Time-reversal symmetry-breaking charge order in a kagome superconductor.

The kagome lattice1, which is the most prominent structural motif in quantum physics, benefits from inherent non-trivial geometry so that it can host diverse quantum phases, ranging from spin-liquid phases, to topological matter, to intertwined orders2-8 and, most rarely, to unconventional superconductivity6,9. Recently, charge sensitive probes have indicated that the kagome superconductors AV3Sb5 (A = K, Rb, Cs)9-11 exhibit unconventional chiral charge order12-19, which is analogous to the long-sought-after quantum order in the Haldane model20 or Varma model21. However, direct evidence for the time-reversal symmetry breaking of the charge order remains elusive. Here we use muon spin relaxation to probe the kagome charge order and superconductivity in KV3Sb5. We observe a noticeable enhancement of the internal field width sensed by the muon ensemble, which takes place just below the charge ordering temperature and persists into the superconducting state. Notably, the muon spin relaxation rate below the charge ordering temperature is substantially enhanced by applying an external magnetic field. We further show the multigap nature of superconductivity in KV3Sb5 and that the [Formula: see text] ratio (where Tc is the superconducting transition temperature and λab is the magnetic penetration depth in the kagome plane) is comparable to those of unconventional high-temperature superconductors. Our results point to time-reversal symmetry-breaking charge order intertwining with unconventional superconductivity in the correlated kagome lattice.

Impact of heterozygous ALK1 mutations on the transcriptomic response to BMP9 and BMP10 in endothelial cells from hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension donors.

Heterozygous activin receptor-like kinase 1 (ALK1) mutations are associated with two vascular diseases: hereditary hemorrhagic telangiectasia (HHT) and more rarely pulmonary arterial hypertension (PAH). Here, we aimed to understand the impact of ALK1 mutations on BMP9 and BMP10 transcriptomic responses in endothelial cells. Endothelial colony-forming cells (ECFCs) and microvascular endothelial cells (HMVECs) carrying loss of function ALK1 mutations were isolated from newborn HHT and adult PAH donors, respectively. RNA-sequencing was performed on each type of cells compared to controls following an 18 h stimulation with BMP9 or BMP10. In control ECFCs, BMP9 and BMP10 stimulations induced similar transcriptomic responses with around 800 differentially expressed genes (DEGs). ALK1-mutated ECFCs unexpectedly revealed highly similar transcriptomic profiles to controls, both at the baseline and upon stimulation, and normal activation of Smad1/5 that could not be explained by a compensation in cell-surface ALK1 level. Conversely, PAH HMVECs revealed strong transcriptional dysregulations compared to controls with > 1200 DEGs at the baseline. Consequently, because our study involved two variables, ALK1 genotype and BMP stimulation, we performed two-factor differential expression analysis and identified 44 BMP9-dysregulated genes in mutated HMVECs, but none in ECFCs. Yet, the impaired regulation of at least one hit, namely lunatic fringe (LFNG), was validated by RT-qPCR in three different ALK1-mutated endothelial models. In conclusion, ALK1 heterozygosity only modified the BMP9/BMP10 regulation of few genes, including LFNG involved in NOTCH signaling. Future studies will uncover whether dysregulations in such hits are enough to promote HHT/PAH pathogenesis, making them potential therapeutic targets, or if second hits are necessary.

Fluoropyrimidine type, patient age, tumour sidedness and mutation status as determinants of benefit in patients with metastatic colorectal cancer treated with EGFR monoclonal antibodies: individual patient data pooled analysis of randomised trials from the ARCAD database.

