OBJECTIVE To evaluate the efficacy and safety of ceftazidime/avibactam （CAZ/AVI） combined with amikacin （AMK） in the treatment of carbapenem-resistant Enterobacteriaceae （CRE） severe pneumonia. METHODS A retrospective cohort study was conducted on 240 patients diagnosed with severe pneumonia caused by CRE infection in the intensive care unit （ICU） of the Affiliated Hospital of Xuzhou Medical University from January 2022 to December 2024. The patients were divided into a combination group （CAZ/AVI combined with AMK， n＝136） and a control group （CAZ/AVI alone， n＝104）. The 28-day mortality rate， clinical efficacy，mechanical ventilation time， ICU stay， infectious markers [C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， white blood cell count （WBC）， and neutrophil percentage （N%）]， Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE Ⅱ） scores， and total incidence of adverse reactions were compared between two groups of patients. At the same time， subgroup analysis was conducted based on the severity of the condition， mechanical ventilation status， and baseline renal function. RESULTS The 28-day mortality rate of patients in the combination group was significantly lower than that in the control group （20.6% vs. 34.6%， P＝0.022）， and the clinical effective rate was significantly higher than that in the control group （80.1% vs. 65.4%， P＝0.004）. The mechanical ventilation time and ICU hospitalization time in the combination group were significantly shorter than those in the control group （[ 7.2±2.4） days vs. （10.4±3.6） days， （10.5±3.1） days vs. （13.7±3.8） days； P＜0.01].After 7 days of treatment， the CRP， PCT， IL-6， WBC， N% and APACHE Ⅱ scores of patients in the combination group significantly decreased compared to before treatment， and the decrease was significantly greater than that of the control group （P＜0.01）. There was no statistically significant difference in the total incidence of adverse reactions between the two groups of patients （11.8% vs. 13.5%， P＝0.690）. Subgroup analysis showed that among high-risk （APACHE Ⅱ score≥15） and mechanically ventilated patients， the 28-day mortality rate and weaning time of the combination group were significantly lower/ shorter than those of the control group （P＜0.05）， while there was no significant difference in the total incidence of adverse reactions between the combination group and the control group after dose adjustment in patients with chronic renal insufficiency （P＞0.05）. CONCLUSIONS The CAZ/AVI combined with AMK regimen has better anti-infective efficacy and good safety in patients with severe pneumonia caused by CRE infection compared to the CAZ/AVI regimen alone； the survival benefits of this joint regimen are more significant in high-risk and mechanically ventilated patients， with critically ill patients being the main beneficiaries.

Although metal blocks have been widely used for reconstructing uncontained tibial bone defects, the influence of their elastic modulus on the stability of tibial prosthesis fixation remains unclear. Based on this, a finite element model incorporating constrained condylar knee (CCK) prosthesis, tibia, and metal block was established. Considering the influence of the post-restraint structure of the prosthesis, the effects of variations in the elastic modulus of the block on the von Mises stress distribution in the tibia and the block, as well as on the micromotion at the bone-prosthesis fixation interface, were investigated. Results demonstrated that collision between the insert post and femoral prosthesis during tibial internal rotation increased tibial von Mises stress, significantly influencing the prediction of block elastic modulus variation. A decrease in the elastic modulus of the metal block resulted in increased von Mises stress in the proximal tibia, significantly reduced von Mises stress in the distal tibia, decreased von Mises stress of the block, and increased micromotion at the bone-prosthesis fixation interface. When the elastic modulus of the metal block fell below that of bone cement, inadequate block support substantially increased the risk of stress shielding in the distal tibia and fixation interface loosening. Therefore, this study recommends that biomechanical investigations of CCK prostheses must consider the post-constraint effect, and the elastic modulus of metal blocks for bone reconstruction should not be lower than 3 600 MPa.
Knee Prosthesis ; Humans ; Finite Element Analysis ; Tibia/surgery* ; Elastic Modulus ; Arthroplasty, Replacement, Knee/methods* ; Stress, Mechanical ; Metals ; Prosthesis Design ; Knee Joint/surgery* ; Biomechanical Phenomena

The intestinal microecology is closely related to the occurrence and development of hepatocellular carcinoma (HCC). The intestinal microbiota and its metabolites can regulate the tumor immune microenvironment through the "gut-liver axis", promoting cancer progression. Therefore, the intestinal microbiome is gradually demonstrating the potential as a biomarker for early diagnosis of HCC and prediction of the efficacy of immunotherapy. Targeted intervention on the intestinal microecology (such as probiotics, fecal microbiota transplantation, dietary regulation, etc.) may enhance the efficacy of immune checkpoint inhibitors (ICIs) and is becoming a promising combination therapy strategy. In the future, HCC treatment will rely on multi-omics integration, artificial intelligence-assisted diagnosis, and synthetic biology tools to promote the translation of precise gut flora intervention strategies from basic research to the clinic. This article summarized the latest research progress of intestinal microecology in HCC, explored its potential value and development direction for precision diagnosis and treatment of HCC, and provided a theoretical basis for the clinical application of related intervention strategies.

