and consensus of rehabilitation medicine published in medical journals in 2022 / 中国康复理论与实践

ObjectiveTo evaluate the Chinese guidelines and consensus of rehabilitation medicine published in the medical journals in 2022 using Scientific, Transparent and Applicable Rankings (STAR). MethodsGuidelines and consensus which were developed by Chinese institutions or led by Chinese scholars were retrieved in databases of CNKI, Wanfang Data, CBM, Chinese Medical Journal Network, PubMed and Web of Science, in 2022, followed by screening for rehabilitation medicine field. The literature were rated with STAR. ResultsSeven guidelines and eleven consensuses were included. The STAR scores ranged from 11.7 to 69.6, with a median score of 25.9 and mean score of 28.3. There was a significant difference in the total score between guidelines and consensus (U = 12.000, P = 0.014). The score ratio was high in the domains of recommendations (73.6%), evidence (39.5%) and others (33.3%), while it was low in the domains of protocol (1.4%), clinical questions (12.5%) and conflicts of interest (13.9%). The score ratio was high in the items of listing the institutional affiliations of all individuals involved in developing the guideline (94.4%), identifying the references for evidence supporting the main recommendations (94.4%), indicating the considerations (e.g., adverse effects) in clinical practice when implementing the recommendations (88.9%), and making the recommendations clearly identifiable, e.g., in a table, or using enlarged or bold fonts (75%); and it was low in the items of describing the role of funder(s) in the guideline development (0), indicating information about the evaluation and management of conflicts of interest (0), providing tailored editions of the guidelines for different groups of target users (0), presenting the guideline or recommendations visually, such as with figures or videos (0), providing details of the guideline protocol (2.8%), assessing the risk of bias or methodological quality of the included studies (2.8%), describing the responsibilities of all individuals or sub-groups involved in developing the guideline (5.6%), indicating how the clinical questions were selected and sorted (5.6%), formating clinical questions in PICO or other formats (5.6%), making the guideline accessible through multiple platforms (5.6%), and declaring that the funder(s) did not influence the guideline's recommendations (8.3%). ConclusionThe quality of current clinical practice guidelines and consensus of rehabilitation medicine is poor, which should be developed in accordance with the relevant standards.

Humanized anti-CD25 monoclonal antibody as a salvage therapy for steroid-refractory acute graft-versus-host disease after hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To investigate the efficacy of humanized anti-CD25 monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: A total of 64 patients with SR-aGVHD between June 2019 and October 2020 in Suchow Hopes Hematology Hospital were enrolled in this study. Humanized anti-CD25 monoclonal antibodies 1 mg·kg(-1)·d(-1) were administered on days 1, 3, and 8, and then once per week according to the disease progression. Efficacy was assessed at days 7, 14, and 28 after humanized anti-CD 25 treatment. Results: Of the 64 patients with a median age of 31 (15-63) years, 38 (59.4%) were male and 26 (40.6%) were female. The overall response (OR) rate of the humanized CD25 monoclonal antibody in 64 patients with SR-aGVHD on days 7, 14, and 28 were 48.4% (31/64), 53.1% (34/64), and 79.7% (51/64), respectively. Liver involvement is an independent risk factor for poor efficacy of humanized CD25 monoclonal antibody for SR-aGVHD at day 28 (OR=9.588, 95% CI 0.004-0.291, P=0.002). The median follow-up time for all patients was 17.1 (0.2-50.8) months from the start of humanized CD25 monoclonal antibody therapy. The 1- and 2-year OS rates were 63.2% (95% CI 57.1% -69.3%) and 52.6% (95% CI 46.1% -59.1%), respectively. The 1- and 2-year DFS rates were 58.4% (95% CI 52.1% -64.7%) and 49.8% (95% CI 43.4% -56.2%), respectively. The 1- and 2-year NRM rates were 28.8% (95% CI 23.1% -34.5%) and 32.9% (95% CI 26.8% -39.0%), respectively. The results of the multifactorial analysis showed that liver involvement (OR=0.308, 95% CI 0.108-0.876, P=0.027) and GVHD grade Ⅲ/Ⅳ (OR=9.438, 95% CI 1.211-73.577, P=0.032) were independent risk factors for OS. Conclusion: Humanized CD25 monoclonal antibody has good efficacy and safety for SR-aGVHD. This study shows that SR-aGVHD with pretreatment grade Ⅲ/Ⅳ GVHD and GVHD involving the liver has poor efficacy and prognosis and requires early intervention.

