Sepsis is a life-threatening organ dysfunction caused by the body's dysregulated response to infection. Reversible myocardial dysfunction caused by sepsis is known as septic cardiomyopathy. A thorough understanding of the pathogenesis of septic cardiomyopathy is crucial for early intervention to prevent its progression and improve the success rate of sepsis treatment. At present, the research on the pathogenesis of septic cardiomyopathy mainly focuses on two aspects: the systemic neuroimmune mechanism and the local changes of cardiomyocytes. The former mainly includes the autonomic nervous dysfunction mainly caused by sympathetic overactivation and the inflammatory storm induced by immune response disorder. The latter covers the dysregulation of calcium homeostasis, mitochondrial dysfunction and energy metabolism disorder of cardiomyocytes. Immune dysfunction is one of the key factors that cause the poor prognosis of patients with septic cardiomyopathy. Macrophages are sentinel cells of the body's innate immunity. Cardiac macrophages have been confirmed to be one of the most heterogeneous immune cells in the heart. According to their origin and differentiation, they can be divided into bone marrow-derived tissue infiltrating macrophages and cardiac resident macrophages, which have roles of polarization, phagocytosis, regulation of inflammatory response, and participate in innate and adaptive immunity. In the occurrence and development of septic cardiomyopathy, cardiac macrophages recruited from the blood participate in balancing the inflammation and repair of myocardial tissue through the conversion of pro-inflammatory phenotype and anti-inflammatory phenotype. Cardiac resident macrophages mediate immune phagocytosis to maintain the local homeostasis of cardiomyocytes, and the glycometabolic reprogramming of macrophages regulates the release of inflammatory factors, while macrophage metabolic reprogramming regulates the release of inflammatory factors. A deeper understanding of the biological behavior of macrophages, and regulating the polarization, metabolism and phagocytosis of cardiac macrophages, could serve as new target for the prevention and treatment of septic cardiomyopathy. Therefore, this article reviews the key pathogenesis of septic cardiomyopathy and the role of macrophages of different origins and differentiation, revealing the possibility of developing new strategies for the prevention and treatment of septic cardiomyopathy.
Humans ; Cardiomyopathies/pathology* ; Macrophages/immunology* ; Sepsis/complications* ; Myocytes, Cardiac

Objective:To systematically review and evaluate the predictive efficacy of various derived indicators of sequential organ failure assessment (SOFA) in mortality rate of sepsis patients.Methods:Literature on sepsis and SOFA scores were searched in PubMed, Embase and Cochrane Library. The retrieval time will be set to the time of database-building to February, 2023. The main outcome measures included 28-day mortality, 30-day mortality, in-hospital mortality, intensive care unit (ICU) mortality and long-term mortality. Literature screening, data extraction and quality evaluation were carried out independently by 2 researchers. Data were analyzed by Revman 5.3.5, Meta-disc and Stata software. Deek funnel plots were used to assess publication bias in the included studies.Results:A total of 40 articles including 51 trials were included. Of these, 32 were in English and 8 in Chinese, 17 were in prospective trials and 34 were in retrospective trials, 38 were in initial SOFA-related trials and 9 were in the change of SOFA score (ΔSOFA)-related studies, a total of 59?962 patients were enrolled. ① The area under the receiver operator characteristic curve (AUC) of initial SOFA and ΔSOFA for predicting outcome in sepsis was 0.773 and 0.787 ( Z = 0.115, P > 0.05), respectively. There was no significant difference between the two indexes in predicting the outcome of patients with sepsis. ② In subgroup analysis, due to limitations in the number of literature articles, the 28-day mortality rate and 30-day mortality rate were merged for discussion. The predictive power of ΔSOFA for 28-day or 30-day mortality was significantly higher than that of initial SOFA (AUC was 0.854, 0.787, Z = 2.603, P ≤ 0.01). ③ There were few studies onΔSOFA in predicting in-hospital mortality, ICU mortality and long-term mortality of sepsis patients. The AUC of the initial SOFA for predicting the study endpoints described above was: ICU mortality (0.814) > 28-day or 30-day mortality (0.787) > in-hospital mortality (0.697) > long-term mortality (0.646). ④ Initial SOFA and ΔSOFA in patients with sepsis of non-Han original had good predictive performance and there was no significant difference between them (AUC was 0.766, 0.811, respectively). However, the pooled sensitivity of ΔSOFA was higher (92%). ⑤ In prospective studies, initial SOFA was better at predicting outcomes in patients with sepsis (AUC was 0.804, pooled sensitivity 64%). The sensitivity of ΔSOFA indicators in predicting the outcome of sepsis patients was significantly higher than the initial SOFA (78% vs. 64%). The funnel plot showed that there was no significant publication bias in the included literature. Conclusion:ΔSOFA has a relatively high diagnostic efficacy in predicting short-term (28-day or 30-day) mortality in patients with sepsis.