The connotation of the "four-dimensional pivot-earth" qi transformation mode is a dialectical system of the ascending and descending of yin-yang qi movement， which presented as "the middle Jiao showing earth qi mediating， the left wheel showing water and wood ascending， and the right wheel showing fire and metal converting and descending". Based on this dialectical thinking， it is believed that the core pathogenesis of myasthenia gravis is deficiency of center qi and transportation failure to pivot-earth； the middle-stage characteristics of the disease progression are the loss of mediation of the central qi， resulting in water coldness and wood constraint， and clear yang failing to ascend； the final outcome of this disease is the loss of astringeing of lung metal and qi sinking. The treatment should be based on the rule of qi movement， so for the start-stage， Buzhong Yiqi Decoction （补中益气汤） should be used as the basis to nourish the earth and consolidate the root， and restrengthen the middle qi； for the middle-stage， herbs like Yingyanghuo （Epimedium brevicornu Maxim.）， Bajitian （Morinda officinalis How） could be combined to warm the water and soothe the wood， raise yang and boost qi； for the final stage， plus Sini Decoction （四逆汤） to astringe metal to stop collapse， and powerfully supplement original qi. All these medicinals can promote pivot-earth re-transportation， four-dimensional transformation， and regular circulation of qi movement， so as to provide thoughts for improving the clinical effectiveness of myasthenia gravis.

Objective:To investigate the use of non-vitamin K antagonist oral anticoagulants(NOACs)and their associated comorbidities in patients aged 80 years and older with non-valvular atrial fibrillation(NVAF), as well as to understand the challenges faced by elderly patients receiving NOAC therapy.Methods:We retrospectively enrolled elderly patients(≥80 years old)with NVAF who were treated with NOACs at a hospital in Beijing from January 2018 to August 2023.Patients were categorized into two age groups: 80-89 years and ≥90 years.We collected baseline data, including demographic characteristics, details of atrial fibrillation, comorbidities, laboratory test results, and medication combinations, for descriptive statistical analysis and intergroup comparisons.Results:A total of 695 elderly patients with NVAF receiving NOACs were included in the study, with a median age of 84 years.Among these patients, there were 328 males(47.19%, 328/695)and 422 cases of paroxysmal atrial fibrillation(60.72%, 422/695).The age group of 80-89 years comprised 640 cases(92.09%, 640/695), while the group aged 90 years and above included 55 cases(7.91%, 55/695).The use of NOACs in patients aged 90 and older exhibited an increasing trend over the years.Inter-group comparisons indicated that the ≥90 years group had lower body mass index, longer hospital stays, increased bedridden time, poorer renal function, lower levels of albumin and hemoglobin, and higher D-dimer levels.Inappropriate dosing of DOACs occurred in 49.64%(345/695)of cases, with 90.72%(313/345)receiving doses lower than recommended.Lower-than-recommended doses were more prevalent in the ≥90 years group, while higher-than-recommended doses were more common in the 80-89 years group.Polypharmacy was noted in 61.29%(426/695)of patients.The concurrent use of antiplatelet drugs, rhythm control medications, and ventricular rate control drugs was observed in 12.52%(87/695), 19.57%(136/695), and 54.53%(379/695)of patients, respectively, with no significant differences between groups.Conclusions:Inappropriate dosing and polypharmacy are prevalent issues among elderly NVAF patients.Therefore, it is essential to enhance multidisciplinary collaboration to optimize anticoagulation treatment strategies.

Objective To investigate the differences of condylar position in patients with temporomandibular disorders(TMD),and to further explore the effects of condylar position displacement and malocclusion factors on TMD.Methods According to the inclusion criteria,normal occlusion subjects without TMD(group A,n=10),normal occlusion subjects with TMD(group B,n=8),malocclu-sion subjects without TMD(group C,n=9)and malocclusion subjects with TMD(group D,n=20)were collected.Condylar position measurement(CPM)and Cadiax Ⅳ were used to locate the position of condyle in RP and ICP,and the displacement and direction of condyle in three-dimensional direction from RP to ICP were measured by vernier caliper.All the data were averaged three times and an-alyzed by SPSS26.0 statistical software.Results In the sagittal direction,the condylar displacement of group A and group B,group C and group D,and group A and group D had statistical differences(P＜0.01).The displacement of the right condyle in the vertical direc-tion of group D was greater than that of group A,and the difference was statistically significant(P＜0.05).The difference among other groups was not statistically significant.There was no significant difference in the lateral displacement of condyle between the four groups.In group A and group D,the largest proportion of condyle deviation was anterior up,while in group B and group C,the largest proportion of condyle deviation was posterior up.Conclusion RP-ICP condylar sagittal displacement is common in people with TMD.The condyle displacement of RP-ICP in malocclusion patients without TMD is not significantly different from that in normal occlusion patients without TMD.Patients with TMD malocclusion are more likely to have condylar displacement in sagittal direction and vertical direction than normal occlusion without TMD.