Hot water washing processing technology of Euodiae Fructus based on change laws of active components and tastes / 中国中药杂志

In order to establish the standardized processing technology of the hot water washing of Euodiae Fructus, this study, based on the traditional processing method of hot water washing of Euodiae Fructus recorded in ancient works and modern processing specifications of traditional Chinese medicine decoction pieces, took the yield of decoction pieces and the content of main components as the indicators and optimized the processing conditions by orthogonal test based on the results of single factor investigation. At the same time, electronic tongue technology was used to analyze the change law of the taste index of Euodiae Fructus during the hot water washing. The results of the single factor investigation showed that the content of the main components in Euodiae Fructus showed some regular changes during the processing. Specifically, the content of chlorogenic acid, hyperin, isorhamnetin-3-O-rutinoside, isorhamnetin-3-O-galactoside, and dehydroevodiamine decreased significantly, with average decreases of-23.75%,-27.80%,-14.04%,-14.03%, and-13.11%, respectively. The content of limonin increased significantly with an average increase of 19.83%. The content of evodiamine, rutaecarpine, evocarpine, and dihydroevocarpine showed fluctuating changes and generally increased, with average variation amplitudes of 0.54%,-3.78%, 2.69%, and 5.13%, respectively. The orthogonal test results showed that the optimum processing parameters for the hot water washing of Euodiae Fructus were as follows: washing time of 2 min, the solid-to-liquid ratio of 1∶10 g·mL~(-1), washing temperature of 80 ℃, washing once, and drying at 50 ℃. After the hot water washing processing, the average yield of Euodiae Fructus pieces was 94.80%. The content of limonin, evodiamine, and rutaecarpine was higher than those of raw pro-ducts, and the average transfer rates were 102.56%, 103.15%, and 105.16%, respectively. The content of dehydroevodiamine was lower than that of the raw products, and the average transfer rate was 83.04%. The results of taste analysis showed that the hot water washing could significantly reduce the salty, astringent, and bitter tastes of Euodiae Fructus. This study revealed the influence of the hot water washing on the content of main components and taste of Euodiae Fructus, and the processing technology of the hot water was-hing of Euodiae Fructus established in this study was stable, feasible, and suitable for industrial production, which laid a foundation for clarifying its processing principle and improving the quality standard and clinical application value of decoction pieces.

Comprehensive analysis of dihydromyricetin metabolites in rats using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry.

As the most abundant and bioactive constituent in vine tea (Ampelopsis grossedentata), dihydromyricetin possesses numerous biological activities. A rapid profiling and identification method for dihydromyricetin metabolites in rats after the oral administration has been established using ultra-high-performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry coupled with multiple data-mining methods. Herein, an efficient analytical strategy characterized by a parallel reaction monitoring mode combining diagnostic fragment ions filtering techniques was developed for the comprehensive identification of dihydromyricetin metabolites in rat plasma, urine, and feces. And then, the biotransformation pathways of dihydromyricetin were further revealed. As a result, a total of 49 metabolites were finally identified by comparing diagnostic fragment ions, chromatographic retention times, neutral loss fragment ions, and accurate mass measurement with those of the dihydromyricetin reference standard. These metabolites were presumed to be dominantly generated through hydroxylation, dehydroxylation, methylation, reduction, sulfation, decarbonylation, glucuronidation, glucosylation, and their composite reactions. In a word, our present results not only supplied a solid foundation to better understand the action mechanism of dihydromyricetin, but also provided some models for the metabolism study of the other compounds in traditional Chinese medicines or natural plants.

Nanoscale Valley Modulation by Surface Plasmon Interference.

Excitons in two-dimensional (2D) materials have attracted the attention of the community to develop improved photoelectronic devices. Previous reports are based on direct excitation where the out-of-plane illumination projects a uniform single-mode light spot. However, because of the optical diffraction limit, the minimal spot size is a few micrometers, inhibiting the precise manipulation and control of excitons at the nanoscale level. Herein, we introduced the in-plane coherent surface plasmonic interference (SPI) field to excite and modulate excitons remotely. Compared to the out-of-plane light, a uniform in-plane SPI suggests a more compact spatial volume and an abundance of mode selections for a single or an array of device modulation. Our results not only build up a fundamental platform for operating and encoding the exciton states at the nanoscale level but also provide a new avenue toward all-optical integrated valleytronic chips for future quantum computation and information applications.

