Objective:To investigate the mechanism of improving liver injury by enhancing the abundance of Akkermansia mu-ciniphila(AKK bacteria)with hepatocyte-specific Yap1 knockout during PD-1 monoclonal antibody treatment.Methods:Hepatocyte-specific Yap1 knockout mice(genotype Yap1Flox/Flox;albumin-Cre,labeled as Yap1LKO)and control mice(genotype Yap1Flox/Flox,labeled Yap1Flox),aristolocholic acidⅠ(AAⅠ)and CCl4 were used to induce liver injury,Yap1LKO mice and Yap1Flox mice were randomly di-vided into control group and PD-1 monoclonal antibody group.After the intervention,real-time PCR detected changes in the abun-dance of AKK bacteria in the fecal microbial DNA of mice,16S rRNA gene sequencing further analyzes intestinal flora changes,the livers of mice were made into wax blocks for HE staining to observe the histopathological changes of the liver.Results:Yap1Flox mice exhibited balloon-like edema degeneration of hepatocytes and infiltration of inflammatory factors in the manifold area,compared with Yap1Flox mice,Yap1LKO mice had reduced the abundance of AKK bacteria in the intestine,fibrosis of the liver,and the degree of dam-age was more serious;PD-1 monoclonal antibody treatment alone did not increase the abundance of AKK bacteria in the intestines of mice,and fibrosis appeared in the liver;however,the abundance of intestinal AKK bacteria in Yap1LKO mice treated with PD-1 mono-clonal antibody increased,the ratio(F/B value)of Firmicutes to Bacteroides at the phylum level decreased,and the morphology of he-patocytes returned to normal and the degree of liver damage decreased.Conclusion:In AAⅠ and CCl4 induced liver injury mice,he-patocyte-specific Yap1 knockout reduced the abundance of AKK bacteria in the intestine,and the degree of liver injury was more se-vere than that in Yap1Flox mice.When treated with PD-1 monoclonal antibody,hepatocyte-specific Yap1 knockout could increase the abundance of AKK bacteria in the intestine,change the composition of intestinal flora,maintain intestinal homeostasis and ameliorate liver injury.

Recent research progress into the use of Chinese medicine has demonstrated good therapeutic effects for increasing numbers of Chinese medicines for immune system diseases.Atopic dermatitis(AD)is an inflammatory disease characterized by type 2 immunity,and research into its pathogenesis and therapeutic immunopharmaceuticals has result ed in various different types of animal models.This review summarizes the existing animal models of AD and their immune-related characteristics,with the aim of providing appropriate references for the selection of future research models related to AD.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective To investigate serum exosomal miRNA spectrum in patients with gestational diabetes mellitus(GDM)and eval-uate its clinical value in the diagnosis of GDM complicated with premature delivery.Methods Serum samples of pregnant women with GDM registered and delivered in our hospital were collected and divided into the premature delivery group and term labor group based on pregnancy outcomes,with 22 cases in each group.Serum exosomal miRNAs were sequenced,and the differentially expressed miRNAs were further verified by fluorescence quantitative PCR.The receiver operating characteristic(ROC)curve was drew according to the verified expression level of miRNAs,and the value of exosomal miRNAs in the diagnosis of GDM complicated with premature de-livery was analyzed.The potential functions of candidate miRNAs were predicted using the Kyoto Encyclopedia of Genes and Genomes(KEGG).Results A total of 94 differentially expressed miRNAs,including 50 up-regulated and 44 down-regulated,were identified in the premature delivery group and term labor group.The verification results of fluorescence quantitative PCR showed that 7 miRNAs had significant difference between the two groups(P<0.05).Moreover,the expression trend was consistent with the sequencing results.The analysis results of the ROC curve showed that the seven miRNAs had good diagnostic efficacy for GDM combined with premature delivery.The areas under the ROC curve(AUCROC)of hsa-miR-16-5p,hsa-miR-25-3p,hsa-miR-30b-5p,and hsa-miR-92a-3p were all more than 0.7.Their sensitivity and specificity were 0.375 and 1.000,0.563 and 0.941,0.563 and 0.824,and 0.765 and 0.647,respectively.The binary logistic regression analysis showed that the AUCROC of the combination of hsa-miR-16-5p,hsa-miR-25-3p,hsa-miR-30b-5p,and hsa-miR-92a-3p for the diagnosis of GDM complicated with premature delivery increased to 0.982,and that its sensi-tivity and specificity were both more than 0.850.These candidate miRNAs were related to the ubiquitin-mediated proteolysis pathway,actin cytoskeleton regulatory pathway,mTOR signaling pathway,and P53 signaling pathway.Conclusion Serum exosomal miRNAs in GDM patients complicated with premature delivery have significant difference,which may be served as potential diagnostic markers.