BACKGROUND: KRAS mutations in metastatic colorectal cancer (mCRC) are used as predictive biomarkers to select therapy with EGFR monoclonal antibodies (mAbs). Other factors may be significant determinants of benefit. METHODS: Individual patient data from randomised trials with a head-to-head comparison between EGFR mAb versus no EGFR mAb (chemotherapy alone or best supportive care) in mCRC, across all lines of therapy, were pooled. Overall survival (OS) and progression-free survival (PFS) were compared between groups. Treatment effects within the predefined KRAS biomarker subsets were estimated by adjusted hazard ratio (HRadj) and 95% confidence interval (CI). EGFR mAb efficacy was measured within the KRAS wild-type subgroup according to BRAF and NRAS mutation status. In both KRAS wild-type and mutant subgroups, additional factors that could impact EGFR mAb efficacy were explored including the type of chemotherapy, line of therapy, age, sex, tumour sidedness and site of metastasis. RESULTS: 5675 patients from 8 studies were included, all with known mCRC KRAS mutation status. OS (HRadj 0.90, 95% CI 0.84-0.98, p = 0.01) and PFS benefit (HRadj 0.73, 95% CI 0.68-0.79, p < 0.001) from EGFR mAbs was observed in the KRAS wild-type group. PFS benefit was seen in patients treated with fluorouracil (HRadj 0.75, 95% CI 0.68-0.82) but not with capecitabine-containing regimens (HRadj 1.04, 95% CI 0.86-1.26) (pinteraction = 0.002). Sidedness also interacted with EGFR mAb efficacy, with survival benefit restricted to left-sided disease (pinteraction = 0.038). PFS benefits differed according to age, with benefits greater in those under 70 (pinteraction = 0.001). The survival benefit was not demonstrated in those patients with mutations found in the KRAS, NRAS or BRAF genes. The presence of liver metastases interacted with EGFR mAb efficacy in patients with KRAS mutant mCRC (pinteraction = 0.004). CONCLUSION: The benefit provided by EGFR mAbs in KRAS WT mCRC is associated with left-sided primary tumour location, younger patient age and absence of NRAS or BRAF mutations. Survival benefit is observed with fluorouracil but not capecitabine. Exploratory results support further research in KRAS mutant mCRC without liver metastases.

Evaluating the Performance of UV Disinfection across the 222-365 nm Spectrum against Aerosolized Bacteria and Viruses.

Bioaerosols play a significant role in the transmission of many infectious diseases, especially in enclosed indoor environments. Ultraviolet (UV) disinfection has demonstrated a high efficacy in inactivating microorganisms suspended in the air. To develop more effective and efficient UV disinfection protocols, it is necessary to evaluate and optimize the effectiveness of UV disinfection against aerosolized bacteria and viruses across the entire UV spectrum. In this study, we evaluated the performance of UV disinfection across the UV spectrum, ranging from 222 to 365 nm, against aerosolized bacteria and viruses, including Escherichia coli, Staphylococcus epidermidis, Salmonella enterica, MS2, P22, and Phi6. Six commonly available UV sources, including gas discharge tubes and light-emitting diodes with different emission spectra, were utilized, and their performance in terms of inactivation efficacy, action spectrum, and energy efficiency was determined. Among these UV sources, the krypton chloride excilamp emitting at a peak wavelength of 222 nm was the most efficient in inactivating viral bioaerosols. A low-pressure mercury lamp emitting at 254 nm performed well on both inactivation efficacy and energy efficiency. A UV light-emitting diode emitting at 268 nm demonstrated the highest bacterial inactivation efficacy, but required approximately 10 times more energy to achieve an equivalent inactivation level compared with that of the krypton chloride excilamp and low-pressure mercury lamp. This study provides insights into UV inactivation on bioaerosols, which can guide the development of effective wavelength-targeted UV air disinfection technologies and may significantly help reduce bioaerosol transmission in public areas.

Radiomics-based distinction of small (≤2 cm) hepatocellular carcinoma and precancerous lesions based on unenhanced MRI.

AIM: To assess the feasibility of a radiomics model based on unenhanced magnetic resonance imaging (MRI) to differentiate small hepatocellular carcinoma (S-HCC) (≤2 cm) and pre-hepatocellular carcinoma (Pre-HCC). MATERIALS AND METHODS: One hundred and fourteen histopathologically confirmed 114 hepatic nodules were analysed retrospectively. All patients had undergone MRI before surgery using a 3 T MRI system. Each nodule was segmented on unenhanced MRI sequences (T1-weighted imaging [T1] and T2WI with fat-suppression [FS-T2]). Radiomics features were extracted and the optimal features were selected using the least absolute shrinkage and selection operator (LASSO). The support vector machine (SVM) was used to establish the radiomics model. One abdominal radiologist performed the conventional qualitative analysis for classification of S-HCC and Pre-HCC. The diagnostic performances of the radiomics and radiologist models were evaluated using receiver operating characteristic (ROC) analysis. RESULT: Radiomics features (n=1,223) were extracted from each sequence and the optimal features were selected from T1, FS-T2, and T1+FS-T2 to construct the radiomics models. The radiomics model based on T1+FS-T2 showed the best performance among the three models, with areas under the ROC curves (AUCs) of 0.95 (95 % confidence interval [CI], 0.875-0.986) and 0.942 (95 % CI, 0.775-0.985), accuracies of 86 % and 88.5 %, sensitivities of 94.12 % and 100 %, and specificities of 85.48 % and 85.19 %, respectively. The radiomics model on FS-T2 showed better performance on a single sequence than that of the T1-based model. The diagnostic performance for the radiomic model was significantly higher than that for the radiologist (AUC = 0.518, p<0.05). CONCLUSION: This study suggested that a radiomics model based on unenhanced MRI may serve as a feasible and non-invasive tool to classify S-HCC and Pre-HCC.