Disruption of O-GlcNAcylation Homeostasis Induced Ovarian Granulosa Cell Injury in Bovine.

O-linked ß-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism.

Oxidative stress, autophagy, and apoptosis induced by doxycycline in loach fin cells in vitro.

Cytotoxicity, molecular function disorder, mitophagy, and apoptosis were studied in loach fin cells in vitro after exposure to doxycycline (DOX). The semi-lethal concentration of DOX in loach cells was calculated as 668.96 ± 2.83 mol/L. Loss of cell viability and increases in vacuoles and autolysosomes were evident in cells exposed to DOX at 200 and 400 µmol/L, and apoptotic bodies occurred at 600 µmol/L. In addition, Superoxide Dismutase (SOD), catalase (CAT), Na+-K+-ATPase, and Ca2+-ATPase activities increased significantly in cells exposed to 200 µmol/L DOX, and dose-dependent inhibitory effects on activities were observed in cells exposed to 400 and 600 µmol/L DOX. Quantitative gene expression showed that 400 and 600 µmol/L DOX could induce caspase-3- and caspase-8-mediated apoptosis as well as caspase-activated DNase in loach cells. Transcriptome sequencing in DOX vs. control groups found 16,288 differentially expressed genes, among which protein binding (2633, 31.91%) was the most significant in Gene Ontology terms. Furthermore, 11,930 genes were enriched in 298 Kyoto Encyclopedia of Genes and Genomes (KEGG)pathways. The top three upregulated pathways included "lysosome", "protein processing in endoplasmic reticulum", and "proteasome". FPKM analysis indicated that most genes associated with autophagy and in "protein processing in the endoplasmic reticulum", "TNF signaling pathway", and "NF-kappa B signaling pathway" were upregulated. This suggests that at lower concentrations, DOX induces reactive oxidative species (ROS) in loach fin cells to reduce cell proliferation. ROS in turn stimulate oxidant stress, ion excretion capability and mitophagy to maintain cell homeostasis. Apoptosis was induced in cells subjected to higher concentrations of DOX. The transcriptome data and pathways determined in this study will provide a foundation for the analysis of DOX toxicity in loach cells, which must be examined thoroughly to further understand the cytotoxic mechanism of antibiotics in fish cells.

Centrifugation-induced assembly of dense hotspots based SERS substrate for enhanced Raman scattering and quenched fluorescence.

Hanging (aggregation stuck to the centrifugal tube) in the centrifugation process is always regarded as an unwanted condition. In this work, we develop a centrifugation-induced assembly of dense hotspots surface-enhanced Raman scattering (SERS) substrates from the hanging phenomenon. We discovered interesting sintering-resistant behavior (maintain the sharp nanotip features) of star-like Au nanoparticles after centrifugation-induced assembly, which is in stark contrast with the sintering phenomenon of sphere-like nanoparticles. We also found that one side of centrifugal-induced Au assemblies is two-dimensional (2D, root mean square (rms) roughness down to ∼10 nm), while the other is three-dimensional (3D, rms roughness more than 100 nm). The close-packed feature of the Au assemblies makes them candidates as dense hotspots based SERS substrates. Through systematic investigation of SERS performance of centrifugation-induced assemblies with different morphology (star-like and sphere-like, 2D and 3D), it was found that the 3D side of star-like Au nanoparticles assembly exhibits the highest SERS enhancement together with quenched fluorescence. The star-like SERS substrate also displays high detection uniformity (with 10-7M Rhodamine 6G) and a low detection limit (down to 10-12M Rhodamine 6G).

Clinical risk factors for fracture risk prediction in patients with type 2 diabetes using adjusted FRAX / 中华内分泌外科杂志

