Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

Backgrounds and Aim: Chronic hepatitis C (CHC) patients who fail antiviral therapy have a high risk of developing hepatocellular carcinoma (HCC). We investigated the effects of metformin and statins, commonly used to treat diabetes mellitus (DM) and hyperlipidemia (HLP), on HCC risk in CHC patients who failed antiviral therapy. Methods: CHC patients with failed interferon-based therapy were enrolled in a large-scale multicenter cohort study in Taiwan (T-COACH). HCC occurrence 1.5 years after the end of antiviral therapy was identified by linking to the cancer registry databases from 2003 to 2019. After considering death and liver transplantation as competing risks, Gray's cumulative incidence and Cox sub-distribution hazards for HCC development were used. Results: Among the 2,779 CHC patients, 480 (17.3%) developed new-onset HCC and 238 (8.6%) died after antiviral therapy. Metformin non-users with DM had a 51% higher risk of liver cancer than patients without DM, while statin users with HLP had a 50% lower risk of liver cancer than patients without HLP. The 5-year cumulative incidence of HCC was 16.5% in metformin non-users, significantly higher in metformin non-users than in patients without DM (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Conversely, HLP statin users had a significantly lower HCC risk than patients without HLP (3.8% vs. 12.5%; aSHR=0.50; P<0.001). Notably, the unfavorable effect of non-metformin use on increased HCC risk was mainly observed among patients without cirrhosis but not in patients with cirrhosis. In contrast, a favorable effect of statins reduced the risk of HCC in both cirrhotic and non-cirrhotic patients. Conclusion: Metformin for DM and statins for HLP have chemopreventive effects on HCC risk in CHC patients who failed antiviral therapy. These findings emphasize the importance of personalized preventive strategies for managing patients with these clinical profiles.

Effects of electroacupuncture on rats with cognitive impairment: An iTRAQ-based proteomics analysis / 中西医结合学报

OBJECTIVE@#The study explores the effects of electroacupuncture (EA) at the governing vessel (GV) on proteomic changes in the hippocampus of rats with cognitive impairment.@*METHODS@#Healthy male rats were randomly divided into 3 groups: sham, model and EA. Cognitive impairment was induced by left middle cerebral artery occlusion in the model and EA groups. Rats in the EA group were treated with EA at Shenting (GV24) and Baihui (GV20) for 7 d. Neurological deficit was scored using the Longa scale, the learning and memory ability was detected using the Morris water maze (MWM) test, and the proteomic profiling in the hippocampus was analyzed using protein-labeling technology based on the isobaric tag for relative and absolute quantitation (iTRAQ). The Western blot (WB) analysis was used to detect the proteins and validate the results of iTRAQ.@*RESULTS@#Compared with the model group, the neurological deficit score was significantly reduced, and the escape latency in the MWM test was significantly shortened, while the number of platform crossings increased in the EA group. A total of 2872 proteins were identified by iTRAQ. Differentially expressed proteins (DEPs) were identified between different groups: 92 proteins were upregulated and 103 were downregulated in the model group compared with the sham group, while 142 proteins were upregulated and 126 were downregulated in the EA group compared with the model group. Most of the DEPs were involved in oxidative phosphorylation, glycolipid metabolism and synaptic transmission. Furthermore, we also verified 4 DEPs using WB technology. Although the WB results were not exactly the same as the iTRAQ results, the expression trends of the DEPs were consistent. The upregulation of heat-shock protein β1 (Hspb1) was the highest in the EA group compared to the model group.@*CONCLUSION@#EA can effect proteomic changes in the hippocampus of rats with cognitive impairment. Hspb1 may be involved in the molecular mechanism by which acupuncture improves cognitive impairment.

Active components and mechanism of Jinwugutong Capsules in treatment of osteoporosis: a study based on UPLC-Q-Exactive-MS/MS combined with network pharmacology / 中国中药杂志