Relationship between fasting prior to contrast-enhanced CT and adverse reaction in patients with allergies history.

AIM: To examine the relationship between fasting prior to contrast-enhanced CT (CECT) and adverse reaction (AR) in patients with allergies history. MATERIALS AND METHODS: Patients with allergies history who underwent CECT from January 2014 to December 2020 (713 cases with iodinated contrast media (ICM)-related allergy history and 27045 cases with unrelated allergies history) were retrospectively analyzed. The occurrence of ICM-related AR and patient information were recorded. The relationship between fasting and AR and emetic complications was analyzed. RESULTS: There was no statistical difference in the overall incidence of AR and emetic complications between fasting group and non-fasting group (P>0.05) and fasting was not an influence factor for overall AR occurrence in patients with both ICM-related and unrelated allergies history. However, the incidence of severe AR in fasting group was higher than that in non-fasting group (P=0.01) in patients with unrelated allergies history. The AR incidence in fasting group was higher than that in non-fasting group (P=0.022) when receiving abdominal examinations in patients with unrelated allergies history. There was no statistical difference in the incidence of AR with different occurrence time between fasting group and non-fasting group (P>0.05) in patients with both ICM-related and unrelated allergies history. CONCLUSIONS: Fasting was associated with higher incidence of severe AR and was associated with higher AR incidence when receiving abdominal examinations in patients with unrelated allergies history. Fasting did not have effects on the occurrence time of AR in patients with allergies history. These provided new guidance for usage of ICM in patients with allergies history.

Survival Analysis as a Basis for Testing Hypotheses when Using Quantitative Ordinal Scale Disease Severity Data.

Disease severity in plant pathology is often measured by the amount of a plant or plant part that exhibits disease symptoms. This is typically assessed using a numerical scale, which allows a standardized, convenient, and quick method of rating. These scales, known as quantitative ordinal scales (QOS), divide the percentage scale into a predetermined number of intervals. There are various ways to analyze these ordinal data, with traditional methods involving the use of midpoint conversion to represent the interval. However, this may not be precise enough, as it is only an estimate of the true value. In this case, the data may be considered interval-censored, meaning that we have some knowledge of the value but not an exact measurement. This type of uncertainty is known as censoring, and techniques that address censoring, such as survival analysis (SA), use all available information and account for this uncertainty. To investigate the pros and cons of using SA with QOS measurements, we conducted a simulation based on three pathosystems. The results showed that SA almost always outperformed midpoint conversion with data analyzed using a t test, particularly when data were not normally distributed. Midpoint conversion is currently a standard procedure. In certain cases, the midpoint approach required a 400% increase in sample size to achieve the same power as the SA method. However, as the mean severity increases, fewer additional samples are needed (approximately an additional 100%), regardless of the assessment method used. Based on these findings, we conclude that SA is a valuable method for enhancing the power of hypothesis testing when analyzing QOS severity data. Future research should investigate the wider use of survival analysis techniques in plant pathology and their potential applications in the discipline.

Associations of ambient temperature and total cloud cover during pregnancy with newborn vitamin D status.

OBJECTIVES: We aimed to estimate the effects of temperature and total cloud cover before birth on newborn vitamin D status. STUDY DESIGN: Prospective birth cohort. METHODS: This study included 2055 mother-newborn pairs in Wuhan, Hubei province, China. The data of temperature and total cloud cover from 30 days before birth were collected, and cord blood 25-hydroxyvitamin D [25(OH)D] were determined. Restricted cubic spline regression models, multiple linear regression models, and logistic regression models were applied to estimate the associations. RESULTS: A "J" shaped curve was observed between temperature and vitamin D status, and an inverse "J" shaped curve was observed between total cloud cover and vitamin D status. Compared to the fourth quartile (75-100th percentile, Q4) of average temperature (30 days before birth), the odds ratio (OR) for Q1 (0-25th percentile) associated with the vitamin D deficiency occurrence (<20 ng/mL) was 3.63 (95% CI, 1.54, 8.65). Compared to Q1 of the average total cloud cover (30 days before birth), the OR associated with the occurrence of vitamin D deficiency was 2.38 (95% CI, 1.63, 3.50) for the Q4. CONCLUSIONS: Low temperature and high cloud cover before delivery were significantly associated with an increased probability of vitamin D deficiency in newborns. The findings suggested that pregnancy women lacking sufficient sunlight exposure still need vitamin D supplement to overcome the potential vitamin D deficiency status.

