ObjectiveTo investigate the molecular mechanisms by which Acan-Gal-1 regulates macrophage immune phenotypes and Annexin A2/S100A10 membrane translocation in Angiostrongylus cantonensis. MethodsImmunofluorescence assay （IFA） was performed to determine the subcellular localization of Annexin A2 and S100A10 in macrophages. Flow cytometry and ELISA were used to assess functional changes in macrophage. siRNA interference of Annexin A2 was used to detect the effect of Acan-Gal-1 on various indicators. The expression levels of related genes and proteins were analyzed by Western blot， qRT-PCR， and ELISA methods. Bioinformatics analyses were conducted to characterize the structural features of Acan-Gal-1， and sequence alignment and molecular interaction prediction were performed to explore its potential interaction with Annexin A2. ResultsThis study found that Acan-Gal-1 can reverse LPS-induced promotion of macrophage migration and phagocytic function； it significantly upregulated M2-type markers in macrophages （Arg-1， IL-10， TGF-β） while inhibiting the expression of M1-type markers （iNOS， IL-6， IL-1β） induced by LPS. Acan-Gal-1 reduced the protein levels of Annexin A2 in macrophages under an immunologically activated state； after interfering with Annexin A2 expression， Acan-Gal-1 not only fails to induce macrophages to transition to an immunologically inhibitory phenotype but also fails to inhibit LPS-induced transition of macrophages to an immunologically activated phenotype. Although Acan-Gal-1 did not affect the expression of Annexin A2 or its chaperone protein S100A10 in macrophages， it markedly promoted their translocation to the plasma membrane. ConclusionsAcan-Gal-1 facilitates the enrichment of the Annexin A2/S100A10 complex at the macrophage membrane， thereby exerting immunomodulatory effects on macrophage polarization.

Objective To investigate the effect of Echinacoside(Ech)on liver injury in hepatitis B rats.Methods SD rats were divided into control group,Hepatitis B(HBV,5 mL/kg HBV virus was injected into the tail vein twice a week for 3 consecutive weeks),low(Ech-L)and high(Ech-H)doses of Ech were injected into the stom-ach for HBV(8.33 and 33.32 mg/kg,respectively),HBV group was treated with positive drugs(lamivudine,10 mg/kg)and Ech-H+BKM120(40 mg/kg BKM120),with 12 animals in each group.The drug was administered once a day for 8 weeks.The activity of ALT and AST in serum of were detected.Serum level of gam-ma-interferon(IFN-γ)and interleukin(IL-4)was detected by ELISA;Flow cytometry was applied to detect Th1/Th2 in peripheral blood;Chromatin immunoprecipitation was applied to detect HBV DNA expression in liver tissue;HE staining was used to detect the pathological changes of liver tissue and score the damage;Western blot was ap-plied to detect phosphorylated phosphatidylinositol 3 kinase(p-PI3K),phosphorylated protein kinase B(p-AKT)proteins in liver tissue.Results Compared with the control group,hepatocytes in the hepatitis B group were swollen,nuclear staining was excessive,hepatic lobular structure was disorganized,pathological injury score,serum AST,ALT activity,IL-4 level,peripheral blood Th2,HBV DNA expression in liver tissue were all increased.Serum IFN-γ level,Th1,Th1/Th2 in peripheral blood,p-PI3K and p-AKT protein in liver tissue were all decreased(P＜0.05);Treatment with Ech-L,Ech-H and lamivudine reduced the swelling of HBV rat hepatocytes,cleared the structure of some liver cords,reduced pathological injury score,the activity of AST,ALT and IL-4 levels in serum,Th2 in peripheral blood and HBV DNA in liver tissue;The level of serum IFN-γ,Th1,Th1/Th2 in peripheral blood,and protein expression p-PI3K and p-AKT protein in liver tissue were increased(P＜0.05).BKM120 attenuated the ameliorative effect of high-dose Ech on hepatitis B-induced liver injury in rats.Conclusions Ech ameliorates liver in-jury in rats with hepatitis B,and the mechanism may be related to the activation of the PI3K/AKT pathway.

Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

Objective By reviewing the access policies for new antimicrobial drugs internationally,this study provides a reference for the development of China's antimicrobial drug access policy.Methods The Chinese and English databases,offi-cial websites of health agencies,and health technology assessment agencies of various countries(CNKI,PubMed,NICE in the UK,HAS in France,etc.)were searched to collect and sort out the access policies of new antibacterial drugs.Taking the antibacte-rial drug ceftazidime-avibactam and the antifungal drug esaconazole sulfate as examples,the key evidence points for the evaluation of antibacterial drugs in the market access process of medical insurance were analyzed.Finally,the author put forward suggestions for China's antibacterial drug access policy based on the opinions of experts in related fields of antibacterial drugs in China.Re-sults Access policies for antimicrobial drugs had already established in the UK,US,EU,Sweden Switzerland,and Republic of Korea.These policies included a series of measures such as evaluation approval rewards,patent extensions,additional reimburse-ment,decoupling sales revenue from sales volume,etc.,with the ultimate goal being to encourage research and development of new antibiotics while reducing resistance rates.The review found that besides evaluating the safety,economy,and cost-effectiveness,some evaluation agencies also consider the actual clinical value and social value of drugs when reviewing the evidence of two types of new antibacterial drugs in the medical insurance access link.Conclusion China can draw upon international framework principles while considering unique demands such as national antibiotic management policy or national healthcare negotiation re-quirements to provide certain policy support throughout the market access process for new antimicrobials due to their unique val-ues so that it can encourage research & development while curbing antibiotic resistance.

Objective By reviewing the access policies for new antimicrobial drugs internationally,this study provides a reference for the development of China's antimicrobial drug access policy.Methods The Chinese and English databases,offi-cial websites of health agencies,and health technology assessment agencies of various countries(CNKI,PubMed,NICE in the UK,HAS in France,etc.)were searched to collect and sort out the access policies of new antibacterial drugs.Taking the antibacte-rial drug ceftazidime-avibactam and the antifungal drug esaconazole sulfate as examples,the key evidence points for the evaluation of antibacterial drugs in the market access process of medical insurance were analyzed.Finally,the author put forward suggestions for China's antibacterial drug access policy based on the opinions of experts in related fields of antibacterial drugs in China.Re-sults Access policies for antimicrobial drugs had already established in the UK,US,EU,Sweden Switzerland,and Republic of Korea.These policies included a series of measures such as evaluation approval rewards,patent extensions,additional reimburse-ment,decoupling sales revenue from sales volume,etc.,with the ultimate goal being to encourage research and development of new antibiotics while reducing resistance rates.The review found that besides evaluating the safety,economy,and cost-effectiveness,some evaluation agencies also consider the actual clinical value and social value of drugs when reviewing the evidence of two types of new antibacterial drugs in the medical insurance access link.Conclusion China can draw upon international framework principles while considering unique demands such as national antibiotic management policy or national healthcare negotiation re-quirements to provide certain policy support throughout the market access process for new antimicrobials due to their unique val-ues so that it can encourage research & development while curbing antibiotic resistance.

Adverse reactions commonly associated with apalutamide include hot flashes, fatigue, joint pain, rash, hypertension, and anemia. Apalutamide-induced agranulocytosis is relatively rare. In this paper, we reported a case with metastatic hormone-sensitive prostate cancer who developed agranulocytosis after taking apalutamide for one month. The patient’s neutrophil count returned to normal with appropriate supportive therapy, and no significant decrease in neutrophil count was observed during 10 months of follow-up after discharge.

