Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

Purpose: Lung cancer is frequently observed as a second primary malignancy following gastric cancer, yet the genetic causality between them remains uncertain. This study aims to evaluate the causal relationship between gastric and lung cancers using Mendelian randomization (MR) analysis. Materials and Methods: Single nucleotide polymorphisms associated with gastric and lung cancers were selected from genome-wide association study in East Asian and European populations as instrumental variables. The causal effects between gastric and lung cancers were evaluated using univariable and multivariable MR analysis, with the inverse variance weighted (IVW) method serving as the primary criterion. Heterogeneity and sensitivity analyses were performed to ensure the robustness of the findings. Results: Univariable MR analysis demonstrated that genetic susceptibility to gastric cancer in the European population was significantly associated with an increased risk of lung cancer (IVW: odds ratio [OR], 1.285; 95% confidence interval [CI], 1.072 to 1.541; p=6.83E-03), which was consistently validated in the East Asian population (IVW: OR, 1.356; 95% CI, 1.114 to 1.651; p=2.40E-03). Multivariable MR analysis further indicated that the significant positive causal relationship between gastric cancer and lung cancer persisted in both populations after adjusting for confounding factors (all p < 0.05). Conversely, no significant causal relationship was observed for the risk of developing gastric cancer following the diagnosis of lung cancer in either population (p > 0.05). Conclusion This study confirms that genetic susceptibility to gastric cancer increases the risk of lung cancer. This finding provides a theoretical basis for exploring the underlying biological mechanisms and suggests that enhancing lung cancer screening in patients with gastric cancer may be necessary to improve patient prognosis.

Objective Jejunal interposition is an important option for restoring gastrointestinal continuity in patients with complex esophageal cancer in whom the stomach is unavailable for reconstruction due to previous gastrectomy, tumor involvement, failed gastric conduit, or other constraints. Although the jejunum offers a caliber similar to the esophagus, a rich blood supply, and preserved peristaltic function, anatomical variations in mesenteric length and vascular arcades render long-segment and high-level reconstruction susceptible to excessive tension, mesenteric torsion, venous congestion, and inadequate distal perfusion. This consensus aims to provide standardized recommendations for the application of jejunal interposition in this specific patient population. Methods This consensus was developed in accordance with the WHO Handbook for Guideline Development and Chinese national guideline development standards, with reference to the Appraisal of Guidelines for Research & Evaluation Ⅱ(AGREE Ⅱ), Reporting Items for Practice Guidelines in Healthcare (RIGHT), and Scientific, Transparent and Applicable Rankings (STAR) checklists. The project was registered on the international practice guidelines registry platform (PREPARE-2026CN1384). The working group systematically searched Chinese and English evidence addressing 12 clinical questions. Evidence was graded using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2009 system, with structured appraisal of risk of bias, inconsistency, indirectness, and imprecision. Recommendations were formulated through two rounds of Delphi surveys and a face-to-face consensus meeting, with an agreement threshold of ≥75%. Results The consensus generated 12 recommendations covering indications, selection between jejunum and colon, preoperative assessment, surgical approach and reconstruction route, pedicled jejunal interposition (PJI), supercharged pedicled jejunal interposition (SPJ), indocyanine green (ICG) perfusion assessment, perioperative nutrition, management of anastomotic leakage, long-term follow-up, and special treatment scenarios. Given that the available direct evidence is predominantly derived from single-center retrospective cohorts and case series, recommendations extrapolated from general esophagectomy or other gastrointestinal surgical evidence are deliberately phrased with caution. Conclusion Jejunal interposition is a safe and effective approach for digestive tract reconstruction in patients with complex esophageal cancer in whom the stomach is unavailable. This consensus emphasizes that clinical decision-making should be individualized based on the patient's prior treatment history, reconstruction height, vascular anatomy, technical availability, and institutional experience in the Chinese context.

Long-term glucose metabolism disorders in patient with diabetes is often accompanied by dyslipidemia, especially the elevated level of low-density lipoprotein cholesterol (LDL-C). It is an important risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). Recent studies at home and abroad have also found that diabetes can lead to increased levels of proprotein convertase subtilisin/kexintype 9 (PCSK9). In view of the profound influence of PCSK9 overexpression on low density lipoprotein cholesterol level, cardiovascular risk and atherosclerosis, it is of great significance to explore whether hypoglycemic drugs can reduce the level of PCSK9 in the treatment of diabetes. We summarized the results of the study on the effects of various hypoglycemic drugs on circulating PCSK9 concentration in order to provide ideas for the optimal treatment of diabetes.

