BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

Reactive oxygen species (ROS) are major contributors to radiation therapy-induced side effects in cancer patients. A fusion antioxidant enzyme comprising glutathione S-transferase (GST), superoxide dismutase 1 (SOD1), and a transmembrane peptide has been shown to effectively mitigate ROS-induced damage. To enhance its targeting capability, the fusion protein was further modified by incorporating a matrix metalloproteinase-2/9 substrate peptide (X) and the transmembrane peptide R9, yielding the antioxidant enzyme GST-SOD1-X-R9 (GS1XR). This modification reduced its transmembrane ability in tumor cells, thereby selectively protecting normal cells from oxidative stress. However, the use of non-human GST poses potential immunogenicity risks. In this study, we employed seamless cloning technology to construct an expression vector containing the human GST gene to replace the non-human GST gene, and then expressed and purified novel fusion antioxidant enzymes GS1R and GS1XR. The protective effects of newly constructed GS1R and GS1XR against hydrogen peroxide (H₂O₂)-induced oxidative damage in L-02 cells were then evaluated using GS1 as a control. Enzymatic activity assays revealed that the specific activity of GST in GS1XR remained unchanged compared to the unmodified protein, while SOD activity was enhanced. Exposure to 200 μmol/L H₂O₂ transiently activated the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway; however, this activation diminished after 24 h, reducing cell viability to 48.4%. Both GS1R and GS1XR effectively scavenged intracellular ROS, directly counteracting oxidative stress and promoting Nrf2 nuclear translocation, thereby activating antioxidant pathways and restoring cell viability to normal levels. The two enzymes showed comparable efficacy. In contrast, GS1, lacking transmembrane capability, was restricted to scavenging extracellular ROS and provided only limited protection. In conclusion, both novel fusion antioxidant enzymes demonstrated significant potential in safeguarding normal cells from ROS-mediated oxidative damage. The findings provide a foundation for further investigation in related field.
Humans ; Oxidative Stress/drug effects* ; Hydrogen Peroxide ; Antioxidants/metabolism* ; Glutathione Transferase/metabolism* ; Recombinant Fusion Proteins/pharmacology* ; Superoxide Dismutase-1 ; Reactive Oxygen Species/metabolism* ; Superoxide Dismutase/biosynthesis*

ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg^-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg^-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg^-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.

Objective:To evaluate the effect of heavy smoking on the dose-effect relationship of ciprofol for painless gastroscopy when combined with alfentanil.Methods:This was a prospective study. American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ male patients, aged 18-64 yr, with body mass index of 18-28 kg/m 2, undergoing elective painless gastroscopy from October 2023 to February 2024 in Baoding First Central Hospital, were divided into non-smoking group and heavy smoking group (smoking index>400) according to the status of smoking. Alfentanil 5 μg/kg and ciprofol were intravenously injected, and gastroscopy was performed after the patient′s eyelash reflex disappeared and the jaw was relaxed. The study was performed by the Dixon′s up-and-down method, and the initial dose of ciprofol was 0.4 mg/kg. The dose of ciprofol increased or decreased by 0.04 mg/kg each time based on the positive or negative response of the previous patient. A positive response was defined as the Modified Observer′s Assessment of Alertness/Sedation Scale score being greater than 1 point at 3 min after ciprofol injection or the occurrence of coughing, swallowing, body movement, or other responses that affected the operation during the insertion of the endoscope. The median effective dose (ED 50) and 95% confidence interval of propofol for painless gastroscopy were determined by the probit analysis. Results:Twenty-five patients were finally included in non-smoking group and 23 patients in heavy smoking group. The ED 50 (95% confidence interval) of ciprofol when combined with alfentanil was 0.205 (0.159, 0.244) mg/kg in non-smoking group and 0.252 (0.184, 0.295) mg/kg in heavy smoking group. The ED 50 was significantly higher in heavy smoking group than in non-smoking group ( u=390, P=0.009). Conclusions:Heavy smoking can weaken the sedative potency of propofol for sedation when used for painless gastroscopy when combined with alfentanil.

