Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

OBJECTIVE To compare the effect of traditional swab sampling method on etiological surveillance of in-fectious diseases for large-scale object surfaces in hospitals and validate the samples processing method based on pre-wet anti-static fabric and modified polyethylene glycol(PEG)precipitation enrichment technology so as to im-prove the capability of early warning of infectious diseases and optimize the environmental surveillance program in the hospitals.METHODS The on-site surveillance was carried out for 8 times in 3 public hospitals(Shenzhen Longgang People's Hospital,the Second People's Hospital of Longgang and Longgang Maternal and Child Health Hospital)from May 2024 to Mar.2025.Totally 23 types of respiratory tract pathogens(18 types of viruses,5 type of pathogenic bacteria)and 6 types of gastrointestinal tract pathogens were simultaneously detected by means of fluorescent quantitative polymerase chain reaction(PCR);the actual isolation rates,etiological spectrum and cycle threshold(Ct)value were compared.The acrylic plate added with standards of different loads of H1NI influ-enza viruses was used as model for laboratory evaluation.The minimum detection limit,sensitivity and repeatabili-ty were observed and compared between the methods.RESULTS The minimum detection limit of both methods was 6.0 × 104 copies/ml,however,the positive rate of nucleic acid testing of the pre-wet fabric method was 100.00％(3/3),higher than 33.33％(1/3)of the swab method;when the low viral load was 6.0× 105 copies/ml,the average concentration of viral nucleic acid of the pre-wet fabric method(X-Ct=36.59)was higher,with the re-peatability(CV=0.99％,＜3.14％)better.The results of the on-site surveillances showed that the total isolation rates of pathogens of the pre-wet fabric method ranged between 42.84％and 64.27％,higher than between 10.71％and 21.43％of the swab method,with the isolated pathogens more abundant,the Ct value lower(P＜0.05).CONCLUSION The pre-wet fabric sampling enrichment method integrated with anti-static fabric sampling and PEG enrichment technology shows higher sensitivity and stability in the etiological surveillance of large-scale object surfaces,raising the isolation rate.

OBJECTIVES: To explore the active components that mediate the therapeutic effect of Centella asiatica on psoriasis and their therapeutic mechanisms. METHODS: TCMSP, TCMIP, PharmMapper, Swiss Target Prediction, GeneCards, OMIM and TTD databases were searched for the compounds in Centella asiatica and their targets and the disease targets of psoriasis. A drug-active component-target network and the protein-protein interaction network were constructed, and DAVID database was used for pathway enrichment analysis. In a RAW264.7 macrophage model of LPS-induced inflammation, the anti-inflammatory effect of 7.5, 15, 30, and 60 μmol/L quercetin, asiaticoside, and asiatic acid, which were identified as the main active components in Centella asiatica, were tested by measuring cellular production of NO, TNF‑α and IL-6 using Griess method and ELISA and by detecting mRNA expressions of IL-23, IL-17A, TNF-α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727) with RT-qPCR and Western blotting. RESULTS: A total of 139 targets of Centella asiatica and 4604 targets of psoriasis were obtained, and among them CASP3, EGFR, PTGS2, and ESR1 were identified as the core targets. KEGG analysis suggested that quercetin, asiaticoside, and asiatic acid in Centella asiatica were involved in cancer and IL-17 and MAPK signaling pathways. In the RAW264.7 macrophage model of inflammation, treatment with quercetin significantly reduced cellular production of NO, TNF‑α and IL-6, and lowered mRNA expressions of IL-23, IL-17A, TNF‑α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727). CONCLUSIONS Quercetin, asiaticoside and asiatic acid are the main active components in Centella asiatica to mediate the therapeutic effect against psoriasis, and quercetin in particular is capable of suppressing cellular production of NO, TNF‑α and IL-6 and regulating the IL-23/IL-17A inflammatory axis by mediating STAT3 phosphorylation to inhibit inflammatory response.
