Objective To explore the possible mechanism of emodin in inhibiting proliferation,migration,and invasion of AGS cells and in suppressing the expressions of YAP1 and FOXD1.Methods Normal gastric cell GES-1 and gastric cancer cell AGS were cultured with different concentrations of emodin.CCK8 test,scratch test and Transwell assay were used to verify changes in the biological phenotype of AGS cells.TCGA database was applied to analyze expressions of HK2,YAP1 and FOXD1 in gastric cancer tissues and normal gastric tissues.Western blotting method was used to detect the impacts of emodin on HK2,YAP1 and FOXD1 proteins in AGS cells.Exogenous pyruvic acid was added to verify the changes in YAP1 and FOXD1.Results The IC50 of emodin was significantly higher in GES-1 cells than in AGS cells(P<0.05).CCK8 proliferation test,scratch test,and Transwell assay showed that emodin significantly inhibited the biological abilities of AGS(P<0.05 for comparisons).Analysis on the TCGA bioinformatics database found that the expression of key enzymes HK2 in the glycolysis pathway and oncogenes YAP1 and FOXD1 was significantly higher in gastric cancer tissues than in normal gastric tissues(P<0.05 for comparisons).Emodin significantly inhibited the protein expressions of key glycolytic enzymes HK2 and oncogenes YAP1 and FOXD1(P<0.05 for comparisons).With supplement of exogenous glycolytic metabolite pyruvate,the protein expressions of oncogenes YAP1 and FOXD1 significantly increased(P<0.05 for comparisons).Conclusions Emodin has a significant pharmacological inhibitory effect on gastric cancer AGS cells,markedly suppressing their biological phenotype.Emodin not only significantly inhibits the key enzyme HK2 in glycolysis metabolism,but also the protein expressions of oncogenes YAP1 and FOXD1.With the addition of exogenous pyruvate to enhance the glycolytic metabolic pathway,the protein expressions of oncogenes YAP1 and FOXD1 significantly increased.The above results suggest a close association of YAP1 and FOXD1 with glycolytic metabolism.Emodin may inhibit oncogenes YAP1 and FOXD1 through the glycolytic metabolism of gastric cancer AGS cells.

OBJECTIVE To clarify the weight index and optimize the technology of compound Mingmu Yijing pills. METHODS Water content, dissolution time limit and bolus-forming pass rate were included as evaluation indexes. The analytic hierarchy process(AHP) and the criterion importance through inter-criteria correlation(CRITIC) method based on the objectivity of indicators were adopted, AHP-CRITIC mixed weighting method. In this way, the relative coefficients of each index were calculated for weight distribution and comprehensive score, and the molding process was optimized and verified by Box-Behnken response surface test. RESULTS Compared with the single weighting method, the AHP-CRITIC mixed weighting method was more reasonable and stable. This method finally optimized the forming process conditions of Mingmu Yijing pills as follows: adding water amount of 0.8 times, the damp mass infiltration for 0.5 h, drying temperature of 60 ℃, drying time of 8 h. The mean comprehensive score of validation experiment was 88.21, RSD was 0.29%. CONCLUSION AHP-CRITIC method scientifically determines the weight of multiple indicators, and the verification test confirms that the optimized molding process is stable and feasible, which can be used in practical large-scale production.