BACKGROUND:Hepatocyte-like cells induced by mesenchymal stem cells are promising seed cells for liver regeneration or liver tissue engineering.The efficiency of traditional two-dimensional culture for hepatocyte induction is low,and more and more research is focused on three-dimensional culture for inducing hepatocyte differentiation.OBJECTIVE:To summarize three-dimensional culture models for the hepatic induction of mesenchymal stem cells,focus on research progress on the epigenetic regulation mechanisms of mesenchymal stem cell hepatogenic differentiation,providing a theoretical basis for improving the differentiation efficiency of mesenchymal stem cells.METHODS:Relevant articles in the PubMed and other databases such as CNKI were searched,using Chinese and English search terms"mesenchymal stem cell,3D culture,hepatogenic differentiation,hepatocyte-like cells,epigenetics."Additionally,the literature tracing method was employed to find some of the literature for a comprehensive review and analysis.RESULTS AND CONCLUSION:(1)Common three-dimensional culture models for the hepatogenic differentiation of mesenchymal stem cells currently include spheroids,biological scaffolds,bioprinting,and microfluidic chips.Each of these models has its own advantages and disadvantages in the process of inducing hepatogenic differentiation.(2)During the differentiation of mesenchymal stem cells into hepatocyte-like cells,epigenetic regulation plays a key role,primarily involving histone modification,DNA methylation,and the regulation of non-coding RNAs.(3)Under three-dimensional culture conditions,epigenetic modifications,especially histone acetylation,play an important role in promoting the hepatogenic differentiation of mesenchymal stem cells.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

[Objective]Using data mining technology,to investigate the common syndrome types and acupoint compatibility rules of auricular point pressing beans in the treatment of pediatric enuresis,and provide reference for auricular point pressing beans in the treatment of pediatric enuresis.[Methods]A computer-based search of the literature on auricular point pressing beans for the treatment of pediatric enuresis from the establishment date of the database to January 8,2025.The search databases including Web of Science,PubMed,Cochrane library,CNKI,China Biology Medicine disc,VIP Database and Wanfang Medical Data.Descriptive analysis and association rule analysis were performed on the auricular data in the literature.[Results]A total of 90 articles were included,among which 88 were in Chinese and 2 in English.There were four main syndrome types in pediatric enuresis:syndrome of non-consolidation of kidney qi,syndrome of qi deficiencey of spleen and lung,syndrome of dampness-heat of liver channel,spleen-kidney deficiency pattern.There were 31 auricular points involved in the treatment of pediatric enuresis by auricular point pressing with beans,among which the commonly used auricular points were Bladder,Kidney,Subcortical Yuanzhong and Shenmen.The commonly used auricular acupoints for the treatment of pediatric enuresis were Bladder-Urethra-Yuanzhong-Subcortical-Kidney,Kidney-Shenmen-Yuanzhong-Bladder,and so on.[Conclusion]Data mining effectively identified common syndrome types of pediatric enuresis,frequently used auricular acupoints,and their combination patterns in auricular acupressure therapy.The findings revealed the characteristics and regularities of syndrome-based auricular nursing interventions,providing a scientific basis for acupoint selection in clinical practice and supporting the precise application of auricular acupressure in the nursing care of pediatric enuresis.

Objective To prepare a variety of quality control(QC)materials for SARS-CoV-2 variants as an addition to the conven-tional SARS-CoV-2 nucleic acid QC products for the laboratory detection of mutant strains by optimizing the preparation and purification process of MS2 phage virus-like particle(VLP)technique,and evaluate their performances.Methods The typical mutation sequence fragments or full length S genes were designed and synthesized according to the genomic information of SARS-CoV-2 variants.Then,they were inserted into the downstream of maturase gene,coat protein and the pac-site of MS2 phage to construct a series of recombi-nant expression vectors.After induced by the prokaryotic expression system,the VLP products were purified through the polyethylenei-mine precipitation,ultrafiltration,nuclease digestion,and gel filtration chromatography.The obtained VLP were validated by the nucle-ic acid electrophoresis,protein electrophoresis,protein concentration determination,and fluorescence PCR,and their performances such as nucleic acid residue and stability were also evaluated.Results A total of 10 kinds of VLP containing the targeted sequences of the gene to be tested were prepared.The length of the foreign sequence wrapped in them ranged from 297 bp to 3 822 bp,which could be combined into a variety of QC materials for the mutation detection of different SARS-CoV-2 variants.The prepared VLP QC materials could not be effectively amplified without nucleic acid extraction or reverse transcription steps during the routine nucleic acid detection.The simulated QC samples remained stable after repeated freeze-thaw cycles.They could be stored stably for 2 months at 25 ℃ and 4 weeks at 37 ℃.Conclusion The established preparation and combined purification process of VLP QC materials can encapsulate vari-ous exogenous nucleic acid sequences with different lengths into the viral coat protein to form VLP,with high production efficiency.The VLP QC products prepared by the above process have stable performance and almost no residual exogenous nucleic acid,which can ef-fectively meet clinical requirements and ensure the quality of laboratory testing.