Quercetin/pharmacology* ; Psoriasis/metabolism* ; STAT3 Transcription Factor/metabolism* ; Mice ; Animals ; Centella/chemistry* ; Triterpenes/pharmacology* ; Phosphorylation ; Interleukin-17/metabolism* ; Interleukin-23/metabolism* ; RAW 264.7 Cells ; Pentacyclic Triterpenes/pharmacology* ; Macrophages/drug effects* ; Signal Transduction ; Plant Extracts

Objective:To investigate the association of serum/body fluid heparin-binding protein (HBP) and blood lactate levels with disease severity and their impact on prognosis in intensive care unit (ICU) patients with sepsis.Methods:Clinical data from 100 sepsis patients admitted to Ma'anshan Shiqiye Hospital ICU (January 2023-September 2024) were retrospectively analyzed. According to Sepsis-3.0 criteria, patients were divided into: uncomplicated sepsis (general group, n=28), sepsis with organ failure/hypotension (severe group, n=61), and septic shock (shock group, n=11). Comparisons included serum/body fluid HBP, lactate, APACHE Ⅱ scores, and mortality across severity groups and laboratory parameters between survivors and non-survivors. Logistic regression was used to identify prognostic predictors. Non-normally distributed data were presented as M(Q1,Q3), comparison between groups were completed by Kruskal-Wallis H test and Mann-Whitney U tests. Spearman correlation was used to analyze relationships between biomarkers and APACHE Ⅱ scores. Categorical data were presented as n(%), and comparison between groups were completed by χ2 test or Fisher's exact tests. ROC curves was used to evaluate predictive value. Results:Shock group demonstrated significantly higher serum HBP [13.3 (12.6-16.4) μg/L], infection-site HBP [230.3 (226.3-241.1) μg/L], lactate [5.4 (4.9-5.6) mmol/L], and APACHE Ⅱ[22.0 (21.0-24.0)] than severe group [9.6 (8.9-10.5) μg/L; 208.9 (200.5-216.1) μg/L; 2.7 (2.6-2.8) mmol/L; 18.0 (17.0-19.0)] and general group [7.4 (6.3-8.1) μg/L; 190.6 (180.5-202.1) μg/L; 1.5 (1.4-1.7) mmol/L; 13.0 (12.0-14.0)] (all P<0.001). There was statistically significant difference in the mortality rate during hospita lization among three groups of patients ( χ2=30.49, P<0.001). Mortality was higher in shock group than severe group than general group [72.7% (8/11) vs. 11.5% (7/61) vs. 3.6% (1/28), all P<0.001]. Non-survivors exhibited elevated lactate [4.8 (2.7-5.5) vs. 2.6 (1.7-2.8) mmol/L, Z=-4.13, P=0.001], serum HBP [12.2 (9.2-13.3) vs. 9.3 (7.8-10.4) μg/L, Z=-3.12, P=0.002], and infection-site HBP [226.8 (209.9-237.6) vs. 203.6 (194.0-212.8) μg/L, Z=-4.32, P<0.001] vs. survivors. Serum HBP ( r=0.74), infection-site HBP ( r=0.64), and lactate ( r=0.86) were all positively correlated with APACHE Ⅱ (all P<0.001). After adjusting for age and APACHE Ⅱ, elevated serum HBP ( OR=3.743, 95% CI:1.834-7.640), infection-site HBP ( OR=3.540, 95% CI:1.932-6.486), and lactate ( OR=5.155, 95% CI:1.868-14.229) independently predicted mortality (all P<0.001). Combined biomarker detection showed superior predictive value (AUC=0.909) versus individual markers (serum HBP:0.747, infection-site HBP:0.842, lactate:0.827, all P<0.001). Conclusion:Elevated blood lactate and serum/infection-site HBP levels correlate with sepsis severity and independently predict mortality. The biomarker combination provides optimal prognostic stratification.

