Luminescence intensity ratio thermometry based on combined ground and excited states absorptions of Tb3+ doped CaWO4.

Luminescence intensity ratio (LIR) thermometry is of great interest, because of its wide applications of noninvasive temperature sensing. Here, a LIR thermometry based on combined ground and excited states absorptions is developed using CaWO4:Tb3+. The ratio of single luminescence (5D4-7F5) intensities under 379 and 413 nm excitations with opposite temperature dependences, attributed to the thermal coupling of ground state 7F6 and excited state 7F5, is used to measure temperature. This LIR method achieves a high relative sensitivity of 2.8% K-1, and can avoid complex spectral splitting by collecting all down-shifting luminescence bands, being a promising accurate luminescence thermometry.

Biomechanical effects of a mandibular advancement device on the periodontal ligament: Based on different bone models.

Obstructive sleep apnea syndrome (OSAS) is recurrent apnoea caused by upper airway obstruction during sleep. In severe cases, OSAS might lead to sudden death. Currently, the mandibular advancement device (MAD) is the preferred product for the treatment of mild to moderate OSAS because of its compliance, portability and low cost. However, many clinical studies have suggested that long-term use of MAD might cause occlusal changes, periodontitis, muscle soreness, and joint damage. In view of the difficulties in the measurement of relevant mechanical factors in vivo, the present work aimed to quantitatively analyze biomechanical mechanisms that might lead to these side effects through computer numerical simulations and a nonhomogeneous alveolar bone model was established to approximate the actual bony features of the jaw in the simulations model. First, a 3D digital model of the teeth, periodontal ligament(PDL), and alveolar bone was created on the basis of computed tomography images and assembled with a 3D model of the MAD. A nonhomogeneous alveolar bone model was created based on computed tomographic images, and the stresses acting on the PDL were computed using the finite element method. The results showed that the nonhomogeneous model could more realistically reflect the mechanical properties of the alveolar bone and obtain the true stresses compared with the homogeneous model, which underestimated the adverse effects of PDL therapy. The numerical simulations in this paper can help doctors make more accurate judgements about MAD treatment from an oral health protection perspective.

NF-κB-Activated lncRNACASC9 Promotes Bladder Cancer Progression by Regulating the TK1 Expression.

Long noncoding RNAs (lncRNA) are involved in cancer development, but the roles of most lncRNAs are undocumented. In this study, we identified lncRNAs that were abnormally expressed in bladder cancer. We found that lncRNACASC9 plays an important role in the progression of bladder cancer. CASC9 was highly expressed in bladder cancer cells and tissues, and the prognosis of bladder cancer patients with high expression of CASC9 was poor. The results of colony formation assays, CCK-8 assays, EdU assays, transwell assays, mouse xenograft models, and tail vein injection lung metastasis model showed that CASC9 could promote bladder cancer cells growth and metastasis both in vitro and in vivo. Mechanistically, through FISH experiments, luciferase reporter experiments, and RIP experiments, we proved that CASC9 regulated the expression of TK1 by adsorbing miR-195-5p, thereby exerting an oncogenic effect in bladder cancer. Taken together, our findings support that the CASC9/miR-195-5p/TK1 axis is a critical pathway in the tumorigenesis and progression of bladder cancer, implicating a new therapeutic direction for the treatment of bladder cancer.

Optimal fluorescence and photosensitivity properties of dual-functional NaYb1-x F4:Tm x 3+ nanoparticles for applications in imaging guided photodynamic therapy.

The fluorescence and photosensitivity properties of NaYb1-x F4:Tm x 3+ nanoparticles were optimized to develop noninvasive near-infrared fluorescence imaging-guided photodynamic therapy. The emission at 800 nm from Tm3+ presented an exponential increase with an increase in the Tm3+ doping concentration from 0 to 2%. The photosensitivity properties of NaYb1-x F4:Tm x 3+ nanoparticles were also studied via the chemoprobe method, which used a reactive oxygen quencher, 1,3-diphenylisobenzofuran (DPBF). With the increase in the doping concentration of Tm3+, the generation rate of reactive oxygen species in NaYb1-x F4:Tm x 3+ nanoparticles decreased linearly at a rate of 0.3. The doping concentration of Tm3+ had two opposite effects on the 800 nm emission and generation rates of reactive oxygen species. The competitive relationship was discussed and an optimal value for the Tm3+ doping concentration of approximately 1% was determined. At this concentration, the energy of the Yb3+ excited state can be fully utilized, and the fluorescence and photosensitivity properties are an effective combination.

Sex Differences in Physiological Stress Induced by a Long-Lasting Adventure Race: A Prospective Observational Analytical Study.