Objective:To discuss the therapeutic effect of resveratrol on the temporomandibular joint osteoarthritis(TMJOA),and to clarify the related mechanism.Methods:Forty-five SD rats were randomly divided into control group,model group,and resveratrol group,and there were 15 rats in each group.The rats in model group and resveratrol group were intra-articularly injected with 50 μL of 20 g·L-1 monosodium iodoacetate(MIA)to set TMJOA rat models,while the rats in control group were injected with an equal volume of normal saline.Three weeks after modeling,the rats in resveratrol group received an injection of 80 μL resveratrol solution,once a week for three weeks,while the rats in control and model groups were injected with an equal volume of normal saline.Micro-computed tomography(Micro-CT)system was used to detect the condyle structure and the bone volume fraction(BV/TV),trabecular thickness(Tb.Th),trabecular spacing(Tb.Sp),and trabecular number(Tb.N)of the rats in various groups were calculated;HE staining and toluidine blue staining were used to observe the pathomorphology of temporomandibular joint(TMJ)tissue of the rats in various groups;immunohistochemistry was used to detect the expression levels of SRY-related HMG box(SOX)-9,matrix metalloproteinase(MMP)-13,silent information regulator(Sirt)1,phosphatidylinositol 3-kinase(PI3K),phosphorylated protein kinase B(p-Akt),and phosphorylated mammalian target of rapamycin(p-mTOR)in TMJ tissue of the rats in various groups;real-time quantitative PCR(RT-qPCR)method was used to detect the expression levels of SOX-9,MMP-13,Sirt1,PI3K,mTOR,and Akt mRNA in TMJ tissue of the rats in various groups.Results:Three weeks after modeling,condylar bone was destructed,the surface was roughness,and continuity interruption were observed,indicating TMJOA model of the rats was established successfully.The Micro-CT system results showed that the condylar surface of the rats in control group was smooth and regularly shaped,with continuous bone texture;the rats in model group had significant condylar destruction,disrupted continuity,surface roughness,and varying degrees of bone defects;the rats in resveratrol group showed alleviated condylar lesions and improved appearance.Compared with control group,the BV/TV and Tb.Th of the rats in model group were significantly decreased(P<0.05),and Tb.Sp was significantly increased(P<0.05);compared with model group,the BV/TV and Tb.Th of the rats in resveratrol group were significantly increased(P<0.05),and the Tb.Sp was significantly decreased(P<0.05).The HE staining results showed clear layers and orderly chondrocyte arrangement in condyle of the rats in control group;the rats in model group showed rough uneven surface,obvious defects,and typical TMJOA features;the rats in resveratrol group showed slightly rough surface with generally clear layers and orderly arranged cells.The toluidine blue staining results showed distinct blue-purple staining of chondrocytes in hypertrophic layer of the rats in control group;pale staining or even loss of staining in some areas of the rats in model group;and distinct and relatively uniform staining in hypertrophic layer of the rats in resveratrol group.The immunohistochemistry results showed that compared with control group,the expression levels of MMP-13,PI3K,p-Akt,and p-mTOR proteins in TMJ tissue of the rats in model group were significantly increased(P<0.05),while the expression levels of SOX-9 and Sirt1 proteins in TMJ tissue of the rats were significantly decreased(P<0.05);compared with model group,the expression levels of SOX-9 and Sirt1 proteins in TMJ tissue of the rats in resveratrol group were significantly increased(P<0.05),whereas the expression levels of MMP-13,PI3K,p-Akt,and p-mTOR proteins were significantly decreased(P<0.05).The RT-qPCR results showed that compared with control group,the expression levels of MMP-13,PI3K,Akt,and mTOR mRNA in TMJ tissue of the rats in model group were significantly increased(P<0.05),while the expression levels of SOX-9 and Sirt1 mRNA were significantly decreased(P<0.05);compared with model group,the expression levels of SOX-9 and Sirt1 mRNA in TMJ tissue of the rats in resveratrol group were significantly increased(P<0.05),whereas the expression levels of MMP-13,PI3K,Akt,and mTOR mRNA were significantly decreased(P<0.05).Conclusion:Resveratrol has therapeutic effect on TMJOA,and its mechanism may be related to the activation of Sirt1 and inhibition of the PI3K-Akt-mTOR signaling pathway.

