ObjectiveTo investigate the effect of SU056， an azo-podophyllotoxin derivative， on carbon tetrachloride （CCl₄）-induced liver fibrosis in mice and related mechanisms of action. MethodsA total of 12 mice were randomly divided into control group， model group （CCl₄+normal saline）， and treatment group （CCl₄+SU056）， with 4 mice in each group. Mice were given intraperitoneal injection of CCl₄ to establish a model of liver fibrosis， and during the middle stage of modeling， the mice in the treatment group were given daily intraperitoneal injection of SU056. Liver histopathological injury， collagen deposition， and liver function were assessed based on HE staining， Masson staining， Sirius Red staining， the content of hydroxyproline in liver tissue， and the serum levels of alanine aminotransferase and aspartate aminotransferase， and immunofluorescence assay was used to measure the expression levels of smooth muscle actin α （α-SMA）， collagen type Ⅰ， and Y-box binding protein 1 （YB1）. The human hepatic stellate cell （HSC） line LX-2 and primary mouse HSC were used， and CCK-8 assay was used to measure cell proliferation； Transwell assay was used to observe cell migration； quantitative reverse transcription-polymerase chain reaction and Western Blot were used to measure the expression levels of collagen type Ⅰ， collagen type Ⅲ， YB1， phosphorylated mammalian target of rapamycin （mTOR）， and phosphorylated S6K， so as to validate the function of the YB1/mTOR signaling axis. The one-way or two-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the mouse model of liver fibrosis induced by CCl₄， compared with the model group， the treatment group had significant alleviation of inflammatory cell infiltration， collagen deposition， and pseudolobule formation in liver tissue and significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of hydroxyproline in liver tissue （all P<0.01）. Immunofluorescence assay showed that SU056 significantly inhibited the abnormal high expression of α-SMA， collagen type I， and YB1 in liver tissue （all P<0.01）. In vitro experiments showed that SU056 inhibited the transforming growth factor-β1-induced proliferation of LX-2 cells （P<0.01）， the migration of LX-2 cells （P<0.05）， and the transcriptional up-regulation of collagen type Ⅰ and collagen type Ⅲ （all P<0.05） in a dose-dependent manner， and SU056 could inhibit the spontaneous activation of primary HSC in vitro. Mechanistic studies revealed that transforming growth factor-β1 simultaneously upregulated the expression levels of YB1， phosphorylated mTOR， and phosphorylated S6K in LX-2 cells， and treatment with SU056 （10 and 20 µmol/L） could downregulate the protein expression levels of collagen type I， YB1， phosphorylated mTOR， and phosphorylated S6K. Specific knockdown of YB1 or administration of the mTOR inhibitor rapamycin exerted a similar effect as SU056. SU056 also inhibited the co-upregulation of α-SMA and phosphorylated mTOR in liver tissue of model mice （P<0.01）. ConclusionSU056 can effectively inhibit HSC activation， proliferation， migration， and extracellular matrix production both in vivo and in vitro and thus delay the progression of liver fibrosis， by disrupting the YB1/mTOR positive feedback signaling axis.

[Purpose]To analyze the survival rate of breast cancer in Qidong City of Jiangsu Province from 1972 to 2019 and to predict the trend in the next 10 years.[Methods]The data of breast cancer collected from Qidong Cancer Registry from 1972 to 2019 were extracted.Observed survival rate(OSR),relative survival rate(RSR),age-adjusted relative survival(ARS)and average annual percentage change(AAPC)of breast cancer were calculated.ARIMA model was used to predict the trend of breast cancer survival rate.[Results]The 5-year RSR increased from 57.30％during 1972-1977 to 89.01％during 2014-2019,and the uptrend of RSR in the 8 periods was statistically significant(P＜0.001).The 5-year ARS increased from 48.12％during 1972-1977 to 85.64％during 2014-2019 with an AAPC of 1.85％(t=10.113,P＜0.001).The 5-year RSR during 1972-2019 for males was 85.22％,and for females was 74.51％.For females,the 5-year RSR in-creased from 56.44％during 1972-1977 to 88.93％during 2014-2019 with an AAPC of 1.29％(t=13.087,P＜0.001),and the 5-year ARS increased from 46.14％during 1972-1977 to 85.23％during 2014-2019 with an AAPC of 1.90％(t=10.369,P＜0.001).The 5-year RSR in the age groups of 25～34,35～44,45～54,55～64,65～74,and over 75 years old were 66.91％,74.69％,76.97％,75.52％,73.44％and 66.40％,respectively;the corresponding AAPCs of 5-RSR in above age groups were 1.02％(t=3.816,P=0.009),1.03％(t=4.936,P=0.003),1.23％(t=5.826,P=0.001),1.86％(t=5.997,P=0.001),2.13％(t=10.245,P＜0.001),and 1.44％(t=6.405,P=0.001),respectively.ARIMA modeling of survival trend prediction showed that 5-RSR and 5-ARS for breast cancer will be ascended to 98.76％and 98.33％by 2028,respectively.[Conclusion]The overall survival rate of registered breast cancer cases in Qidong City has been greatly improved and will be further improved in the future,more attention should be paid to the prevention and treatment of breast cancer.