BACKGROUND: In order to provide additional information on the behaviour of biochemical parameters related to stress responses to a specific long-term competition, we aimed to compare the stressful effects of a long-lasting competition on physiological variables in men and women. METHODS: This is a prospective observational analytical study. Twenty-five professional athletes, 15 men and 10 women, travelled 460 km for 4 days in an international edition of the Ecomotion/Pro AR World. RESULTS: After the competition, we detected an increase in α-amylase and cortisol levels and a decrease in salivary immunoglobulin A (lgA) levels. The relative percentage changes in α-amylase, IgA and cortisol levels were significantly higher in women than in men, whereas women had lower relative percentage changes in glucose and lactate levels compared with men. There was a decrease in lymphocyte, eosinophil and monocyte counts, with relative percentage decreases in lymphocytes and monocytes being significantly higher in female athletes than in males. There were increases in the serum activities of total creatine kinase (CK), the creatine kinase myocardial isoform (CKMB), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) at the end of the test, with significantly higher elevations of total CK, CKMB and LDH in men and ALT in women. CONCLUSION: Long-lasting competition induced stress, muscle damage, anaemia and changes in the immune system. Women had more intense responses of cortisol and leukocytes.

Analysis of Intervention of Erxiantang in Ovariectomized Rats by LC-MS Serum Metabolomics / 中国实验方剂学杂志

ObjectiveTo investigate the changes of endogenous metabolites in serum of ovariectomized rats and the effect of Erxiantang on them based on liquid chromatography-mass spectrometry（LC-MS）. MethodTwenty-four healthy female SD rats were randomly divided into sham-operated group， model group and Erxiantang group（7.5 g·kg-1）， with 8 rats in each group. Bilateral ovarian tissues were excised in the model and Erxiantang groups， and small pieces of adipose tissues were excised in the abdominal cavity of the sham-operated group bilaterally， and gastric administration was started 2 weeks after surgery， and equal volumes of distilled water were gavaged in the sham-operated and model groups. After 12 weeks of administration， blood was collected from abdominal aorta， and non-targeted metabonomics was performed on rat serum by LC-MS， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to screen differential metabolites. Metabolic pathway analysis was performed based on Kyoto Encyclopedia of Genes and Genomes（KEGG）， and the levels of key enzymes of metabolic pathways were verified by enzyme-linked immunosorbent assay（ELISA）. ResultThe results of metabonomics showed that 82 differential metabolites between the model group and the sham-operated group were glycerophospholipids， fatty acyls， steroids and steroid derivatives， of which the most significant difference was glycerophospholipids. At the same time， Erxiantang could call back 65 out of 82 differential metabolites， of which 11 were statistically significant， mainly phosphatidylcholine（PC） and lysophosphatidylcholine（LysoPC） in glycerophospholipids， followed by corticosterone and 11-deoxycortisol in steroids and steroid derivatives. Metabolic pathway analysis showed that the pathways of glycerophospholipid metabolism and steroid hormone biosynthesis in model group were changed， and were recovered after the administration of Erxiantang. ELISA results showed that compared with the sham-operated group， serum levels of cholinephosphate cytidylytransferase（CCT）， secretory phospholipase A2（sPLA2） and lysophosphatidylcholine acyltransferase（LPCAT）， which were the key metabolic enzymes of glycerophospholipid metabolite PC and LysoPC， were significantly decreased in the model group（P<0.05， P<0.01）， and choline phosphotransferase 1（CPT1） levels decreased but the difference was not statistically significant， compared with the model group， the levels of CCT， sPLA2 and CPT1 were significantly increased in Erxiantang group（P<0.01）. In addition， compared with the sham-operated group， the levels of cholesterol（TC）， triglyceride（TG） and low density lipoprotein cholesterol（LDL-C） were significantly increased in the model group（P<0.01）， the high density lipoprotein cholesterol（HDL-C） level was decreased（P<0.05）， compared with the model group， the levels of TC， TG and LDL-C were significantly decreased and the level of HDL-C was significantly increased in Erxiantang group（P<0.01）. ConclusionEndogenous metabolites and related metabolic pathways in ovariectomized rats were altered， and Erxiantang can reverse some of the different metabolites and related pathways， such as regulating glycerophospholipid metabolism by regulating metabolic enzymes CCT， sPLA2 and CPT1 to increase the levels of PC and LysoPC， and then improve the pathological changes such as lipid metabolism disorder in ovariectomized rats.

Human 8-cell embryos enable efficient induction of disease-preventive mutations without off-target effect by cytosine base editor

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.