Objective:To evaluate the effect of age on the sedative potency of remimazolam.Methods:This was a prospective study. Patients of either sex, aged 40-80 yr, with body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for elective surgery with general anesthesia, were divided into middle age group (40-64 yr) and elderly group (65-80 yr) based on the age of the patients. The test was performed by the Dixon′s up-and-down method. The initial dose of remimazolam was 0.3 mg/kg. The Modified Observer′s Assessment of Alertness/Sedation Scale score ≤1 and bispectral index value≤60 within 3 min after administration were considered as an effective sedation. The dose of remimazolam was increased/decreased by 0.03 mg/kg based on the sedative efficacy in the previous patient. The 50% effective dose (ED 50) and 95% confidence interval ( CI) of remimazolam were calculated by the probit method. The time to the loss of consciousness was recorded. Results:The ED 50 (95% CI) of remimazolam was 0.345 (0.306-0.384) mg/kg in middle age group, while the ED 50 (95% CI) of remimazolam was 0.322 (0.303-0.339) mg/kg in elderly group. The ED 50 was significantly higher in middle age group than in elderly group ( u=417.00, P=0.022). The time to loss of consciousness was significantly longer in elderly group than in middle age group ( t=-2.96, P=0.008). Conclusions:For middle-aged and elderly patients aged 40-80 yr, the sedative potency of remimazolam increases with age.

AIM:To investigate of the effect of Shenqifuzheng injection(SFI)combined with PD-L1 antibody on tumor immune microenvironment and its efficacy.METHODS:A subcutaneous transplanta-tion tumor model for B16F10-LUC melanoma was created.The expression of Ki67,CD31,CD8,CD16,CD163,FOXP3,LY6C,LY6G with labeling antibodies was used to detect CD8+T cells,Treg cells,NK cells,MDSCs cells,centrocytes,and granulocytes in the tumor tissues via immunohistochemistry.Flow cy-tometry was used to measure the ratios of CD11c+,IA/IE+,and CD80+cells in splenic tissue,as well as the ratios of CD8+T,CD4+T,and Treg cells in tumor tissue.Additionally,granulocyte count and NK cell expression were analyzed.RESULTS:The immuno-histochemistry results indicate that the drug admin-istration group effectively suppressed tumor angio-genesis and cell proliferation,while decreasing the expression level of immunosuppressive cytokines CD4+T cells,Treg cells,MDSCs and centroblasts.Ad-ditionally,CD8 and NK cell infiltration was promot-ed compared to the control group.The results of the flow analysis demonstrated a significant in-crease in the expression level of CD8+T cells within tumor tissues,as well as inhibition of CD4+T,Treg,and DC cell infiltration within the spleen in the drug administration group.Additionally,the tumor volume analysis indicated that the drug administra-tion group effectively inhibited tumor growth.The flow results illustrate that the group administering treatment exhibited significant increases in CD8+T cell expression levels in tumor tissue and DC cells in the spleen.Furthermore,the treatment effec-tively inhibited the infiltration of CD4+T and Treg cells.The results also indicate that the treatment significantly reduced tumor growth,with the tumor inhibition rate being better with PD-L1 antibody alone than with the SFI group.Additionally,combin-ing drugs resulted in superior results compared to the PD-L1 antibody group alone.CONCLUSION:SFI combined with a PD-L1 antibody can have synergis-tic anti-tumor effects,potentially enhancing DC cell infiltration and promoting T cell activation.Immu-nohistochemistry results indicate a positive impact on the tumor immune microenvironment.

