OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

Objective To evaluate the changes of bronchial mucosa observed by fiberoptic bronchoscopy after bronchial arterial embolization(BAE)treatment.Methods A total of 176 patients,who received BAE at the First Affiliated Hospital of Guangzhou Medical University of China from May 2019 to March 2024,were enrolled in this study.The pre-BAE and post-BAE bronchial mucosa was checked by fiberoptic bronchoscopy.Results Of the 176 patients,fiberoptic bronchoscopy showed no abnormal findings in 143 and showed abnormal findings in 33.All the abnormal findings were mucosal congestion and oedema,in some cases coexisting vascular bulge was seen,but no manifestations of ischemia or necrosis of the bronchial mucosa could be found.In 22 patients,the preoperative and postoperative 7-day fiberoptic bronchoscopy revealed that both preoperative and postoperative examinations showed no obvious abnormalities of the bronchial mucosa in 13 patients,preoperative examination had abnormalities of the bronchial mucosa in 9 patients,postoperative examination showed no obvious abnormalities of the bronchial mucosa in 3 patients,and in one patient the postoperative degree of bronchial mucosal congestion and oedema was significantly improved when compared with its preoperative degree.Conclusion BAE does not cause ischemic necrosis or shedding of bronchial mucosa,and BAE can reduce the degree of bronchial mucosal congestion in some patients.

Objective:To analyze the distribution characteristics and influencing factors of prolonged length in the elderly patients at a tertiary hospital.Methods:Medical records of patients receiving inpatient care at Xiangya Hospital, Central South University in Hunan province during January 1, 2021 and December 31, 2023 were collected.The generalized estimating equation(GEE)model was used to analyze the factors influencing prolonged hospitalization in elderly patients.Results:A total of 144 921 elderly inpatients were included, aged 60 to 104 years, with 84 950 males and 59 971 females.The average length of hospitalization was 7.81 days, with 2 614 patients hospitalized for more than 30 days (1 663 males and 951 females), and the average length of stay for these patients was 44.93 days.Most of the patients with prolonged length were hospitalized for 30 to 40 days, and in the group of aged 60-74 years.Disease categories mainly were related to health conditions, healthcare facility contact, tumors, and circulatory system diseases.The GEE model analysis showed that nosocomial infection [ OR(95% CI): 5.836(4.716-7.221)], age≥90 [ OR(95% CI): 2.415(1.680-3.472)], surgery [ OR(95% CI): 3.543(2.925-4.291)], number of complications>4[ OR(95% CI): 2.378(2.091-2.704)], unplanned hospital readmissions within 31 days [ OR(95% CI): 1.748(1.525-2.004)]were risk factors of prolonged hospitalization; female [ OR(95% CI): 0.901(0.824-0.986)] and no transferred hospitalization [ OR(95% CI): 0.154(0.140-0.169)] were protective factors. Conclusions:Prolonged hospitalization is related to the clinical and social factors.Administration department of the hospital should strengthen the monitoring of these influencing factors, reduce or prevent the occurrence of prolonged length of stay by adopting targeted measures, and further realize rational allocation of medical resources.

Objective:To establish a set of reasonable,reliable and easy-to-operate evaluation index system for the clinical application of ventilators,so as to carry out all-round clinical evaluation for application of ventilators.Methods:A research group on the evaluation index system for the clinical application of ventilators was formed by 5 clinical engineers,who came from the Department of Medical Engineering of the First Affiliated Hospital of Zhejiang University School of Medicine,to form a primary evaluation index system for the clinical application of ventilators through literature review and internal discussion,and invited 14 experts from different provinces and cities engaged in respiratory therapy or ventilator maintenance management,after two rounds of online discussion and optimization,the importance scores of each evaluation index were obtained by the Delphi method,and the relative importance of each evaluation index was calculated by analytic hierarchy process.An evaluation index system for the clinical application of ventilators was established from three dimensions:technical performance,clinical effect and after-sales service.The ventilators of brand A and brand B used in the hospital during the same period were selected,and the clinical application of the two different brands of ventilators was compared and evaluated by using the evaluation index system.Results:The constructed evaluation index system for clinical application of ventilator included 3 first-level indicators(technical performance,clinical effect and after-sale service),and 8 second-level indicators and 35 third-level indicators.The combined weight of indicators showed that the ratio of importance of"technical performance"of the first-level indicators accounted for more than half,and the relatively important indicators in the second-level indicators were successively design for safety,static performance,reliability,service quality and applicability.The comprehensive average score of ventilator A was 4.468 points,and that of ventilator B was 4.117 points.The overall performance of ventilator A was better than that of ventilator B in the evaluation of this round,which was consistent with the actually clinical application of the two ventilators.Conclusion:The evaluation index system for clinical application of ventilator can conduct comprehensive evaluation for the effect of clinical application of various kinds of ventilators,and clarify the advantages and disadvantages of various kinds of ventilators,and provide reference basis for medical institutions in selecting ventilator's brands,and for manufacturers in improving product's performance.