Objective:To investigate the differences in protein profile expression in serum samples from children with corona virus disease 2019（COVID-19）related encephalopathy and to explore the underlying mechanisms.Methods:From December 1,2022 to January 31,2023,28 children with COVID-19 who were admitted to the Department of Pediatric Intensive Medicine at Shandong Provincial Hospital Affiliated to Shandong First Medical University were collected,including 21 patients with encephalopathy(COVID-19 with encephalopathy group) and seven patients without encephalopathy(COVID-19 without encephalopathy group).Three children from each group were selected for serum proteomic analysis using tandem mass spectrometry labeling proteomics technology.Proteins were considered significantly different if the fold change was >1.2 or <0.8，with P<0.05.Bioinformatics analysis，including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Pathway Enrichment were performed on differentially expressed proteins.Protein-protein interaction networks were analyzed using the STRING database.Selected proteins were further validated by enzyme-linked immunosorbert assay. Results:A total of 41 differentially expressed proteins were identified between the two groups.Among these，14 proteins were upregulated and 27 proteins were downregulated in COVID-19 patients with encephalopathy compared to those without encephalopathy.Bioinformatics analysis revealed that these proteins were primarily enriched in critical signaling pathways，including complement and coagulation regulation，neutrophil degranulation and activation，and platelet degranulation.Enzyme-linked immunosorbert assay validation confirmed significant differences in key coagulation-regulating proteins(von willebrand factor upregulated，serpin family F member 2 downregulated in COVID-19 patients with encephalopatly）between the two groups.Conclusion:Coagulation dysfunction may play a role in the development of COVID-19 associated encephalopathy in children，providing valuable insights for future research.

Objective:To investigate the differences in protein profile expression in serum samples from children with corona virus disease 2019（COVID-19）related encephalopathy and to explore the underlying mechanisms.Methods:From December 1,2022 to January 31,2023,28 children with COVID-19 who were admitted to the Department of Pediatric Intensive Medicine at Shandong Provincial Hospital Affiliated to Shandong First Medical University were collected,including 21 patients with encephalopathy(COVID-19 with encephalopathy group) and seven patients without encephalopathy(COVID-19 without encephalopathy group).Three children from each group were selected for serum proteomic analysis using tandem mass spectrometry labeling proteomics technology.Proteins were considered significantly different if the fold change was >1.2 or <0.8，with P<0.05.Bioinformatics analysis，including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Pathway Enrichment were performed on differentially expressed proteins.Protein-protein interaction networks were analyzed using the STRING database.Selected proteins were further validated by enzyme-linked immunosorbert assay. Results:A total of 41 differentially expressed proteins were identified between the two groups.Among these，14 proteins were upregulated and 27 proteins were downregulated in COVID-19 patients with encephalopathy compared to those without encephalopathy.Bioinformatics analysis revealed that these proteins were primarily enriched in critical signaling pathways，including complement and coagulation regulation，neutrophil degranulation and activation，and platelet degranulation.Enzyme-linked immunosorbert assay validation confirmed significant differences in key coagulation-regulating proteins(von willebrand factor upregulated，serpin family F member 2 downregulated in COVID-19 patients with encephalopatly）between the two groups.Conclusion:Coagulation dysfunction may play a role in the development of COVID-19 associated encephalopathy in children，providing valuable insights for future research.