Objective:To explore the experience of self-management dilemma ofadults with emerging ankylosing spondylitis, and to provide reference for the construction of self-management intervention strategies for emerging adults with ankylosing spondylitis.Methods:Descriptive phenomenology was used to conduct in-depth interviews with 14 adults with emerging ankylosing spondylitis in the Rheumatology and Immunology Department of Drum Tower Hospital Affiliated to Medical College of Nanjing University from August 2022 to March 2023. The interview data were analyzed by Colaizzi′s seven-step analysis method.Results:A total of 14 patients completed the interview,10 males, 4 females, aged 21-30 years. In adults with emerging ankylosing spondylitis, there were dilemmas of role maladjustment and disease management disorder, including role maladjustment of disease management and social role maladjustment. Barriers to disease management included weak self-management awareness, insufficient support for self-management information, inadequate self-management skills, and poor compliance with self-management behaviors.Conclusions:The role adaptation and self-management ability of adults with emerging ankylosing spondylitis are seriously inadequate. It is urgent to construct health management strategies for adults with emerging ankylosing spondylitis to help them improve the level of role adaptation and disease management.

Objective To explore the correlations of evaluations of right heart function parameters in patients with Ebstein anomaly(EA)using echocardiography and cardiac MRI.Methods Data of transthoracic echocardiography and cardiac MRI in 32 patients with EA confirmed by operation were retrospectively analyzed.The correlations of cardiac cavity size,right ventricular function and strain parameters obtained using echocardiography and the functional right ventricular(fRV)ejection fraction(EF)measured using MRI were explored.Results MRI fRV-EF in 32 cases of EA was(23.20± 7.61)％.Among echocardiographic parameters in 32 cases of EA,fractional area change(FAC)of fRV(r=0.347,P=0.015)was slightly,while global longitudinal strain(GLS)of fRV(r=0.801,P＜0.001)was highly positively correlated with MRI fRV-EF,respectively,whereas atrialized right ventricle(aRV)area/fRV area(r=-0.730,P=0.007)was highly negatively,aRV area/left ventricular area(r=-0.450,P=0.042)and right ventricular anterior-posterior diameter(r=-0.650,P=0.022)were both moderately negatively correlated with MRI fRV-EF.Both the left ventricular eccentricity index(r=-0.347,P=0.049)and Glasgow outcome scale extended(r=-0.336,P=0.024)obtained with echocardiography were slightly negatively correlated MRI fRV-EF.Conclusion Right heart function parameters in EA patients obtained with echocardiography were correlated with those of MRI fRV-GLS,among which aRV area/fRV area were highly positively correlated with MRI fRV-EF,hence having great value for evaluating right heart function in EA patients.