UPLC-Q-Exactive-MS/MS and network pharmacology were employed to preliminarily study the active components and mechanism of Jinwugutong Capsules in the treatment of osteoporosis. Firstly, UPLC-Q-Exactive-MS/MS was employed to characterize the chemical components of Jinwugutong Capsules, and network pharmacology was employed to establish the "drug-component-target-pathway-disease" network. The key targets and main active components were thus obtained. Secondly, AutoDock was used for the molecular docking between the main active components and key targets. Finally, the animal model of osteoporosis was established, and the effect of Jinwugutong Capsules on the expression of key targets including RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA). A total of 59 chemical components were identified from Jinwugutong Capsules, among which coryfolin, 8-prenylnaringenin, demethoxycurcumin, isobavachin, and genistein may be the main active components of Jinwugutong Capsules in treating osteoporosis. The topological analysis of the protein-protein interaction(PPI) network revealed 10 core targets such as AKT1, ALB, catenin beta 1(CTNNB1), TNF, and epidermal growth factor receptor(EGFR). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that Jinwugutong Capsules mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, neuroactive ligand-receptor interaction, mitogen-activated protein kinase(MAPK) signaling pathway, Rap1 signaling pathway and so on. Molecular docking showed that the main active components of Jinwugutong Capsules well bound to the key targets. ELISA results showed that Jinwugutong Capsules down-regulated the protein levels of AKT1 and TNF-α and up-regulated the protein level of ALB, which preliminarily verified the reliability of network pharmacology. This study indicates that Jinwugutong Capsules may play a role in the treatment of osteoporosis through multiple components, targets, and pathways, which can provide reference for the further research.

Clinical and genetic analysis of a patient with Loeys-Dietz syndrome due to variant of TGFBR2 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of a patient with clinically suspected Loeys-Dietz syndrome (LDS).@*METHODS@#A child who had presented at Beijing Anzhen Hospital in September 2018 was selected as the study subject. Clinical data and family history of the patient were collected, along with peripheral blood samples of the proband and his parents. Whole exome sequencing (WES) was carried out through next-generation sequencing.@*RESULTS@#Candidate variants were searched through bioinformatic analysis focusing on genes associated with hereditary aortic aneurysms. Candidate variant was verified by Sanger sequencing. The patient was found to have cardiovascular abnormalities including early-onset aortic dilatation and coarctation, and LDS syndrome was suspected. WES revealed that he has harbored a heterozygous c.1526G>T missense variant of the TGFBR2 gene. The same variant was not found in either parent and was predicted as likely pathogenic (PM1+PM2_Supporting+ PM6+PP3+PP4) based on the guidelines from the American College for Medical Genetics and Genomics (ACMG).@*CONCLUSION@#The TGFBR2 c.1526G>T variant probably underlay the LDS in this patient and was unreported previously in China. Above finding has enriched the mutational spectrum of the TGFBR2 gene associated with the LDS and provided a basis for the genetic counseling for the patient.

[Research progress on common pesticide residues in Chinese medicinal materials].

Chinese medicinal materials are the precious resources of China and favored by patients at home and abroad because of their natural sources and curative effects. Pesticides are often used to prevent and control diseases and insect pests and regulate the growth of Chinese medicinal plants, so as to improve the yield and quality of Chinese medicinal materials. Most of the pesticides can play a role in pest control through systemic action, stomach toxicity, contact, fumigation and other ways, especially the systemic pesticides can kill hidden pests by entering the Chinese medicinal plants. Despite the good pest control effect, it is difficult to remove the systemic pesticides by simple cleaning, which poses a great risk to the safety of Chinese medicinal materials. At the same time, excessive or non-standard use of pesticides leads to serious pesticide residues in Chinese medicinal materials, which affects not only the quality and efficacy of the materials and harm human health but also the international development of Chinese medicinal materials industry. Pesticide residues have become a bottleneck affecting the industry development and hindering the export of Chinese medicinal materials. Therefore, it is of great significance to study how to quickly, sensitively, and accurately detect and remove pesticide residues in Chinese medicinal materials. We reviewed the common pesticide residues in Chinese medicinal materials in recent years in terms of characteristics, harm, and detection and removal techniques, and discussed the future development of the detection and removal deve-lopment. With this review, we aimed to provide a reference for the quality control of Chinese medicinal materials and promote the healthy development of Chinese medicine industry.

More than just statics: altered complexity of dynamic amplitude of low-frequency fluctuations in the resting brain after stroke.