Objective To explore the effect of galangin(Gal)on inflammation in hepatitis B rats.Methods The rats were randomly divided into control group,hepatitis B group,Gal-L and Gal-H groups,positive drug lamivudine group and Gal-H+AMPK inhibitor(compound C)group with 12 in each.After modeling,medication treatment was performed once a day for 8 weeks.The level of alanine aminotransferase(ALT),total bilirubin(TBIL)and aspartate aminotransferase(AST)in the serum of rats were detected.HE staining microscopy was ap-plied to detect pathological changes in liver tissue.TUNEL staining microscopy was applied to detect cell apoptosis in liver tissue.Chromatin immuno-precipitation was applied to detect HBV viral load in liver tissue.ELISA was ap-plied to detect the levels of monocyte chemotactic protein-1(MCP-1),interleukin-12(IL-12),and tumor necrosis factor-α(TNF-α)in liver tissue.Western blot was applied to detect the expression of caspase-3,Bcl-2 associated X protein(Bax),p-AMPK and SIRT1 proteins in liver tissue.Results Compared with hepatitis B group,the liver damage of rats in the Gal-L group,Gal-H group and lamivudine group was alleviated;The level of serum AST,TBIL,and ALT,apoptosis rate,HBV viral load and the level of MCP-1,IL-12,TNF-α as well as the expression of caspase-3 and Bax proteins in liver tissue were all reduced.The expression of p-AMPK and SIRT1 proteins in liv-er tissue increased(P＜0.05).Compound C baffled inhibitory effects of high-dose Gal on inflammation,cell apopto-sis,and HBV viral load in liver tissue of hepatitis B rats.Conclusions The mechanism of Gal in inhibiting inflam-mation,cell apoptosis and HBV virus replication in hepatitis B rats is potentially attributed to up-regulation of the AMPK/SIRT1 pathway.

Pediatric calyceal diverticulum (CD) is a relatively rare entity. Fewer cases were reported in China treated by retroperitoneal laparoscoopic surgery in children. In this paper, 2 cases of children with CD admitted to our hospital were reported. CT urography showed cystic low-density mass without obvious enhancement, and delayed contrast agent was found to enter the lesion. Both cases underwent cystoscopy + retroperitoneoscopy + diverticular neck suture. They were followed up for 15 months and 9 months after the surgery, respectively, with favorable outcomes and no recurrence of CD.

