OBJECTIVE To explore the effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis （PM）. METHODS A total of 131 PM patients treated with meropenem at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2022 to June 2025 were prospectively included. Relevant data were collected and divided into a cured group （91 cases） and a non-cured group （40 cases） based on the efficacy. High-performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of meropenem and its open-loop metabolites. Risk factors that affect efficacy were screened， and their predictive power and correlation were evaluated by univariate analysis， and multivariate Logistic regression analysis， receiver operating characteristic （ROC） curves， and correlation analysis. RESULTS Univariate analysis showed that serum creatinine， creatinine clearance rate， minimum inhibitory concentration of meropenem ≥16 μg/mL， cerebrospinal fluid red blood cell count， cerebrospinal fluid white blood cell count， cerebrospinal fluid glucose content， blood trough concentration， blood open-loop metabolite concentration/trough concentration ratio， and intrathecal injection were all correlated with efficacy （P＜0.05）. The results of multiple Logistic regression analysis showed that serum creatinine blood open-loop metabolite concentration/trough concentration ratio， intrathecal injection， and cerebrospinal fluid glucose content were influencing factors for suboptimal anti-infective ltt efficacy （P＜0.05）. ROC curve analysis showed that when the blood open-loop metabolite concentration/trough concentration ratio was greater than 2.854 （AUC＝0.647）， serum creatinine was less than 59.5 μmol/L （AUC＝0.647）， and cerebrospinal fluid glucose content was less than 3.37 mmol/L （AUC＝0.709）， the risk of treatment failure significantly increased （P＜0.05）. Correlation analysis showed that the blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites （R 2＝0.134 5， P＜0.000 1）. CONCLUSIONS Insufficient exposure level and rapid degradation of meropenem are key mechanisms affecting the anti-infective efficacy of PM. Elevated blood open-loop metabolite concentration/ trough concentration ratio， low serum creatinine level， lack of intrathecal injection， and low cerebrospinal fluid glucose content are independent risk factors for poor efficacy.

Objective To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate(NaB)in a mouse model of Parkinson's disease(PD)via the gut-brain axis.Methods Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group,PD model group,and NaB treatment group.In the latter two groups,PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once daily for 5 consecutive days,and normal saline was injected in the control group.After modeling,the mice received daily gavage of NaB(300 mg/kg)or an equal volume of saline for 14 days.Behavioral tests were carried out to assess the changes in motor function of the mice,and Western blotting was performed to detect the expressions of tyrosine hydroxylase(TH)and α-synuclein(α-syn)in the striatum and nuclear factor-κB(NF-κB),tumor necrosis factor(TNF-α),interleukin 6(IL-6),and the tight junction proteins ZO-1,Occludin,and Claudinin the colon.HE staining was used to observe inflammatory cell infiltration in the colon of the mice.RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues,and their expressions were verified using qRT-PCR and Western blotting.Results The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH,Occludin,and Claudin and downregulated expressions of α-syn,NF-κB,TNF-α,and IL-6(all P<0.05).HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice.RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice(P<0.05).Conclusion NaB can improve motor dysfunction,reduce dopaminergic neuron loss in the striatum,and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.

Objective To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate(NaB)in a mouse model of Parkinson's disease(PD)via the gut-brain axis.Methods Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group,PD model group,and NaB treatment group.In the latter two groups,PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once daily for 5 consecutive days,and normal saline was injected in the control group.After modeling,the mice received daily gavage of NaB(300 mg/kg)or an equal volume of saline for 14 days.Behavioral tests were carried out to assess the changes in motor function of the mice,and Western blotting was performed to detect the expressions of tyrosine hydroxylase(TH)and α-synuclein(α-syn)in the striatum and nuclear factor-κB(NF-κB),tumor necrosis factor(TNF-α),interleukin 6(IL-6),and the tight junction proteins ZO-1,Occludin,and Claudinin the colon.HE staining was used to observe inflammatory cell infiltration in the colon of the mice.RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues,and their expressions were verified using qRT-PCR and Western blotting.Results The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH,Occludin,and Claudin and downregulated expressions of α-syn,NF-κB,TNF-α,and IL-6(all P<0.05).HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice.RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice(P<0.05).Conclusion NaB can improve motor dysfunction,reduce dopaminergic neuron loss in the striatum,and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.

Purpose/Significance To review digital health literacy assessment tools for the elderly,and to provide a theoretical basis for assessment,intervention and optimization.Method/Process A scoping review method is used to systematically review and evaluate digital health literacy assessment tools for the elderly.Result/Conclusion The 10 included assessment tools are generally applicable to the elderly population,but research targeting specific groups remains insufficient.These assessment tools should be further integrated in the future to promote the understanding and research of digital health literacy measurement methods.

