Objective To explore the mechanism of hydroxyl safflower flavin A(HSYA)in the treatment of sepsis-induced liver injury by using metabolomics and network pharmacology.Methods A total of 50 male C57BL/6 mice were randomly divided into sham-operation group(10 mice),sepsis group(20 mice)and HSYA group(20 mice).Cecal ligation and puncture was conducted to establish the sepsis-induced liver injury mouse model.The mice in HSYA group were subcutaneously injected with HSYA after 2 hours of modeling.The content of serum inflammatory factors and liver function were detected,and the pathological changes of liver tissue were observed with HE staining,UPLC-Q-TOF-MS metabolomics was used to analyze liver tissue,screening for differential metabolites using multivariate statistical methods,network pharmacology was used to predict potential targets for HSYA treatment of sepsis-induced liver injury,and conduct GO and KEGG pathway enrichment analysis on potential targets,Metabo Analyst 5.0 database was used to match differential metabolites and potential targets between the model group and HSYA group,a targets metabolite-metabolism pathway network was constructed.AutoDock Vina software was used to perform molecular docking between HSYA and core genes,and finally RT-qPCR was used to verify the expression of core genes.Results HSYA can reduce the contents of IL-6,IL-1β and TNF-α in serum,restore liver function,and alleviate the morphological alternation in liver induced by sepsis.A total of 26 differential metabolites identified by metabolomics were screened out,including flufenamic acid,cryptolepine,opthalmic acid,fenpropathrin etc.,which were mainly involved in 5 metabolic pathways such as biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism.Network pharmacology identified 81 potential targets,2 735 items enriched in GO and 124 signaling pathways enriched in KEGG;a total of 5 differential metabolites were matched for joint analysis,corresponding to 14 targets including IL1B,STAT3,PTGS2,TP53,etc.,involved in the regulation of metabolic disorders in sepsis-induced liver injury by HSYA.Molecular docking results showed that HSYA had good binding activity to IL1B,STAT3,PTGS2 and TP53 targets.RT-qPCR results showed that HSYA could inhibit the expressions of IL1B,STAT3 and PTGS2 in liver tissue.Conclusions HSYA may inhibit the release of inflammatory cytokines,maintain metabolic homeostasis,and alleviate sepsis-induced liver injury through modulating the expressions of IL1B,STAT3,and PTGS2.

OBJECTIVE To investigate the mechanisms by which Pinggan Yishen Decoction(PGYSD)contributes to alleviating target organ damage in spontaneously hypertensive rats.METHODS The chemical components of PGYSD were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)and were analyzed by target a-nalysis and functional enrichment combined with network pharmacology methods to predict the potential mechanism of PGYSD in trea-ting hypertension and its target organ damage.Spontaneously hypertensive rats were randomly divided into the model group,low-dose PGYSD group(2 g·kg-1),high-dose PGYSD group(5 g·kg-1),and valsartan group(7.2 mg·kg-1),with 6 rats in each group.Wistar-Kyoto rats were used as the control group,and the control group and the model group were gavaged with normal saline for 8 consecutive weeks.HE and Masson staining were used to observe the pathological damage and fibrosis degree of rat heart and tho-racic aorta.Immunohistochemical staining and Western blot were used to detect the expression level of EGFR in the heart,liver and kidney of rats.Immunofluorescence staining was used to detect the co-localization of EGFR and EEA1 in the heart,liver and kidney of rats.RESULTS Twenty-six components of PGYSD were detected by UPLC-Q-TOF/MS.Network pharmacology revealed that EG-FR,PIK3R1 and EP300 may be key therapeutic targets of action of PGYSD for the treatment of hypertension and its target organ dam-age,and that the treatment of hypertension and its target organ damage by PGYSD may be closely related to EGFR tyrosine kinase in-hibitor resistance,lipids and atherosclerosis and HIF-1 signaling pathway.The high-dose group of PGYSD significantly reduced sys-tolic blood pressure and mean blood pressure in rats(P<0.05,P<0.01),attenuated pathological damage and fibrosis in the heart and thoracic aorta(P<0.01,P<0.001),significantly reduced the expression level of EGFR in the liver and kidney of rats(P<0.01),and treated fibrosis in liver and kidney,reduced the co-localization of EGFR and EEA1 in the kidney of rats(P<0.001),attenuated fibro-sis in kidney.CONCLUSION The paper integrates UPLC-Q-TOF/MS,network pharmacology and spontaneously hypertensive rat model and preliminarily explores the effect mechanism of PGYSD in the treatment of hypertension and its target organ damage,provi-ding a scientific basis for further mechanism research and clinical application of PGYSD in the treatment of hypertension.