Acute lung injury （ALI） refers to the rapid onset of dyspnea, hypoxemia, and diffuse alveolar damage induced by various direct and indirect injurious factors, representing one of the clinically common diseases with a high mortality rate. However, there is currently a lack of specific therapeutic interventions targeting their underlying pathological mechanisms. Western medical treatment primarily relies on supportive care, and the existing pharmacological agents for ALI are predominantly corticosteroids, which, while efficacious, often accompany severe adverse effects. Recent research has revealed that numerous active components in Traditional Chinese Medicine （TCM） exhibit remarkable efficacy in the prevention and treatment of ALI, providing new insights into the therapeutic approaches for ALI. In this article, the pathological mechanisms of ALI and the roles and mechanisms of active components from TCM in the prevention and treatment of ALI were reviewed, aiming to provide a theoretical basis for the development of new drugs for the prevention and treatment of ALI.

Objective To investigate the inhibitory effect of MKK6(E)fusion protein on the growth of o-varian cancer graft tumors in nude mice and its possible mechanism.Methods A subcutaneous transplantation tumor model in nude mice was constructed using subcutaneous injection of human ovarian cancer HO8910PM cells,which were divided into model group,paclitaxel(positive control,3 mg/mL)group,MKK6(E)fusion protein(1.2 mmol/L)group and MKK6(E)fusion protein+SB202190(p38 agonist,10 μmol/L)group by numerical randomization table,each with 6 animals.The drug was administered continuously in the tail vein for 21 d,once every 3 d.At the end of the administration,the tumor was exfoliated and the tumor volume,mass and tumor inhibition rate were calculated.Serum carbohydrate antigen(CA)125 level was detected by enzyme linked immunosorbent assay(ELISA),histopathology of the tumor was detected by HE staining,and apoptosis of the tumor cells was detected by TUNEL staining.In addition,expression of Fibronectin,matrix metallo-peptidase(MMP)2,and MMP9 were detected by immunohistochemistry,apoptosis and the p38/ATF-2 pathway-related proteins were detected by Western blot.Results Compared with the model group,the tumor volume,mass and serum CA125 level of nude mice in the paclitaxel group and the MKK6(E)fusion protein group were reduced,the tumor suppression rate and the apoptosis rate of cancer cells were increased,the volume of cancer cells in the transplanted tumor tissue was reduced,the nucleus was lightly stained,the di-viding heterogeneity was reduced compared with that of the model group,and the large area of lamellar nec-rotic zone and apoptotic cells were seen,and the expression of Fibronectin,MMP2 and MMP9 was reduced.Bax and Cleaved caspase 3 expression was up-regulated,and Bcl-2 expression and phosphorylated p38(p-p38)/p38 and p-ATF-2/ATF-2 were down-regulated(P＜0.05).Compared with the MKK6(E)fusion pro-tein group,nude mice in the MKK6(E)fusion protein+SB202190 group showed increased tumor volume,mass and serum CA125 levels,decreased tumor suppression and cancer cell apoptosis,better cancer cell status,decreased necrotic areas,increased expression of Fibronectin,MMP2 and MMP9,and down-regulated Bax and Cleaved caspase 3 expression was down-regulated,and Bcl-2 expression and p-p38/p38 and p-ATF-2/ATF-2 were up-regulated(P＜0.05).While p-ERK/ERK and p-JNK/JNK were compared among the 4 groups,the difference was not statistically significant(P＞0.05).Conclusion MKK6(E)fusion protein inhibits the growth of ovarian cancer subcutaneous graft tumors,and its mechanism may be related to the inhibition of p38/ATF-2 signa-ling pathway activation.