Objective:To explore the correlation between frailty and carotid plaque stability in patients with ischemic stroke.Methods:This study was a cross-sectional study. From May to December 2023, convenience sampling was used to select 360 patients with ischemic stroke in the Department of Neurology of Affiliated Hospital of Jining Medical University and underwent carotid artery color Doppler ultrasound examination as the study subject. Patients were surveyed using the General Information Questionnaire, Barthel Index and the Edmonton Frail Scale. Carotid artery color Doppler ultrasound was used to evaluate the stability of carotid plaques in patients. Multivariate Logistic regression was used to explore the correlation between frailty and carotid plaque stability.Results:A total of 360 questionnaires were distributed, and 352 valid questionnaires were collected, with a valid response rate of 97.78%. The incidence of frailty in 352 ischemic stroke patients was 44.89% (158/352). Multivariate analysis showed that compared to stable plaques, unstable carotid plaques were an independent risk factor for frailty in patients with ischemic stroke ( OR=2.127, 95% confidence interval: 1.247-3.626) . Conclusions:Compared to stable plaques, unstable carotid plaques increase the risk of frailty in patients with ischemic stroke. Strengthening the assessment of carotid plaques in patients with ischemic stroke by nursing staff can early identify high-risk individuals for frailty, and timely carry out personalized interventions, thereby reducing the occurrence of adverse health events in patients.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To compare the effects of auricular point intradermal needling with auricular point sticking on digestive symptoms and quality of life in patients undergoing platinum-based chemotherapy regimens. Methods:Ninety-six patients receiving platinum-based chemotherapy were randomly assigned to three groups using the random number table method,with 32 cases in each group.The control group received conventional nursing care plus 5-hydroxytryptamine receptor antagonist,and the other two groups received additional auricular point intradermal needling or sticking.For the three groups of participants,the acute and delayed vomiting and nausea severity,quality of life,and the additional antiemetic consumption rate were observed. Results:The three groups had no significant differences in the acute vomiting frequency and nausea severity and appetite(P>0.05)but had significant differences in the delayed vomiting frequency and nausea severity(P<0.05);the auricular point intradermal needling group won over the auricular point sticking group.The three groups showed significant differences in comparing the appetite in the delayed stage(P<0.05);both auricular point intradermal needling and sticking groups showed advantages over the control group(P<0.05),but no significant difference existed between the auricular point intradermal needling and sticking groups(P>0.05).There were significant differences in comparing the functional living index-emesis(FLIE)score in both acute and delayed stages among the three groups(P<0.05)and the result favored the auricular point intradermal needling group over the auricular point sticking group(P<0.05).The additional antiemetic consumption rate was higher in the control group than in the other groups(P<0.05). Conclusion:Based on the conventional nursing and 5-hydroxytryptamine receptor antagonist,adding either auricular point intradermal needling or auricular point sticking can lower the vomiting frequency and nausea severity in the delayed stage and improve appetite in patients receiving platinum-based chemotherapy regimen,but they have no notable impact on digestive symptoms in the acute stage;auricular point intradermal needling is superior to auricular point sticking in comparing the overall efficacy.Both auricular point intradermal needling and auricular point sticking can enhance the quality of life in patients undergoing chemotherapy and reduce their additional antiemetic consumption.

Sepsis is an organ dysfunction caused by dysregulation of the body's response to infection, with high morbidity and mortality. The pathogenesis of sepsis is still unclear, and there are no specific treatment drugs. As a cell energy supply unit, the dynamic changes of mitochondria are closely related to various diseases. Studies have shown that structure and function of mitochondria are changed in different organs during sepsis. The energy shortage, oxidative stress change, imbalance of fusion and fission, autophagy reduce, biological functions of mitochondria play important roles in sepsis progress, which can provide a research target for the treatment of sepsis.