Objective:To establish a high-performance liquid chromatography (HPLC) characteristic spectrum of Radix Actinidiae Chinensis decoction pieces, standard decoction and formula granules; To simultaneously determine the contents of index components; To study the transfer law of formula granules based on the extraction amount, content of Catechin and characteristic spectrum of standard decoction.Methods:15 batches of Radix Actinidiae Chinensis decoction pieces were collected, the standard decoction was prepared, and the extraction amount was measured. The HPLC fingerprints of decoction pieces, standard decoction and formula granules were established, and the characteristic peaks were calibrated and attributed. The content of Catechins in decoction pieces, standard decoction and formula granules was measured, and the transfer rate law was calculated. The yield rate, the common peak transmission number of fingerprints, the content and the transfer rate were the main evaluation indexes, and the law of the transmission of the magnitude value was analyzed.Results:The paste yield of 15 batches of Radix Actinidiae Chinensis standard decoction ranged from 3.9%-6.3%. A total of 4 characteristic peaks were calibrated in the feature map, and peak 2 was identified as Protocatechuic acid and peak 4 as Catechin; 6 characteristic peaks were detected in Actinidia chinensis Planchon decoction pieces, standard decoction and formula granules, and their relative retention times were all within the specified range. The content of Catechins in Radix Actinidiae Chinensis decoction pieces was 0.4%-1.4%, which was 3.8%-4.9% in formula granules. The transfer rate of decoction pieces-standard decoction was 13.6%-38.3%, and the decoction-formula granules was 15.5%-21.2%.Conclusions:The mass transfer between Radix Actinidiae Chinensis decoction pieces, standard decoction and formula granules has a good migration. The formula granules also have a good correlation and consistency with the standard decoction, which indicating that the preparation process of Radix Actinidiae Chinensis is reasonable and feasible.

The challenging clinical outcomes associated with advanced cervical cancer underscore the need for a novel therapeutic approach. Monensin, a polyether antibiotic, has recently emerged as a promising candidate with anti-cancer properties. In line with these ongoing efforts, our study presents compelling evidence of monensin's potent efficacy in cervical cancer. Monensin exerts a pronounced inhibitory impact on proliferation and anchorage-independent growth. Additionally, monensin significantly inhibited cervical cancer growth in vivo without causing any discernible toxicity in mice. Mechanism studies show that monensin's anti-cervical cancer activity can be attributed to its capacity to inhibit the Wnt/β-catenin pathway, rather than inducing oxidative stress. Monensin effectively reduces both the levels and activity of β-catenin, and we identify Akt, rather than CK1, as the key player involved in monensin-mediated Wnt/β-catenin inhibition. Rescue studies using Wnt activator and β-catenin-overexpressing cells confirmed that β-catenin inhibition is the mechanism of monensin’s action. As expected, cervical cancer cells exhibiting heightened Wnt/β-catenin activity display increased sensitivity to monensin treatment. In conclusion, our findings provide pre-clinical evidence that supports further exploration of monensin's potential for repurposing in cervical cancer therapy, particularly for patients exhibiting aberrant Wnt/β-catenin activation.