Study on the original pathogenesis of primary osteoporosis / 国际中医中药杂志

The original meaning of pathogenesis refers to the cardinal mechanism of the occurrence, development and change of disease, which has three characteristics: cardinal, dominant and directional. The original pathogenesis of primary osteoporosis includes aging and renal failure, which was determined through ancient Chinese medicine books and modern researches. The basic contradiction and evolutionary law of diseases from the level of original pathogenesis were identified, that contribute to the prevention and treatment of primary osteoporosis with Traditional Chinese Medicine.

Grouping rules and implications of MS-DRG in the United States / 中华医院管理杂志

The United States is the first country to implement DRG payment in the world, and its MS-DRG(medical severity DRG)version has been used for reference by many countries and regions. In order to ensure the universal applicability of DRG grouping scheme and adapt to the clinical reality, the MS-DRG grouping scheme should follow such grouping rules as similarity of resource consumption, clinical similarity and easy management of DRG groups. This paper presented the evolution of MS-DRG and expounded on its grouping rules in detail, for reference in the amendment and improvement of grouping rules in CHS-DRG.

Unexpected antibody screening of thalassemia children in Yunnan Province and the blood transfusion strategies / 中国输血杂志

【Objective】 To study the yielding rate and distribution of unexpected antibodies in blood transfusion children with thalassemia in Yunnan province, and to explore the blood transfusion strategies. 【Methods】 From January 2016 to December 2021, 298 children with thalassemia, who received blood transfusion treatment in Kunming, Xishuangbanna, Wenshan, Dehong, Yuxi and Baoshan hospitals across Yunnan Province, were selected. The unexpected antibodies of blood plasma were screened by microcolumn gel card. The samples with positive antibodies were identified for alloantibody specificity. 【Results】 Unexpected antibodies were yielded in 67 out of 298(22.48%) transfused children with thalassemia. The positive rates of unexpected antibodies in boys and girls were 16.55%(24/145) and 28.10%(43/153), respectively. The positive rates of unexpected antibodies in Han, Dai, Zhuang, Yi, Bulang, Jinuo and Miao people were 14.06%(18/128), 30.80%(32/104), 35.71%(10/28), 36.36%(8/22), 50.00%(4/8), 60.00%(3/5)and 66.67%(2/3), respectively, with statistically significant differences between each other. The positive rate of unexpected antibodies in ethnic minorities was higher than that in Han. The positive rates of unexpected antibodies in children who received the first transfusion at birth-one year old, 1~3 years old, 3~6 years old and above 6 years old were 12.50%(3/24), 10.14%(7/69), 24.54%(40/163)and 40.48%(17/42), respectively. The positive rates of unexpected antibodies in children with first transfusion after 3 years old were significantly higher than those before 3 years old. The positive rates of unexpected antibodies in children with one transfusion, 1~3, 3~10, 10~20 and more than 20 transfusions were 4.76%(1/21), 12.07%(7/58), 23.71%(23/97), 28.16%(29/103)and 36.84%(7/19), respectively, with statistically significant differences between each other. The number of blood transfusions was positively correlated with the unexpected antibody yielding. The yielding rate of unexpected antibodies in children with α thalassemia, βthalassemia, δ+ βthalassemia and untyped thalassemia was 7.50%(3/40), 17.62%(34/193), 53.70%(29/54)and 9.09%(1/11), respectively(P<0.05). The yielding rate of unexpected antibodies in transfused children with δ+ βthalassemia was the highest. And 57 unexpected antibodies of Rh blood group system were yielded, 6 anti-M antibodies, 2 anti-N antibodies and 2 undetermined. 【Conclusion】 The positive rate of unexpected antibodies in transfused children with thalassemia in Yunnan province is high. Routine antibody screening should be carried out for transfusion children with thalassemia, and blood units, compatible with ABO, Rh and MNS typing results, should be selected to ensure the safety and effectiveness of clinical blood use.

Self-assembly of an amphiphilic derivative of chitosan and micellar solubilization of puerarin.

A kind of amphiphilic derivatives of chitosan (2-hydroxyl-3-butoxyl)-propylcarboxymethyl-chitosan (HBP-CMCHS), has been synthesized, and the critical micelle concentration (cmc) of HBP-CMCHS was detected by the fluorescence method. The puerarin-loaded HBP-CMCHS micellar system was prepared by physical entrapped method. Result showed that when adding the same amount of puerarin, the solubilizing capacity was enhanced by increasing the concentration of HBP-CMCHS and temperature. Puerarin-loaded micellar system of HBP-CMCHS was characterized by TEM and DLS. TEM photograph revealed that the micelles were spherical and puerarin was solubilized in the cores of the spherical polymeric micelles. DLS showed that after solubilization the size of the micelles became bigger. In vitro tests showed that puerarin was slowly released from micellar solution and the release lasted up to 60 h by means of the dialysis method.