Objective.Previous neuroimaging studies mainly focused on static characteristics of brain activity, and little is known about its characteristics over time, especially in post-stroke (PS) patients. In this study, we aimed to investigate the static and dynamic characteristics of brain activity after stroke using functional magnetic resonance imaging (fMRI).Approach.Twenty ischemic PS patients and nineteen healthy controls (HCs) were recruited to receive a resting-state fMRI scanning. The static amplitude of low-frequency fluctuations (sALFFs) and fuzzy entropy of dynamic ALFF (FE-dALFF) were applied to identify the stroke-induced alterations.Main results.Compared with the HCs, PS patients showed significantly increased FE-dALFF values in the right angular gyrus (ANG), bilateral precuneus (PCUN), and right inferior parietal lobule (IPL) as well as significantly decreased FE-dALFF values in the right postcentral gyrus (PoCG), right dorsolateral superior frontal gyrus (SFGdor), and right precentral gyrus (PreCG). The receiver operating characteristic analyses demonstrated that FE-dALFF and sALFF possess comparable sensitivity in distinguishing PS patients from the HCs. Moreover, a significantly positive correlation was observed between the FE-dALFF values and the Fugl-Meyer Assessment (FMA) scores in the right SFGdor (r= 0.547), right IPL (r= 0.522), and right PCUN (r= 0.486).Significance.This study provided insight into the stroke-induced alterations in static and dynamic characteristics of local brain activity, highlighting the potential of FE-dALFF in understanding neurophysiological mechanisms and evaluating pathological changes.

Rising resistance of urinary tract pathogens in children: a cause for concern.

BACKGROUND: Urinary tract infection (UTI) is one of the common infections in childhood. Prompt diagnosis and treatment reduces the risk of complications. The choice of antibiotic to treat UTI varies from region to region. Rational use and appropriately chosen antibiotic reduces the emergence of resistant uropathogens. OBJECTIVE: We investigated the resistance pattern of uropathogens for commonly used antibiotics to treat UTI locally. METHODS: Data was collected between 2009 and 2019 on all infants and children under 16 years of age with culture proven UTI. Results were compared with previously published figures between 2002 and 2008. RESULTS: A total of 1002 samples were analysed (91/year). Male to female ratio was 1:4.6. About 94% of the samples grew E. coli. As before, high resistance rates were recorded to Amoxicillin and Trimethoprim (Z = -0.325: P = 0.7452; not significant). Overall, average resistance has decreased for Nitrofurantoin from 10% between 2002 and 2008 to 5.84% between 2009 and 2019 (Z = 3.002: P = 0.0027). On the other hand, Cefalexin resistance has increased from 7.4 to 14.56% between the two study periods (Z = -4.2: P = < 0.0002). CONCLUSION: Despite rising resistance rates, we recommend that Cefalexin should cautiously remain the antibiotic of choice for empirically treating uncomplicated urinary tract infections in secondary care pending urine culture. Nitrofurantoin should be reserved for treating non-coliform/atypical UTIs or multi-drug resistant UTIs. There is an ongoing need for clinicians in all geographic regions to continue to monitor antibiotic resistance rates every few years.

Rapid determination of sulfamethoxazole and trimethoprim illegally added to health products using excitation-emission matrix fluorescence coupled with the second-order calibration method.

In this work, a simple and fast analytical method based on a self-weighted alternating trilinear decomposition (SWATLD) algorithm coupled with excitation-emission matrix (EEM) fluorescence was developed for the simultaneous determination of sulfamethoxazole (SMZ) and trimethoprim (TMP) illegally added to health products. With the second-order advantage, the proposed method obtained satisfactory results in the presence of peak overlap and unknown interferences. The analysis time for a single sample is only 0.8 minutes. The average spiked recoveries of SMZ and TMP in three health product spiked samples were in the range of 91.0-106.2% and 86.8-107.8%, respectively. The relative standard deviations (RSDs) were lower than 8.6%. In addition, verification parameters including sensitivity (SEN), selectivity (SEL), the limit of detection (LOD), the limit of quantification (LOQ), intra-day precision, and inter-day precision were calculated, and the results show that the proposed method is feasible. The quantitative results of the proposed method were further confirmed by the LC-MS/MS method, which proved that the proposed method was efficient and green for drug-abuse monitoring of SMZ and TMP in health products.

Fast identification of the geographical origin of Gastrodia elata using excitation-emission matrix fluorescence and chemometric methods.