Objective To construct recombinant human butyrylcholinesterase(rhBChE)knock-in goat fetal fibroblast cell lines(GFFs)by using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)-mediated homology-directed repair mechanism for subsequent production of goat expressing rhBChE.Methods The efficient sgRNA sites targeting goat[3-casein(CSN2)gene were designed and screened,and the targeting efficiency of the sgRNA in goat mammary epithelial cells(GMECs)was confirmed by electro-transfection,flow sorting,and sequencing of PCR products.The red fluorescent reporter gene homology repair vector(P2A-mCherry)targeting the sgRNA was constructed,and then the integration and expression efficiency was detected by flow cytometry.The rhBChE homology repair vector(P2A-rhBChE)targeting the sgRNA of CSN2 gene was constructed in GFFs,the rhBChE positive cell clones were obtained via electro-transfection and flow sorting,and the rhBChE knock-in cell lines was identified by sequencing of PCR products.Results The sgRNA4 was identified as an efficient target of goat CSN2 gene,which could be also used for targeted integration of other genes.Three rhBChE knock-in cell lines were successfully constructed.Conclusion The rhBChE knock-in GFFs targeting goat CSN2 gene lays the foundation for the production of mammary bioreactors expressing rhBChE.

ObjectiveTo investigate the inhibitory effect of Mahuang Xixin Fuzitang on the migration of dendritic cells （DCs） in mice and its underlying mechanism. MethodMouse bone marrow-derived DCs were isolated and cultured. The morphological changes of the cells at different stages were observed under a microscope， and the CD11c⁺ proportion was detected by flow cytometry to identify DC purity. Cells were treated with Mahuang Xixin Fuzitang （1， 2， 5， 10， 20， 40， 50， 100 g·L^-1） for 24 hours， and the effect of Mahuang Xixin Fuzitang on cell proliferation was assessed using the cell counting kit-8 （CCK-8） assay to determine the appropriate concentrations for treatment. After modeling by lipopolysaccharide （LPS） induction， DCs were divided into a blank group， a model group， and Mahuang Xixin Fuzitang groups （2， 4， 8 g·L^-1）. The expression of surface molecules CD80， CD86， and major histocompatibility complex-Ⅱ （MHC-Ⅱ） were detected by flow cytometry. Transwell chamber assay was used to observe cell migration. The levels of chemokine C-C-primitive receptor 7 （CCR7） and chemokine C-X-C-primitive receptor 4 （CXCR4） on the cell surface were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of filamentous actin （F-actin） in the cell microfilament cytoskeleton was detected by immunofluorescence （IF） staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA expression levels of Ras homolog family member A （RhoA） and Rho-associated coiled-coil containing protein kinase 1 （ROCK1）. Western blot analysis was performed to detect the protein expression of RhoA and ROCK1. ResultCompared with the blank group， the model group exhibited significantly higher expression levels of CD80， CD86， and MHC-Ⅱ （P<0.01）， a significantly increased number of cells migrating to the lower chamber （P<0.01）， and significantly elevated levels of CCR7 and CXCR4 （P<0.05， P<0.01）. Additionally， F-actin expression was significantly increased （P<0.01）， and both RhoA and ROCK1 mRNA and protein expression levels were significantly higher （P<0.05， P<0.01）. Compared with the model group， treatment with Mahuang Xixin Fuzitang （2， 4， 8 g·L^-1） for 24 hours resulted in significantly lower expression levels of CD80， CD86， and MHC-Ⅱ （P<0.01）， a significantly reduced number of cells migrating to the lower chamber （P<0.05）， and significantly decreased levels of CCR7 and CXCR4 （P<0.05， P<0.01）. Furthermore， F-actin expression was significantly reduced （P<0.01）， and both RhoA and ROCK1 mRNA and protein expression levels were significantly decreased （P<0.05， P<0.01）. ConclusionMahuang Xixin Fuzitang can inhibit the migration of DCs in mice， and its mechanism of action may be related to reducing the activity of the Rho/ROCK signaling pathway， thereby affecting changes in the cell cytoskeleton.

Background/Aims: Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). Methods: Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. Results: The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. Conclusions The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