A comparison of multimodal biomarkers for chronic hepatitis B assessment using recursive feature elimination.

An effective assessment of liver fibrosis in patients with chronic hepatitis B (CHB) is highly desired because it is important not only for clinical courses prediction, but also for the determination of antiviral therapy schemes. In recent years, various approaches for liver biopsies analysis have been highlighted, such as elastography techniques and serum markers, due to their properties of non-invasiveness. The aim of this study is to determine the best biomarkers or their combination by comparing multimodal biomarkers (ultrasound elastography parameters, biochemical hematologic parameters, and clinical parameters) for fibrosis assessment in chronic hepatitis B using a support vector machine combined with recursive feature elimination (RFE-SVM) approach. Results revealed that biomarkers from ultrasound elastography techniques achieved better prediction performance than others in the assessment of significant fibrosis (≥ F2) and cirrhosis (F4), and the best prediction performance were (1) ≥ F2: AUC = 0.902, ACC = 86.697%; (2) F4: AUC = 0.976, ACC = 90.364%. The findings are useful in guiding biomarkers selection and features optimization and in simplifying the prediction system for evaluation of liver fibrosis stage.

Research progress of leptin resistance mechanism / 中华内分泌代谢杂志

With the progress of society and the improvement of living standard, the incidence of obesity is increasing. Serum leptin level increased significantly in the obese patients with hyperinsulinemia. However, the response to leptin is weakened, and then " leptin resistance" is widely concerned. Previous studies have focused on serum leptin levels and leptin receptor expression. In recent years, the mechanism of leptin resistance has been elucidated from different perspectives. This article tries to review the recent progress in the mechanism for leptin resistance, and briefly discusses the relationship between leptin resistance and insulin resistance, as well as the latest treatment measures for leptin resistance. With the development of leptin resistance research, it is believed that the increasing leptin sensitivity will be an important measure in obesity treatment.

Joint collaborative representation based sleep stage classification with multi-channel EEG signals.

Multi-channel electroencephalography (EEG) signals have been effectively used for sleet staging. However, it is still a challenge to effectively fuse and represent multi-channel EEG features. The coding based feature representation methods, such as sparse representation (SR), have achieved great success in computer vision and pattern recognition. Collaborative representation (CR) is a new coding method, which effectively works as a classifier. In this work, we first employ CR as a feature representation method. Moreover, a new joint CR (JCR) model is proposed for fusing multi-view data, which can represent not only the individual view information, but also the inner-correlative information between multi-views. JCR method is then applied to fuse and represent the features of multi-channel EEG signals for the classification of sleep stages. The experimental results indicate that CR feature outperforms SR feature, and JCR achieves best performance for sleep stage classification by effectively fusing multi-channel EEG signals.

L0-regularized time-varying sparse inverse covariance estimation for tracking dynamic fMRI brain networks.

Exploration of time-varying functional brain connectivity based on functional Magnetic Resonance Imaging (fMRI) data is important for understanding dynamic brain mechanisms. l1-penalized inverse covariance is a common measure for the inference of sparse structure of functional brain networks, and it has been recently extended to estimate time-varying sparse brain networks by using a sliding window and incorporating a smoothing constraint on temporal variation. However, l1 penalty cannot induce maximum sparsity, as compared with l0 penalty, so l0 penalty is supposed to have superior quality on inverse covariance estimation. This paper introduces a novel time-varying sparse inverse covariance estimation method based on dual l0-penalties (DLP). The new DLP method estimates the sparse inverse covariance by minimizing an l0-penalized log-likelihood function and an extra l0 penalty on temporal homogeneity. A cyclic descent optimization algorithm is further developed to localize the minimum of the objective function. Experiment results on simulated signals show that the proposed DLP method can achieve better performance than conventional l1-penalized methods in estimating time-varying sparse network structures under different scenarios.

Supervised nonlinear dimension reduction of functional magnetic resonance imaging data using Sliced Inverse Regression.

