OBJECTIVE To evaluate the efficacy and safety of high-dose ilaprazole combined with amoxicillin for newly diagnosed elderly patients with Helicobacter pylori （Hp） infection， and analyze independent risk factors for failure of Hp infection eradication treatment. METHODS Totally 200 cases of newly diagnosed elderly patients with Hp infection in Xinxiang Central Hospital from August 1， 2021 to December 1， 2024 were selected and randomly divided into control group and study group， with 100 cases in each group. The control group was treated with classic quadruple therapy regimen （Amoxicillin capsules+ Clarithromycin tablets+Bismuth potassium citrate tablets+Ilaprazole enteric-coated tablets）. The study group was treated with high- dose Ilaprazole enteric-coated tablets+Amoxicillin capsules. All patients were administered medication for 2 weeks. Hp eradication rates in the two groups were compared using intention-to-treat （ITT） and per-protocol （PP） analyses. The incidence of adverse reactions in both groups was also recorded. The multiple-factor Logistic regression analysis was used to identify independent risk factors for failure of Hp infection eradication treatment. RESULTS In ITT and PP analyses， there was no significant difference of Hp eradication rates between the two groups （P＞0.05）. There was no significant difference in incidence of mild to moderate adverse reactions between the two groups （P＞0.05）. BMI ≤18.5 kg/m2， BMI ＞23.9 kg/m2， rural residence， concomitant diabetes and concomitant heart disease were identified as independent risk factors influencing the failure of Hp infection eradication treatment （P＜0.05）. CONCLUSIONS The efficacy and safety of high-dose ilaprazole combined with amoxicillin are comparable to classic quadruple therapy regimen in treating newly diagnosed elderly patients with Hp infection. Independent risk factors influencing the failure of Hp infection eradication treatment include BMI ≤18.5 kg/m2， BMI ＞23.9 kg/m2， rural residence， concomitant diabetes and concomitant heart disease.

A-kinase anchor protein 12 (AKAP12) is a scaffold protein that improves the specificity and efficiency of spatio-temporal signals by assembling intracellular signal proteins into specific complexes. In recent years, the role of AKAP12 in chronic liver diseases has attracted more and more attention. This article introduces the physiological functions of AKAP12 and reviews the role of AKAP12 in chronic liver diseases, in order to lay a foundation for the use of AKAP12 small molecule as a new therapeutic target for chronic liver diseases.

Liver fibrosis (LF) is a pathological process of hepatic stellate cell (HSC) activation and excessive deposition of extracellular matrix caused by chronic liver injury and inflammation. HSC activation is the core mechanism of LF, and inhibiting HSC activation is the key to promoting the reversal of LF. In recent years, rapid development has been achieved for the application of nanomedicine targeting HSC in the treatment of LF. This article mainly introduces nanomedicine, the mechanism of action of nanomedicine in the treatment of LF, and potential targets, and it is pointed out that nanomedicine may become a new method for the treatment of LF.