Geographical origin is an important factor affecting the quality of traditional Chinese medicine. In this paper, the identification of geographical origin of Gastrodia elata was performed by using excitation-emission matrix fluorescence and chemometric methods. Firstly, excitation-emission matrix (EEM) fluorescence spectra of Gastrodia elata samples from different geographical origins were obtained. And then three chemometric methods, including multilinear partial least squares discriminant analysis (N-PLS-DA), unfold partial least squares discriminant analysis (U-PLS-DA), and k-nearest neighbor (kNN) method, were applied to build discriminant models. Finally, 45 Gastrodia elata samples could be differentiated from each other by these classification models according to their geographical origins. The results showed that all models obtained good classification results. Compared with the N-PLS-DA and U-PLS-DA, kNN got more accurate and reliable classification results and could identify Gastrodia elata samples from different geographical origins with 100% accuracy on the training and test set. Therefore, the proposed method was available for easily and quickly distinguishing the geographical origin of Gastrodia elata, which can be considered as a promising alternative method for determining the geographic origin of other traditional Chinese medicines.

Excitation-emission matrix fluorescence spectroscopy coupled with multi-way chemometric techniques for characterization and classification of Chinese lager beers.

This paper proposed excitation-emission matrix fluorescence spectroscopy coupled with multi-way chemometric techniques for characterization and classification of Chinese pale lager beers produced by different manufacturers. The undiluted and diluted beer samples presented different fluorescence fingerprints. Three-way and four-way parallel factor analysis (PARAFAC) were used to decompose the skillfully constructed three-way and four-way data arrays, respectively, to further achieve beer characterization and feature extraction. Based on the features extracted in different ways, four strategies for beer classification were proposed. In each strategy, three supervised classification methods including linear discriminant analysis (LDA), partial least squares discriminant analysis (PLS-DA) and k-nearest neighbor (kNN) were used to build discriminant models. By comparison, PARAFAC-data fusion-kNN method in strategy 3 and four-way PARAFAC-kNN method in strategy 4 obtained the best classification results. The classification strategy based on four-way sample-excitation-emission-dilution level data array was proposed to solve the problem of beer classification for the first time.

A chemometric comparison of different models in fluorescence analysis of dabigatran etexilate and dabigatran.

In this paper, a simple, rapid, low-cost and potential method was established for the simultaneous quantitative analysis of dabigatran etexilate (DABE) and dabigatran (DAB) in spiked biological fluids. It combined excitation-emission matrix fluorescence (EEMF) with different second-order calibration methods, including the self-weighted alternating normalized residue fitting (SWANRF) algorithm based on trilinear decomposition model, the multivariate curve resolution - alternating least-squares (MCR-ALS) based on bilinear decomposition model and the unfolded partial least-square coupled with residual bilinearization (U-PLS/RBL) based on latent variables model. The proposed method showed "second-order advantage", that is, satisfactory quantitative results were successfully obtained even in the presence of unknown interferences and serious spectral overlap. The recoveries of DABE and DAB in spiked biological fluids were 91.7%-101.7% for SWANRF, 95.9%-117.8% for MCR-ALS, 83.0%-109.6% for U-PLS/RBL, respectively. Figures of merit and other statistical parameters were also calculated to assess the performance of the proposed method. Moreover, the modeling procedures and characteristics of three different models in EEMF analysis were discussed and compared.

Effects of fluoride on growth and development, learning and memory, and oxidative stress in serum of offspring rats / 中华地方病学杂志

