ObjectiveTo establish an ultra-performance liquid fingerprint and multi-components determination method for Naomaili granules. To evaluate the quality of different batches by chemometrics， and the anti-neuroinflammatory effects of water extract and main components of Naomaili granules were tested in vitro. MethodsThe similarity and common peaks of 27 batches of Naomaili granules were evaluated by using Ultra performance liquid chromatography （UPLC） fingerprint detection. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） technology was used to determine the content of the index components in Naomaili granules and to evaluate the quality of different batches of Naomaili granules by chemometrics. LPS-induced BV-2 cell inflammation model was used to investigate the anti-neuroinflammatory effects of the water extract and main components of Naomaili granules. ResultsThe similarity of fingerprints of 27 batches of samples was > 0.90. A total of 32 common peaks were calibrated， and 23 of them were identified and assigned. In 27 batches of Naomaili granules， the mass fractions of 14 components that were stachydrine hydrochloride， leonurine hydrochloride， calycosin-7-O-glucoside， calycosin，tanshinoneⅠ， cryptotanshinone， tanshinoneⅡ_A， ginsenoside Rb₁， notoginsenoside R₁， ginsenoside Rg₁， paeoniflorin， albiflorin， lactiflorin， and salvianolic acid B were found to be 2.902-3.498， 0.233-0.343， 0.111-0.301， 0.07-0.152， 0.136-0.228， 0.195-0.390， 0.324-0.482， 1.056-1.435， 0.271-0.397， 1.318-1.649， 3.038-4.059， 2.263-3.455， 0.152-0.232， 2.931-3.991 mg∙g^-1， respectively. Multivariate statistical analysis showed that paeoniflorin， ginsenoside Rg₁， ginsenoside Rb₁ and staphylline hydrochloride were quality difference markers to control the stability of the preparation. The results of bioactive experiment showed that the water extract of Naomaili granules and the eight main components with high content in the prescription had a dose-dependent inhibitory effect on the release of NO in the cell supernatant. Among them， salvianolic acid B and ginsenoside Rb₁ had strong anti-inflammatory activity， with IC₅₀ values of （36.11±0.15） mg∙L^-1 and （27.24±0.54） mg∙L^-1， respectively. ConclusionThe quality evaluation method of Naomaili granules established in this study was accurate and reproducible. Four quality difference markers were screened out， and eight key pharmacodynamic substances of Naomaili granules against neuroinflammation were screened out by in vitro cell experiments.

Objective: To develop and validate a clinically actionable prediction model for postoperative pulmonary complications (PPCs) in cardiac surgery patients, focusing on modifiable preoperative risk factors amenable to targeted optimization. Methods: In this prospective observational cohort study, 492 adults undergoing open-chest cardiac surgery between August 15, 2023 and December 31, 2023 were analyzed. Prespecified predictors included gas exchange variables, pulmonary function, inspiratory muscle strength, and physical performance. Univariable and multivariable logistic regression analyses were used to develop the prediction model. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC). Results: A total of 90 patients (14.1%) developed PPCs after surgery. Five independent predictors were identified: elevated arterial PaCO2 (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.00–1.26), oxygen desaturation (SpO2<93%) (OR 12.47, 95% CI 3.51–48.13), reduced gait speed (OR 0.17, 95% CI 0.04–0.71), lower FEV1/FVC ratio (OR 0.96, 95% CI 0.92–1.00), and diminished inspiratory muscle strength (MIP % predicted) (OR 0.96, 95% CI 0.92–0.99). The model demonstrated good discriminative ability with an AUC of 0.86 (95% CI 0.80–0.93) in the training cohort and 0.87 (95% CI 0.74–0.93) in the validation cohort. Conclusion This parsimonious model achieved high predictive accuracy using five modifiable physiological variables. By targeting abnormalities in gas exchange, pulmonary mechanics, muscle strength, and functional reserve, the model offers a practical tool to guide individualized prehabilitation strategies for reducing PPC risk in cardiac surgery patients.

BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Background: and Purpose Although amyloid positron emission tomography (PET) might provide a molecular diagnosis for cerebral amyloid angiopathy (CAA), it does not have sufficient specificity for this condition relative to incipient Alzheimer’s disease (AD). To identify a regional amyloid uptake pattern specific to CAA, we attempted to reduce this overlap by selecting “pure CAA” (i.e., fulfilling the criteria for probable CAA but without tau PET AD signature) and “pure AD” (i.e., positive amyloid PET and presence of tau PET AD signature, but without lobar hemorrhagic lesions). We hypothesized that occipital tracer uptake relative to the whole cortex (WC) would be higher in patients with pure CAA and may serve as a specific diagnostic marker. Methods: Patients who fulfilled these criteria were identified. In addition to the occipital region of interest (ROI), we assessed the frontal and posterior cingulate cortex (PCC) ROIs that are sensitive to AD. Amyloid PET uptake was expressed as the absolute standardized uptake value ratio (SUVR) and ROI/WC ratio. The diagnostic utility of amyloid PET was assessed using the Youden index cutoff. Results: Eighteen patients with AD and 42 patients with CAAs of comparable age were eligible. The occipital/WC was significantly higher in CAA than AD (1.02 [0.97–1.06] vs. 0.95 [0.87–1.01], P=0.001), with an area under curve of 0.762 (95% confidence interval [CI] 0.635–0.889) and a specificity of 72.2% (95% CI 46.5–90.3) at Youden cutoff (0.98). The occipital lobe, frontal lobe, PCC and WC SUVRs were significantly lower in CAA than in AD. The frontal/WC and PCC/WC ratios did not differ significantly between the groups. Conclusion Using stringent patient selection to minimize between-condition overlap, this study demonstrated the specificity of higher relative occipital amyloid uptake in CAA than in AD.

Background: Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency. Results: In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation ­(SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen ­(PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide ­(PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7. Conclusions This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Objective To explore the impact factors of misjudge of pneumoconiosis stage based on GBZ70-2015 criteria.Methods Sixty-five case of pneumoconiosis were retrospectively enrolled.Chest high-resolution CT were independently analyzed by one associate chief physician,one attending physician and one resident physician,respectively.The stage of pneumoconiosis was judged,and the inter-observer consistency was observed.Taken the results of 5 experts using Delphi method as gold standard,the impact factors of misjudge of pneumoconiosis stage were analyzed.Results Among 65 cases,there were 42 cases of stage 1,16 cases of stage 2 and 7 cases of stage 3 pneumoconiosis.The inter-observer consistency of pneumoconiosis stage was relatively high(Kappa=0.653),of stage 3 pneumoconiosis was the best(Kappa=0.803),followed by stage 1(Kappa=0.661),while of stage 2 was the lowest(Kappa=0.518).Radiologist lack experience(OR=4.872),the lesions mainly located in the posterior upper area of lungs(OR=2.317),the present of r-type small shadows(OR=3.105)and high CT pulmonary emphysema index(OR=1.214)were all independent impact factors of misjudge of pneumoconiosis stage(all P＜0.05).Conclusion Both the experience of radiologist and lesions'heterogeneity were main impact factors of misjudge of pneumoconiosis stage based on GBZ70-2015 criteria.

Objective To explore the application value of MRI diaphragmatic navigation technology combined with three dimensional liver acquisition with volume acceleration-flexible(3D LAVA-FLEX)sequence in abdominal enhanced imaging of infants and young children.Methods A retrospective analysis was conducted on imaging data of 84 infants and young children who underwent abdominal enhanced MRI examination in our hospital between January 2021 and December 2023.All 84 infants and young children initially underwent conventional dynamic contrast-enhanced 3D LAVA-FLEX sequence scanning;the delayed phase images obtained were included in the dynamic enhancement group.Subsequently,diaphragmatic navigation combined with 3D LAVA-FLEX sequence examination was implemented,and the obtained images were included in the diaphragm navigation group.Subjective scoring was performed for images in both groups,while the signal to noise ratio(SNR),contrast to noise ratio(CNR),and artifact quantification(AQ)were measured and compared between the two groups.Results The respiratory motion artifacts,the clarity of liver parenchyma enhancement,the clarity of liver vascular enhancement,the clarity of spleen parenchyma enhancement and the overall image quality score in the diaphragm navigation group were higher than those in the dynamic enhancement group,and the differences were statistically significant(P<0.05).There were statistically significant differences in SNR and AQ between the two groups of images(P<0.000 1),while there was no statistically significant difference in CNR between the two groups of images(P>0.05).Conclusion Diaphragmatic navigation technology combined with 3D LAVA-FLEX sequence imaging can improve the image quality of abdominal MRI enhanced imaging in infants and young children,and provide a reference for clinical diagnosis and treatment.