Objective:To construct a fuzzy comprehensive evaluation model for life support equipment of hospital,so as to improve quality of management for equipment.Methods:Based on the operating status of life support equipment in Jiangmen Maternal and Child Health Care Hospital of Guangdong Province,a fuzzy comprehensive evaluation model was constructed,and the indicators of different levels were set.The index weights were calculated according to the Analytic Hierarchy Process(AHP),and the equipment management strategy was formulated based on the evaluated results.A total of 98 life support equipment in clinical use in our hospital from January 2023 to July 2024 were selected.In them,49 equipment were managed under the conventional management mode,and the other 49 equipment were managed under the assessment system management mode of the kind of life support equipment based on fuzzy comprehensive evaluation model(model management mode)according to the random number table method.The timeliness,management effect and management efficiency of the two management modes for equipment were compared.A self-made satisfaction questionnaire was used to investigate the satisfaction scores of equipment engineers,clinicians and managers of relevant departments in usage management for equipment in the equipment usage of the two management modes.Results:The timeliness of equipment early warning,the timeliness of maintenance personnel's arrival,and the timeliness of proposing maintenance opinions were respectively(0.78±0.14)min,(5.14±2.11)min,and(10.69±3.11)min in the model management mode,all which were shorter than those in the conventional management mode,and the differences were statistically significant(t=16.697,11.857,16.117,P<0.05).The regular maintenance rate of equipment adopting the model management mode was higher than that adopting the conventional management mode,and the failure rate was lower than that adopting the conventional management mode,and the differences were statistically significant(x2=12.274,12.261,P<0.05),respectively.The maintenance time of the model management mode was shorter than that of the conventional management mode,and the operation and maintenance cost of the model management mode was lower than that of the conventional management mode,and the differences were statistically significant(t=17.451,12.707,P<0.05).The scores of management efficiencies of resource allocation,technical support,environmental guarantee and information infrastructure of the model management mode were all higher than those of the conventional management mode,and the differences were statistically significant(t=12.268,14.908,16.128,13.920,P<0.05).In usage management for equipment,the satisfaction scores of equipment engineers,clinicians and managers of relevant departments for equipment management adopting the model management mode were higher than those adopting the conventional management mode,and the differences were statistically significant(t=13.118,16.209,12.557,P<0.05).Conclusion:The assessment system of hospital for life support equipment based on the fuzzy comprehensive evaluation model can enhance the quality of management and operation for equipment,and improve the service level of equipment,and increase the operational efficiency of equipment.

ObjectiveTo explore whether fluoroethylnormemantine （FENM）， an NMDA receptor antagonist， could improve compulsive-like behaviors and to investigate its underlying mechanisms in the RU24969-induced obsessive-compulsive disorder （OCD） mouse model. MethodsThirty-two mice were randomly assigned to four groups： Saline （n=8）， RU24969 （n=8）， RU+FENM （n=8）， and FENM （n=8）. Mice received FENM or an equivalent volume of saline for pre-treatment， followed by RU24969 or saline for model induction 30 minutes later. Behavioral tests were performed 1 hour after modeling， and serum samples were collected to measure the level of brain-derived neurotrophic factor （BDNF）. Evans Blue dye was intravenously injected to assess dye content in brain tissue， thereby evaluating potential blood-brain barrier damage. ResultsFENM treatment significantly improved repetitive stereotyped circling behavior （F=39.850， P＜0.001） and alleviated persistent motor activity （F=50.200， P＜0.001） in RU24969 model mice. Additionally， FENM treatment significantly increased serum BDNF level in RU24969-induced OCD mice （F=18.930， P＜0.001）. ConclusionsFENM ， an NMDA receptor antagonist， may alleviate compulsive behaviors in OCD mice by modulating BDNF levels ， thereby exerting anti-compulsive effects. Neither the RU24969 model nor FENM treatment significantly affectes blood-brain barrier integrity.