Objective To establish an acute rejection model of cervical heart transplantation in mice and evaluate the survival and dynamic rejection process post-transplantation. Methods Mice were randomly divided into sham operation group (n=10), syngeneic transplantation group (n=21), and allogeneic transplantation group (n=65). Sham operation, syngeneic cervical heart transplantation, and allogeneic cervical heart transplantation were performed respectively. The survival of recipient mice and grafts, histopathological changes of graft tissues, subpopulations of splenic lymphocytes, and expression of inflammatory factors in serum and grafts were observed. Results The survival rate and graft survival rate of the sham operation group and syngeneic transplantation group were 100% at 7 days after surgery. In the allogeneic transplantation group, 5 cases failed and died on the first day after surgery. The survival rate at 7 days after surgery was 86%, and all surviving mice had grafts that stopped beating at 7 days after surgery. The allogeneic transplantation group showed significant rejection at 7 days after surgery, accompanied by tissue damage and CD8⁺ T cell infiltration. The proportion of CD8⁺ T cells in the spleen continued to rise post-operation, while the proportion of CD4⁺ T cells showed a downward trend. The expression of interferon-γ in serum and grafts peaked at 5 days after surgery, while the expression of tumor necrosis factor-α showed no statistical significance. Conclusions Acute rejection following heart transplantation in mice intensifies between 5 to 7 days after surgery, which may be a critical time window for immunological intervention.

To explore the impact of an airway stepwise management strategy in the treatment of hospital acquired pneumonia (HAP) in the ultra elderly critically ill patients.

Objective To systematically evaluate the effect of exercise therapy on body structure,function,and activity and partici-pation in patients with chronic nonspecific neck pain(CNSNP)based on the International Classification of Func-tioning,Disability and Health(ICF)framework. Methods A PICO framework was constructed,and randomized controlled trials(RCTs)on the intervention of different types of exercise therapy for patients with CNSNP were retrieved from databases of CBM,Wanfang data,VIP,CNKI,Cochrane Library,Embase,PubMed and Web of Science,from the establishment to March,2024.The quality of the literature was evaluated with Cochrane Risk of Bias Tool and Physiotherapy Evidence Database(PEDro)scale,and the evidence quality of the outcome indicators was evaluated using GRADE.Data were syn-thesized and analyzed using RevMan 5.3,and the risk of bias was evaluated using Stata 18.0. Results A total of eleven RCTs involving 668 subjects were included.The scores of PEDro scale were five to eight.The types of interventions included muscle strength training,stability training,proprioception training,Yoga and Pi-lates.The control groups received placebo,physical factor therapy and health education.Exercise therapy could increase the craniovertebral angle(SMD=0.84,95%CI 0.42 to 1.26,P<0.001),reduce the Visual Analogue Scale score(SMD=-2.05,95%CI-2.58 to-1.52,P<0.001),increase the pressure pain threshold(MD=112.27,95%CI 75.03 to 149.50,P<0.001),increase the range of motion of cervical forward(SMD=1.24,95%CI 0.34 to 2.15,P=0.007)and lateral(SMD=1.52,95%CI 0.40 to 2.65,P=0.008)flexion,and improve the endurance of the deep cervical flexors(SMD=1.02,95%CI 0.10 to 1.94,P=0.03)and position sense of the cervical spine(SMD=-1.00,95%CI-1.47 to-0.53,P<0.001);however,it was not significant in improving the range of motion of backward flexion(SMD=0.85,95%CI-1.04 to 2.75,P=0.38)and rotation(SMD=1.65,95%CI-0.35 to 3.65,P=0.11).Exercise therapy could also reduce the Neck Disability Index score(MD=-11.88,95%CI-16.09 to-7.68,P<0.001),and it was no significant in the Short-Form-36 score(MD=19.04,95%CI-3.00 to 41.08,P=0.09). Conclusion Exercise therapy can improve head posture,pain,motion of forward flexion and lateral flexion,endurance of the cervical flexors and joint position sense,and the overall function in patients with CNSNP.However,fur-ther researches are needed to verify the effects on cervical backward flexion and rotation,and quality of life.

Myocardial fibrosis is a common pathological manifestation of various heart diseases,with hidden onset and the possibility of evolving into irreversible heart failure.Currently,there is still insufficient diagnosis and treatment of myocardial fibrosis.Traditional Chinese medicine can regulate myocardial fibrosis at multiple levels,targets,and pathways,and has significant advantages in treating myocardial fibrosis.Its underlying mechanisms are worth further exploration.The theory of"yang generating qi,yin constituting the body"in Huangdi Neijing embodies the meaning of yin and yang,containing a profound outlook on life and disease.Pathological changes in the initial,progressive,and final stages of myocardial fibrosis conform to the yin-yang theory of"yang generating qi,yin constituting the body".Insufficient yang generating qi and excessive yin constituting the body constitutes the core pathogenesis of myocardial fibrosis.This article proposes a treatment approach for myocardial fibrosis by tonifying yang and abating yin.The treatment of warming yang,unblocking yang,removing blood stasis,resolving phlegm,detoxifying,and promoting diuresis is applied to broaden the clinical treatment approach for myocardial fibrosis.