Objective To develop a refined management model for operating rooms and assess its clinical impact on op-erational efficiency and cost control.Methods The study included 10,728 elective surgeries from January to June 2024 as the study group and 9 414 elective surgeries from January to June 2023 as the control group.The differences in operational metrics before and after implementing the refined management model were compared.The model was developed through comprehensive management by hospital leadership and multi-department collaboration,focusing on management structure,systems,processes,information technology,and resource allocation.Results In terms of efficiency,the on-time start rate of the first surgeries in the study group was significantly higher than in the control group(P＜0.05).The turnover time between surgeries was shorter in the study group(P＜0.01),and the rate of unexpected surgery cancellations was lower(P＜0.01).The average cost per surgery for consumables,excluding the impact of centralized procurement of consumables,was approximately 971 yuan,representing an 11% reduction compared to the previous year,despite a 14% increase in surgical volume.The average daily operating cost per operating room was about 12 303 yuan,a 7% reduction.Economic benefits increased by 8.43 million yuan,a 38% year-on-year increase.Conclusion Implementing a refined management model in operating rooms can significantly enhance efficiency,re-duce costs,and achieve dual improvements in social and economic benefits.

Objective To develop a refined management model for operating rooms and assess its clinical impact on op-erational efficiency and cost control.Methods The study included 10,728 elective surgeries from January to June 2024 as the study group and 9 414 elective surgeries from January to June 2023 as the control group.The differences in operational metrics before and after implementing the refined management model were compared.The model was developed through comprehensive management by hospital leadership and multi-department collaboration,focusing on management structure,systems,processes,information technology,and resource allocation.Results In terms of efficiency,the on-time start rate of the first surgeries in the study group was significantly higher than in the control group(P＜0.05).The turnover time between surgeries was shorter in the study group(P＜0.01),and the rate of unexpected surgery cancellations was lower(P＜0.01).The average cost per surgery for consumables,excluding the impact of centralized procurement of consumables,was approximately 971 yuan,representing an 11% reduction compared to the previous year,despite a 14% increase in surgical volume.The average daily operating cost per operating room was about 12 303 yuan,a 7% reduction.Economic benefits increased by 8.43 million yuan,a 38% year-on-year increase.Conclusion Implementing a refined management model in operating rooms can significantly enhance efficiency,re-duce costs,and achieve dual improvements in social and economic benefits.

[Purpose]To analyze the survival rate of breast cancer in Qidong City of Jiangsu Province from 1972 to 2019 and to predict the trend in the next 10 years.[Methods]The data of breast cancer collected from Qidong Cancer Registry from 1972 to 2019 were extracted.Observed survival rate(OSR),relative survival rate(RSR),age-adjusted relative survival(ARS)and average annual percentage change(AAPC)of breast cancer were calculated.ARIMA model was used to predict the trend of breast cancer survival rate.[Results]The 5-year RSR increased from 57.30％during 1972-1977 to 89.01％during 2014-2019,and the uptrend of RSR in the 8 periods was statistically significant(P＜0.001).The 5-year ARS increased from 48.12％during 1972-1977 to 85.64％during 2014-2019 with an AAPC of 1.85％(t=10.113,P＜0.001).The 5-year RSR during 1972-2019 for males was 85.22％,and for females was 74.51％.For females,the 5-year RSR in-creased from 56.44％during 1972-1977 to 88.93％during 2014-2019 with an AAPC of 1.29％(t=13.087,P＜0.001),and the 5-year ARS increased from 46.14％during 1972-1977 to 85.23％during 2014-2019 with an AAPC of 1.90％(t=10.369,P＜0.001).The 5-year RSR in the age groups of 25～34,35～44,45～54,55～64,65～74,and over 75 years old were 66.91％,74.69％,76.97％,75.52％,73.44％and 66.40％,respectively;the corresponding AAPCs of 5-RSR in above age groups were 1.02％(t=3.816,P=0.009),1.03％(t=4.936,P=0.003),1.23％(t=5.826,P=0.001),1.86％(t=5.997,P=0.001),2.13％(t=10.245,P＜0.001),and 1.44％(t=6.405,P=0.001),respectively.ARIMA modeling of survival trend prediction showed that 5-RSR and 5-ARS for breast cancer will be ascended to 98.76％and 98.33％by 2028,respectively.[Conclusion]The overall survival rate of registered breast cancer cases in Qidong City has been greatly improved and will be further improved in the future,more attention should be paid to the prevention and treatment of breast cancer.