Objective To study the traditional Chinese medicine(TCM)syndromes of patients with chronic heart failure(CHF)combined with diuretic resistance by using the Wenyang Huayin Yangxin Prescription,and to observe its therapeutic efficacy.Methods A total of 68 CHF patients complicated with diuretic resistance and who had Yangqi deficiency and presenting blood stasis syndrome combined with Tanyin were randomly assigned to a control group and an observation group.The control group was given intravenous furosemide(≥ 80 mg/d)via infusion pump in addition to standard Western medical treatment,while the observation group was given intravenous furosemide(＜80 mg/d)via infusion pump along with the Wenyang Huayin Yangxin Prescription(30 g Astragalus,15 g Poria,15 g Baizhu,15 g Chuanxiong,10 g Danfu tablet,10 g Cassia,10 g Alisma,and 10 g Zhimu).The quantitative index of diuretic resistance was used as the primary outcome measure.In addition,the differences between the two groups in TCM syndromes,cardiac function-related indicators,incidence of endpoint events,and readmission rate were compared.Results After 2 weeks of treatment,the filtration sodium excretion fraction(FENa)in the observation group was(0.18±0.04)％,while that of the control group was(0.16±0.03)％,showing a statistically significant difference(P=0.037).The 24-hour urine volume and urine Na+/K+ratio in the observation group increased significantly from baseline levels and were higher than those in the control group(P＜0.05).The differences in the changes of 24-hour urine volume,urine sodium,FENa,and urine Na+/K+ratio between the two groups were statistically significant(P＜0.05).The TCM syndrome scores decreased in both groups after 2 weeks of treatment,with the observation group showing a significantly greater reduction compared with the control group(P＜0.001).The differences in the changes of TCM syndrome scores between the two groups were statistically significant(P＜0.001).After 2 weeks of treatment,the observation group showed significant improvements in palpitations,shortness of breath,facial and limb edema,spontaneous sweating,chest tightness(pain),asthma,and oliguria compared with the baseline data(P＜0.05),while the control group showed improvements only in facial and limb edema,asthma,and oliguria(P＜0.05).Except for the asthma syndrome after 2 weeks of treatment,the observation group showed better outcomes in spontaneous sweating,chest tightness(pain),asthma,and oliguria at various time points after treatment compared with the control group(P＜0.05).After 2 weeks of treatment,the observation group had significantly better cardiac output(CO)and stroke volume(SV)compared with those of the control group(P＜0.05).The differences in the changes in N-terminal pro-brain natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF),SV,and CO between the two groups were statistically significant(P＜0.05).After 24 weeks of follow-up,no significant differences in the incidence of end-point events or readmission rates between the two groups were observed.Conclusion The Wenyang Huayin Yangxin Prescription,combined with low-dose intravenous furosemide administered through an infusion pump,can improve the TCM syndromes of patients with Yangqi deficiency and blood stasis syndrome combined with Tanyin in addition to CHF complicated by diuretic resistance.This treatment improves the patients'heart function and diuretic resistance,reduces the intravenous dosage of diuretic,and enhances clinical efficacy.This approach should be more widely applied in clinical settings.

Objectives:To summarize the relevant evidence of non-invasive cardiac output monitoring management in critically ill patients and provide evidence-based basis for strengthening the standardization and accuracy of non-invasive cardiac output monitoring by clinical medical staff.Methods:We searched UpToDate,British Medical Journal Best Practice Database,The UK National Institute of Clinical Medicine guideline library,PubMed,Embase,American Society of Critical Care Medicine,American Association of Critical Care Nurses,Wanfang database,China Knowledge Network,SinoMed and other databases to collect relevant clinical decisions,guidelines,best practices,evidence summaries,systematic reviews,expert consensuses and randomized controlled trials related to non-invasive cardiac output monitoring management.The search period is from the inception to August 2023.After screening and quality evaluation by the evidence-based team,relevant evidence that meets the standards was extracted.Results:A total of 11 articles were obtained,including 7 systematic reviews,4 expert consensus.Finally,20 best evidences were obtained about the non-invasive cardiac output monitoring management in critically ill patients,including the patients suitable for non-invasive cardiac output monitoring,correlation with the invasive cardiac output monitoring,and the source of error in the monitoring process,involving 5 aspects such as monitoring population,clinical application,interference factors,precautions and personnel training.Conclusions:Clinical medical staffshould strengthen the training of non-invasive cardiac output monitoring technology in critically ill patients,and appropriate practical evidence should be selected in combination with the specific clinical situation to improve the application standardization and measurement accuracy of non-invasive cardiac output monitoring in critically ill patients.