Humans ; Mitochondria/pathology* ; Sepsis/drug therapy* ; Oxidative Stress ; Autophagy

Objective:To research whether clinical outcomes of patients with sepsis can be improved by higher enteral nutritional support.Methods:A retrospective cohort method was applied. 145 patients with sepsis who were hospitalized in intensive care unit (ICU) of Peking University Third Hospital from September, 2015 to August, 2021 and met inclusion criteria as well as exclusion criteria were selected, including 79 males and 66 females, the median age was 68 (61, 73). Researchers evaluated whether there was correlation between improved modified nutrition risk in critically ill score (mNUTRIC), daily energy intake and protein supplement of patients and their clinical outcomes through Poisson log-linear regression analysis and Cox regression analysis.Results:The median of mNUTRIC score of 145 hospitalized patients was 6 (3, 10), wherein 70.3% of patients (102 cases) were in high-score group (≥ 5 scores) and 29.7% of patients (43 cases) were in low-score group (< 5 scores); the average of daily protein intake in ICU was about 0.62 (0.43, 0.79) g·kg -1·d -1, and the average of daily energy intake was about 64.4 (48.1, 86.2) kJ·kg -1·d -1. As shown by Cox regression analysis, increase of mNUTRIC score, sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) were correlated to growth of in-hospital mortality [hazard ratio ( HR) = 1.12, 95% confidence interval (95% CI) was 1.08-1.16, P = 0.006; HR = 1.04, 95% CI was 1.01-1.08, P = 0.030; HR = 1.08, 95% CI was 1.03-1.13, P = 0.023]. Higher average daily intake of protein and energy as well as lower mNUTRIC, SOFA, and APACHE Ⅱ scores were also significantly correlated to lower 30-day mortality ( HR = 0.45, 95% CI was 0.25-0.65, P < 0.001; HR = 0.77, 95% CI was 0.61-0.93, P < 0.001; HR = 1.10, 95% CI was 1.07-1.13, P < 0.001; HR = 1.07, 95% CI was 1.02-1.13, P = 0.041; HR = 1.15, 95% CI was 1.05-1.23, P = 0.014); however, there was no significant correlation between gender as well as number of complications and in-hospital mortality. Within 30 days of attack of sepsis, the average daily intake of protein and energy were not correlated to days of non-ventilator ( HR = 0.66, 95% CI was 0.59-0.74, P = 0.066; HR = 0.78, 95% CI was 0.63-0.93, P = 0.073). Increase of patients' average daily intake of protein and energy were significantly correlated to a lower in-hospital mortality ( HR = 0.41, 95% CI was 0.32-0.50, P < 0.001; HR = 0.87, 95% CI was 0.84-0.92, P < 0.001), shorter ICU stay ( HR = 0.46, 95% CI was 0.39-0.53, P < 0.001; HR = 0.82, 95% CI was 0.78-0.86, P < 0.001), and hospital stay ( HR = 0.51, 95% CI was 0.44-0.58, P < 0.001; HR = 0.77, 95% CI was 0.68-0.88, P < 0.001). According to correlation analysis, among patients with mNUTRIC score ≥ 5, increasing daily intake of protein and energy can reduce in-hospital mortality ( HR = 0.44, 95% CI was 0.32-0.58, P < 0.001; HR = 0.73, 95% CI was 0.69-0.77, P < 0.001), and 30-day mortality ( HR = 0.51, 95% CI was 0.37-0.65, P < 0.001; HR = 0.90, 95% CI was 0.85-0.96, P < 0.001); the receiver operator characteristic curve (ROC curve) further confirmed that higher protein intake had good predictive value for inpatient mortality area under the curve (AUC) = 0.96 and 30-day mortality (AUC = 0.94); higher emergy intake had good predictive value for inpatient mortality (AUC = 0.87) and 30-day mortality (AUC = 0.83). By contrast, among patients with mNUTRIC score < 5, it is only discovered that increasing daily intake of protein and energy can reduce 30-day mortality of patients ( HR = 0.76, 95% CI was 0.69-0.83, P < 0.001). Conclusions:The increase of average daily intake of protein and energy for patients with sepsis is significantly correlated to reduction of in-hospital mortality and 30-day mortality, shorter ICU stay, and hospital stay. The correlation is more significant in patients with high mNUTRIC score, and higher intake of protein and energy can bring down in-hospital mortality and 30-day mortality. As for patients with low mNUTRIC score, nutritional support cannot improve prognosis of the patients significantly.