To establish a highly specific,sensitive,and efficient method for detecting antibodies a-gainst the Erns protein of classical swine fever virus(CSFV),and to distinguish CSFV vaccine strains from wild strains infections in combination with the E2 subunit vaccine.The purified Erns protein of the CSFV expressed by baculovirus was conjugated to carboxylated magnetic beads as a solid-phase carrier and horseradish peroxidase(HRP),separately.A double-antigen sandwich chemiluminescent enzyme immunoassay(CLEIA)was developed by optimizing various reaction parameters using a fully automated chemiluminescence analyzer.This method was then applied to quantitatively detect Erns protein antibodies in sera from pigs infected with prevalent strains and those immunized with the CSFV E2 subunit vaccine and challenged with field strains.The results showed that the optimal conditions for coupling protein-to-magnetic bead were as follows:coupling buffer pH of 8.0,a protein coupling amount of 2.5 mg/g,blocking solution of 10％BSA,serum sample volume of 20 μL.The optimal dilution of enzyme-labeled antigen was at 1:500 with a one-step reaction time of 15 minutes.The cutoff value of the established CLEIA method for detecting CSFV Erns protein antibodies was 5.83 U/mL and a diagnostic sensitivity of 1:128.No cross-reac-tivity was observed with positive sera against African swine fever virus,pseudorabies virus,porcine circovirus type 2,porcine epidemic diarrhea virus,porcine reproductive and respiratory syndrome virus,or porcine gastroenteritis virus.Additionally,the method yielded negative results with sera from pigs immunized with the E2 subunit vaccine.In repeatability tests,the intra-assay coefficient of variation(CV)ranged from 0.77％to 11.56％,and the inter-assay CV ranged from 10.30％to 14.55％,both below 15％.The positive and negative concordance rates with a commercial CSFV Erns protein antibody detection kit were 95.24％and 92.71％,separately,with an overall concord-ance rate of 93.23％.The double-antigen sandwich chemiluminescence method established in this study exhibits high sensitivity,excellent repeatability,and suitability for automated detection,making it applicable for serological differentiation between CSFV E2 subunit vaccination and infec-tion with prevalent strains.

To establish a highly specific,sensitive,and efficient method for detecting antibodies a-gainst the Erns protein of classical swine fever virus(CSFV),and to distinguish CSFV vaccine strains from wild strains infections in combination with the E2 subunit vaccine.The purified Erns protein of the CSFV expressed by baculovirus was conjugated to carboxylated magnetic beads as a solid-phase carrier and horseradish peroxidase(HRP),separately.A double-antigen sandwich chemiluminescent enzyme immunoassay(CLEIA)was developed by optimizing various reaction parameters using a fully automated chemiluminescence analyzer.This method was then applied to quantitatively detect Erns protein antibodies in sera from pigs infected with prevalent strains and those immunized with the CSFV E2 subunit vaccine and challenged with field strains.The results showed that the optimal conditions for coupling protein-to-magnetic bead were as follows:coupling buffer pH of 8.0,a protein coupling amount of 2.5 mg/g,blocking solution of 10％BSA,serum sample volume of 20 μL.The optimal dilution of enzyme-labeled antigen was at 1:500 with a one-step reaction time of 15 minutes.The cutoff value of the established CLEIA method for detecting CSFV Erns protein antibodies was 5.83 U/mL and a diagnostic sensitivity of 1:128.No cross-reac-tivity was observed with positive sera against African swine fever virus,pseudorabies virus,porcine circovirus type 2,porcine epidemic diarrhea virus,porcine reproductive and respiratory syndrome virus,or porcine gastroenteritis virus.Additionally,the method yielded negative results with sera from pigs immunized with the E2 subunit vaccine.In repeatability tests,the intra-assay coefficient of variation(CV)ranged from 0.77％to 11.56％,and the inter-assay CV ranged from 10.30％to 14.55％,both below 15％.The positive and negative concordance rates with a commercial CSFV Erns protein antibody detection kit were 95.24％and 92.71％,separately,with an overall concord-ance rate of 93.23％.The double-antigen sandwich chemiluminescence method established in this study exhibits high sensitivity,excellent repeatability,and suitability for automated detection,making it applicable for serological differentiation between CSFV E2 subunit vaccination and infec-tion with prevalent strains.

