ObjectiveTo understand the current status of Cronobacter sakazakii (Cronobacter spp.) infection and its molecular epidemiological characteristics among patients with diarrhea, so as to provide evidence for the prevention and control of diarrhea disease caused by infection with Cronobacter spp. in Changping District, Beijing. Methods760 stool samples were collected from the diarrhea patients in a sentinel hospital in 2019, for the detection of Cronobacter spp., Salmonella, diarrheogenic Escherichia coli (DEC), and Vibrio Parahaemolyticus. Meanwhile, drug sensitivity experiment and pulsed-field gel electrophoresis (PFGE) typing analysis were conducted on the Cronobacter spp. strains isolated. ResultsA total of 20 Cronobacter spp. strains (2.63%) were isolated, with a lower detection rate than that of Salmonella and Vibrio Parahaemolyticus (χ²=9.052, P=0.011). However, there were no statistically significant differences between the detection rates in Cronobacter spp. and DEC (χ²=1.076, P=0.300). Seasonal characterization analysis showed that Cronobacter spp. could be detected in spring (1.00%), summer (4.17%), autumn (3.00%) and winter (1.67%), and the differences were statistically significant (χ²=662.700, P<0.001). The PFGE analysis showed that 20 PFGE banding patterns were found in 20 Cronobacter spp. strains, with a similarity coefficient ranging from 56.30% to 90.09% and a diverse PFGE banding pattern. The drug sensitivity experiment results showed that 18 (90.00%) strains were resistant to cefazolin, and2 (10.00%) strains were intermediate. While, as for cefoxitin, 2 (10.00%) strains were resistant to it, and 5 (25.00%) strains were intermediate. All the 20 strains were 100.00% sensitive to the other 11 antibiotics. ConclusionIn the study, Cronobacter spp. is detected in all seasons through the year, with a high resistance rate to cefazolin, no multi-drug resistant bacteria appeared, and diverse PFGE banding patterns.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

ObjectiveAcute myocardial infarction (AMI) is a highly prevalent and deadly disease globally, with its incidence continuing to rise in recent years. Timely reperfusion therapy is crucial for improving the prognosis of AMI patients. However, myocardial reperfusion can lead to irreversible myocardial ischemia/reperfusion (MI/R) injury, which is associated with adverse cardiovascular outcomes following AMI. Studies have shown that microRNAs (miRNAs) are abnormally expressed during MI/R injury and play an important role in the fate of cardiomyocytes. Effective preventive and therapeutic strategies against MI/R injury remain lacking in clinical practice, necessitating elucidation of the molecular mechanisms underlying MI/R onset and progression. This study investigated the role of microRNA-878 (miR-878) in the regulation of mitochondria-mediated apoptosis in MI/R injury. MethodsThe H9c2 cells were flushed with a gas mixture containing 1% O₂, 5% CO₂ and 94% N₂ for 3 h. Then the cells were incubated in complete culture medium under 5% CO₂ and 95% air for 6 h to mimic in vivo hypoxia/reoxygenation (H/R) injury. Cell viability were detected by CCK-8 assay. The concentrations of lactate dehydrogenase (LDH) were then measured.The level of apoptosis was analyzed by flow cytometry. The morphology of mitochondria was analyzed by immunofluorescence and laser confocal microscopy. The levels of mitochondrial reactive oxygen species (mtROS) were detected by immunofluorescence. Dual luciferase reporter gene assay was used to study the binding site of miR-878 and Pim1. RNA immunoprecipitation (RIP) assay was used to verify the binding relationship between miR-878 and Pim1. The gene expression levels were detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blot. ResultsThe study found that compared with the control group, the expression of miR-878 in H/R-treated H9c2 cells was significantly increased ((1.00±0.25) vs (9.70±2.63), P<0.01). In H/R-induced cells, transfection of miR-878 inhibitor significantly increased cell viability ((46.67±3.00) vs (74.62±4.08), P<0.000 1), and decreased LDH release ((358.58±41.71) vs (179.09±15.59), P<0.000 1) and cell apoptosis rate ((43.41±0.72) vs (27.42±4.48), P<0.01). At the same time, downregulation of miR-878 expression significantly inhibited DRP1-mediated mitochondrial overdivision and mtROS production ((6.60±0.57) vs (4.32±0.91), P<0.000 1). The mechanism study showed that miR-878 could target and bind Pim1 and inhibit the expression level of Pim1 ((1.00±0.13) vs (0.38±0.03), P<0.01). Rescue experiments confirmed that down-regulation of Pim1 expression significantly reversed the anti-injury effect of miR-878 inhibitor in H9c2 cells (P<0.01), promoted mitochondrial overdivision and mtROS production ((1.00±0.12) vs (2.41±0.12), P<0.01), and decreased the expression level of p-DRP1 ((1.00±0.15) vs (0.59±0.06), P<0.05). ConclusionThe present study demonstrates that miR-878 expression is upregulated in H9c2 cardiomyocytes subjected to H/R injury. Inhibition of miR-878 expression alleviates H/R-induced cardiomyocyte damage. Notably, downregulation of miR-878 significantly inhibits DRP1-mediated mitochondrial fission and mitigates mtROS production. Mechanistically, miR-878 targets and binds to the 3'-UTR of the Pim1 gene, thereby suppressing Pim1 protein expression. Collectively, these findings suggest that under H/R conditions, miR-878 promotes excessive mitochondrial fragmentation through DRP1 activation by targeting Pim1, ultimately contributing to cardiomyocyte injury. Modulation of the miR-878/Pim1 axis may represent a potential therapeutic strategy for mitigating MI/R-induced cardiac damage.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