Objective:To explore the potential mechanism of Tianshui Dichang Decoction in the treatment of ulcerative colitis through network pharmacology and experimental verification.Methods:The active components and targets of Tianshui Dichang Decoction were screened by TCMSP. The related targets of ulcerative colitis were screened by OMIM, GeneCard and TTD databases, and the effective component targets of Tianshui Dichang Decoction were intersected with the potential targets of ulcerative colitis. The PPI network was constructed by STRING database to screen the core targets, and the "Chinese materia medica-disease-active components-target" network was constructed by Cytoscape 3.8.0 software. GO function and KEGG pathway enrichment analysis were carried out using Metascape database. 48 mice were divided into control group, model group, mesalazine group (0.3 g/kg) and Tianshui Dichang Decoction low-, medium-, and high-dosage groups (7.5,15 and 30 g/kg) according to random number table method, with 8 mice in each group. Except the control group, the ulcerative colitis model was established in other groups. After 7 days of intervention with corresponding drugs, the disease activity index (DAI) was scored, the pathological changes of colon were observed by HE staining, and the expressions of IL-6, STAT3mRNA and protein in colon tissue were detected by PCR and Western blot methods.Results:Totally 127 active components in Tianshui Dichang Decoction and 560 targets of ulcerative colitis were obtained. 89 intersecting targets of Tianshui Dichang Decoction and ulcerative colitis were obtained, and the core targets included IL6, TNF, IL1B, AKT1, TP53, VEGFA, JUN, PTGS2, CXCL8, CCL2, STAT3, MMP9 and so on. Oxidative stress response, lipopolysaccharide metabolism, bacterial response, signal transduction and other biological processes were mainly involved, mainly through the cancer pathway, IL17, TNF, MAPK and other signal pathways to play a role in the treatment of ulcerative colitis. The results of experimental verification showed that the DAI score, the expressions of IL-6 and STAT3 protein in colon tissue of Tianshui Dichang Decoction medium- and high-dosage groups.decreased ( P<0.05). The levels of IL-6 and STAT3 mRNA in colon tissue decreased in the Tianshui Dichang Decoction low-, medium- and high-dosage groups.groups ( P<0.05). Conclusion:Tianshui Dichang Decoction has a certain therapeutic effect on UC through component-multitarget-signal pathway, and its mechanism is related to regulating IL-6/STAT3 signal pathway and inhibiting intestinal mucosal inflammation.

Objective:In order to investigate the status quo of central line-associated bloodstream infections (CLABSI) prevention among ICU nurses and analyze its influencing factors.Methods:A total of 245 ICU nurses from Harbin Medical University Affiliated First, Second, and Cancer Hospitals from December 2021 to January 2022 were selected by convenience sampling method. To evaluate the status quo of CLABSI prevention among ICU nurses by using Central Line-associated Bloodstream Infections Prevention Knowledge and Practice Scale, a cross-sectional survey was conducted among ICU nurses by using General Data Questionnaire and ICU Nurse Alarm Fatigue Scale, and the influencing factors of CLABSI prevention were evaluated.Results:The knowledge, attitude, behavior dimensions and alarm fatigue scores of ICU nurses on CLABSI prevention were (13.74 ± 2.87), (50.92 ± 4.10), (85.44 ± 8.52), and (31.35 ± 5.06), respectively. The score of ICU nurses′ alarm fatigue was negatively correlated with the score of knowledge, attitude and behavior dimensions in CLABSI prevention knowledge and practice ( r=-0.360, -0.378, -0.408, all P<0.01). The results of multiple regression analysis showed that alarm fatigue, CLABSI training and first education degree were the main influencing factors of ICU nurses′ knowledge and attitude to CLABSI prevention ( P<0.01). Alarm fatigue, CLABSI training and the highest education degree were the main influencing factors of ICU nurses ′ CLABSI prevention ( P<0.01). Conclusions:ICU nurses′ knowledge and practice of CLABSI prevention were at the middle level. Alarm fatigue, participation in CLABSI training, and educational background (first and highest) are the influencing factors for the prevention of CLABSI among ICU nurses in terms of knowledge, belief, and behavior. The administrators should pay more attention to CLABSI prevention, provide more opportunities and ways to train and examine ICU nurses, strengthen the weak links of CLABSI prevention, and make ICU nurses master the Knowledge System of CLABSI prevention as soon as possible.