Burden of gastrointestinal cancers among people younger than 50 years in China, 1990 to 2019.

OBJECTIVES: This study aimed to assess the burden of early-onset gastrointestinal (GI) cancers in China over three decades. STUDY DESIGN: A comprehensive analysis was performed using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS: Data on early-onset GI cancers in 2020 and from 1990 to 2019 were extracted from GLOBOCAN 2020 database and GBD 2019, respectively. The average annual percent change (AAPC) was calculated to analyze the temporal trends using the Joinpoint Regression Program. The Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2030. RESULTS: In China, there were 185,980 incident cases and 119,116 deaths of early-onset GI cancer in 2020, with the highest incidence and mortality observed in liver cancer (new cases: 71,662; deaths: 62,412). The spectrum of early-onset GI cancers in China has transitioned over the last 30 years. The age-standardized rates of incidence, mortality, and disability-adjusted life years for colorectal and pancreatic cancers exhibited rapid increases (AAPC >0, P ≤ 0.001). The fastest-growing incidence rate was found in colorectal cancer (AAPC: 3.06, P < 0.001). Despite the decreases in liver, gastric, and esophageal cancers, these trends have been reversed or flattened in recent years. High body mass index was found to be the fastest-growing risk factor for early-onset GI cancers (estimated annual percentage change: 2.75-4.19, P < 0.05). Projection analyses showed an increasing trend in age-standardized incidence rates for almost all early-onset GI cancers during 2020-2030. CONCLUSIONS: The transitioning pattern of early-onset GI cancers in China emphasizes the urgency of addressing this public health challenge.

Novel sfericase protease improves amino acid digestibility of soybean meal and rapeseed meal in broiler chickens.

1. Two experiments were conducted to explore the effects of an exogenous sfericase protease on the apparent ileal nutrient digestibility of soybean meal (SBM) and rapeseed meal (RSM) in broiler chickens.2. In each experiment, a total of 256 sixteen-day-old male Cobb 500 broilers were fed one of four semi-purified experimental diets, comprising two different batches (A and B) of samples for either SBM (Exp. 1) or RSM (Exp. 2) without or with an exogenous sfericase (0 or 30,000 NFP/kg). Each experimental diet was fed to eight replicate pens of broiler chickens from 16 to 21 d of age (eight birds per cage), and ileal digesta were collected for measuring the digestibility coefficients.3. In Exp. 1, the amino acid digestibility was greater (P < 0.05) in SBM B compared with SBM A for Arg and Val, and a similar trend (P < 0.1) was observed for Tyr, Leu and Thr. Exogenous sfericase increased (P < 0.10) digestibility of most of amino acids except Gly, His and Trp. There was an interaction between SBM source and sfericase, whereby digestibility of P, N and Asp was increased by sfericase for SBM B but not for SBM A. In Exp. 2, there was no interaction (P > 0.05) between RSM source and sfericase for ileal nutrient digestibility. Digestibility was greater in RSM A compared to RSM B for all non-essential AA and most essential AA (except for Trp), while the reverse was noted for Ca and P (P < 0.05). Exogenous sfericase increased (P < 0.1) digestibility for all amino acids except Cys and Met.4. In conclusion, the current studies showed that both SBM and RSM batches influenced amino acid digestibility. Sfericase protease supplementation increased amino acid digestibility for both SBM and RSM. The digestibility effects were greater in the SBM batch with low digestibility for N and Asp which was in line with an increase in P digestibility.

Genome-wide association study identifies multiple loci influencing duck serum biochemical indicators in the laying period.