Objective To investigate shared mechanisms and therapeutic targets between heart failure(HF)and vascular de-mentia(VaD),and identify natural compounds for dual-organ protection.Methods Single-cell data(8 samples)from GEO were processed via Seurat for clustering.Through CellChat,inter-organ communication was constructed,and top 95%ligand-receptor pairs were analyzed by KEGG enrichment.Bulk RNA-seq(70 samples)underwent differential gene(limma)and immune infiltra-tion(CIBERSORT)analyses.31186 compounds from TCMbank werescreened by AutoDock Vina,followed by molecular dynam-ics validation.Results HF fibroblasts(43.75%,7 subclusters)and VaD oligodendrocytes(76.57%,6 subclusters)dominated re-spective tissues.Cross-disease integration revealed HF-driven fibrosis(COLLAGEN)and VaD-associated neuroinflammation(SPP1),converging on PI3K-Akt and ECM pathways.HF-specific markers(TNXB/THBS4/COL1 A2)and VaD signatures(SPP1/PDGFC/TGFA)were identified,with FOXC1 identified as a shared transcriptional regulator.B cell activation character-ized immune dysregulation.Among 8 FOXC1 inhibitors,Qingdainone showed optimal binding[affinity:-9.0 kcal/mol;RMSD:(0.2±0.06)nm].Conclusion This study uncovers fibrosis-neuroinflammation crosstalk in HF-VaD comorbidity and proposes Qingdainone as a FOXC1-targeting therapeutic candidate.

Objective To investigate shared mechanisms and therapeutic targets between heart failure(HF)and vascular de-mentia(VaD),and identify natural compounds for dual-organ protection.Methods Single-cell data(8 samples)from GEO were processed via Seurat for clustering.Through CellChat,inter-organ communication was constructed,and top 95%ligand-receptor pairs were analyzed by KEGG enrichment.Bulk RNA-seq(70 samples)underwent differential gene(limma)and immune infiltra-tion(CIBERSORT)analyses.31186 compounds from TCMbank werescreened by AutoDock Vina,followed by molecular dynam-ics validation.Results HF fibroblasts(43.75%,7 subclusters)and VaD oligodendrocytes(76.57%,6 subclusters)dominated re-spective tissues.Cross-disease integration revealed HF-driven fibrosis(COLLAGEN)and VaD-associated neuroinflammation(SPP1),converging on PI3K-Akt and ECM pathways.HF-specific markers(TNXB/THBS4/COL1 A2)and VaD signatures(SPP1/PDGFC/TGFA)were identified,with FOXC1 identified as a shared transcriptional regulator.B cell activation character-ized immune dysregulation.Among 8 FOXC1 inhibitors,Qingdainone showed optimal binding[affinity:-9.0 kcal/mol;RMSD:(0.2±0.06)nm].Conclusion This study uncovers fibrosis-neuroinflammation crosstalk in HF-VaD comorbidity and proposes Qingdainone as a FOXC1-targeting therapeutic candidate.

Objective:To investigate the expression characteristics of plasma proteins in patients with acute diquat poisoning by proteomic technology, and to screen the targets and biomarkers related to the diagnosis, treatment and prognosis of acute diquat poisoning.Methods:This study was a retrospective case-control study. Patients with diquat poisoning admitted to Nanjing University Affiliated Drum Tower Hospital from August 2022 to December 2023 were enrolled. Healthy volunteers matched for age and gender during the same period were selected as the control group. The general clinical data and plasma samples were collected, and qualitative and quantitative analyses of plasma proteins were performed by proteomic technology based on nanoliter liquid chromatography tandem quadrupole time-of-flight mass spectrometry. Mann-Whitney U test was used to compare differences of plasma protein expression between the two groups. Results:A total of 8 diquat poisoning patients and 7 healthy individuals were included in this study, and 491 plasma proteins were identified. Compared with control group, 76 differentially expressed proteins were obtained from the poisoned group, including 35 up-regulated proteins and 41 down-regulated proteins. GO analysis showed that the differentially expressed proteins were mainly associated with oxygen transporter activity, receptor binding, and hyaluronic acid-binding endopeptidase inhibitor activity. KEGG pathway enrichment analysis revealed that differentially expressed proteins were associated with complement and coagulation cascades, neutrophil extracellular trap formation, and platelet activation. In addition, the expression of adiponectin (ADIPOQ) was not only increased in poisoned patients, but also significantly higher in non-survivors than in survivors ( P<0.01). Conclusions:Multiple plasma proteins with abnormal expression may be involved in the pathological process of acute diquat poisoning. ADIPOQ may have potential application value in the diagnosis, treatment, and prognosis of acute diquat poisoning.