N1-methyladenosine(m1A)RNA methylation is critical for regulating mRNA translation;however,its role in the development,progression,and immunotherapy response of head and neck squamous cell carcinoma(HNSCC)remains largely unknown.Using Tgfbr1 and Pten conditional knockout(2cKO)mice,we found the neoplastic transformation of oral mucosa was accompanied by increased m1A modification levels.Analysis of m1A-associated genes identified TRMT61A as a key m1A writer linked to cancer progression and poor prognosis.Mechanistically,TRMT61A-mediated tRNA-m1A modification promotes MYC protein synthesis,upregulating programmed death-ligand 1(PD-L1)expression.Moreover,m1A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus(oHSV),contributing to reactive PD-L1 upregulation.Therapeutic m1A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth,representing a promising strategy to alleviate resistance.These findings indicate that m1A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression,providing a mutually reinforcing combination immunotherapy approach.

Objective:To investigate the relationship between cerebrovascular variation and the occurrence and recurrence of cerebral infarction, and provide a theoretical basis for the precise prevention and treatment of cerebral infarction.Methods:Totally 13 939 patients who underwent magnetic resonance imaging(MRI) and magnetic resonance angiography(MRA) examination at the Second Affiliated Hospital of Shandong First Medical University from January 2020 to December 2021 were grouped according to clinical symptoms combined with the imaging report, including 4 412 cases in the cerebral infarction group and 9 527 cases in the control group.2 048 patients in the cerebral infarction group were eventually enrolled in the study according to the inclusion and exclusion criteria, including 1 479 cases of initial cerebral infarction and 569 cases of recurrent cerebral infarction.SPSS 25.0 statistical software was used for data analysis.The χ2 test was used to compare the incidence of cerebral infarction with different cerebrovascular variations.Univariate analysis of suspected risk factors for recurrent cerebral infarction was performed with χ2 test, nonparametric test and t test.The binary logistic regression was used to analyze independent risk factors of recurrent cerebral infarction. Results:The incidence of cerebral infarction in the dual-system cerebrovascular variant patients, the single-system cerebrovascular variant patients, and the non-cerebrovascular variant patients were 40.9%, 30.7% and 31.8% respectively.The incidence of cerebral infarction in the dual-system cerebrovascular variant patients was the highest compared with those in the single-system cerebrovascular variant patients and the non-cerebrovascular variant patients (both P<0.05). The incidence rates of embryonic posterior cerebral artery, vertebral artery dominance, and bilateral common origin anterior cerebral arteries were 14.09%, 10.76% and 5.32%, respectively.The incidence of bilateral common origin anterior cerebral arteries in the cerebral infarction group was significantly higher than that in the control group and the difference was statistically significant.Patients with cerebral infarction who were familial aggregation ( OR=2.207, 95% CI=1.591-3.062), hyperhomocysteinemia ( OR=1.262, 95% CI=1.014-1.570), hypertension ( OR=1.461, 95% CI=1.114-1.918), diabetes mellitus ( OR=1.348, 95% CI=1.072-1.694), coronary heart disease ( OR=1.491, 95% CI=1.196-1.858) were more likely to recurrent cerebral infarction ( P<0.05), and patients with cerebral infarction had a significantly increased risk of recurrent cerebral infarction with age ( OR=1.031, 95% CI=1.020-1.042, P<0.05). Conclusion:Dual-system cerebrovascular variation and bilateral common origin anterior cerebral arteries are risk factors for cerebral infarction.