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.

AIM:To investigate the impact of core 1 β3-galactosyltransferase-specific molecular chaperone(COSMC)on the stem cell-like properties of gastric adenocarcinoma cells,and to elucidate its underlying mechanism.METHODS:GEPIA(Gene Expression Profiling Interactive Analysis),TIMER(Tumor IMmune Estimation Resource),Wei Sheng Xin platform,UALCAN(University of Alabama at Birmingham Cancer Data Analysis Portal)and UCSC(Uni-versity of California,Santa Cruz)Xena databases were employed to analyze COSMC expression levels across various carci-noma types.The COSMC expression in gastric cancer tissues and cell lines was evaluated using Western blot analysis.Transfection of small interfering RNA was used to knock down COSMC in MKN-45 cell line.In vitro experiments were con-ducted to explore the relationship between the COSMC expression and the stem cell-like properties of gastric cancer.The qPCR,sphere formation assay,soft agar colony formation assay and CCK-8 assay were used to evaluate the effect of COSMC on the stem cell-like properties of gastric cancer cells.Tn+and Tn-cells were isolated using Vicia villosa lectin(VVL)-conjugated immunomagnetic beads to investigate the influence of Tn structure on the stem cell-like characteristics of gastric cancer cells.Finally,the effect of COSMC knockdown on the mitogen-activated protein kinase(MAPK)signal-ing pathway was evaluated by Western blot analysis.RESULTS:(1)The COSMC exhibited differential expression across pancarcinoma,gastric cancer tissues and gastric cancer cell lines,with elevated expression levels in gastric cancer tissues and gastric cancer cell lines compared with normal tissues and gastric epithelial cell line.(2)Knockdown of COSMC sig-nificantly down-regulated the mRNA levels of stem cell markers NANOG,OCT-4 and CD44 in gastric cancer cells,re-duced the efficiency of soft agar colony formation and sphere formation,and increased the sensitivity of the cells to 5-fluo-rouracil(5-FU).(3)The efficiency of tumor sphere formation and soft agar colony formation in Tn-cells,and the resis-tance to 5-FU were significantly higher than those in Tn+cells.(4)Knockdown of COSMC decreased the protein levels of MAPK signaling pathway-related molecules,including c-Jun N-terminal kinase(JNK),p38 and phosphorylated extracel-lular signal-regulated kinase(p-ERK).CONCLUSION:The COSMC has the potential to enhance the stem cell-like properties of gastric cancer cells,which was likely mediated through the activation of the MAPK signaling pathway.

Objective:To investigate the correlation between oral cleanliness and secondary Pulmonary infection in patients with severe chronic obstructive pulmonary disease (COPD) in mechanical ventilation, and to investigate the predictive effect of oral cleanliness on the risk of secondary pulmonary infection.Methods:Using the cross-sectional survey method, the purposeful sampling method was adopted to select 216 patients with severe COPD who were hospitalized in Hangzhou First People′s Hospital from June 2020 to December 2023 and received mechanical ventilation. The oral cleanliness index and general clinical data of patients at admission were collected using the hospital electronic medical record system. The independent influencing factors of secondary lung infection were analyzed by univariate analysis and multivariate Logisitic regression. The predictive value of oral cleanliness index on secondary lung infection was analyzed by patient operating characteristic (ROC) curve.Results:216 patients with severe COPD who underwent mechanical ventilation were included.Patients aged 37-84 (66.81 ± 8.98) years were included, including 125 males and 91 females.Among them, 89 cases developed secondary pulmonary infection, with an infection rate of 41.20%.Univariate analysis and multivariate Logistic regression analysis showed that, Beck Oral Rating Scale (BOAS) score ( OR = 1.371), visual simulation score of oral odor ( OR = 1.405), gum index ( OR = 3.508), plaque index ( OR = 14.357), smoking history ( OR = 6.772), duration of disease ( OR = 1.391), COPD assessment test score ( OR = 1.269) and mechanical ventilation time ( OR = 1.302) were independent factors for secondary pulmonary infection (all P<0.05). ROC curve analysis showed that oral cleanliness index combined with infection prediction was effective (the area under the ROC curve was 0.833) . Conclusions:Oral cleanliness was closely related to secondary pulmonary infection in patients with severe COPD with mechanical ventilation. BOAS score, visual simulation score of oral odor, gingival index and plaque index could predict secondary pulmonary infection independently, and combined test could predict secondary pulmonary infection.