1. Laying performance is an important economic trait in poultry. The blood is essential in transporting nutrients to the yolk and albumen and is necessary for egg formation.2. This study calculated the phenotypic relationships of duck egg quality, egg production efficiency and 22 serum parameters in the egg-laying stage. Using a variety of methodologies, a genome-wide association study (GWAS) was carried out to uncover the genetic foundations of the 22 serum biochemical markers of laying ducks.3. Spearman correlation coefficients between the egg production (226-329 per day) and the serum parameters were all weak, being less than 0.3. This analysis was done on 22 serum parameters, with total protein (TP), total triglycerides (TG), calcium (Ca) and phosphorous (P) having the highest correlation coefficients (r = 0.56-0.88). The coefficients for blood markers, such as total cholesterol (CHOL), total bilirubin (TBIL), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) varied from 0.70-0.94.4. Based on single-marker single-trait genome-wide analyses by a mixed linear model program of EMMAX, nine candidate genes were associated with enzyme traits (AST/ALT aspartate transaminase/glutamic-pyruvic transaminase, creatine kinase) and 19 candidate genes were associated with metabolism and protein-related serum parameters (glucose, total bile acid, uric acid (UA), albumin (ALB).5. The mvLMM (multivariate linear mixed model) of GEMMA software was used to carry out multiple trait integrated GWAS. Two candidate genes were found in the TP-TG-CA-P analysis and seven candidate genes in the CHOL_LDL-C_HDL-C_TBIL study. There was a high genetic correlation between the two groups.

Limosilactobacillus reuteri peptidoglycan alleviates aflatoxin B1-induced toxicity through adsorbing toxins and improving growth, antioxidant status, immunity and liver pathological changes in chicks.

1. The objective of this study was to investigate the protective effects of a peptidoglycan produced by Limosilactobacillus reuteri against aflatoxin B1 (AFB1) induced toxicity in vitro and in vivo in broiler chicks.2. Toxin adsorption experiments were carried out firstly in vitro. These experiments indicated that the absorption efficiency of the peptidoglycan for AFB1 was 64.3-75.9%.3. In the in vivo experiments, Hy-Line Brown chicks were fed a diet containing AFB1 at 71.43 µg/kg with and without peptidoglycan supplementation at concentrations of 100, 200, or 300 g/kg feed from 0-42 d of age.4. The peptidoglycan supplementation in AFB1-contaminated diets resulted in significant improvements in terms of average daily gain, feed intake, feed conversion ratio, white blood cell count, haemoglobin content, glutathione peroxidase activity, immunoglobulin (Ig) A, IgG, IgM and Newcastle disease virus antibody titres (p < 0.05) and diminished liver steatosis.5. In conclusion, peptidoglycan supplementation alleviated AFB1-induced toxicity through adsorbing toxins and improving growth performance, antioxidant ability, immunity and liver pathological changes in chicks. The optimal supplemental dose was 200 mg/kg in feed.

Genetic analysis of a Kaijiang duck conservation population through genome-wide scan.

1. The Kaijiang duck is a native Chinese breed known for its excellent egg laying performance, killing-out percentage (88.57%), and disease resistance. The assessment of population genetic structure is the basis for understanding the genetics of indigenous breeds and for their protection and management.2. In this study, whole-genome sequencing was performed on 60 Kaijiang ducks to identify genetic variations and investigate the population structure. Homozygosity (ROH) analysis was conducted to assess inbreeding levels in the population.3. The study revealed a moderate level of inbreeding, indicated by an average inbreeding coefficient of 0.1043. This may impact the overall genetic diversity.4. Genomic Regions of Interest identified included 168 genomic regions exhibiting high levels of autozygosity. These regions were associated with processes including muscle growth, pigmentation, neuromodulation, and growth and reproduction.5. The significance of these pathways indicated their potential role in shaping the desirable traits of the Kaijiang duck. These findings provide insights into the genetic basis of the Kaijiang duck's desirable traits and can inform future breeding and conservation efforts.

[A Mendelian randomization study on the relationship between insomnia and osteoporosis].