Objective:To Investigate comprehensive predictive ability of first-trimester complete blood count combined with maternal characteristics for gestational diabetes mellitus (GDM).Methods:From May 2015 to July 2018, 1 412 pregnant women were retrospectively screened at the Fifth People′s Hospital of Shanghai, Fudan University. We recruited 258 women who developed GDM and 1 154 women who had normal glucose level during pregnancy. At the first visit, clinical data and complete blood count result were obtained. GDM prediction models were established through logistic regression analysis of GDM related risk factors and the prediction abilities of each model were compared.Results:Logistic regression analyses identified age, pre-pregnancy body mass index, previous GDM history, family history of diabetes mellitus, the neutrophil-to-lymphocyte ratio, leukocyte, neutrophil, and monocyte counts were significantly independent predictors of GDM. In the entire cohort, the predictive ability of neutrophil and monocyte counts together with maternal basal characteristics model for the development of GDM [areas under the receiver operating characteristic curve (AUC-ROC)=0.809, integrated discrimination improvement (IDI)=0.056, P=0.001] was the best among various models (basal characteristics model, AUC-ROC=0.753; Monocyte count+ basal characteristics model, AUC-ROC=0.764; neutrophil count + basal characteristics model, AUC-ROC=0.775). Similar results obtained by the same way in all pregnant women without previous GDM history. Conclusion:It could improve the prediction of GDM with model incorporated maternal characteristics and first-trimester neutrophil and monocyte counts.

Objective To discuss the distribution characteristics of the Bragg peak in proton therapy using the SRIM code. Methods Based on the SRIM code, the transport processes of a high-energy proton beam injecting into different materials (H₂O, C₂H₆O、C₈H₈、Al and Fe)with incident energies of 50 MeV～250 MeV have been simulated and analyzed. And the relationship between the incident energies, different materials and thickness, and the depth of the Bragg peak was also discussed when the protons injected into different materials and compared with the simulation results of professional Monte Carlo code, such as Fluka 2011 and MCNPX. Results The simulation results indicate that the depths of the Bragg peak increase gradually and the peaks broaden with the increase of incident proton energies for different materials; The ratio of the depth of the Bragg peak in different materials to that in water under the same incident energy changes little and is approximately a constant which doesn’t depend on the proton incident energy. A good consistency was found between the results and those obtained using Fluka and MCNPX programs. Conclusion The simulation accuracy of the SRIM on the proton beam transport is acceptable, and is suitable for the beginning learners.

Objective:To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations.Methods:The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR.Results:From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission.Conclusion:It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.

Objective To investigate the threshold values of insulin resistance ( IR) assessed by homeostasis model and the prevalence of IR in elderly people over 60 years old in Minhang district of Shanghai, and to evaluate the relationship between IR and metabolic syndrome ( MS) . Methods A total of 3003 elderly people aged 60 and over in the Jiangchuan community of Minhang District, Shanghai, were recruited, including 1286 males and 1717 females. Blood pressure, waist circumference, BMI, blood routine, serum creatinine, blood lipids, glucose, and fasting insulin were measured in all populations studied. Homeostasis model assessment ( HOMA) was used to estimate IR, and MS, and defined according to three diagnostic criteria including NCEP-ATPIII, IDF, and CDS. Results 75th percentile, 80th percentile and 90th percentile of HOMA values in 268 subjects with normotensive and normal BMI, glucose tolerance were considered as the thresholds of IR. The cut-off values were 2. 78, 3. 01 and 3. 56, respectively. And the prevalence of IR were 50. 0％, 42. 1％, and 27. 2％, respectively. IR level was significantly higher in people with MS. Based on the receiver operating characteristic ( ROC ) curve analysis, HOMA-IR and QUICKI index predicted MS well, and the optimal thresholds for diagnosing MS of HOMA-IR were 3. 17 for NCEP-ATPⅢ, 3. 02 for IDF and 3. 03 for CDS. BMI was the best factor for diagnosing IR among different MS components. Logistic regression analysis showed that gender, WC, BMI, SBP, HDL-C, TG, FBG and WBC were independent risk factors for IR. FBG≥5.84 mmol/L was the most dangerous factor of IR (OR=3.603,P<0.01), followed by WC≥85.4 cm(OR=2.152, P<0.01) and BMI≥24.6 kg/m2(OR=2.150,P<0.01). Conclusion The cut-off values of IR estimated by HOMA and the prevalence of IR were higher in elder subjects than other populations. IR was significantly positively correlated with MS. Excluding the conditions that insulin measurement were affected by external factors, HOMA-IR may predict the risk of MS. The components of MS were relative specific measurements of IR, FBG, BMI and WC were important risk predictors of IR in the elderly.