Objective To explore the role of miR-1260b targeting activating transcription factor 6β(ATF6β)in osteogenic differentia-tion of human periodontal ligament stem cells(hPDLSCs).Methods The periodontal ligament tissue was scraped from the third molar extracted from the patient with periodontitis,and hPDLSCs were isolated and cultured.The proportions of positive cells of CD34,CD45,CD29,CD90 and CD105 were detected by flow cytometry,and the expression of vimentin and pan-cytokeratin were detected by immunofluo-rescence staining.The cellular luciferase activities of ATF6β-WT and ATF6β-MUT in the miR-1260b mimic+WT/MUT group(transfected with miR-1260b mimic and ATF6β-WT/MUT)and the mimic-NC group(transfected with miR-NC and ATF6β-WT/MUT)were analyzed by the dual luciferase reporter gene assay.In addition,the cells were divided into the miR-1260b mimic group(transfected with miR-1260b mimic alone),the ATF6β-OE group(transfected with the ATF6β overexpression vector alone),the combined group(transfected with miR-1260b mimic and ATF6β overexpression vector simultaneously),and the NC group(transfected with empty vector).Alizarin red S staining and alkaline phosphatase staining were performed on hPDLSCs in the NC group,the miR-1260b mimic group,the ATF6β-OE group and the combined group.Meanwhile,the mRNA expression levels of miR-1260b,ATF6β,Runt-related transcription factor 2(Runx2),osteocalcin(OCN),and osteopontin(OPN)in each group of cells were detected by qRT-PCR.The protein expressions of glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP),and protein kinase R-like endoplasmic reticulum kinase(PERK)in each group of cells were detected by Western blot.Results The flow cytometry detection showed that CD29,CD90 and CD105 on the surface of the isolated and cultured cells were positive,while CD34 and CD45 were negative.Immunofluorescence staining showed that vimentin in the cells was positive and pan-cytokeratin was negative,which was in line with the characteristics of hPDLSCs.Luciferase assay showed that miR-1260b mimic could significantly reduce the luciferase activity of ATF6β-WT(P<0.05),but had no significant effect on the luciferase activity of ATF6β-MUT(P>0.05).After alizarin red S staining,the staining of hPDLSCs gradually deepened after 3 days,5 days and 7 days of culture,suggesting an enhanced osteogenic differentiation ability.With the enhancement of osteogenic differentiation ability of hPDLSCs,the expression of miR-1260b in the cells showed a gradually increasing trend,while the mRNA and protein expression levels of ATF6β showed a gradually decreasing trend(P<0.05).The results of alizarin red S staining and alkaline phosphatase staining showed that the proportions of positive area in the miR-1260b mimic group were higher than those in the NC group(P<0.05),while the proportions of positive area in the ATF6β-OE group and the combined group were lower than those in the NC group(P<0.05).The mRNA and protein levels of ATF6β in the miR-1260b mimic group were lower than those in the NC group(P<0.05),while the mRNA and protein levels of ATF6β in the ATF6β-OE group and the combined group were higher than those in the NC group(P<0.05).The mRNA levels of Runx2,OCN and OPN in the miR-1260b mimic group were significantly higher than those in the NC group(P<0.05).The mRNA levels of Runx2,OCN and OPN in the ATF6β-OE group and the combined group were significantly lower than those in the NC group(P<0.05).The protein expression levels of GRP78,CHOP and PERK in the miR-1260b mimic group were significantly lower than those in the NC group(P<0.05).The protein expression levels of GRP78,CHOP and PERK in the ATF6β-OE group and the combined group were significantly higher than those in the NC group(P<0.05).Conclusion miR-1260b can inhibit endoplasmic reticulum stress level and promote osteogenic differentiation of hPDLSCs by targeting ATF6β.

Objective To analyze the influencing factors of emergency coordination in the target hospital using an opti-mized SFIC model,identify key factors,and provide decision-making basis and recommendations.Methods A research frame-work was established through literature analysis.Experts were organized to score various factors via a questionnaire survey.The SFIC model and DEMATEL method were applied to analyze the relationships among the factors.Results An SFIC framework suitable for the target hospital was constructed,comprising 5 first-level indicators and 16 second-level indicators,with 10 core el-ements identified.Conclusion Establishing a coordinated emergency mechanism in the target hospital requires full consideration of its own characteristics and the 10 core elements.It is recommended that senior leadership be deeply involved,coordinate pa-tient triage,material storage,and personnel allocation mechanisms,and adopt a flat management concept to construct an emer-gency coordination management system for the target hospital.