Objective: To explore the relationship between insomnia and osteoporosis. Methods: Mendelian randomization (MR) analysis were used in this study. The single nucleotide polymorphisms (SNPs) related to insomnia from genome-wide association analysis research data were selected as the instrumental variables by using inverse variance weighted (IVW), MR-Egger regression, weighted median method, maximum likelihood, penalized weighted median estimator, and Mendelian randomization robust adjusted profile score (MR-RAPS) to determine the causal relationship between insomnia and osteoporosis. Odds ratio (OR) and 95% confidence interval (CI) values were used to evaluate the association between insomnia and osteoporosis. Cochran's Q-test was used to detect heterogeneity of SNPs, MR-Egger regression was used to test for level pleiotropy, and the leave-one-out method was used to test sensitivity, MR pleiotropy residual sum and outlier (MR-PRESSO) method and radial MR were used to detect erroneous outliers. Results: The screening criteria were set based on the three major assumptions of MR; finally, 31 SNPs were included in the MR analysis. The results of MR causal effect analysis using the IVW method showed that insomnia increased the risk of osteoporosis by about 0.7% (OR=1.007, 95%CI 1.001-1.014, P=0.044); heterogeneity testing showed heterogeneity between SNPs (Q=57.91, P<0.001); and the MR- Egger intercept test did not indicate horizontal pleiotropy in this study (intercept value=3.807×10-5, P=0.888). Leave-one-out method showed that no single SNP had a significant impact on the overall results. No abnormal SNP was detected according to the MR-PRESSO results (P=0.059), and radial MR did not detect any outliers. Conclusion: Mendelian randomization analysis showed that insomnia can increase the risk of osteoporosis.

[Expert consensus on the application of critical care ultrasonography in invasive procedures].

The evolution of critical care medicine is inextricably linked to the development of critical care procedures. These procedures not only facilitate diagnosis and treatment of critically ill patients, but also provide valuable insights into disease pathophysiology. While critical care interventions offer undeniable benefits, the potential for iatrogenic complications necessitates careful consideration. The recent surge in critical care ultrasound (US) utilization is a testament to its unique advantages: non-invasiveness, real-time bedside availability, direct visualization of internal structures, elimination of ionizing radiation exposure, repeatability, and relative ease of learning. Recognizing the need to optimize procedures and minimize complications, critical care utrasound study group of Beijing critical care ultrasound research assocition convened a panel of critical care experts to generate this consensus statement. This document serves as a guide for healthcare providers, aiming to ensure patient safety and best practices in critical care.

[Diagnostic value of apparent diffusion coefficient histograms using multiplexed sensitivity encoding diffusion-weighted imaging for distinguishing nasopharyngeal carcinoma from benign hyperplasia].

The data of 115 patients with nasopharyngeal masses (78 males and 37 females) aged between 12 and 78 years at the Sun Yat-sen University Cancer Center from May 2022 to July 2023 were retrospectively reviewed, including 70 cases of nasopharyngeal carcinoma and 45 cases of benign hyperplasia. The mean, median, and percentiles (10th, 25th, 75th, and 90th) of the apparent diffusion coefficient (ADC) histogram derived from multiplexed sensitivity encoding diffusion-weighted imaging (MUSE-DWI) of the benign hyperplasia group were significantly higher than those of the nasopharyngeal carcinoma group (all P<0.05). Conversely, the kurtosis and skewness of benign hyperplasia group were significantly lower than those of the nasopharyngeal carcinoma group (both P<0.05). The area under receiver operating characteristic (ROC) curve of the combined ADC histogram parameters was 0.812 (95%CI: 0.732-0.892), and the sensitivity, specificity and accuracy were 92.86%, 57.78% and 79.13%, respectively. The current study indicates ADC histogram parameters derived MUSE-DWI exhibit significant discriminatory value between nasopharyngeal carcinoma and benign hyperplasia.

[Study on the inhibitory and pro-apoptotic effects of different concentrations of total tanshinone alone and in combination with tyrosine kinase inhibitors on human myeloid leukemia cell lines].

Objective: To explore the effect and investigate the molecular mechanism of different concentrations of total tanshinones alone and in combination with tyrosine kinase inhibitors (TKIs) on the proliferation inhibition and apoptosis of human myeloid leukemia cell lines. Methods: K562 and Kasumi-1 cell lines were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences, and the TKIs-resistant strain K562/T315I cell line was constructed in Molecular Medicine Research Center, Beijing Lu Daopei Institute of Hematology. Logarithmic growth phase cells were taken and divided into intervention groups with total tanshinone of 0, 2.19, 4.38, 8.75, 17.50 and 35.00 µg/ml intervention groups, which were inoculated in 96-well plates at a density of 1×104 cells/well and exposed to the drug for 24 h, and a control group treated with dimethyl sulfoxide was also set up simultaneously. All experiments were repeated independently 3-5 times. The proliferative activity of the cells was assessed using the CCK-8 assay, the apoptotic rates were measured by flow cytometry, and the expression levels of apoptosis-regulating proteins Bcl-2 and Bax were analyzed by Western blotting. The cell lines treated and untreated with total tanshinone were subjected to transcriptome sequencing and gene set enrichment analysis to identify differentially expressed genes. Results: The half-inhibitory concentration (IC50) values of 8.75 µg/ml total tanshinone at 24 h for K562, K562/T315I and Kasumi-1 cells were (4.11±0.02), (4.95±0.04) and (3.98±0.01) µg/ml, respectively. When combined with 0.25 µmol/L imatinib, 8.75 µg/ml total tanshinone could enhance the induction of apoptosis effects on K562 and K562/T315I cell lines. After being treated with 4.38, 8.75, and 17.50 µg/ml of total tanshinone for 24 h, compared with the control group, total tanshinone upregulated the expression level of Bax protein, downregulated the expression level of Bcl-2 protein, and decreased the Bcl-2/Bax ratio (all P<0.05). Total tanshinone inhibited the proliferation-related signaling pathway and DNA damage repair pathway of myeloid leukemia cell lines, and activated the signaling pathway that induces apoptosis in leukemia cells. Conclusion: Different concentrations of total tanshinoneinhibites proliferation and promote apoptosis in K562, Kasumi-1 and TKIs-resistant K562/T315I cell lines, and further enhance the anti-leukemic effect when combined with TKIs.