The pathogenesis theory of"spleen deficiency and stasis toxin"in gastric cancer holds that spleen is the source of generation and transformation of qi and blood,that spleen deficiency is the internal basis of disease and throughout the disease.Stasis toxin is based on spleen deficiency,which is the fundamental pathogenesis of gastric cancer.In the pathological process of gastric cancer,a variety of metabolic substances in tumor cells and tumor microenvironment,mainly glucose metabolic reprogramming,undergo metabolic changes to reconstruct the phenotype and function of tumor-related macrophages,which is consistent with the pathogenesis theory of"spleen deficiency and stasis toxin".Therefore,this article focused on the reprogramming of glucose metabolism in tumor microenvironment to drive the phenotypic remodeling of tumor-related macrophages,explored the scientific connotation of the pathogenesis theory of"spleen deficiency and stasis toxin"of gastric cancer,and provided references for the theoretical and clinical research on the treatment of gastric cancer by TCM.

Objective To investigate the clinical outcomes of cranioplasty with polyether ether ketone(PEEK)or titanium after large craniectomy in patients.Methods Clinical data of 150 patients undergoing skull repair due to large frontotemporal skull defect in our hospital from April 2018 to June 2022 were retrospectively analyzed,and they were divided into titanium mesh group and PEEK group according to different repair materials.The conditions of surgical site infection,bleeding,subcutaneous effusion,seizure,implant rupture or exposure in the two groups were compared.Results In the PEEK group,96.3％of patients needed to implant the repair material under the temporal muscle,which was significantly higher than that in the titanium mesh group(78.1％)(P＜0.05).There were no significant differences in postoperative complications including infection,bleeding,seizure,implant rupture or leakage between the two groups(P＞0.05).However,the incidence of postoperative subcutaneous effusion in PEEK group was higher than that in titanium mesh group(14.8％VS4.2％,P＜0.05),and the difference was statistically significant.Conclusion Both titanium and PEEK can be used in cranioplasty for patients with large frontotemporal cranial defects.Subcutaneous effusion is common in patients underwent cranioplasty with PEEK postoperatively,which needs to be paid more attention.