Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is the primary cause of mortality in sepsis, with its core pathophysiological mechanism being severe ischemia and hypoxia in critical units—composed of microcirculation and the mitochondria of functional cells—resulting from disruptions in blood flow and oxygen flow following a dysregulated host response. Due to the systemically convergent yet clinically heterogeneous nature of the host response, current understanding and management strategies for hemodynamics remain inconsistent, often leading to inadequate resuscitation or overtreatment. To improve the quality of care, based on a systematic review of the "blood flow-oxygen flow" theory, an expert panel emphasizes reevaluating septic shock from an integrated perspective of blood flow and oxygen flow, and has formulated the Expert Consensus on Blood Flow and Oxygen Delivery Phenotyping and Clinical Management of Septic Shock (2025). The consensus proposes that clinical typing of blood flow-oxygen flow should comprehensively consider cardiac function, vascular tone, oxygen flow utilization status in critical units, and disease trajectory, while optimizing subtype identification by integrating host response phenotypes and artificial intelligence technologies. It advocates establishing a continuous assessment system through multi-site oxygen flow monitoring for organ perfusion, peripheral perfusion monitoring, and critical care ultrasound. Under the framework of the "critical care triangle", the consensus promotes the implementation of individualized, bundled management strategies, providing guidance for multiple management points to restore blood flow-oxygen flow matching, reduce the risk of organ failure, and decrease patient mortality.

BACKGROUND:Multiple studies have confirmed that mitogen-activated protein kinase(MAPK)signaling pathway is involved in cell proliferation,and microRNA(miR)is involved in the occurrence and development of hypertrophic scars.Therefore,the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE:To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS:The primary fibroblasts were isolated and collected from the skin samples.The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence.The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR.The target genes of hsa-miR-27a-3p were predicted using the database,and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes.There were seven groups:blank control,negative control,miR-27a-3p mimic,miR-27a-3p inhibitor,miR-27a-3p mimic+p38 MAPK inhibitor,miR-27a-3p mimic+extracellular regulated protein kinase inhibitor,miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor.Western blot was used to detect the levels of extracellular regulated protein kinase,c-Jun N-terminal kinase inhibitor.and p38 kinase and their phosphorylation levels.Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION:Compared with normal skin fibroblasts,hypertrophic scar fibroblasts had stronger proliferative activity(P<0.05)and faster proliferation level(P<0.001).Compared with normal skin,miR-27a-3p was highly expressed in hypertrophic scars(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p could promote cell proliferation activity(P<0.001)and proliferation levels(P<0.001).Compared with the negative control group,knockdown of miR-27a-3p could inhibit the proliferation activity(P<0.05)and proliferation levels(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase(P<0.05).Compared with the negative control group,knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK(P<0.05).Compared with the miR-27a-3p mimic group,specific inhibitors of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity(P<0.01)and proliferation level(P<0.001)of fibroblasts.To conclude,these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway.

We analyzed the epidemiological features and spatial distribution characteristics of human brucellosis in Jining city from 2014 to 2023,to provide a reference for further development of targeted prevention and control strategies and measures.Descrip-tive epidemiological methods were used to analyze the epidemiological characteristics of brucellosis cases in Jining from 2014 to 2023.The spatial regional correlation of brucellosis incidence in Jining and the clustering patterns of local areas were studied through spatial autocorrelation analysis with townships as the basic unit.A total of 3 520 cases of brucellosis were reported in Jining from 2014 to 2023,and the average annual incidence rate was 4.23/100 000,thus indicating a fluctuating trend overall.Reported cases peaked from March to August,and a sex ratio of 2.71 males to 1 female was observed.The 40-59 year age group had the most reported cases(50.39％).The incidence of brucellosis in Jining showed an imbalanced spatial distribution.Brucellosis incidence showed a spatially clustered distribution(Moran's I>0,P<0.05).Hotspots were distributed primarily in Sishui,Qufu,and Zoucheng.A total of one class Ⅰ clustering area and one class Ⅱ clustering area were detected in the spatial and temporal scans,and were located in Sishui,Qufu,and Liangshan county.After pathogenic AMOS-PCR typing analysis,64 Brucella isolates collected from Jinan City from 2022 to 2024 were all of the sheep strain,and sheep biovar 3 was predominant(70.31％).In 2014-2023,although Jining City experienced a high incidence of brucellosis,a downward trend was observed.Brucellosis showed a spatial clustering pattern concentrated in the northeastern region.Therefore,awareness and education must be strengthened among brucellosis practitioners in cluster areas,to en-hance case surveillance,improve the level of protection,and achieve early detection and treatment.