[Correlation between weight variability and the risk of diabetic nephropathy in patients with type 2 diabetes mellitus].

Objective: To evaluate the relationship between different indexes of weight variability and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A retrospective cohort study. The clinical data of 2 180 T2DM patients without DKD who underwent case management at Lee's United Clinic in Taiwan, China from 2002 to 2018 were retrospectively analyzed, including 1 103 females and 1 077 males, with an average age of (64.8±12.4) years. Regular follow-up was conducted for patients for at least 2 years, and their metabolic indexes were monitored annually. BMI variability independent of the mean (BMI-VIM), average yearly mean square successive difference (BMI-ASV), coefficient of variation (BMI-CV) and standard deviation (BMI-SD) were calculated,based on the body mass index (BMI) recorded annually by the patients. Patients were divided into four groups (Q1-Q4) based on the quartiles of the four weight variability indexes. DKD group and non-DKN group(NDKD group) were defined based on the occurrence of DKD at the end of the follow-up. Cox proportional hazards regression models were used to analyze the relationship between the four weight variability indicators and the incidence of DKD. Subgroup analysis was performed by categorizing patients into non-obesity (BMI<28 kg/m2) and obesity groups (BMI≥28 kg/m2) to investigate the impact of the four weight variability indicators on the risk of DKD. Results: After a follow-up of (4.55±2.13) years, 904 patients developed DKD. Compared with the NDKD group, patients in the DKD group had a higher proportion of females, older age, longer duration of diabetes, more insulin users, higher waist-to-hip ratio, higher levels of BMI-VIM, BMI-ASV, BMI-CV, BMI-SD, systolic blood pressure, diastolic blood pressure, and urine albumin-creatinine ratio, a lower proportion of hypoglycemic drugs, estimated glomerular filtration rate, and high-density lipoprotein cholesterol level, with statistically significant differences between the two groups(all P<0.05). Cox proportional hazards regression analysis results revealed that the risk of DKD in T2DM patients increased with the increase in BMI-SD, BMI-CV, BMI-VIM, and BMI-ASV after correcting a series of influencing factors. In the BMI-VIM subgroup, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.4% [HR=1.224 (95%CI:1.008-1.487), P=0.041]. In the BMI-ASV group, compared with the Q1 group, the risk of DKD in the Q4 group increased by 51.1% [HR=1.511 (95%CI:1.240-1.841), P<0.01]. In the BMI-CV group, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.2% [HR=1.222 (95%CI:1.006-1.485), P=0.044]. In the BMI-SD subgroup, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.2% [HR=1.222 (95%CI:1.002-1.490), P=0.048]. Sub-group analysis showed that when the non-obesity group was grouped by BMI-ASV, after correcting a series of influencing factors, compared with the Q1 group, the highest risk of DKD occurred in the Q4 group [HR=1.551 (95%CI:1.228-1.958), P<0.001];when the obesity group was grouped by BMI-ASV, after correcting a series of influencing factors, compared with the Q1 group, the highest risk of DKD occurred in the Q4 group [HR=1.703 (95%CI:1.168-2.485), P=0.006]. Conclusion: Increases in BMI-VIM, BMI-ASV, BMI-CV, and BMI-SD are associated with an increased risk of DKD in T2DM patients.

[Imaging characteristics and surgical effect for symmetrical lumbar hemivertebrae].

