ObjectiveThis study aimed to establish a monocrotaline （MCT）-induced pulmonary arterial hypertension （PAH） rat model to systematically evaluate the protective effect of Xiao Qinglongtang （XQLT） on right cardiac function in model rats and further elucidate the underlying regulatory mechanism. MethodsSixty male SD rats were randomly assigned to the normal group， model group， XQLT low-， medium-， and high-dose groups （XQLT-L/M/H）， and the beraprost sodium tablet group （BST）. Except for the normal group， rats in all other groups were given a single subcutaneous injection of MCT （60 mg·kg^-1） to induce PAH. Three weeks after injection， rats in the XQLT-L/M/H groups were administered XQLT intragastrically at 3.07， 6.14， 12.28 g·kg^-1·d^-1， respectively. Rats in the BST group received beraprost sodium at 12.6 μg·kg^-1·d^-1， and rats in the model group received an equal volume of saline. All treatments lasted for 3 weeks. Right ventricular systolic pressure （RVSP） was measured by right ventricular catheterization. Cardiac function was assessed by echocardiography. The right ventricle was weighed to calculate the right ventricular hypertrophy index （RVHI）. Hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy were used to observe myocardial morphology. Serum metabolomic changes were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）. Data-independent acquisition （DIA） proteomics was used to detect differentially expressed （DE） proteins in the right ventricle， and Western blot was used to measure the expression of uncoupling protein 3 （UCP3）， phosphatidylinositol 3-kinase catalytic subunit p110α （PIK3CA）， L1 cell adhesion molecule （L1CAM）， and quinone oxidoreductase （CRYZ）. UPLC-MS/MS was used to analyze the chemical components of XQLT. ResultsCompared with the normal group， the model group showed significantly increased RVSP and RVHI （P<0.05）， along with pathological changes in myocardial morphology. Compared with the model group， all XQLT-treated groups exhibited reductions in RVSP and RVHI as well as significant improvements in cardiac function and myocardial morphology. Among the XQLT groups， XQLT-M showed the most pronounced effects （P<0.05）， comparable to the BST group. Serum metabolomics revealed 105 differential metabolites in the XQLT groups versus the model group ［variable importance in projection （VIP） >1， P<0.05］， including 58 upregulated and 47 downregulated metabolites. KEGG enrichment analysis indicated that XQLT intervention downregulated phenylalanine metabolism （P<0.01） and upregulated unsaturated fatty acid biosynthesis （P<0.05）. Proteomics analysis showed that 982 DE proteins were identified in the MCT groups versus the normal group， including 455 upregulated and 527 downregulated proteins （|fold change （FC）| >1.3， P<0.05）. Compared with the model group， 237 DE proteins were identified in the XQLT groups， including 124 upregulated and 113 downregulated proteins （|FC| >1.3， P<0.05）， with 57 overlapping DE proteins. KEGG enrichment suggested that XQLT mainly modulated pathways related to mineral absorption， ribosomal biogenesis， peroxisomes， glycolysis/gluconeogenesis， spliceosomes， and thyroid hormone signaling. Western blot analysis showed that， compared with the model group， XQLT increased the expression of UCP3， PIK3CA， and L1CAM， while decreasing the expression of CRYZ （P<0.05）. ConclusionXQLT exerts a protective effect on right heart function in MCT-induced PAH rats， and its mechanism is associated with maintaining myocardial homeostasis and alleviating right ventricular remodeling.

Objective: To explore the management of blood donors tested reactive to HCV in blood screening based on confirmation of HCV infection. Methods: Multiple HCV antibody assays, repeating HCV RNA testing, follow-up of blood donors and retesting of archive samples were performed to confirm HCV infection, identify infection status, and exclude false positives in blood donors reactive to HCV in blood screening. Results: From 2011 to 2024, the unqualified rate of HCV detection in blood screening was 2.45‰(2 751/1 122 026). Among these, anti-HCV+-&NAT-accounted for 1.85‰, followed by anti-HCV++ at 0.60‰. The proportion of anti-HCV+-&NAT-and HCV RNA yields was extremely low (0.007‰). The positive rate of anti-HCV+-&NAT-samples tested by electrochemiluminescence method (ELCIA) was approximately 7.5%, differing among reagents (P<0.05). The follow-up of anti-HCV+-&NAT-donors showed that 96.2% (202/210) were false positives, but 51.4% of donors remained anti-HCV+-&NAT-during follow-up. Among them, 8 donors (3.8%) could not be ruled out from HCV infection due to positive retesting by ELCIA. Of the anti-HCV+-&NAT-donors who were reactive at the first follow-up, 86.8% remained anti-HCV+-&NAT-at the second follow-up. The sampling confirmation data showed that all of 260 anti-HCV++ donors were confirmed as anti-HCV positive, and the proportion of false positives or missed detections by NAT was very low. Two occult HBV infections (OBIs) and one HBsAg carrier were identified among the 3 anti-HCV +-&NAT+ donors, and no HCV infection was confirmed in 5 anti-HCV--&HCV RNA + donors. Conclusion: The prevalence of HCV among blood donors in Dalian was about 0.06%, with extremely low proportion of window-period infection and slightly higher proportion of resolved infections than that of current infections. The majority of anti-HCV+-&NAT-were false positive. Blood donors confirmed as false positive should be qualified in blood screening 3 months later before next donation. In order to reduce the false positive results, it was advisable to avoid the same type of supplementary reagents as the initial reagents when performing confirmation.