Objective:New HIV infections serve as a crucial indicator for assessing the dynamic changes in the HIV epidemic. This study aims to estimate the number of new HIV infections in Dehong Dai and Jingpo Autonomous Prefecture of Yunnan Province (Dehong), using a back-calculation method that integrates diagnosis delay approaches and Bayesian theory. Additionally, it compares the differences between these two estimation methods.Methods:Data were obtained from the Chinese Information System for Disease Control and Prevention. Based on CD4 + T lymphocytes (CD4) counts depletion model, the first CD4 count prior to antiretroviral therapy of HIV-infected individuals diagnosed in Dehong from 2010 to 2023 was utilized to retroactively determine the infection date of HIV-infected individuals and ascertain the annual number of new HIV infections who had been diagnosed. Subsequently, the diagnosis delay distribution method and Bayesian theory were leveraged to assess the diagnosis probability of newly infected individuals, thereby projecting the number of new HIV infections in the region over the specified period. Results:During 2010-2023, a total of 5 693 individuals aged 15 and above, excluding mother-to-child transmission, were diagnosed with HIV in Dehong. After excluding 364 cases due to missing CD4 count results or abnormal first CD4 counts (≥2 000 cells/μl), 5 329 HIV-infected individuals were included in the final analysis. Through CD4 counts back-calculation from 2010 to 2023, the annual number of new infections diagnosed was 479, 427, 337, 305, 256, 219, 194, 193, 131, 166, 120, 71, 42 and 47. When using the diagnosis delay distribution method and life table analysis, the cumulative diagnosis probability rose from 0.301 within one year to 0.913 within 14 years, leading to a reduction in the number of estimated new infections from 577 in 2010 to 168 in 2023, with a total estimate of 4 412 (95% CI:4 350-4 480). Alternatively, based on Bayesian theory, the diagnosis probability increased from 0.413 within one year to 0.946 within 14 years, leading to a reduction in the number of estimated new infections from 557 in 2010 to 122 in 2023, with a total of 3 814 (95% CI: 3 787-3 837). Conclusions:Both methods yielded consistent results in estimating new HIV infections in Dehong from 2010 to 2023. Given the region's ongoing expansion of HIV testing, the estimates derived from Bayesian theory may more accurately reflect the actual situation. These findings provide a reference basis for formulating and optimizing HIV/AIDS prevention and control strategies in Dehong, facilitating progress toward the goal of eliminating AIDS by 2030 in the region.

AIM:To investigate the impact of core 1 β3-galactosyltransferase-specific molecular chaperone(COSMC)on the stem cell-like properties of gastric adenocarcinoma cells,and to elucidate its underlying mechanism.METHODS:GEPIA(Gene Expression Profiling Interactive Analysis),TIMER(Tumor IMmune Estimation Resource),Wei Sheng Xin platform,UALCAN(University of Alabama at Birmingham Cancer Data Analysis Portal)and UCSC(Uni-versity of California,Santa Cruz)Xena databases were employed to analyze COSMC expression levels across various carci-noma types.The COSMC expression in gastric cancer tissues and cell lines was evaluated using Western blot analysis.Transfection of small interfering RNA was used to knock down COSMC in MKN-45 cell line.In vitro experiments were con-ducted to explore the relationship between the COSMC expression and the stem cell-like properties of gastric cancer.The qPCR,sphere formation assay,soft agar colony formation assay and CCK-8 assay were used to evaluate the effect of COSMC on the stem cell-like properties of gastric cancer cells.Tn+and Tn-cells were isolated using Vicia villosa lectin(VVL)-conjugated immunomagnetic beads to investigate the influence of Tn structure on the stem cell-like characteristics of gastric cancer cells.Finally,the effect of COSMC knockdown on the mitogen-activated protein kinase(MAPK)signal-ing pathway was evaluated by Western blot analysis.RESULTS:(1)The COSMC exhibited differential expression across pancarcinoma,gastric cancer tissues and gastric cancer cell lines,with elevated expression levels in gastric cancer tissues and gastric cancer cell lines compared with normal tissues and gastric epithelial cell line.(2)Knockdown of COSMC sig-nificantly down-regulated the mRNA levels of stem cell markers NANOG,OCT-4 and CD44 in gastric cancer cells,re-duced the efficiency of soft agar colony formation and sphere formation,and increased the sensitivity of the cells to 5-fluo-rouracil(5-FU).(3)The efficiency of tumor sphere formation and soft agar colony formation in Tn-cells,and the resis-tance to 5-FU were significantly higher than those in Tn+cells.(4)Knockdown of COSMC decreased the protein levels of MAPK signaling pathway-related molecules,including c-Jun N-terminal kinase(JNK),p38 and phosphorylated extracel-lular signal-regulated kinase(p-ERK).CONCLUSION:The COSMC has the potential to enhance the stem cell-like properties of gastric cancer cells,which was likely mediated through the activation of the MAPK signaling pathway.