Objective:To investigate the effects of propionic acid produced by Akkermansia muciniphila on the radiosensitivity of colorectal cancer and the underlying mechanism. Methods:Normal human colon mucosal epithelial cells (NCM460) were used to determine the appropriate concentration of propionic acid. Human colorectal cancer cells (HCT-8) were treated with A. muciniphila-conditioned medium or propionic acid, followed by exposure to 6 Gy γ-ray irradiation, and cell survival and proliferation were measured by clone formation assay and Cell Counting Kit-8 (CCK-8) assay, respectively. A mouse model of colorectal cancer was established using azoxymethane/dextran sodium sulfate. The mice were divided into control model group, irradiation group, and irradiation+ propionic acid group. Their body weight, colorectal length, tumor count, and tumor area were recorded. The radiosensitizing effect of propionic acid was assessed with HE staining, immunohistochemical staining, and enzyme-linked immunosorbent assay. The mechanism was explored by using RT-PCR and flow cytometry. Results:CCK-8 assay showed that 1-mmol/L propionic acid had no significant effect on the proliferation of NCM460 cells ( P>0.05), which was used for subsequent experiments. Pretreated with A. muciniphila-conditioned medium or propionic acid, the survival and proliferation abilities of irradiated HCT cells were significantly decreased ( t=3.14-34.98, P<0.05). Compared with the irradiation group, the colorectal cancer mice in the irradiation+ propionic acid group showed a significantly longer colorectal length ( t=3.50, P<0.05) and a significantly smaller number of tumors ( t=3.48, P<0.05); the two groups had significantly smaller tumor areas than the control model group ( t=5.97, 7.30, P<0.05). HE staining and immunohistochemical staining showed that propionic acid restored colorectal structure, and decreased Ki67 expression in colorectal tissue ( t=14.50, 3.40, P<0.05). Propionic acid treatment significantly reduced the levels of the inflammatory factors interleukin-6 and tumor necrosis factor-α, as compared with the mice receiving irradiation alone ( t=4.86, 5.06, P<0.05). Irradiation plus propionic acid treatment significantly increased p53 expression and significantly aggravated G 2/M phase block and cell apoptosis ( t=20.35, 13.05, P<0.05). Conclusions:The A. muciniphila metabolite propionic acid plays a sensitizing role in radiation therapy for colorectal cancer by promoting G 2/M phase block and apoptosis in colorectal cancer cells.

Objective To investigate the relation between obstructive sleep apnea(OSA)and tinnitus.Meth-ods The data of subjects aged 20 years or above who participated in tinnitus and sleep questionnaire survey from the 2005-2008 and 2015-2018 National Health and Nutrition Surveys(NHANES)had been used,the people at risk of OSA were selected via the STOP-Bang questionnaire,and the association between the people at risk of OSA and tinnitus was determined by a Logistic regression model.Results Among the 5 183 participants,83.3％(4 320/5 183)and 16.7％(863/5 183)were classified into the non-tinnitus and tinnitus group,respectively.The tinnitus group had higher STOP-Bang scores(3.71±1.51)than those of the group without tinnitus(2.81±1.62)(P＜0.001).The observed prevalence rates of tinnitus in the low-risk,middle-risk and high-risk group were 8.1％(175/1 973),20.5％(435/1 689),27.8％(253/658),respectively.The multivariate Logistic regression model showed that patients with middle-risk and high-risk of OSA had an increased risk of tinnitus compared with low-risk group,with the OR values and confidence intervals of 2.348(1.920～2.871)and 3.136(2.488～3.953),respec-tively(P＜0.001).Conclusion People at risk of OSA are independently risk factors of tinnitus.Higher risk of OSA is associated with higher prevalence and higher risk of tinnitus.