Objective To verify the performance of an non competitive immune sandwich method(candidate method)in detecting 25(OH)D,and evaluate the measurement agreement of candidate method with liquid chromatography tandem mass spectrometry(LC-MS/MS,reference method).Methods According to the comparison of documents such as China National Accreditation Service for Conformity Assessment(CNAS)-GL037,the precision,linear interval,lower limit of quantitation(LOQ)and accuracy of the method for detecting 25(OH)D were verified.1 073 residual serum samples were collected from March to July 2021 and 25(OH)D was detected by the two methods.Passing-bablok regression,concordance correlation coefficient(CCC),Bland altman plots and Kappa test were used to analyze the consistency and bias.Weighted Kappa test was conducted to evaluate the consistency of two methods for clinical assessment of vitamin D nutritional status.Results The performance of candidate method:the within-run CV was lower than 5%and the in laboratory CV were lower than 10%;test results between 2.88～52.45 ng/ml showed good linear relationship;the lower limit of quantitation was 2.26 ng/ml,the bias of candidate method measuring standard reference materials were within±6%and within 15%measuring vitamin D external quality assessment scheme(DEQAS)samples.The comparison method and the reference method showed good correlation(r=0.965,CCC=0.946)with an average deviation of-1.54 ng/ml(-7.42%).The two methods coincidence rate in judging vitamin D status was 85.96%(918/1 068),and the weighted kappa value was 0.801.Conclusions The candidate method measurement performance met the clinical requirements,and showed good correlation and consistency with the reference method.

Objective To evaluate the comprehensive value of methicillin-resistant Staphylococcus aureus(MRSA)treatment drugs in artificial joint infections from multiple perspectives and to solve the problem of MRSA infections in artificial joints.Methods Through literature research,relevant literature was retrieved and clinical studies meeting the requirements were selected and summarized.The Analytic Hierarchy Process(AHP)was applied to collect comprehensive clinical evaluation evidence and to conduct evaluations across different dimensions according to evaluation guidelines;the Delphi method combined with AHP was used for expert anonymous questionnaire evaluation,and the data was compared and analyzed.Results A clini-cal comprehensive evaluation index model for the treatment of artificial joint infections was successfully established,and the yaahp analysis software was used to score the comprehensive clinical evaluation evidence in various directions.Treatment drugs,vancomy-cin,daptomycin,and linezolid,at various levels were calculated through the software,and it was concluded that linezolid has the highest clinical comprehensive evaluation score.Conclusion Among the treatment drugs for MRSA infections in artificial joints,linezolid has a higher clinical comprehensive value and can provide a reference for the clinical treatment of MRSA infec-tions in artificial joints.

We analyzed the epidemiological features and spatial distribution characteristics of human brucellosis in Jining city from 2014 to 2023,to provide a reference for further development of targeted prevention and control strategies and measures.Descrip-tive epidemiological methods were used to analyze the epidemiological characteristics of brucellosis cases in Jining from 2014 to 2023.The spatial regional correlation of brucellosis incidence in Jining and the clustering patterns of local areas were studied through spatial autocorrelation analysis with townships as the basic unit.A total of 3 520 cases of brucellosis were reported in Jining from 2014 to 2023,and the average annual incidence rate was 4.23/100 000,thus indicating a fluctuating trend overall.Reported cases peaked from March to August,and a sex ratio of 2.71 males to 1 female was observed.The 40-59 year age group had the most reported cases(50.39％).The incidence of brucellosis in Jining showed an imbalanced spatial distribution.Brucellosis incidence showed a spatially clustered distribution(Moran's I>0,P<0.05).Hotspots were distributed primarily in Sishui,Qufu,and Zoucheng.A total of one class Ⅰ clustering area and one class Ⅱ clustering area were detected in the spatial and temporal scans,and were located in Sishui,Qufu,and Liangshan county.After pathogenic AMOS-PCR typing analysis,64 Brucella isolates collected from Jinan City from 2022 to 2024 were all of the sheep strain,and sheep biovar 3 was predominant(70.31％).In 2014-2023,although Jining City experienced a high incidence of brucellosis,a downward trend was observed.Brucellosis showed a spatial clustering pattern concentrated in the northeastern region.Therefore,awareness and education must be strengthened among brucellosis practitioners in cluster areas,to en-hance case surveillance,improve the level of protection,and achieve early detection and treatment.