In response to the high risk of recurrence and metastasis after breast cancer surgery， this paper proposes a six-dimensional integrated preventive and therapeutic model， namely the "disease-syndrome-constitution-trend-strategy-efficacy" framework， including disease identification， syndrome differentiation， constitution differentiation， trend assessment， strategy implementation， and effect evaluation. This model builds upon the traditional three-dimensional approach of disease identification， syndrome differentiation and constitution differentiation， and introduces "trend" to dynamically capture the evolving tendencies of disease progression and the transformation of syndrome and constitution， thereby operationalizing the concept of "treating before disease onset". The "strategy" dimension enables the organic integration and individualized regulation of TCM and western medical interventions， while the "efficacy" dimension establishes a multidimensional evaluation system integrating TCM and western medicine to assess the efficacy of the "strategy"， so as to promote the systematic， dynamic， and precise development of treating before disease onset in TCM.

Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

ObjectiveTo analyze the correlation between family nurturing care environment and children with autism spectrum disorder (ASD) or at high risk, and to provide scientific evidence for the tertiary prevention of ASD in children at high risk. MethodsA case-control study, enrolling 30 children with ASD or at high risk for ASD as the case group, and 113 normal children who underwent routine physical examinations at the community health service centers and district maternal and child health care hospital during the same period as the control group, was conducted. The information for maternal pregnancy and childbirth, children, and family nurturing care was collected through the child healthcare system and a self-designed questionnaire survey. Multivariate logistic regression analyses were used to identify the relevant factors for ASD or high-risk status in children. ResultsMultivariate logistic regression analyses showed that among maternal and child factors, maternal adverse conditions during the3 months before pregnancy and throughout pregnancy (OR=6.026, 95%CI: 1.575‒23.062), and male gender (OR=4.064, 95%CI: 1.046‒15.784) were positively correlated with ASD or high risk status in children (P<0.05). Among family nurturing care factors, unbalanced dietary structure (OR=7.281, 95%CI: 1.819‒29.148) was positively correlated with ASD or high-risk status in children (P<0.05), while paternal companionship >2 h·d^-1 (OR=0.025, 95%CI: 0.001‒0.426) and parent-child interaction with responsive care (OR=0.824, 95%CI: 0.704‒0.963) were negatively correlated with ASD or high-risk status in children (P<0.05). ConclusionFactors positively correlated with ASD or high-risk status in children include maternal adverse conditions during the 3 months before pregnancy and throughout pregnancy, male gender, and unbalanced dietary structure. Factors negatively correlated with it include paternal companionship and parent-child interaction with responsive care. Clinically, comprehensively management of maternal pre-pregnancy and prenatal health, children’s diet and family nurturing care, along with focused developmental monitoring of boys, and efforts toward early detection, early diagnosis and early intervention should be strengthened.

[Objective] To explore the effects of different methods on antibody detection through investigating the causes of cross-matching incompatible in a patient with gastric malignant tumor, and to establish flow cytometry protocol for confirming hemolytic transfusion reaction (HTR). [Methods] Antibodies in the patient's serum were identified by red blood cells (RBCs) blood grouping, antibody screening and identification, acid elution test and PEG enhancement test. To confirm HTR, patient RBCs, proximal and distal ends RBCs, separated by capillary centrifugation, were tested by direct antiglobulin test (DAT) and Jk^a antigen single label and double label flow cytometry. [Results] Routine serological technology revealed the presence of anti-C, e (titer:2) and anti-Jka (titer >1) in the patient’s serum. After separation using capillary centrifugation technology, both the proximal and distal DAT and Jk^a antigen tests were negative. Both DAT and Jk^a antigen positive red blood cells (0.21%, 6/6 327) were found in the patient's blood samples by flow cytometry. After separation of blood samples by capillary centrifugation, there were significantly more DAT and Jk^a antigen double-positive RBCs in the distal end (0.43%, 33/7 707) than in the proximal end (0.09%, 15/7 225). Two blood samples were screened from over 100 donor blood samples that are compatible with the patient's cross-matching, and the transfusion effect was favorable. [Conclusion] Serological methods combined with flow cytometry could improve the sensitivity of antibody detection, provide a more accurate basis for the diagnosis of HTRs, and guarantee the safety of blood transfusion.