Background::Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.Methods::Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation. Results::Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI ( P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models ( P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species ( P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD). Conclusions::YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

Objective:To construct and validate a nomogram model for predicting the risk of 28-day mortality in sepsis patients.Methods:A retrospective cohort study was conducted. 281 sepsis patients admitted to the department of intensive care unit (ICU) of the 940th Hospital of the Joint Logistics Support Force of PLA from January 2017 to December 2022 were selected as the research subjects. The patients were divided into a training set (197 cases) and a validation set (84 cases) according to a 7∶3 ratio. The general information, clinical treatment measures and laboratory examination results within 24 hours after admission to ICU were collected. Patients were divided into survival group and death group based on 28-day outcomes. The differences in various data were compared between the two groups. The optimal predictive variables were selected using Lasso regression, and univariate and multivariate Logistic regression analyses were performed to identify factors influencing the mortality of sepsis patients and to establish a nomogram model. Receiver operator characteristic curve (ROC curve), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to evaluate the nomogram model.Results:Out of 281 cases of sepsis, 82 cases died with a mortality of 29.18%. The number of patients who died in the training and validation sets was 54 and 28, with a mortality of 27.41% and 33.33% respectively. Lasso regression, univariate and multivariate Logistic regression analysis screened for 5 independent predictors associated with 28-day mortality. There were use of vasoactive drugs [odds ratio ( OR) = 5.924, 95% confidence interval (95% CI) was 1.244-44.571, P = 0.043], acute physiology and chronic health evaluation Ⅱ (APACHEⅡ: OR = 1.051, 95% CI was 1.000-1.107, P = 0.050), combined with multiple organ dysfunction syndrome (MODS: OR = 17.298, 95% CI was 5.517-76.985, P < 0.001), neutrophil count (NEU: OR = 0.934, 95% CI was 0.879-0.988, P = 0.022) and oxygenation index (PaO 2/FiO 2: OR = 0.994, 95% CI was 0.988-0.998, P = 0.017). A nomogram model was constructed using the independent predictive factors mentioned above, ROC curve analysis showed that the AUC of the nomogram model was 0.899 (95% CI was 0.856-0.943) and 0.909 (95% CI was 0.845-0.972) for the training and validation sets respectively. The C-index was 0.900 and 0.920 for the training and validation sets respectively, with good discrimination. The Hosmer-Lemeshoe tests both showed P > 0.05, indicating good calibration. Both DCA and CIC plots demonstrate the model's good clinical utility. Conclusions:The use of vasoactive, APACHEⅡ score, comorbid MODS, NEU and PaO 2/FiO 2 are independent risk factors for 28-day mortality in patients with sepsis. The nomogram model based on these 5 indicators has a good predictive ability for the occurrence of mortality in sepsis patients.

Objective:To investigate the prevalence of albuminuria in Chinese residents aged >35 years and its potential association with cardiovascular disease (CVD).Methods:A total of 34 647 Chinese subjects aged ≥35 years were selected by stratified multi-stage random sampling from 2012 to 2015. Data were collected through questionnaires, physical examinations, and laboratory tests. Albuminuria was categorized into 3 types according to urinary albumin-to- creatinine ratio: normal (<30 mg/g), microalbuminuria (MAU, 30-300 mg/g), and macroalbuminuria (≥300 mg/g). Measurement data were expressed as xˉ±s, and t-tests were used for comparisons between indicators. Qualitative data were expressed as rate or constituent ratio, and the χ2 test or Kruskal-Wallis test was used to examine differences. Logistic regression was used for multivariate analyses. SAS 9.4 software was used for statistical analyses, and P<0.05 was considered statistically significant. Results:The prevalence of abnormal albuminuria was 19.1%; the prevalence was 17.2% for MAU and lower in males (13.8%) than females (20.1%, P<0.01). The risk of CVD was higher among subjects with MAU ( OR=1.23, 95% CI 1.12-1.35) and macroalbuminuria ( OR=1.86, 95% CI 1.50-2.32). When MAU was complicated by hypertension and diabetes mellitus, the CVD risk was 1.76 times higher. Conclusions:The prevalence of MAU is high among Chinese subjects aged 35 years and over. Those with MAU have higher CVD risk, especially those with hypertension and diabetes mellitus.