Dimension reduction is essential for identifying a small set of discriminative features that are predictive of behavior or cognition from high-dimensional functional magnetic resonance imaging (fMRI) data. However, conventional linear dimension reduction techniques cannot reduce the dimension effectively if the relationship between imaging data and behavioral parameters are nonlinear. In the paper, we proposed a novel supervised dimension reduction technique, named PC-SIR (Principal Component - Sliced Inverse Regression), for analyzing high-dimensional fMRI data. The PC-SIR method is an important extension of the renowned SIR method, which can achieve the effective dimension reduction (e.d.r.) directions even the relationship between class labels and predictors is nonlinear but is unable to handle high-dimensional data. By using PCA prior to SIR to orthogonalize and reduce the predictors, PC-SIR can overcome the limitation of SIR and thus can be used for fMRI data. Simulation showed that PC-SIR can result in a more accurate identification of brain activation as well as better prediction than support vector regression (SVR) and partial least square regression (PLSR). Then, we applied PC-SIR on real fMRI data recorded in a pain stimulation experiment to identify pain-related brain regions and predict the pain perception. Results on 32 subjects showed that PC-SIR can lead to significantly higher prediction accuracy than SVR and PLSR. Therefore, PC-SIR could be a promising dimension reduction technique for multivariate pattern analysis of fMRI.

Profile and inspirations of hospital value-based purchasing of MS-DRG in the United States / 中华医院管理杂志

Pay-for-performance(P4P) is the third stage of payment evolution in the United States. As of 2010, the Centers for Medicare and Medicaid Services launched a series of P4P programs, including hospital value-based purchasing(HVBP) program. This paper introduced the background and eligibility of HVBP in the United States, focusing on the contents and calculation methods of HVBP as references for the reform of payment methods in China.

Profile and inspirations of hospital value-based purchasing of MS-DRG in the United States / 中华医院管理杂志

Pay-for-performance(P4P) is the third stage of payment evolution in the United States. As of 2010, the Centers for Medicare and Medicaid Services launched a series of P4P programs, including hospital value-based purchasing(HVBP) program. This paper introduced the background and eligibility of HVBP in the United States, focusing on the contents and calculation methods of HVBP as references for the reform of payment methods in China.

Efficacy of β-elemene combined with gefitinib in the treatment of advanced lung adenocarcinoma patients with slow progression after first-line gefitinib treatment / 国际肿瘤学杂志

Objective:To investigate the efficacy of β-elemene combined with gefitinib in the treatment of advanced lung adenocarcinoma patients with slow progression after first-line gefitinib treatment and its effects on quality of life and immune function.Methods:A prospective cohort study design was used to enroll patients with advanced lung adenocarcinoma who met the inclusion criteria from June 2017 to December 2018 in our hospital. They were divided into experimental group and control group by random number table method. The experimental group was given elemene combined with gefitinib, and the control group was only given gefitinib. The clinical efficacy, quality of life and immune function of the two groups were compared after 2 cycles of treatment. The PFS2 (time from slow progression of disease to rapid progression of disease) was followed up.Results:A total of 61 patients were included. There were 30 cases in the experimental group and 31 cases in the control group. The disease control rates of the experimental group and the control group were 83.3% (25/30) and 58.1% (18/31) respectively, and the difference was statistically significant ( χ2=4.680, P=0.031). The short-term efficacy of the experimental group was better than that of the control group, and the difference was statistically significant ( Z=-2.623, P=0.009). The median PFS2 of the experimental group was 4.20 months (95% CI: 3.94-4.46), and the median PFS2 of the control group was 4.00 months (95% CI: 2.94-5.07), with a statistically significant difference ( χ2=4.948, P=0.026). Quality of life was compared between the two groups: in terms of physical function, emotional function and overall quality of life, score differences before and after treatment of the experimental group were higher than those of the control group, with statistically significant differences [6.67(-6.66, 20.00) vs. 0(-6.66, 6.66), Z=-2.429, P=0.015; 29.17(2.08, 56.26) vs. 12.49(-14.59, 39.57), Z=-2.263, P=0.024; 16.67(-33.33, 56.67) vs. 8.34(-18.74, 35.42), Z=-2.249, P=0.025]. In terms of immune function, CD4 + T cells level in the experimental group increased after treatment compared with that before treatment (44.27%±6.78% vs. 41.17%±3.73%, t=-2.426, P=0.022), and CD8 + T cells level decreased compared with that before treatment (21.47%±3.18% vs. 23.50%±2.37%, t=2.532, P=0.017). After treatment, the level of CD4 + T cells in the experimental group was significantly higher than that in the control group (44.27%±6.78% vs. 39.63%±5.80%, t=2.725, P=0.011). Conclusion:β-elemene combined with gefitinib has a certain effect in the treatment of advanced lung adenocarcinoma patients with slow progression after first-line gefitinib treatment, and the quality of life and immune function are improved. It is worthy of further clinical research.

Culture-Positive Spontaneous Ascitic Infection in Patients with Acute Decompensated Cirrhosis: Multidrug-Resistant Pathogens and Antibiotic Strategies