Objective:New HIV infections serve as a crucial indicator for assessing the dynamic changes in the HIV epidemic. This study aims to estimate the number of new HIV infections in Dehong Dai and Jingpo Autonomous Prefecture of Yunnan Province (Dehong), using a back-calculation method that integrates diagnosis delay approaches and Bayesian theory. Additionally, it compares the differences between these two estimation methods.Methods:Data were obtained from the Chinese Information System for Disease Control and Prevention. Based on CD4 + T lymphocytes (CD4) counts depletion model, the first CD4 count prior to antiretroviral therapy of HIV-infected individuals diagnosed in Dehong from 2010 to 2023 was utilized to retroactively determine the infection date of HIV-infected individuals and ascertain the annual number of new HIV infections who had been diagnosed. Subsequently, the diagnosis delay distribution method and Bayesian theory were leveraged to assess the diagnosis probability of newly infected individuals, thereby projecting the number of new HIV infections in the region over the specified period. Results:During 2010-2023, a total of 5 693 individuals aged 15 and above, excluding mother-to-child transmission, were diagnosed with HIV in Dehong. After excluding 364 cases due to missing CD4 count results or abnormal first CD4 counts (≥2 000 cells/μl), 5 329 HIV-infected individuals were included in the final analysis. Through CD4 counts back-calculation from 2010 to 2023, the annual number of new infections diagnosed was 479, 427, 337, 305, 256, 219, 194, 193, 131, 166, 120, 71, 42 and 47. When using the diagnosis delay distribution method and life table analysis, the cumulative diagnosis probability rose from 0.301 within one year to 0.913 within 14 years, leading to a reduction in the number of estimated new infections from 577 in 2010 to 168 in 2023, with a total estimate of 4 412 (95% CI:4 350-4 480). Alternatively, based on Bayesian theory, the diagnosis probability increased from 0.413 within one year to 0.946 within 14 years, leading to a reduction in the number of estimated new infections from 557 in 2010 to 122 in 2023, with a total of 3 814 (95% CI: 3 787-3 837). Conclusions:Both methods yielded consistent results in estimating new HIV infections in Dehong from 2010 to 2023. Given the region's ongoing expansion of HIV testing, the estimates derived from Bayesian theory may more accurately reflect the actual situation. These findings provide a reference basis for formulating and optimizing HIV/AIDS prevention and control strategies in Dehong, facilitating progress toward the goal of eliminating AIDS by 2030 in the region.

Clinical management of atopic dermatitis (AD) is challenged by its susceptibility to recurrence, side effects, and high costs. We found that Portulaca oleracea L.-derived nanovesicles (PDNV) exert anti-inflammatory effects by modulating macrophage M1/M2 polarization. These effects were achieved through pathways including inhibition of nuclear factor-κB (NF-κB) and stimulator of interferon genes (STING) protein expression in diseased tissues, demonstrating their potential to ameliorate AD symptoms. To increase the transdermal permeation of PDNV, dissolvable microneedles composed primarily of hyaluronic acid (HA) were developed as an adjunctive means of delivery. Meanwhile, polysaccharides of Portulaca oleracea L., which were synergistic with PDNV, were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA. This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD. In addition, transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L. are closest to those of ferns, which may shed light on related evolutionary and plant species identification studies.

Objective:To investigate the correlation between oral cleanliness and secondary Pulmonary infection in patients with severe chronic obstructive pulmonary disease (COPD) in mechanical ventilation, and to investigate the predictive effect of oral cleanliness on the risk of secondary pulmonary infection.Methods:Using the cross-sectional survey method, the purposeful sampling method was adopted to select 216 patients with severe COPD who were hospitalized in Hangzhou First People′s Hospital from June 2020 to December 2023 and received mechanical ventilation. The oral cleanliness index and general clinical data of patients at admission were collected using the hospital electronic medical record system. The independent influencing factors of secondary lung infection were analyzed by univariate analysis and multivariate Logisitic regression. The predictive value of oral cleanliness index on secondary lung infection was analyzed by patient operating characteristic (ROC) curve.Results:216 patients with severe COPD who underwent mechanical ventilation were included.Patients aged 37-84 (66.81 ± 8.98) years were included, including 125 males and 91 females.Among them, 89 cases developed secondary pulmonary infection, with an infection rate of 41.20%.Univariate analysis and multivariate Logistic regression analysis showed that, Beck Oral Rating Scale (BOAS) score ( OR = 1.371), visual simulation score of oral odor ( OR = 1.405), gum index ( OR = 3.508), plaque index ( OR = 14.357), smoking history ( OR = 6.772), duration of disease ( OR = 1.391), COPD assessment test score ( OR = 1.269) and mechanical ventilation time ( OR = 1.302) were independent factors for secondary pulmonary infection (all P<0.05). ROC curve analysis showed that oral cleanliness index combined with infection prediction was effective (the area under the ROC curve was 0.833) . Conclusions:Oral cleanliness was closely related to secondary pulmonary infection in patients with severe COPD with mechanical ventilation. BOAS score, visual simulation score of oral odor, gingival index and plaque index could predict secondary pulmonary infection independently, and combined test could predict secondary pulmonary infection.