Objective:To investigate the association of serum/body fluid heparin-binding protein (HBP) and blood lactate levels with disease severity and their impact on prognosis in intensive care unit (ICU) patients with sepsis.Methods:Clinical data from 100 sepsis patients admitted to Ma'anshan Shiqiye Hospital ICU (January 2023-September 2024) were retrospectively analyzed. According to Sepsis-3.0 criteria, patients were divided into: uncomplicated sepsis (general group, n=28), sepsis with organ failure/hypotension (severe group, n=61), and septic shock (shock group, n=11). Comparisons included serum/body fluid HBP, lactate, APACHE Ⅱ scores, and mortality across severity groups and laboratory parameters between survivors and non-survivors. Logistic regression was used to identify prognostic predictors. Non-normally distributed data were presented as M(Q1,Q3), comparison between groups were completed by Kruskal-Wallis H test and Mann-Whitney U tests. Spearman correlation was used to analyze relationships between biomarkers and APACHE Ⅱ scores. Categorical data were presented as n(%), and comparison between groups were completed by χ2 test or Fisher's exact tests. ROC curves was used to evaluate predictive value. Results:Shock group demonstrated significantly higher serum HBP [13.3 (12.6-16.4) μg/L], infection-site HBP [230.3 (226.3-241.1) μg/L], lactate [5.4 (4.9-5.6) mmol/L], and APACHE Ⅱ[22.0 (21.0-24.0)] than severe group [9.6 (8.9-10.5) μg/L; 208.9 (200.5-216.1) μg/L; 2.7 (2.6-2.8) mmol/L; 18.0 (17.0-19.0)] and general group [7.4 (6.3-8.1) μg/L; 190.6 (180.5-202.1) μg/L; 1.5 (1.4-1.7) mmol/L; 13.0 (12.0-14.0)] (all P<0.001). There was statistically significant difference in the mortality rate during hospita lization among three groups of patients ( χ2=30.49, P<0.001). Mortality was higher in shock group than severe group than general group [72.7% (8/11) vs. 11.5% (7/61) vs. 3.6% (1/28), all P<0.001]. Non-survivors exhibited elevated lactate [4.8 (2.7-5.5) vs. 2.6 (1.7-2.8) mmol/L, Z=-4.13, P=0.001], serum HBP [12.2 (9.2-13.3) vs. 9.3 (7.8-10.4) μg/L, Z=-3.12, P=0.002], and infection-site HBP [226.8 (209.9-237.6) vs. 203.6 (194.0-212.8) μg/L, Z=-4.32, P<0.001] vs. survivors. Serum HBP ( r=0.74), infection-site HBP ( r=0.64), and lactate ( r=0.86) were all positively correlated with APACHE Ⅱ (all P<0.001). After adjusting for age and APACHE Ⅱ, elevated serum HBP ( OR=3.743, 95% CI:1.834-7.640), infection-site HBP ( OR=3.540, 95% CI:1.932-6.486), and lactate ( OR=5.155, 95% CI:1.868-14.229) independently predicted mortality (all P<0.001). Combined biomarker detection showed superior predictive value (AUC=0.909) versus individual markers (serum HBP:0.747, infection-site HBP:0.842, lactate:0.827, all P<0.001). Conclusion:Elevated blood lactate and serum/infection-site HBP levels correlate with sepsis severity and independently predict mortality. The biomarker combination provides optimal prognostic stratification.