Objective:To observe the change of growth and development, learning and memory, and oxidative stress in serum of offspring rats with fluorosis, and to explore the mechanism of fluoride on neurobehavioral development of offspring rats.Methods:Seventy-two SD rats (female and male ratio 3 ∶ 1) were fed adaptively for one week. According to their body mass [(80 ± 20) g], they were divided into control group (drinking tap water, containing less than 0.5 mg/L fluoride), low fluorine group (drinking water containing 10.0 mg/L of fluoride), and high fluorine group (drinking water containing 100.0 mg/L of fluoride) with random number table. After six months of feeding, they mated freely and gave birth in each group (24 rats with 18 females and 6 males). The rats in each group continued to be exposed to fluoride after giving birth, and the offspring rats were exposed to fluoride through breast milk feeding until the 28th day after birth. Body and brain weight, growth and development indicators (auricle separation, eyes opening, teeth eruption and hair growth) and neurobehavioral development indicators (cliff avoidance, auditory startle, surface righting and vibrissa positioning) were recorded. On the 28th day after birth, the learning and memory abilities (escape latency) of offspring rats were tested by Morris water maze; blood samples were taken from eyeballs to detect the content of nitric oxide (NO), the activity of nitric oxide synthase (NOS) and inducible nitric oxide synthase (iNOS).Results:On the 21st day and 28th day after birth, the differences of body weight among control group, low fluorine group and high fluorine group [21st day: (54.70 ± 3.02), (52.30 ± 2.58), (51.30 ± 2.71) g, 28th day: (91.70 ± 5.03), (90.40 ± 4.76), (86.00 ± 4.55) g] were statistically significant ( F = 3.96, 3.70, P < 0.05); on the 21st day, the body weight of high fluorine group was lower than that of control group ( P < 0.05); on the 28th day, the body weight of the high fluorine group was lower than those of control group and low fluorine group ( P < 0.05). On the 28th day, the difference of brain weight of control group, low fluorine group and high fluorine group was statistically significant ( F = 6.19, P < 0.05); and the low fluorine group and high fluorine group were lower than that of control group ( P < 0.05). Among the growth development indicators, the difference of time of completing eyes opening in control group, low fluorine group and high fluorine group was statistically significant ( F = 3.64, P < 0.05); and the high fluorine group was higher than that of control group ( P < 0.05). In neurobehavioral development indicators, the differences of time of completing cliff avoidance, surface righting between the control group, low fluorine group and high fluorine group were statistically significant ( F = 8.29, 7.69, P < 0.05); and the time of completing cliff avoidance in high fluorine group was higher than those of control group and low fluorine group ( P < 0.05), the time of completing surface righting was higher than that of control group ( P < 0.05). In Morris water maze, on the 4th day, the escape latencies of low fluorine group and high fluorine group were higher than that of control group ( P < 0.05). The results of oxidative stress in serum showed that there were statistically significant differences in serum NO content, NOS and iNOS activitives between the control group, low fluorine group and high fluorine group ( F = 4.86, 66.48, 70.95, P < 0.05); and the NO content of the high fluoirne group was higher than that of the control group ( P < 0.05), the activities of NOS and iNOS of the high fluoirne group were higher than those of control group and the low fluorine group ( P < 0.05). Conclusion:Excessive fluoride can increase the level of oxidative stress in serum, which may be closely related to the neurobehavioral retardation and the decline of learning and memory ability of offspring rats.

Small molecule proteomics quantifies differences between normal and fibrotic pulmonary extracellular matrices / 中华医学杂志(英文版)

BACKGROUND@#Pulmonary fibrosis is a respiratory disease caused by the proliferation of fibroblasts and accumulation of the extracellular matrix (ECM). It is known that the lung ECM is mainly composed of a three-dimensional fiber mesh filled with various high-molecular-weight proteins. However, the small-molecular-weight proteins in the lung ECM and their differences between normal and fibrotic lung ECM are largely unknown.@*METHODS@#Healthy adult male Sprague-Dawley rats (Rattus norvegicus) weighing about 150 to 200 g were randomly divided into three groups using random number table: A, B, and C and each group contained five rats. The rats in Group A were administered a single intragastric (i.g.) dose of 500 μL of saline as control, and those in Groups B and C were administered a single i.g. dose of paraquat (PQ) dissolved in 500 μL of saline (20 mg/kg). After 2 weeks, the lungs of rats in Group B were harvested for histological observation, preparation of de-cellularized lung scaffolds, and proteomic analysis for small-molecular-weight proteins, and similar procedures were performed on Group C and A after 4 weeks. The differentially expressed small-molecular-weight proteins (DESMPs) between different groups and the subcellular locations were analyzed.@*RESULTS@#Of the 1626 small-molecular-weight proteins identified, 1047 were quantifiable. There were 97 up-regulated and 45 down-regulated proteins in B vs. A, 274 up-regulated and 31 down-regulated proteins in C vs. A, and 237 up-regulated and 28 down-regulated proteins identified in C vs. B. Both the up-regulated and down-regulated proteins in the three comparisons were mainly distributed in single-organism processes and cellular processes within biological process, cell and organelle within cellular component, and binding within molecular function. Further, more up-regulated than down-regulated proteins were identified in most sub-cellular locations. The interactions of DESMPs identified in extracellular location in all comparisons showed that serum albumin (Alb) harbored the highest degree of node (25), followed by prolyl 4-hydroxylase beta polypeptide (12), integrin β1 (10), apolipoprotein A1 (9), and fibrinogen gamma chain (9).@*CONCLUSIONS@#Numerous PQ-induced DESMPs were identified in de-cellularized lungs of rats by high throughput proteomics analysis. The DESMPs between the control and treatment groups showed diversity in molecular functions, biological processes, and pathways. In addition, the interactions of extracellular DESMPs suggested that the extracellular proteins Alb, Itgb1, Apoa1, P4hb, and Fgg in ECM could be potentially used as biomarker candidates for pulmonary fibrosis. These results provided useful information and new insights regarding pulmonary fibrosis.