Objective:To study the clinical risk factors for osteoporotic fracture (OF) risk prediction in patients with type 2 diabetes mellitus (T2DM) using adjusted fracture risk assessment tool (FRAX) .Methods:A cross-sectional study of 429 patients with T2DM who were hospitalized in the Department of Endocrinology and Geriatrics of the Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University from Sep. 2019 to Sep. 2020 was conducted. Participants were divided into OF low-risk group and OF high-risk group. Participant characteristics (age, gender, height, weight, waist, blood pressure, history of drug treatment, serum glucose, glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol (LDL-C) , high-density lipoprotein cholesterol (HDL-C) , triglyceride, serum uric acid, alkaline phosphatase, and thyroid stimulating hormone levels, urine protein/creatinine ratio, urea, creatinine and TPOAB) and dual energy x-ray absorptiometry results were obtained and analyzed. Logistic regression model was used to investigate the relationship between the OF risk of T2DM assessed by adjusted FRAX and clinical risk factors.Results:Patients in the OF high-risk group accounted for 9.09% of the subjects. After adjustment for other variables, the duration of diabetes was still positively associated with significantly elevated risk of OF assessed by adjusted FRAX ( OR 7.660, 95% CI 1.661-35.334, P=0.009) , whereas the blood uric acid was negatively associated with significantly elevated risk of OF assessed by adjusted FRAX ( OR 0.345, 95 % CI 0.128-0.928, P=0.035) .Likewise, LDL-C levels decreased the odds of the risk of OF assessed by adjusted FRAX ( OR 0.316, 95 % CI 0.114-0.881, P=0.028) . There was no significant relationship between alkaline phosphatase ( OR 1.902, 95 % CI 0.904-4.004, P=0.090) as well as total cholesterol ( OR 0.297, 95% CI 0.056~1.560, P=0.151) levels and the elevated risk of OF assessed by adjusted FRAX. Conclusion:Diabetes duration could be a risk factor for OF risk prediction in patients with T2DM using adjusted FRAX, and serum uric acid and LDL-C could be protective factors for OF risk prediction in patients with T2DM using adjusted FRAX.

Vegetarian diet and vitamin B 12 level in Chinese pregnant women / 中华围产医学杂志

Objective:To explore the relationship between vegetarian diets and vitamin B 12 levels in Chinese pregnant women. Methods:A cross-sectional survey was used to explore the relationship between vegetarian diets and vitamin B 12 levels in Chinese pregnant women based on data from the Chinese National Nutrition and Health Surveillance (2015-2017). Maternal serum vitamin B 12 concentration was determined by electrochemiluminescence. Background and diet information of all subjects were collected using general and food frequency questionnaires. General Linear Model was used to analyze the difference in serum vitamin B 12 levels between vegetarian and non-vegetarian pregnant women and multivariate logistic regression for examining the relationship between vegetarian diets and vitamin B 12 deficiency (vitamin B 12<150 pmol/L) in pregnant women. Results:A total of 8 366 pregnant women were included in the analysis, and vegetarians accounted for 1.2% (102/8 366). The median serum vitamin B 12 concentrations were 155.8(93.6-212.4) pmol/L and 187.2(127.4-267.6) pmol/L ( Z=－4.22, P<0.001), and the vitamin B 12 deficiency rates were 48.0% (49/102) and 35.0% (2 896/8 264) in vegetarian and non-vegetarian women, respectively. The vitamin B 12 deficiency rate in vegetarian women was 0.89-fold higher than in non-vegetarians (95% CI: 1.24-2.89). Among the vegetarian and non-vegetarian pregnant women, vitamin B 12 deficiency rates during the first, second, and third trimesters were 34.8%(16/46), 54.3%(19/35), 66.7%(14/21), and 20.4%(521/2 559), 32.6%(941/2 886), 50.9%(1 430/2 807), noting for an increasing trend ( Z=23.54 and 2.57, P=0.010 and P<0.001). Conclusions:Vegetarian pregnant women are at high risk of vitamin B 12 deficiency. Compared with non-vegetarian women, vegetarian pregnant women in China have lower vitamin B 12 levels and a higher risk of vitamin B 12 deficiency. Moreover, the risk of vitamin B 12 deficiency will gradually increase during pregnancy.

Pathological features related to onco-immunity and their clinical significance of pancreatic ductal adenocarcinoma / 中华病理学杂志

Objective: To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-Ⅰ, PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. Results: There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3+T cells were deficient in 124 cases (124/192, 66.31%). CD8+T cells were deficient in 152 cases (152/192, 79.58%). MHC-Ⅰ expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (P=0.035), perineural invasion (P=0.002), stage (P=0.004) and long-term alcohol consumption (P=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (P=0.002), and negatively with tumor differentiation (P=0.024). CD8+T cells were positively correlated with CD3+T cells (P=0.032), MHC-Ⅰ expression (P<0.001) and PD-L1 expression (P=0.001), and negatively correlated with long-term smoking (P=0.016). Univariate analysis showed that histological nonspecific type (P=0.013) and TII-N (P<0.001) were the factors for good prognosis. Vascular invasion (P=0.032), perineural invasion (P=0.001), high stage (P=0.003) and long-term alcohol consumption (P=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. Conclusions: TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.