Objective:To understand the incidence of diabetes and influencing factors, the trend of FPG change and risk for mortality in HIV-infected individuals after antiretroviral therapy (ART) in Dehong Dai and Jingpo Autonomous Prefecture (Dehong).Methods:The HIV/AIDS treatment database was collected from China Information System for Disease Control and Prevention. This retrospective cohort study was conducted in HIV-infected individuals with access to ART in Dehong during 2004-2020.The Cox proportional hazard regression model was used to analyze the incidence density of diabetes, the influencing factors and risk for mortality in HIV-infected individuals with access to ART, mixed linear effects model was used to analyze the trend of FPG change and predict FPG in those with different glucose metabolic status at baseline survey. Statistical analysis was performed using software SAS 9.4.Results:A total of 8 763 HIV-infected individuals were included, in whom 8 432 (96.2%) had no diabetes, 331 had diabetes. The incidence density of diabetes was 2.31/1 000 person years. Multivariate Cox proportional hazard regression analysis revealed that 30- 59 years old, BMI ≥24.0 kg/m 2, Efavirenz (EFV) based initial treatment regimen and impaired fasting glucose (IFG) at baseline survey were significantly and positively associated with incidence of diabetes. Mixed effect model revealed that FPG was positively correlated with the duration of ART, age and baseline FPG. Suffering from diabetes was a risk factor for mortality in HIV-infected individuals both at baseline survey and during follow-up. Conclusions:The risk for diabetes increased in HIV-infected individuals who were 30-59 years old, baseline BMI ≥24.0 kg/m 2, received EFV based initial treatment, and IFG in HIV-infected individuals after antiretroviral therapy in Dehong, 2004-2020. It is important to pay close attention to their blood glucose, and patients with high blood glucose should receive treatment as early as possible.

Objective To investigate the difference of electrocardiographic(ECG)features between total left main artery(LM)occlusion and subtotal occlusion,and analyze risk factors of in-hospital mortality.Methods A total of 94 patients with left main complete occlusion and 99 patients with subtotal occlusion were included.ECG characteristics,coronary angiography and other clinical data were compared,and factors of hospital death were analyzed.The receiver operating characteristics(ROC)curve was used to analyze the predictive value of ECG characteristics in hospital death risk in patients with LM occlusion.The relationship between ECG characteristics,shock and collateral circulation were analyzed in patients with LM occlusion.Results Compared with the subtotal occlusion group,patients with LM occlusion presented with more ST-segment elevation(STE)in Ⅰ,avL,V2-V5,more STE in avR and avL,more left anterior fascicular block+right bundle branch block,prolonged QRS duration,less STE in avR and less STE in avR+V1.The in-hospital mortality was 46.8%(44/94)in LM occlusion and 14.1%(14/99)in LM subtotal occlusion.STE in avR+avL predicted total LM occlusion with a specificity of 0.97,and left anterior branch+right bundle branch block predicted total LM occlusion with a specificity of 1.00.In patients with total LM occlusion,STE in Ⅰ,avL,V2-V5,prolongation of QRS duration,shock,no collateral circulation,STE in Ⅰ,avL,V2-V5 combined with left anterior fascicular block+right bundle branch block,and STE in Ⅰ,avL,V2-V5 combined with shock predicted in-hospital mortality,with the area under the curve of 0.716,0.619,0.766,0.688,0.572,0.785,respectively.The diagnostic specificity of STE in Ⅰ,avL,V2-V5 combined with shock was 0.82,and the sensitivity was 0.75.STE in Ⅰ,avL,V2-V5 combined with left anterior fascicular block+right bundle branch block predicted in-hospital death in LM occlusion with a specificity of 0.94.The proportion of shock was higher in patients with STE in Ⅰ,avL,V2-V5,left anterior fascicular block+right bundle branch block and collateral flow absence(P＜0.05).In patients with total occlusion,no collateral flow was observed in patients with STE in Ⅰ,avL,V2-V5.In patients with STE in avR(including avR+V1),82.4%of patients presented with right coronary collateral circulation supplying the left anterior descending coronary artery and left circumflex artery territory.In patients with STE in avR+avL,69.2%of patients presented with right coronary collateral circulation supplying left anterior descending coronary artery territory.Conclusion Total LM occlusion presents with different ECG features compared with subtotal occlusion.In LM total occlusion,the ECG features predict in-hospital mortality and are associated with different collateral circulation.