objective:To investigate the factors influencing failure of preoperative optimisation with exclusive enteral nutrition(EEN)in patients with Crohn's disease(CD)and to construct a predictive model.Methods:Clinical data of 161 patients with Crohn's disease who underwent surgical treatment after preoperative EEN optimization at the Inflammatory Bowel Disease Center of General Surgery of the Eastern Theater General Hospital from June 2021 to November 2023 were retrospectively analyzed.Patients were divided into two groups according to the preoperative EEN optimisation effect:optimisation success and optimisation failure.Logistic regression analysis was used to determine the factors influencing optimisation failure,and a column line graphical model was constructed using R4.4.0 software.Results:After at least 4 weeks of EEN treatment,a total of 44 patients(27.33%)failed preoperative optimization.Multifactorial analysis showed that FC>500 μg/g and use of corticosteroids were independent risk factors for failure of preoperative optimization,and an increase in prealbumin after 1 week of treatment was a protective factor for successful preoperative optimization.Based on the results of the multivariate analysis,a column graph was constructed,and the C-index was 0.873(95%CI=0.783～0.964).The calibration curve shows that the probability of failure predicted by the nomogram model prior to optimization is in good agreement with the actual probability.The clinical decision curve confirms that the risk threshold is between 0.03～0.96,and the nomogram model can be used to predict the failure of preoperative EEN optimization over other treatment options.Conclusion:FC>500μg/g and history of corticosteroid use were independent risk factors for failure of preoperative optimization,and an increase in prealbumin after 1 week of treatment was a protective factor for successful preoperative optimization.The nomogram constructed on the basis of these results has a good predictive value and is clinically applicable.

In recent years,the incidence of heat-related diseases has been on a steady upward trend,which is closely associated with environmental factors such as climate change and air pollution.Exposure to a hot environment and/or strenuous physical activities can progress to heat stroke(HS),an acute disease that can lead to death.Current research indicates that gut injury occupies the most crucial initiating position in the pathophysiological changes and pathogenesis of HS.Probiotics can reduce the incidence and mortality of HS through maintaining the health of the gut microbiota,regulating the intestinal immune system,and other effects.In addition,the gut microbiota can construct axis systems to interact with multiple organs such as the liver,lungs,and brain,which is of great significance for alleviating the damage to distant organs caused by HS.This paper reviews the regulation of the gut microbiota by probiotics to improve the intestinal heat tolerance ability and barrier function,aiming to provide references for the prevention and treatment of heat stroke in clinical practice.

Objective To investigate the role and mechanism of paeoniflorin(PF)in sepsis-associated acute kidney injury(SA-AKI)in mice.Methods Mouse SA-AKI model was constructed by intraperitoneal injection of 15 mg/kg LPS.Twenty-four male C57BL/6J mice(6～8 weeks old,weighing 20～25 g)were randomly divided into Control group,model group,PF group(intraperitoneally injected with 50 mg/kg PF 30 min before LPS administration),and β-catenin specific agonist BML284 group(10 mg/kg BML284 by intraperitoneal injection after 50 mg/kg PF administration).The renal histopathological changes were observed by HE staining and Paller scoring.ELISA was used to determine the contents of serum creatinine(Scr),neutrophil gelatinase-associated lipocalin(NGAL)and lactate,and renal contents of hexokinase 2(HK2),lactate dehydrogenase A(LDHA),IL-1β and IL-18.Western blotting was performed to detect the expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc.Results Compared with the Control group,the LPS group showed obviously damaged renal tissue,higher Paller score(P＜0.05),increased serum Scr and NGAL levels(P＜0.05),elevated renal contents of aerobic glycolytic indexes such as HK2,LDHA and serum lactate,as well as contents of IL-1β and IL-18(P＜0.05),and enhanced expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc in the renal tissue(P＜0.05).PF treatment attenuated the renal tissue damage,decreased Paller score(P＜0.05),reduced serum Scr and NGAL levels(P＜0.05),HK2,LDHA and serum lactate levels,and contents of IL-1 β and IL-18 in renal tissues(P＜0.05),and down-regulated the renal expression of total β-catenin,p-β-cateninY654,nucleusβ-catenin and c-Myc when compared with the levels in the model group(P＜0.05).While,addition of BML284 reversed above effects of PF treatment with significant differences(P＜0.05).Conclusion PF can alleviate SA-AKI,and its mechanism may be through its inhibiting the β-catenin/c-Myc pathway,thus reducing the aerobic glycolysis level and inflammatory response in renal tissue.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People