Objective To predict the potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest (RF) and maximum entropy (MaxEnt) models, so as to provide insights into O. hupensis surveillance and control in Yunnan Province. Methods The O. hupensis snail survey data in Yunnan Province from 2015 to 2016 were collected and converted into O. hupensis snail distribution site data. Data of 22 environmental variables in Yunnan Province were collected, including twelve climate variables (annual potential evapotranspiration, annual mean ground surface temperature, annual precipitation, annual mean air pressure, annual mean relative humidity, annual sunshine duration, annual mean air temperature, annual mean wind speed, ≥ 0 ℃ annual accumulated temperature, ≥ 10 ℃ annual accumulated temperature, aridity and index of moisture), eight geographical variables (normalized difference vegetation index, landform type, land use type, altitude, soil type, soil textureclay content, soil texture-sand content and soil texture-silt content) and two population and economic variables (gross domestic product and population). Variables were screened with Pearson correlation test and variance inflation factor (VIF) test. The RF and MaxEnt models and the ensemble model were created using the biomod2 package of the software R 4.2.1, and the potential distribution of O. hupensis snails after 2016 was predicted in Yunnan Province. The predictive effects of models were evaluated through cross-validation and independent tests, and the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS) and Kappa statistics were used for model evaluation. In addition, the importance of environmental variables was analyzed, the contribution of environmental variables output by the models with AUC values of > 0.950 and TSS values of > 0.850 were selected for normalization processing, and the importance percentage of environmental variables was obtained to analyze the importance of environmental variables. Results Data of 148 O. hupensis snail distribution sites and 15 environmental variables were included in training sets of RF and MaxEnt models, and both RF and MaxEnt models had high predictive performance, with both mean AUC values of > 0.900 and all mean TSS values and Kappa values of > 0.800, and significant differences in the AUC (t = 19.862, P < 0.05), TSS (t = 10.140, P < 0.05) and Kappa values (t = 10.237, P < 0.05) between two models. The AUC, TSS and Kappa values of the ensemble model were 0.996, 0.954 and 0.920, respectively. Independent data verification showed that the AUC, TSS and Kappa values of the RF model and the ensemble model were all 1, which still showed high performance in unknown data modeling, and the MaxEnt model showed poor performance, with TSS and Kappa values of 0 for 24%(24/100) of the modeling results. The modeling results of 79 RF models, 38 MaxEnt models and their ensemble models with AUC values of > 0.950 and TSS values of > 0.850 were included in the evaluation of importance of environmental variables. The importance of annual sunshine duration (SSD) was 32.989%, 37.847% and 46.315% in the RF model, the MaxEnt model and their ensemble model, while the importance of annual mean relative humidity (RHU) was 30.947%, 15.921% and 28.121%, respectively. Important environment variables were concentrated in modeling results of the RF model, dispersed in modeling results of the MaxEnt model, and most concentrated in modeling results of the ensemble model. The potential distribution of O. hupensis snails after 2016 was predicted to be relatively concentrated in Yunnan Province by the RF model and relatively large by the MaxEnt model, and the distribution of O. hupensis snails predicted by the ensemble model was mostly the joint distribution of O. hupensis snails predicted by RF and MaxEnt models. Conclusions Both RF and MaxEnt models are effective to predict the potential distribution of O. hupensis snails in Yunnan Province, which facilitates targeted O. hupensis snail control.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To explore the mediating effect of carotid atherosclerosis on serum triglyceride-glucose (TyG) index and silent lacunar infarction (SLI) in non-diabetic population.Methods:A total of 2 482 patients were selected from the Health Examination Center of Hebei General Hospital from January 2019 to December 2021. The basic demographic information, biochemical parameters, calculated TyG index and carotid plaque score were collected. SLI was diagnosed according to the criteria formulated by Chinese Society of Neurology. Participants were divided into SLI group and non-SLI group according to whether there was SLI in brain magnetic resonance imaging, and the non-SLI group was normal without lacunar infarction. Spearman correlation analysis was used to explore the correlation between TyG index and carotid plaque score. Binary Logistic regression analysis was used to analyze the effects of TyG index and carotid plaque score on SLI. Bootstrap was used to explore whether carotid plaque score mediated the association between TyG index and SLI.Results:There were 471 patients (18.98%) who had SLI, and 2 011 patients (81.02%) did not. Carotid plaque score [2(0, 5) vs 1(0, 3)] and TyG index [7.17(6.81, 7.64) vs 7.12(6.77, 7.54)] were increased in the SLI group compared with the non-SLI group ( Z=-4.213, Z=-2.636, P<0.05). Spearman correlation analysis showed that carotid plaque score was positively correlated with TyG index ( r=0.083, P<0.001). Multivariate Logistic regression analysis indicated that carotid plaque score ( OR=1.047, 95% CI 1.002-1.094) and TyG index ( OR=1.329, 95% CI 1.106-1.598) were independent risk factors for SLI ( P<0.05). Mediated effect analysis showed that TyG index had a direct effect on the incidence of SLI (β=0.265, 95% CI 0.102-0.428). Carotid plaque score partially mediated the effect of TyG index on the incidence of SLI (β=0.024, 95% CI 0.009-0.043), and the mediating effect accounted for 8.30% of the total effects. Conclusion:In non-diabetic population, TyG index and carotid plaque score are predictors of SLI, and the carotid plaque score is a partial mediator in the effect of TyG index on the incidence of SLI.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To study the incidences of complications in twins with birth weight discordance (BWD) during hospitalization.Methods:From January 2011 to December 2020, twins born in the Department of Obstetrics and hospitalized in NICU of our hospital were retrospectively studied. Twins with BWD>15% were assigned into BWDT group and BWD≤15% into twins with birth weight concordant (BWCT) group. Complications during hospitalization were compared between the two groups.Results:A total of 1 546 pairs of twins were enrolled, including 486 (31.4%) in BWDT group and 1 060 (68.6%) in BWCT group. Compared with BWCT group, BWDT group had significantly higher incidences of pulmonary surfactant (PS) utilization (47.7% vs. 42.2%), continuous positive airway pressure ≥ 24 h (40.5% vs. 35.0%), high-flow nasal cannula ≥ 24 h (22.8% vs. 16.3%), neonatal respiratory distress syndrome (52.9% vs. 47.1%), bronchopulmonary dysplasia (BPD) (15.6% vs. 11.1%), persistent pulmonary hypertension of the newborn (3.1% vs. 1.4%) and anemia (79.6% vs. 70.1%) (all P<0.05). After adjusting for confounding factors, the risks of pulmonary hemorrhage ( OR=2.036, 95% CI 1.119-3.703, P=0.020) and BPD ( OR=2.960, 95% CI 1.656-5.219, P=0.010) in BWDT group were higher than BWCT group. Conclusions:BWD twins has higher incidences of complications during hospitalization than BWC twins.