Objective:To investigate the therapeutic efficacy of venetoclax combined with avapritinib in treatment of refractory/relapsed acute myeloid leukemia (AML) with KIT gene mutation.Methods:The clinical data of 2 AML patients with KIT gene mutation who received venetoclax combined with avapritinib admitted to Canglang Hospital of Suzhou in October 2022 and November 2022 were retrospectively analyzed, and the relevant literature was reviewed.Results:Both patients with high-risk relapsed/refractory AML and KIT gene mutation were females; the one was 53 years and the other was 17 years. Case 1 was diagnosed with AML-M 2, and genetic testing revealed positive mutations in ASXL1, KIT, and RUNX1. The patient relapsed after transplantation and then was treated with venetoclax combined with avapritinib achieving morphologic leukemia-free status (MLFS). Case 2 was diagnosed with AML, and RUNX1-RUNX1T1 (AML1-ETO) fusion gene and KIT and DX15 gene mutations were detected. The patient was treated with venetoclax combined with avapritinib regimen after relapse, and the treatment regimen significantly reduced the tumor load. Complete remission was achieved after bridging to allogeneic hematopoietic stem cell transplantation. Conclusions:AML with KIT gene mutation is heterogeneous and some patients are difficult to treat with very poor prognosis. Bridging (secondary) hematopoietic stem cell transplantation can be the better treatment choice for relapsed patients achieving MLFS or complete remission after venetoclax combined with avapritinib treatment regimen.

Objective:Our study aims to determine histological regression and clinical improvement after long-term antiviral therapy in hepatitis B virus-related cirrhosis patients.Methods:Treatment-na?ve chronic hepatitis B patients with histologically or clinically diagnosed liver cirrhosis were enrolled. Liver biopsies were performed after 5 years entecavir-based antiviral treatment. Patients were followed up every 6 months. Cirrhosis regression was evaluated based on Metavir system and P-I-R score. Clinical improvement was evaluated before and after the long-term treatment. Kruskal Wallis test and Wilcoxon signed-rank test were used for continuous variables, Fisher's exact test was used for categorical variables and multivariate analysis was performed using logistic regression analysis.Results:Totals of 73 patients with HBV-related liver cirrhosis were enrolled. Among them, 30 (41.1%) patients were biopsy proved liver cirrhosis and the remaining 43 (58.9%) cirrhotic patients were diagnosed by clinical features. Based on Metavir system and P-I-R score, 72.6% (53/73) patients attained histological regression. Furthermore, 30.1% (22/73) were defined as significant regression (Metavir decrease ≥2 stage), 42.5% (31/73) were mild regression (Metavir decrease 1 stage or predominantly regressive by P-I-R system if still cirrhosis after treatment) and 27.4% (20/73) were the non-regression. Compared to levels of clinical characteristics at baseline, HBV DNA, ALT, AST, liver stiffness(decreased from 12.7 to 6.4 kPa in significant regression, from 18.1 to 7.3 kPa in mild regression and from 21.4 to 11.2 kPa in non-regression)and Ishak-HAI score significantly decreased after 5 years of anti-HBV treatment, while serum levels of platelets and albumin improved remarkably ( P<0.05). In multivariate analysis, only the pre-treatment liver stiffness level was associated with significant regression ( OR=0.887, 95% CI: 0.802-0.981, P=0.020). Conclusions:After long-term antiviral therapy, patients with HBV-related cirrhosis are easily to attain improvements in clinical parameters, while a certain percentage of these patients still cannot achieve histological reversal.

Objective:To clarify the effect and related factors of antiviral therapy on the change of esophageal varices in patients with hepatitis B virus-related cirrhosis.Methods:Fifty-two cases with hepatitis B virus-related cirrhosis who underwent endoscopy before and after antiviral therapy were selected from prospective cohorts. Patients were divided into three groups: no, mild, and moderate-severe based on the degree of esophageal varices. The changes in the severity of esophageal varices in each group were compared after antiviral therapy. Clinical characteristics (platelet, liver and kidney function, liver stiffness, and virological response) of patients with different regressions were analyzed. Measurement data were analyzed by independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test, and Chi-Square test was used for count data.Results:All patients received entecavir-based antiviral therapy. The median treatment time was 3.1 (2.5-4.4) years. The proportion of patients without esophageal varices increased from 30.8% to 51.9%, the proportion of mild esophageal varices decreased from 40.4% to 30.8%, and the proportion of patients with moderate-to-severe esophageal varices decreased from 28.8% to 17.3% ( χ2=14.067, P=0.001). A total of 40.4% of patients had esophageal varices regression, and 13.5% had esophageal varices progression. The progression rate was significantly higher in patients with moderate-severe esophageal varices than patients with mild and no esophageal varices ( χ2=28.126, P<0.001), and 60.0% of patients with moderate-severe esophageal varices still remained in moderate-severe state after antiviral treatment. Baseline platelet count and 5-year mean change rates were significantly lower in patients with progressive moderate-to-severe esophageal varices than in those without progression (+3.3% vs. +34.1%, Z=7.00, P=0.027). Conclusion:After effective antiviral treatment, 40.4% of patients with hepatitis B virus-related cirrhosis combined with esophageal varices has obtained esophageal varices regression, but those with moderate to severe esophageal varices still have a considerable risk of progression while receiving mono antiviral treatment only. Thrombocytopenia and without significant improving are the clinical signs of progression risk after receiving antiviral treatment.