Objective:To explore the efficacy and safety of sivelestat, a neutrophil elastase (NE) inhibitor, in the treatment of acute lung injury (ALI) in the intensive care unit (ICU).Methods:A retrospective analysis was performed on 171 patients with ALI in the ICU of the First Affiliated Hospital of Zhengzhou University from June 2020 to June 2021, including 77 patients in the sivelestat group and 94 patients in the conventional treatment group. Acute physiology and chronic health evaluation (APACHE) Ⅱ score, Murray lung injury score, oxygenation index (PaO 2/FiO 2 ratio), inflammatory cytokines (IL-6, IL-10, TNF-α), ventilator-free days (VFD), the length of ICU stay, and the 28-day mortality were collected to assess the efficacy of sivelestat. At the same time, adverse reactions and laboratory test results within 30 days after the use of sivelestat were recorded to assess the safety. Results:Compared with conventional treatment, oxygenation index, Murray lung injury scores, IL-6, IL-10, and TNF-α were significantly improved after 7 days of sivelestat treatment. Compared with the conventional treatment group, the VFD was significantly longer ( P = 0.0119) and the length of ICU stay was significantly shorter ( P = 0.0269) in the sivelestat group. The mortality was 14.29% in the sivelestat group and 22.34% in the conventional treatment group and, with no statistically significant. In the meantime, sivelestat did not increase adverse reactions within 30 days after treatment. Conclusions:Sivelestat treatment is safe and more effective than conventional treatment for ALI patients in the ICU.

Objective To explore the molecular genetic characteristics of primary and recurrent glioblastomas (GBMs) from the same patient in vivo, primary glioma stem cells cultured in vitro, and patient-derived xenograft (PDX). Methods (1) The primary and recurrent GBM specimens from one patient during surgical resection were collected; and the expressions of glial fibrillary acidic protein (GFAP), nestin and Ki-67 were detected by immunohistochemical staining; the methylation of O6-methylguanine DNA methyltransferase (MGMT) gene, mutation of isocitrate dehydrogenase (IDH) gene and amplification of epidermal growth factor receptor (EGFR) gene were analyzed. (2) The primary and recurrent GBM stem cells were cultured in vitro and named as SU5-1 and SU5-2 cells, respectively; the expressions of nestin and CD133 were detected by immunohistochemical staining; GFAP expression was detected by immunohistochemical staining after induced differentiation, and the growth curve was detected by CCK-8 assay; Transwell invasion assay was used to detect the invasion ability; cell resistance to temozolomide (TMZ), carboplatin (CBP), cisplatin (DDP) and adriamycin (ADM) was detected by CCK-8 assay; the protein expression of programmed death receptor-ligand 1 (PD-L1) was detected by Western blotting. The rate of PD-L1 positive cells was detected by flow cytometry; genetic testing analysis was as above. (3) The primary and recurrent in situ PDX models in nude mice were established, and the expressions of nestin, GFAP and Ki-67 were detected by immunohistochemical staining. Results (1) As compared with the primary GBM, the recurrent GBM had significantly higher percentages of Ki-67 and nestin positive cells, while statistically lower percentage of GFAP positive cells (P<0.05); genetic analysis showed that there was no mutation in IDH gene in the primary GBM tissues and recurrent GBM tissues; the MGMT gene in the primary GBM tissues was methylated and EGFR gene was not amplified, while the MGMT gene in recurrent GBM tissues was demethylated and EGFR gene amplification was positive. (2) Both SU5-1 and SU5-2 cells expressed nestin and CD133, and GFAP was expressed after induced differentiation; the growth curve showed that the proliferation of SU5-2 cells started earlier than that of SU5-1 cells, the two were equal on the 3rd, 4th, and 5th d, and the proliferation of SU5-1 cells was faster than that of SU5-2 cells from the 6th d; the invasion ability of SU5-2 cells was statistically stronger than that of SU5-1 cells (P<0.05); the inhibition rates of SU5-2 cells treated with 5, 10, and 15 mmol/L CBP, 0.3125, 1.25, and 5 mmol/L DDP, 0.5 and 2 mmol/L ADM, and 125 and 500 mmol/L TMZ were significantly lower than those of SU5-1 cells treated with the same concentrations and same drugs (P<0.05); the protein expression of PD-L1 in SU5-2 cells was higher than that in SU5-1 cells; the positive rate of PD-L1 in SU5-2 cells was statistically higher than that in SU5-1 cells (P<0.05); the results of genetic analysis were consistent with those of the primary and recurrent GBM samples. (3) As compared with those in the primary PDX model, the nestin and Ki-67 expressions were significantly higher and GFAP expression was significantly lower in the recurrent PDX model (P<0.05); the results of genetic analysis were consistent with those of the primary and recurrent GBM samples. Conclusions Genetic differences are detected between primary and recurrent GBMs; recurrent GBM has stronger invasive capacity and multi-drug resistance. The primary stem cells derived from surgical specimens and corresponding PDX models could replicate the molecular genetic characteristics of original tumors, which provide a reliable experimental platform for both tumor translation researches and screening of molecular therapeutic targets.