Cordycepin is the key active component of medicinal fungus Cordyceps militaris, and it shows multiple functional activities such as anti-tumor and anti-virus. Cordycepin was conventionally produced by liquid fermentation of C. militaris, but the long production cycle and the low productivity constrained its development and application. In this study, two key genes for cordycepin biosynthesis (ScCNS1 and ScCNS2) were introduced into Saccharomyces cerevisiae S288C, producing 67.32 mg/L cordycepin at 240 h. Analysis of gene expression profiles indicated that ZWF1, PRS4, ADE4, ScCNS1 and ScCNS2 which encode enzymes involved in pentose phosphate pathway, purine metabolism and cordycepin biosynthesis pathway, were significantly up-regulated in the late phage of fermentation. Optimization of fermentation medium determined that 50 g/L initial glucose followed by feeding, supplemented with 5 mmol/L Cu²⁺ and 1.0 g/L adenine were the best condition. Fed-batch fermentation using the engineered yeast in a 5 L stirred fermenter produced 137.27 mg/L cordycepin at 144 h, with a productivity up to 0.95 mg/(L·h) reached, which was 240% higher than that of the control.
Cordyceps ; Culture Media ; Deoxyadenosines ; Saccharomyces cerevisiae/genetics*

Objective:To investigate the value of pericoronary adipose tissue histogram parameters based on coronary CT angiography (CTA) images for the differentiation of acute coronary syndrome and stable coronary artery disease.Methods:The clinical data and CTA images of 93 patients with coronary CTA examination in Suzhou Kowloon Hospital from 2013 to 2018 were analyzed retrospectively. There were 39 patients with acute coronary syndrome (acute coronary syndrome group) and 54 patients with stable coronary artery disease (stable coronary artery disease group). A region of interest (ROI) was drawn around the stenosis of the coronary arteries, with CT attenuation ranging from-190 to -30 HU to exclude non-adipose tissue. The CT attenuation of ROI excluding non-adipose were measured and histogram analysis was performed. The obtained parameters included the mean value, median value and the 5th, 10th, 45th, 55th, 70th and 95th percentiles. The differences in histogram parameters between the two groups were compared, and then the value of each parameter in differentiating acute coronary syndrome and stable coronary artery disease was evaluated based on receiver operating characteristic (ROC) analysis. The stepwise regression of multivariate logistic regression analysis was used to identify the useful features and establish the final prediction model. The ROC curve of the final model was calculated and its value was analyzed.Results:The mean, median and the 5th, 10th, 45th, 55th,70th and 95th percentile differences between the acute coronary syndrome group and the stable coronary artery disease group were statistically significant (all P<0.05). The ROC curve for the median and the 95th percentile had the same area under curve (AUC) of 0.73. The sensitivity, specificity and AUC of the diagnostic model established by multiple logistic regression were 82.1%, 89.1% and 0.90 respectively. Conclusion:CT attenuation histogram of pericoronary adipose tissue is of high value in differentiating acute coronary syndrome from stable coronary artery disease.

Identification of genetic variants via high-throughput sequencing (HTS) technologies has been essential for both fundamental and clinical studies. However, to what extent the genome sequence composition affects variant calling remains unclear. In this study, we identified 63,897 multi-copy sequences (MCSs) with a minimum length of 300 bp, each of which occurs at least twice in the human genome. The 151,749 genomic loci (multi-copy regions, or MCRs) harboring these MCSs account for 1.98％of the genome and are distributed unevenly across chromosomes. MCRs containing the same MCS tend to be located on the same chromosome. Gene Ontology (GO) anal-yses revealed that 3800 genes whose UTRs or exons overlap with MCRs are enriched for Golgi-related cellular component terms and various enzymatic activities in the GO biological function cat-egory. MCRs are also enriched for loci that are sensitive to neocarzinostatin-induced double-strand breaks. Moreover, genetic variants discovered by genome-wide association studies and recorded indbSNP are significantly underrepresented in MCRs. Using simulated HTS datasets, we show that false variant discovery rates are significantly higher in MCRs than in other genomic regions. These results suggest that extra caution must be taken when identifying genetic variants in the MCRs via HTS technologies.