The prevalence of heart failure(HF) is increasing worldwide, and mitral regurgitation(MR) is a common manifestation in patients with end-stage HF. Currently, the indications for concomitant surgical intervention of significant preoperative MR during left ventricular assist device(LVAD) implantation are still controversial. Based on discussing the etiology, classification, and pathophysiology of functional MR in patients with end-stage HF, this paper reviews the relevant factors affecting the prognosis of such patients and the progress of research related to whether to perform mitral valve surgery to intervene in significant MR during LVAD implantation, to provide a further reference for clinical practice.

OBJECTIVE: To investigate the effect of electroacupuncture on osteoarthritis in rats and explore the possible mechanism. METHODS: Thirty SD rats were randomly divided into osteoarthritis model group, electro-acupuncture group and control group (n=10), and in the former two groups, early osteoarthritis was induced using a modified DMM surgical modeling method. After successful modeling, the rats in the electro-acupuncture group were treated with electro-acupuncture at bilateral "Housanli" and "Anterior knee point". Behavioral tests of the rats were performed and scored using the LequesneMG scale. Subchondral bone degeneration was observed in each group, and serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP were measured using ELISA. The mRNA and protein expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7, and MMP-3 in the cartilage tissue of the knee joints were detected using RT-PCR and Western blotting. RESULTS: In behavioral tests, the rats in the model and electroacupuncture groups had significantly higher LequesneMG scores after modeling than those in the control group (P < 0.05). After 20 days of treatment, LequesneMG scores were significantly lowered in rats in the electroacupuncture as compared with the model rats (P < 0.05). Imaging examination revealed obvious subchondral bone damage in both the electroacupuncture group and the model group, but the damages were significantly milder with former group. Compared with the model rats, the rats receiving electroacupuncture had significantly lower serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP (P < 0.05) with also lower expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7 and MMP-3 in the cartilage tissues at both the mRNA and protein levels (P < 0.05). CONCLUSION Electroacupuncture can alleviate joint pain and improve subchondral bone damage in rats with osteoarthritis by reducing IL-1β levels in the joint cartilage tissue and serum to alleviate joint inflammation and by reducing such cytokines as ADAMTS-7 and MMP-3 via regulating the Wnt-7B/β-catenin signaling pathway.
Rats ; Animals ; Electroacupuncture ; Matrix Metalloproteinase 3/metabolism* ; Rats, Sprague-Dawley ; beta Catenin/metabolism* ; Osteoarthritis/metabolism* ; Wnt Signaling Pathway ; Cartilage, Articular ; Inflammation/metabolism*

Long noncoding RNAs (lncRNAs) are expressed in different species and different tissues, and perform different functions, but little is known about their involvement in the synthesis or secretion of follicle-stimulating hormone (FSH). In general, we have revealed lncRNA‍‒‍microRNA (miRNA)‍‒‍‍messenger RNA (mRNA) interactions that may play important roles in rat primary pituitary cells. In this study, a new lncRNA was identified for the first time. First, we analyzed the gene expression of lncRNA-m18as1 in different tissues and different stages by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and observed the localization of lncRNA-m18as1 with fluorescence in situ hybridization, which indicated that this lncRNA was distributed mainly in the cytoplasm. Next, we used RT-qPCR and enzyme-linked immunosorbent assay (ELISA) to analyze the regulation of FSH synthesis and secretion after overexpression or knockdown of lncRNA-m18as1 and found that lncRNA-m18as1 was positively correlated with FSH synthesis and secretion. In addition, mothers against decapentaplegic homolog 2 (Smad2) was highly expressed in our sequencing results. We also screened miR-18a-5p from our sequencing results as a miRNA that may bind to lncRNA-m18as1 and Smad2. We used RNA immunoprecipitation-qPCR (RIP-qPCR) and/or dual luciferase assays to confirm that lncRNA-m18as1 interacted with miR-18a-5p and miR-18a-5p interacted with Smad2. Fluorescence in situ hybridization (FISH) showed that lncRNA-m18as1 and miR-18a-5p were localized mainly in the cytoplasm. Finally, we determined the relationship among lncRNA-m18as1, miR-18a-5p, and the Smad2/3 pathway. Overall, we found that lncRNA-m18as1 acts as a molecular sponge of miR-18a-5p to regulate the synthesis and secretion of FSH through the Smad2/3 pathway.
Animals ; Cell Line, Tumor ; Cell Proliferation ; Follicle Stimulating Hormone/metabolism* ; Gene Expression Regulation, Neoplastic ; In Situ Hybridization, Fluorescence ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Rats