Objective:Based on multi-parametric prostate magnetic resonance imaging (mpMRI) and related clinical indicators, a nomogram model for patients with PI-RADS ≥3 and PSA 4-20ng/ml was developed and validated, and the predictive value of the model in diagnosing clinically significant prostate cancer was evaluated.Methods:The clinical and pathological data of 865 patients who underwent ultrasound-guided transperineal prostate biopsy for the first time at the Department of Urology, Second Hospital of Tianjin Medical University from January 2020 to August 2023, with PI-RADS scores ≥3 and PSA levels between 4-20 ng/ml were retrospectively analyzed. These 865 patients were included in Cohort A, and from them, 437 patients with PHI were selected in Cohort B. In Cohort A, the median age was 68(64, 73); the median f/tPSA was 14.36 (10.63, 19.74); the median PSAD was 0.17(0.11, 0.25); 375 cases (43.35%) with PV≤50 ml and 490 cases (56.65%) with PV>50 ml; PSA fluctuation <-50% 84 cases (9.71%), -50%--20% in 206 cases (23.82%), and >-20% in 575 cases (66.47%); PI-RADS v2.1 3 scores 546 cases (63.12%), 4 in 230 cases (23.59%), and 5 in 89 cases (10.29%); localization of suspicious lesions on mpMRI in the peripheral zone in 619 cases (71.56%), transitional zone in 181 cases (20.92%), others in 42 cases (4.86%), and both peripheral and transitional zones in 23 cases (2.66%). In Cohort B, the median PSAD was 0.17 (0.12, 0.25); the median D-dimer was 310.00 (230.00, 411.48); the median PHI was 49.75 (35.90, 73.27); with 198 cases (45.31%) with PV≤50 ml and 239 cases (54.69%) with PV>50 ml; PSA fluctuation<-50% was in 40 cases (9.15%), -50%--20% in 107 cases (24.49%), and>-20% in 290 cases (66.39%); PI-RADS v2.1 scores 3 was in 289 cases (66.13%), 4 in 103 cases (23.57%), and 5 in 45 cases (10.30%).Patients in cohorts A and B were randomly assigned to the training set and validation set using R language with " 123" as the random number seed, at a ratio of 7∶3.There was no statistically significant difference between the clinical data of the training and validation sets for both groups ( P>0.05).Univariate and multivariate logistic regression analyses were used to identify independent risk factors for CsPCa, and a nomogram model was constructed using R. The diagnostic performance of the prediction model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis(DCA).External validation of the model was conducted in the validation set. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and missed diagnosis rate analyses were performed on nomogram models A and B, as well as PSAD and PHI, under different thresholds. Results:Cohort A training set has 608 cases, and the validation set has 257 cases.The results of multivariate backward regression analysis in the training set show that age( OR=1.06, P=0.001), f/tPSA( OR=0.96, P=0.008), prostate volume (PV)>50ml( OR=0.36, P<0.01), prostate-specific antigen density(PSAD)( OR=145.19, P<0.01), PSA fluctuation(-50%--20%: OR=1.97, P=0.234; >-20%: OR=6.81, P<0.01), PI-RADS v2.1 score(4: OR=10.65, P<0.01; 5: OR=21.20, P<0.01), and localization of suspicious lesions on mpMRI(TZ: OR=0.57, P=0.074; Others: OR=0.26, P=0.022) were all risk factors for CsPCa. Nomogram A was developed based on these risk factors and had an area under the ROC curve (AUC) of 0.905 (95% CI 0.881-0.928) for the training set and 0.893 (95% CI 0.854-0.931) for the validation set. Cohort B training set developed based on age( OR=1.05, P=0.053), PV>50ml( OR=0.18, P<0.01), PSAD( OR=54.14, P=0.021), PSA fluctuation(-50%--20%: OR=4.78, P=0.100; >-20%: OR=20.37, P=0.001), PHI( OR=1.02, P=0.002), D-Dimer( OR=1.00, P=0.031), and PI-RADS scores(4: OR=11.35, P<0.01; 5: OR=57.61, P<0.01) as risk factors for CsPCa. Nomogram B had an AUC of 0.933(95% CI 0.906-0.959) for the training set and 0.908 (95% CI 0.859-0.958) for the validation set.The two nomogram models mentioned above both have excellent discrimination, and the calibration curves also indicated that the calibration of the two models were good.Moreover, both nomogram A and nomogram B demonstrate good clinical net benefits in the DCA curves of the training and validation sets, especially when applying nomogram B to predict CsPCa, with an accuracy rate of up to 85.82%. Conclusions:The two nomogram models developed in study, based on mpMRI and related clinical indicators, both have excellent predictive value for the diagnosis of clinically significant prostate cancer prior to prostate biopsy in patients with PI-RADS≥3 and PSA 4-20ng/ml.

Objective To explore the changes and significance of hepatic cytokines during ischemia and reperfusion in rats undergoing donation after circulatory death (DCD) liver transplantation in different functional warm ischemic durations.Methods Maastricht Ⅲ DCD liver transplantation was simulated and a rat model of functional warm ischemia established.DCD liver transplantation was established by cutting diaphragm.There were four groups of functional warm ischemia 0/15/30 min and living donor liver transplantation control.Liver tissues and serum samples were obtained after donor liver acquisition and 6-hour reperfusion respectively.Luminex liquid chip was employed for detecting the concentrations of 23 cytokines in liver tissue,superoxide dismutase or malondialdehyde (SOD/MDA) expression in liver tissue and alanine transaminase or aspartate aminotransferase (ALT/AST) expression in sera.And hematoxylin-eosin (HE) staining was utilized for detecting liver tissue damage.Results The levels of cytokines in liver tissues during ischemia and reperfusion were significantly different in different functional warm ischemic durations.SOD/MDA in liver tissue,AST/ALT in sera and pathological examinations also showed that,with the prolongation of functional warm ischemic duration,the degree of liver tissue injury gradually aggravated.Conclusions Functional warm ischemic duration has a significant effect on cytokines during ischemia and reperfusion in rat DCD liver transplantation.This phenomenon can help us further elucidate the mechanism of ischemia-reperfusion injury and provide new ideas for preventing ischemia-reperfusion injury during DCD liver transplantation.