Tracheal intubation in emergency and complex scenarios is difficult for critical care medicine residents.Virtual reality(VR)technology has not been used in the training of tracheal intubation in critical care scenarios in China.This project team has developed an emergency tracheal intubation training system for the intensive care unit(ICU)based on virtual simulation technology,and has obtained the computer software copyright registration certificate from the National Copyright Administration(registration number:2024SR1139484).This system uses a case script of acute respiratory distress syndrome(ARDS)secondary to severe acute pancreatitis,sets the roles of patients,family members,nurses and residents,collects digital resources of ICU rescue scenes,computer-aided design(CAD)drawings,instrument models and equipment photos,models instruments and equipment,and uses PICO 4 Pro VR helmets to display the ICU environment in the virtual scene.The key points of skill assessment include tracheal intubation operation,the ability to interpret laboratory results,the ability to judge diseases and the ability to work in teams.The user center contains 3 submodules,namely,the score center,skill analysis and user management.There are 3 user roles in the system,namely,residents,teachers and administrators.The system can track and record the entire operation process,including video recording and playback,and score and comprehensively evaluate each step,thereby realizing an objective and quantitative training and assessment system.By simulating the three-dimensional clinical operation environment of the ICU,the entire process of real tracheal intubation is fully reproduced.Resident doctors are placed in the ICU rescue scene,focusing on training tracheal intubation skills,the ability of doctor-patient communication,on-the-spot response,and teamwork,which is expected to become an important type of standardized teaching in critical care medicine.

The aim of this study is to establish an gene editing method of Mesomycoplasma hyo-pneumoniae(Mhp)based on the homologous recombination principle.The restriction enzyme di-gestion and ligation method combined with gene synthesis were used to construct a shuttle plasmid to achieve replication in both Mhp and Escherichia coli(E.coli).The pGEM?-T vector was used as the skeleton.The oriC sequence of Mhp which can achieve the replication of the plasmid in Mhp was inserted into the vector.Sequences of the Spiroplasma promoter and puromycin resistance gene were then inserted into the above constructed plasmid to screen recombinant clones.The up-stream and downstream homologous arms of p97 were constructed to initiate homologous recombination.The recA gene of E.coli is inserted to improve the efficiency of homologous recom-bination.The obtained shuttle plasmid was then delivered into Mhp by electro-transformation or chemical transformation.A shuttle plasmid,pGEM?-Mhp-oriC-p 97,which can replicate in both Mhp and E.coli was constructed.With the transformation of this plasmid,the carried puromycin gene and recA gene can be expressed,the p97 gene can be edited.Finally,the genetically unstable p97 gene mutant was initially obtained.In this study,a tool for Mhp gene editing based on the principle of homologous recombination was established,which laid a foundation for the develop-ment of tools for studying the pathogenesis of Mhp.

Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals ; Liver Neoplasms/etiology* ; Humans ; Carcinoma, Hepatocellular/immunology* ; Liver Cirrhosis/complications* ; Macrophages/drug effects* ; Male ; Rats ; Chemokine CXCL12/genetics* ; Diarylheptanoids/pharmacology* ; Rats, Sprague-Dawley ; beta Catenin/genetics*

Objective To explore the effectiveness of a tracheal intubation training system based on virtual reality(VR)technology in cultivating the clinical practice abilities of resident physicians.Methods Twenty-five first-year resident physicians who were enrolled in the residency programme at Peking University Third Hospital from August 2024 to February 2025 were recruited for this study.All participants completed a questionnaire after receiving VR-based intensive care unit(ICU)emergency tracheal intubation training,to share their experiences with the VR technology-based ICU emergency tracheal intubation training and the shortcomings encountered during the process.Results ① General information:a total of 25 resident physician questionnaires were distributed in this study and received 25 valid responses(response rate 100%).Among the 25 residents,there were 15 males(60%)and 10 females(40%),with an average age of(25.3±0.8)years.Clinical experience was categorised as≤1 year 4 residents(16%),>1-3 years 8 residents(32%),>3-<5 years 5 residents(20%)and≥5 years 8 residents(32%).Among them,3 residents(12%)had no prior tracheal intubation experience,while 11(44%)had performed>10 intubations.Prior to this training,3 residents(12%)had received other forms of virtual tracheal intubation training,whereas 22(88%)had not.During traditional tracheal intubation training,18 residents(72%)reported that they monitored heart rate and blood pressure,whereas 7(28%)did not.In real-world emergency tracheal intubation scenarios,21 residents(84%)experienced role confusion.Additionally,23 residents(92%)believed that opportunities for tracheal intubation practice were too limited,17(68%)thought traditional training provided more guidance from instructors,and 15(60%)valued practical operation opportunities more in tracheal intubation training.②VR-based ICU emergency tracheal intubation training experience:23 residents(92%)considered the VR-based ICU emergency tracheal intubation training effective,with 13(52%)believing it to be more effective than traditional training.Furthermore,23 residents(92%)felt that the VR-based training created a more relaxed learning atmosphere,heightened their interest in learning tracheal intubation,and had better future prospects;22 residents(88%)believed that VR technology facilitated a better understanding of the laryngeal structure;24 residents(96%)thought that VR-based training reduced practical operation risks and better simulated real-world conditions;16 residents(64%)were highly satisfied with the VR-based ICU emergency tracheal intubation operating system;24 residents(96%)considered the case scenarios in the VR-based training reasonable.17 residents(68%)believed that VR-based training offered more learning opportunities,and 19 residents(76%)thought it reduced anxiety during the intubation process.③ Disadvantages of VR-based ICU emergency tracheal intubation:9 residents(36%)tended to overlook obtaining family consent before emergency tracheal intubation prior to the training.Regarding interactivity,5 residents(20%)rated it as excellent,9(36%)as average,and 11 residents(44%)believe that the interactivity was poor;22 residents(88%)felt a lack of tactile feedback during practical operations;20 residents(80%)recommended adding more simulated scenarios;11 residents(44%)believed that,compared to traditional training,VR training lacked practical operation opportunities.Additionally,17 residents(68%)experienced discomfort such as dizziness during the operation.Conclusion VR-based intubation training effectively enhances technical proficiency and psychological preparedness in ICU clinicians,particularly in anatomical visualization and risk-controlled rehearsal.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.