OBJECTIVE To compare the effect of traditional swab sampling method on etiological surveillance of in-fectious diseases for large-scale object surfaces in hospitals and validate the samples processing method based on pre-wet anti-static fabric and modified polyethylene glycol(PEG)precipitation enrichment technology so as to im-prove the capability of early warning of infectious diseases and optimize the environmental surveillance program in the hospitals.METHODS The on-site surveillance was carried out for 8 times in 3 public hospitals(Shenzhen Longgang People's Hospital,the Second People's Hospital of Longgang and Longgang Maternal and Child Health Hospital)from May 2024 to Mar.2025.Totally 23 types of respiratory tract pathogens(18 types of viruses,5 type of pathogenic bacteria)and 6 types of gastrointestinal tract pathogens were simultaneously detected by means of fluorescent quantitative polymerase chain reaction(PCR);the actual isolation rates,etiological spectrum and cycle threshold(Ct)value were compared.The acrylic plate added with standards of different loads of H1NI influ-enza viruses was used as model for laboratory evaluation.The minimum detection limit,sensitivity and repeatabili-ty were observed and compared between the methods.RESULTS The minimum detection limit of both methods was 6.0 × 104 copies/ml,however,the positive rate of nucleic acid testing of the pre-wet fabric method was 100.00％(3/3),higher than 33.33％(1/3)of the swab method;when the low viral load was 6.0× 105 copies/ml,the average concentration of viral nucleic acid of the pre-wet fabric method(X-Ct=36.59)was higher,with the re-peatability(CV=0.99％,＜3.14％)better.The results of the on-site surveillances showed that the total isolation rates of pathogens of the pre-wet fabric method ranged between 42.84％and 64.27％,higher than between 10.71％and 21.43％of the swab method,with the isolated pathogens more abundant,the Ct value lower(P＜0.05).CONCLUSION The pre-wet fabric sampling enrichment method integrated with anti-static fabric sampling and PEG enrichment technology shows higher sensitivity and stability in the etiological surveillance of large-scale object surfaces,raising the isolation rate.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective To analyze the expression levels of serum microRNA(miR)-211 and miR-202 in patients with Alzheimer's disease and their correlation with cognitive function,anxiety and depression.Methods A total of 90 patients with Alzheimer's disease admitted to Hebei Yanda Hospital from March 2019 to March 2022 were selected as the research group.According to the Clinical Dementia Rating(CDR)score,the patients were grouped into mild group(n=24),moderate group(n=48)and severe group(n=18).Another 90 healthy individuals who underwent physical examination were collected as the control group.The expression levels of miR-211 and miR-202 in serum were compared.Pearson method and Spearman method were used to analyze serum miR-211 and miR-202 and their correlation with cognitive function,anxiety and depression.Logistic regression analysis was used to analyze the influencing factors of Alzheimer's disease.Results The expression levels of serum miR-211(0.59±0.16,1.01±0.31)and miR-202(0.35±0.10,1.00±0.32)were significantly reduced in the research group and control group,with significant differences(t=11.422,18.393,all P<0.05).Serum miR-211(0.73±0.21,0.62±0.17,0.32±0.08)expression levels,miR-202(0.51±0.15,0.33±0.10,0.19±0.04)expression levels,mini-mental state examination(MMSE)score(22.54±1.41 score,19.35±1.01 score,16.23±1.00 score)and Montreal cognitive assessment(MoCA)score(25.35±2.60 score,18.59±1.32 score,16.59±1.24 score)in the mild,moderate and severe groups gradually decreased,and the differences were statistically significant(F=32.006,46.917,163.048,163.703,all P<0.05).Compared with mild group,the serum miR-211,miR-202,MMSE and MoCA scores of severe group and moderate group were reduced,and the differences were statistically significant(t=3.685～25.375,all P<0.05).The mild,moderate and severe groups had a gradual increase in Hamilton anxiety scale(HAMA)score(12.34±1.27 score,20.59±2.09 score and 31.29±2.19 score)and Hamilton depression scale(HAMD)score(14.35±2.13 score,23.89±2.20 score and 35.35±1.21 score),and the differences were statistically significant(F=496.059,553.939,all P<0.05).According to Pearson correlation analysis,miR-211 was positively correlated with miR-202(r=0.651,P<0.05).According to Spearman correlation analysis,miR-211 and miR-202 were positively correlated with MMSE and MoCA(r=0.539～0.585,all P<0.05)and negatively correlated with HAMA and HAMD(r=-0.651～-0.539,all P<0.05).Logistic regression analysis showed that the low expression of miR-211[OR(95%CI):5.321(1.648～17.180)]and miR-202[OR(95%CI):3.158(1.989～5.012)]were risk factors for Alzheimer's disease(P<0.05).Conclusion The serum expression levels of miR-211 and miR-202 in patients with Alzheimer's disease were reduced,indicating miR-211 and miR-202 were closely related to cognitive function,anxiety and depression.