Objective: To analyze the imaging characteristics and surgical effect for symmetrical lumbar hemivertebrae in pediatric patients. Methods: The data of 13 patients with hemivertebrae locating in the lumbar spine symmetrically were retrospectively analyzed, and all the patients were treated in Beijing Children's Hospital from January 2015 to September 2021. The mean age of the patients was 6.2 (2.9, 9.3) years. There were 8 males and 5 females. The data of coronal/sagittal plane including segmental Cobb angle, cranial/caudal compensatory curve, thoracic kyphosis, thoracolumbar kyphosis, sacral obliquity, and lumbar lordosis were recorded through long cassette spinal radiographs. Associated anomalies and the relationship between hemivertebrae and posterior component were recorded through computerized tomography (CT) and magnetic resonance imaging (MRI). All the patients received surgery, and their pre-and postoperative imaging data were compared. Results: A total of 26 hemivertebraes were found, in which 80.8% (21/26) located below L2. Hemivertebraes in 10 patients were separated by a mean 1-2 normal vertebrae. Most hemivertebraes along with the corresponding posterior component were unison (21/26, 80.8%). The Cobb angles of cranial compensatory curve (13.9°±7.2°) was more serious than that of caudal compensatory curve (5.5°±5.0°)(P=0.04). The lumbar lordosis and thoracic kyphosis was 20.2°±15.0° and 18.7°±9.2°, respectively. Six patients complicated with sacral obliquity, while 7 patients complicated with thoracolumbar lordosis. Associated anomalies were found in 6 (46.2%) patients through CT and MRI. Eleven patients received one-or two-stage posterior hemivertebrae resection with short segmental fusion, and 2 patients received one-stage hemivertebrae resection with long segmental fusion. All the surgery were completed successfully without serious complications such as nerve injury, infection, and implant failure. The mean follow-up period was (42.4±10.2) months. At the last follow-up point, the correction rate of segmental Cobb angle and cranial compensatory curve was 83.3%±15.6% and 38.1%±10.4%, respectively, showing significant improvement (P<0.05). Although the caudal compensatory curve, sacral obliquity, and thoracic kyphosis improved after surgery, the data showed no significant difference compared to that before surgery. Thoracolumbar lordosis in all patients were corrected. Conclusions: Most hemivertebraes in such spinal deformity locate in lower lumbar region with a high incidence of anomalies. Individualized treatment based on patients' condition is essential for the complicated spinal deformity.

[The ventilation efficacy and safety of new nasopharyngeal airway applied in left atrial appendage occlusion].

Objective: The present retrospective study aimed to analyses the ventilation efficacy and safety of new nasopharyngeal airway applied in left atrial appendage occlusion. Methods: A total of 37 advanced aged patients diagnosed with atrial fibrillation(>65 years)who underwent left atrial appendage occlusion (LAAO) in Xuanwu Hospital of Capital Medical University from March 2021 to March 2022 were enrolled in this study. All patients received supplemental oxygen by a new nasopharyngeal airway to ensure intraoperative ventilation. The primary outcome was the occurrence of hypoxemia. The secondary outcomes included the incidence of hypotension after anesthesia, the incidence of body movement during surgery, significant fluctuations of the vital signs such as mean arterial pressure (MAP), heart rate (HR), saturation of pulse oxygen (SpO2) and respiratory rate (RR) at different time points (T1: pre-operation; T2: at the time of placing nasopharyngeal airway; T3: at the time of placing transesophageal echocardiography(TEE); T4: at the time of TEE intraoperative exploration; T5: end of the surgery; T6: at the time of patient woke up), and the incidence of postoperative adverse events. Results: There were 24 males and 13 females with a mean age of (73.8±7.7) years. The incidence of hypoxemia was 16.2% (6/37), which could return to normal after simple treatment. The incidence of hypotension was 27.0% (10/37), occurred after anesthesia induction mainly.32.4% (12/37) of the patients experienced movements, but no adverse events led to surgical termination. MAP at different time points was significantly different (P=0.001), but other vital signs of HR, SpO2 and RR were not significantly different(all P>0.05), without serious hemodynamic fluctuations. The incidence of postoperative adverse cardiovascular events was 10.8% (4/37), and delirium was 2.7% (1/37). All patients successfully completed the surgery and were safely discharged from the hospital. Conclusion: The new nasopharyngeal airway can meet the requirements of airway management during left atrial appendage occlusion under intravenous anesthesia without serious adverse events.