A simple method for direct modeling of second-order liquid chromatographic data with retention time shifts and holding the second-order advantage.

Retention time shifts in chromatographic data severely affect the quantitative analysis of analytes of interest in complex systems. This paper offers a simple method for directly handing second-order liquid chromatographic data with retention time shift, and achieving qualitative and quantitative analysis of target analytes in the presence of overlapping peaks and unknown interference, which is the so-called "second-order advantage". The proposed method is named the alternating trilinear decomposition-assisted multivariate curve resolution (ATLD-MCR) because it absorbs the basic philosophy of alternating trilinear decomposition (ATLD) algorithm and multivariate curve resolution (MCR). ATLD-MCR was implemented by using the pre-decomposition results of ATLD as the initial values, MCR strategy for each sample slice matrix and the least squares optimization strategy. Three simulated data sets, a semi-simulated LC-MS data set and a real HPLC-DAD data set were investigated by the proposed method, respectively. In addition, the resolved qualitative profiles and concentration values were compared with those obtained by the other three classical second-order calibration algorithms. ATLD-MCR performed well and obtained satisfactory qualitative and quantitative results for the analytes of interest in both the simulated and experimental systems, which proved that the newly proposed method could properly model the second-order chromatographic data with retention time shifts and severe signal overlapping.

Rapid identification and quantification of cheaper vegetable oil adulteration in camellia oil by using excitation-emission matrix fluorescence spectroscopy combined with chemometrics.

Camellia oil is a high quality oil mainly produced in southern China. It is common that unscrupulous merchants attempt to make huge profits by adulterating camellia oil with other cheaper or lower-quality vegetable oils. Therefore, this paper proposed excitation-emission matrix fluorescence spectroscopy combined with chemometric methods for the rapid identification and quantification of camellia oil adulteration with other cheaper vegetable oils. A five-component parallel factor analysis (PARAFAC) model roughly completed spectral characterization of oil samples, and obtained chemically meaningful information. Four advanced chemometrics methods were used for the classification of camellia oil and other vegetable oils (model 1) and the classification of camellia oil and adulterated camellia oil (models 2 and 3), respectively. Two-directional two-dimensional linear discriminant analysis ((2D)2LDA) was used for chemical data for the first time and showed huge potential. Furthermore, the developed N-PLS regression model used for the prediction of adulteration level in camellia oil showed satisfactory accuracy.

Mechanism and research progress on radiotherapy combined with immunotherapy / 中华放射肿瘤学杂志

In recent years, the incidence rate of malignant tumors has been ever increased. As the persistent advancement of various therapeutic techniques, the therapeutic plans of cancer have been improved. Radiotherapy takes effect mainly by killing the topical tumor cells by radiation. During radiotherapy, the anti-tumor immune response can be induced or enhanced. Appropriate radiotherapy dose and segmentation model combined with certain immunotherapy plays a more and more significant role in the treatment of tumors. In this article, the underlying mechanisms of radiation-enhanced anti-tumor immune response and the current status and research prospects of radiotherapy combined with immunotherapy were reviewed.

Effect of fluoride on expression of phosphorylated NMDAR protein in rat hippocampal neurons / 中华地方病学杂志