Gliomas are one of the most common types of brain cancers. Numerous efforts have been devoted to studying the mechanisms of glioma genesis and identifying biomarkers for diagnosis and treatment. To help further investigations, we present a comprehensive database named GliomaDB. GliomaDB includes 21,086 samples from 4303 patients and integrates genomic, transcriptomic, epigenomic, clinical, and gene-drug association data regarding glioblastoma multiforme (GBM) and low-grade glioma (LGG) from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), the Chinese Glioma Genome Atlas (CGGA), the Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), the US Food and Drug Administration (FDA), and PharmGKB. GliomaDB offers a user-friendly interface for two main types of functionalities. The first comprises queries of (i) somatic mutations, (ii) gene expression, (iii) microRNA (miRNA) expression, and (iv) DNA methylation. In addition, queries can be executed at the gene, region, and base level. Second, GliomaDB allows users to perform survival analysis, coexpression network visualization, multi-omics data visualization, and targeted drug recommendations based on personalized variations. GliomaDB bridges the gap between glioma genomics big data and the delivery of integrated information for end users, thus enabling both researchers and clinicians to effectively use publicly available data and empowering the progression of precision medicine in glioma. GliomaDB is freely accessible at http://bigd.big.ac.cn/gliomaDB.

Objective To explore the effect of " hospital informationized blood glucose management" on perioperative diabetic patients. Methods Three hundred patients with type 2 diabetes mellitus, who underwent selective operations from orthopedics, general surgery, urological surgery, and thoracic surgery were divided into two groups: 150 cases of blood glucose information management group and 150 cases of traditional blood glucose monitoring and management group. The blood glucose on target rate, percent of hypoglycemic events, percent of hyperglycemic events, the blood glucose level on the first postoperative day, the average hospitalization day, perioperative infection rate were evaluated for efficacy. Results The blood glucose on target rate in informationized blood glucose management group was significantly higher than that of the control group [(52.52 ± 18.31)%vs (14.88 ± 8.39)%, P＜0.01]. The frequency of hyperglycemia, the average daily blood glucose, the average blood glucose on fasting, after three meals and at night, the fasting and postprandial blood glucose level on the first postoperative day in informationized blood glucose management group were significantly lower than that of the control group [( 45. 31 ± 18.87)%vs (84.41±8.86)%, (8.59±1.34 vs 12.47±2.37) mmol/L, (7.33±1.41 vs 10.01±1.99)mmol/L, (8.89 ±2.34vs13.61±3.47)mmol/L,(9.47±1.94vs13.46±2.77)mmol/L,(9.40±2.72vs13.28±2.94)mmol/L, (8.28±2.11vs11.31±2.89)mmol/L,(8.29±2.51vs11.58±3.52)mmol/L,(8.25±3.67vs17.65±19.68) mmol/L, all P＜0.01]. In addition, the average hospitalization day of the informationized blood glucose management group was significantly shorter than that of the control group [(16±7 vs 21±15)d, P＜0.05]. The infection rate of the management group and the control group were 41. 2% and 58. 8% respectively. There was no significant difference between two groups (P＞0.05). Conclusion The " hospital informationized blood glucose management" is simple and practical, which may significantly improve the rate of blood glucose control in each period, reduce the average hospitalization day, and decrease perioperative infection tendency.