Objective:To investigate the effects of different feeding formulas on the feeding and growth and metabolism of premature infants in the early postnatal period.Methods:Eligible premature infants with the gestational age of ≤ 34 weeks hospitalized from March 2023 to March 2024 were selected as per inclusion criteria, excluding those with congenital metabolic diseases, severe congenital heart disease and developmental malformations of digestive tract. According to the feeding formulas within 2 weeks after birth, premature infants were divided into three groups, namely donor human milk (DHM) group, preterm formula (PF) group and extensively hydrolyzed formula (eHF) group. The characteristics of premature infants, perinatal condition, feeding formulas, milk intake on the 7th and 14th day, the time to the daily milk intake of 120ml/kg and 150ml/kg respectively, the time on parenteral nutrition, the length of hospitalization, feeding intolerance, cholestasis, extrauterine growth retardation and biochemical metabolic indexes at 7 days, 14 days and discharge were collected. The differences of feeding and biochemical metabolic parameters were compared across the three groups.Results:A total of 108 cases were enrolled ,of whom 39 were in DHM group, 37 in PF group and 32 in eHF group. There was no significant difference in gestational age, birth weight, head circumference and maternal complications across the three groups. The milk intake in the DHM group was (50.7±29.1) ml/(kg·d) on the 7th day, compared with (34.2±27.3) ml/(kg·d) in PF group ( P=0.031), and (103.1±36.7) ml/(kg·d) on the 14th day, compared with (73.9±39.2) ml/(kg·d) in the PF group. Compared with the PF group, the DHM group reached the daily milk intake of 120 ml/(kg·d) earlier [(18.5±10.4) days vs. (24.1±10.3) days, P=0.020], had shorter duration of parenteral nutrition [(17.9±10.9) days vs. (23.2±11.2) days, P=0.042], and lower incidence of feeding intolerance (28.2% vs. 48.6%). The length of hospitalization in DHM group was shorter than that in PF group [(33.8±15.5) days vs. (37.8±17.6) days], but there was no significant difference ( P>0.05). There was no significant difference between the DHM group and the eHF group in terms of the milk intake on the 7th and 14th day, the time to the daily milk intake of 120 ml/(kg·d), the time on parenteral nutrition, the length of hospitalization and feeding intolerance. At 1 and 2 weeks after birth, alkaline phosphatase in DHM group was higher than that in PF group and eHF group ( P<0.05), but there was no significant difference in biochemical nutritional metabolism parameters (hemoglobin, urea nitrogen, albumin, prealbumin, alkaline phosphatase and total bile acid) across the three groups at discharge( P>0.05). Conclusion:Early use of DHM in premature infants is better tolerated than PF and can help achieve complete enteral nutrition earlier and shorten the use of parenteral nutrition, while not affecting the growth and development of premature infants.

Objective To develop a pressure swing adsorption oxygen generating device that is workable at altitudes of 0 to 7000 meters.Methods The three-bed molecular sieve oxygen production process was adopted.The switching time of air circuit solenoid valve and the rotation speed of the compression pump were taken as controllable variables.The performance of the oxygen generating device was tested in a normal atmospheric environment and a low-pressure environment corresponding to altitudes of 0 to 7000 meters.The optimal values of controllable oxygen generating parameters corresponding to 10 low-pressure environments(89.9,79.7,69.7,65.0,62.0,57.7,53.8,47.6,43.0,41.0 kPa)were obtained.Results The oxygen concentration could reach 94％,oxygen flow rate was 9 L/min and oxygen outlet pressure stood at 44 kPa in a normal atmospheric environment(altitude 416 meters),compared with 94％,6.3 L/min and 30 kPa in a low-pressure environment of 41 kPa(altitude 7000 meters).Conclusion The oxygen generating device can meet the oxygen needs of two persons within the altitude range of 0 to 7000 meters.

Objective To analyze the basic case data and laboratory test index characteristics of patients with myasthenia gravis(MG),so as to evaluate the application value of common clinical laboratory indicators in the construction of a diagnostic model for MG.Methods A retrospective analysis was performed on the basic data and laboratory indicators of MG patients and gender and age-matched healthy controls diagnosed at Beijing Tiantan Hospital,Capital Medical University from April 2021 to April 2023.A diagnostic model was constructed,and the receiver operating characteristic(ROC)curve was drawn to analyze the area under the curve(AUC).Results The BMI,heart rate,systolic blood pressure,and diastolic blood pressure in the MG group were significantly higher than those in the control group,with statistical significance(P＜0.05).There were significant differences in total protein,albumin,white blood cell count,proportion of large platelets,abso-lute value of monocyte and triiodothyronine between MG group and control group(P＜0.05).Seven indexes of heart rate,diastolic blood pressure,albumin,creatine kinase,cholinesterase,triglyceride and apolipoprotein B were selected to construct the diagnostic model.The area under the curve of the combined application of multiple indexes could reach 0.995,with a sensitivity and specificity of 97.60％and 96.10％,respectively.Conclusion In this study,the laboratory test indexes that can be used for the diagnosis of MG are successfully selected,and the sensitivity and specificity of the combined application of multiple indexes are high,which can be used for the auxiliary diagnosis of MG.