Objective To observe the expression of phosphorylated N-methyl-D-aspartate receptor (P-NMDAR) protein in hippocampal neurons of rats with fluorosis and explore the mechanism of neuronal damage caused by fluorosis.Methods Sixteen Sprague-Dawley rats within 24 h after birth were selected,and hippocampus of the brain was isolated after sacrifice.The primary neurons were cultured in vitro.Observation of the cell morphology under an inverted microscope,neurons were identified by immunofluorescence staining.In the 7th day of cultivation,the neurons were divided into control group,low fluoride group,high fluoride group,antagonist group,low fluoride antagonist group and high fluoride antagonist group.The control group was treated with the same volume of medium as the experimental group.The concentration of NaF was 0.2 and 2.0 mmol/L in the low fluoride group and the high fluoride group,respectively.The antagonist group was treated with 10.0 μ mol/L NMDAR antagonist (MK-801).The low fluoride antagonist group and the high fluoride antagonist group were treated with 0.2 mmol/L NaF + 10.0 μmol/L MK-801,2.0 mmol/L NaF + 10.0 μmol/L MK-801,respectively.The culture time was 24 hours.The expression levels of phosphorylated protein (P-NMDAR1,P-NMDAR2A,P-NMDAR2B) of NMDAR subunits were detected by Western blotting.Results Under inverted microscope,the primary cell body of the cultured in vitro for 2-3 days became larger,and many protrusions appeared outward,showing a small spider shape;6-7 days,the cells synaptic long and slender,a network-like interlaced form.Under fluorescent microscope,NeuN positive cells (neurons) with red fluorescence were observed,and the cell purity exceeded 80％.There was no significant difference in the expression of P-NMDAR1 protein between the control group,the low fluoride group,the high fluoride group,the antagonist group,the low fluoride antagonist group and the high fluoride antagonist group (0.44 ± 0.12,0.46 ± 0.06,0.46 ± 0.12,0.56 ± 0.10,0.70 ± 0.12,0.46 ± 0.09,F=2.75,P ＞ 0.05);P-NMDAR2A and P-NMDAR2B protein expressions were statistically significant between the six groups (0.75 ± 0.17,0.74 ± 0.08,1.13 ± 0.27,0.87 ± 0.15,0.67 ± 0.11,0.66 ± 0.09;0.68 ± 0.24,0.66 ± 0.12,1.46 ±0.27,0.74 ± 0.16,0.56 ± 0.13,0.91 ± 0.35,F =3.68,6.11,P ＜ 0.05),and the expressions of P-NMDAR2A and P-NMDAR2B protein in high fluoride group were higher than those in the control group (P ＜ 0.05);the expressions in the high fluoride antagonist group were lower than those in the high fluoride group (P ＜ 0.05).Conclusion Excessive fluoride can increase the expressions of P-NMDAR2A and P-NMDAR2B protein of hippocampal neurons,and co-culture of MK-801 and NaF can antagonize the damage of fluoride to neurons.

Chemometrics-assisted liquid chromatography with full scan mass spectrometry for the interference-free determination of glucocorticoids illegally added to face masks.

A smart chemometrics-assisted strategy that combines the full scan mode of liquid chromatography with mass spectrometry with second-order calibration method based on alternating trilinear decomposition algorithm was developed for the rapid determination of 15 glucocorticoids including the epimers betamethasone and dexamethasone illegally added into face masks. Fifteen glucocorticoids were rapidly eluted (11 min) under a simple elution program. By means of the second-order calibration method, 15 target analytes were successfully quantified in the presence of peak overlaps, unknown interferences and baseline drifts. Notably, the epimers, namely, betamethasone and dexamethasone, were simultaneously quantified by the proposed method under a simple elution program. The average spiked recoveries for all target analytes ranged from 87.3 ± 2.2 to 119.4 ± 5.8%. The validation parameters including sensitivity, selectivity, limit of detection, limit of quantitation, and precision were calculated to validate the accuracy of the proposed method, and the quantitative analysis results were further confirmed by liquid chromatography with tandem mass spectrometry. All results proved that the proposed chemometrics-assisted liquid chromatography with mass spectrometry strategy was an accurate and fast method to determine epimers and multiple glucocorticoids in complex face mask samples.

Mechanism of nerve injury caused by fluorosis: a review of recent studies / 中华地方病学杂志

Excessive exposure to fluoride in the environment leads to a variety of health hazards,especially in the nervous system damage.Great number of experimental and clinical data have confirmed that excessive intake of fluoride can cause neurotoxicity,and produce a series of symptoms of central nervous system dysfunction.This review summarizes the mechanisms of neurotoxicity induced by fluorosis in recent years,including oxidative stress,neurotransmitters and receptors,central nervous system signaling molecules,neuronal energy metabolism,and glycosylation end products.This paper analyzes the effects of fluorine exposure on nervous system,thus providing a reliable basis for further prevention and treatment of fluorosis.