Objective To verify the performance of an non competitive immune sandwich method(candidate method)in detecting 25(OH)D,and evaluate the measurement agreement of candidate method with liquid chromatography tandem mass spectrometry(LC-MS/MS,reference method).Methods According to the comparison of documents such as China National Accreditation Service for Conformity Assessment(CNAS)-GL037,the precision,linear interval,lower limit of quantitation(LOQ)and accuracy of the method for detecting 25(OH)D were verified.1 073 residual serum samples were collected from March to July 2021 and 25(OH)D was detected by the two methods.Passing-bablok regression,concordance correlation coefficient(CCC),Bland altman plots and Kappa test were used to analyze the consistency and bias.Weighted Kappa test was conducted to evaluate the consistency of two methods for clinical assessment of vitamin D nutritional status.Results The performance of candidate method:the within-run CV was lower than 5%and the in laboratory CV were lower than 10%;test results between 2.88～52.45 ng/ml showed good linear relationship;the lower limit of quantitation was 2.26 ng/ml,the bias of candidate method measuring standard reference materials were within±6%and within 15%measuring vitamin D external quality assessment scheme(DEQAS)samples.The comparison method and the reference method showed good correlation(r=0.965,CCC=0.946)with an average deviation of-1.54 ng/ml(-7.42%).The two methods coincidence rate in judging vitamin D status was 85.96%(918/1 068),and the weighted kappa value was 0.801.Conclusions The candidate method measurement performance met the clinical requirements,and showed good correlation and consistency with the reference method.

Objective To evaluate the comprehensive value of methicillin-resistant Staphylococcus aureus(MRSA)treatment drugs in artificial joint infections from multiple perspectives and to solve the problem of MRSA infections in artificial joints.Methods Through literature research,relevant literature was retrieved and clinical studies meeting the requirements were selected and summarized.The Analytic Hierarchy Process(AHP)was applied to collect comprehensive clinical evaluation evidence and to conduct evaluations across different dimensions according to evaluation guidelines;the Delphi method combined with AHP was used for expert anonymous questionnaire evaluation,and the data was compared and analyzed.Results A clini-cal comprehensive evaluation index model for the treatment of artificial joint infections was successfully established,and the yaahp analysis software was used to score the comprehensive clinical evaluation evidence in various directions.Treatment drugs,vancomy-cin,daptomycin,and linezolid,at various levels were calculated through the software,and it was concluded that linezolid has the highest clinical comprehensive evaluation score.Conclusion Among the treatment drugs for MRSA infections in artificial joints,linezolid has a higher clinical comprehensive value and can provide a reference for the clinical treatment of MRSA infec-tions in artificial joints.

Objective:To explore the mediating role of coping strategies in the relationship between disease uncertainty and post-discharge coping difficulties in mothers of preterm infants.Methods:A convenience sampling method was used to select 255 mothers of preterm infants from Shandong Provincial Hospital Affiliated to Shandong First Medical University, Linyi People 's Hospital, Weifang Maternal and Child Health Hospital, Maternal and Child Care Center of Dezhou, Dongying People 's Hospital between March and May 2023. General information surveys, the Parents ' Perception of Uncertainty Scale, the Simple Coping Style Questionnaire, and Post-Discharge Coping Difficulty Scale-Parent Form were administered on the day of discharge and 3 weeks post-discharge. Structural equation modeling was constructed using AMOS 23.0 software, and the mediating effect was tested using the Bootstrap method. Results:The disease uncertainty score for the 255 mothers of preterm infants was 66.00 (53.00, 77.00), the active coping score was 23.00 (17.00, 27.00), the passive coping score was 10.00 (7.00, 13.00), and the post-discharge coping difficulties score was 42.00 (26.00, 55.00). Mediating effect analysis showed that active and passive coping partially mediated the relationship between disease uncertainty and post-discharge coping difficulties, with mediating effects of 18.73% and 17.06%, respectively.Conclusions:Disease uncertainty can indirectly affect post-discharge coping difficulties through active and passive coping strategies. Healthcare providers should assist mothers of preterm infants in appropriately managing disease uncertainty and actively coping with challenges.

Objective:To investigate the current status of fertility concerns among early-stage endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) patients with fertility preservation, and analyze its influencing factors.Methods:Convenience sampling was used to select early-stage EC and AEH patients with fertility preservation at Peking University People's Hospital from January to December 2021 as study subjects. The study subjects were surveyed using the General Information Questionnaire, Chinese version of the Reproductive Concerns after Cancer Scale (RCAC), and Social Support Rating Scale (SSRS). Pearson correlation was employed to examine the relationship between fertility concerns and social support in early-stage EC and AEH patients with fertility preservation. Single-factor analysis and multiple linear regression analysis were used to examine the factors influencing fertility concerns in early-stage EC and AEH patients with fertility preservation.Results:A total of 170 questionnaires were distributed, and 167 valid questionnaires were collected, with a valid response rate of 98.24% (167/170). The RCAC and SSRS scores of 167 early-stage EC and AEH patients with fertility preservation were (56.58±10.58) and (34.22±8.21), respectively. Educational level, disease type and staging, marital status, and social support were statistically significant factors influencing fertility concerns among early-stage EC and AEH patients undergoing fertility preservation ( P<0.05), explaining 32.80% of the total variance. Conclusions:Early-stage EC and AEH patients with fertility preservation exhibit high levels of fertility concerns. Clinical practice should develop individualized psychological intervention programs for patients with high education level, unmarried status, high pathological grading, and lack of social support to improve their physical and mental health.