Objective To explore the protective effect and mechanism of glycyrrhizic acid on hippocampal neuron injury in epileptic rat models. Methods The epileptic rat models were established by lithium and pilocarpine kindling. The successful models were randomly divided into epilepsy group and glycyrrhizic acid group. In addition, the rats without any treatment were used as the normal control group, with 12 rats in each group. Hippocampal neuron injury and apoptosis were detected by Nissl and TUNEL staining. Mitochondrial membrane potential in the hippocampal neurons of rats was detected by JC-1 method. The activity of aspartic acid protein hydrolase 3 (caspase 3) and caspase 9 was detected by colorimetric assay. The expressions of cleaved-caspase 3, 9, B lymphocyte tumor-2 (Bcl-2), Bcl-2 related X protein (Bax), cytochrome C (CytC) and apoptotic protease-activating factor (Apaf-1) protein in the hippocampal tissues of rats were detected by western blot assay. Results Compared with the normal group, the number of neurons was reduced (P＜0. 01), the number of TUNEL-positive cells was increased (P＜ 0. 01), mitochondrial membrane potential was decreased (P＜ 0. 01), caspase 3 and 9 activity was increased (P＜ 0. 01), the expressions of Bcl-2 and mitochondrial CytC were down-regulated (P＜ 0. 01), the expressions of Bax, cytoplasm CytC and Apaf-1 were up-regulated (P＜ 0. 01) in the epilepsy group. Compared with the epilepsy group, the number of neurons was increased (P ＜ 0. 01), the number of TUNEL-positive cells was reduced (P＜ 0. 01), mitochondrial membrane potential was increased (P＜ 0. 01), caspase 3 and 9 activity was decreased (P ＜ 0. 01 ), the expressions of Bcl-2 and mitochondrial CytC were up-regulated (P ＜0. 01), the expressions of Bax, cytoplasm CytC and Apaf-1 were down-regulated (P ＜ 0. 01) in the glycyrrhizic acid group. Conclusions These results suggest that glycyrrhizic acid can inhibit the hippocampal neuron injury in epileptic rats by blocking the mitochondrial pathway.

Objective To develop the analytical method of dexmedetomidine in human plasma by solid phase extraction with gas chromatography-mass spectrometry(SPE-GC/ MS). Methods The human plasma were extracted with a solid phase extraction(SPE) and determined by GC/MS. Results The lowest detectable limit was 0.05μg/mL, the standard curve was linear over the range of 0.2μg/mL~5μg/mL. The absolute recovery was 86.1%~91.5%. The intra-and interday precision was within 7.86% at three concentrations. Conclusion Since the procedure proved to be simple, quick and sensitive, it could be used for the determination of dexmedetomidine in human plasma.

Objective To develop the analytical method to determine the content of dexamethasone in human plasma by solid phase extraction with ultra performance liquid chromatography-tandem mass spectrometer. Methods The human plasma was extracted with a solid phase extraction(SPE) and determined by UPLC-MS/MS. LC-MS/MS was performed in ESI source with MRM mode for quantification. Results The lowest detectable limit was 0.05ng/mL, the linear range was 1~100ng/mL. The absolute recovery was more than 78.1%. The intra- and inter day precision was within 15% at three concentrations. Conclusion Since the procedure proved to be simple, quick and effective, it could be used for the determination of dexamethasone in human plasma.