Myocardial fibrosis (MF) is a common pathological hallmark of cardiovascular diseases, reflecting shared mechanisms in their progression. However, the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery, highlighting the urgent need for more effective therapeutic agents. Herein, a novel contractile three-dimensional (3D) myocardial tissue model integrating cardiomyocytes, cardiac-fibroblasts, and bone marrow-derived macrophages in collagen hydrogel was developed to simulate the fibrotic changes of cardiovascular disease, and facilitate the screening of anti-MF compounds. The 3D myocardial tissue model exhibited precise, visualizable, and quantifiable contractile characteristics under hypoxia and drug interventions. 76 compounds extracted from the resins of Toxicodendron vernicifluum, a traditional Chinese medicine with clear clinical benefits for fibrotic diseases, were screened for anti-fibrotic activity. Using an in vitro 3D oxygen-glucose deprivation (OGD)-treated myocardial tissue model instead of a two-dimensional transforming growth factor-β treated cardiac-fibroblasts model, two candidates including LQ-40 and SQ-3 exert impressive anti-MF activity, which was further validated in left anterior descending coronary artery ligation-induced MF mouse model. The current results demonstrate the feasibility and advantage of the novel contractile 3D tissue model with multi-cell types in discovering candidates for MF, further stressing the great potential of regulating macrophages in the treatment of MF.

Purpose To detect the expression of peroxiso-mal membrane protein 4(PXMP4)in breast cancer tissues and to explore the effect of PXMP4 on the proliferation,invasion,and epithelial-mesenchymal transition(EMT)of breast cancer cells.Methods Bioinformatics and immunohistochemistry(IHC)were used to detect the expression of PXMP4 in breast cancer tissues.In breast cancer cells,Western blot was used to detect the expression of Cyclin D1,E-cadherin,vimentin and N-cadherin after knockdown and overexpression of PMXP4.The proliferation ability of breast cancer cells was analyzed by CCK-8 and plate cloning assay.Scratch healing and Transwell assay an-alyzed the migration and invasion ability of breast cancer cells.Lentivirus was used to construct a PXMP4-silenced MCF-7 cell line,and the PXMP4-silenced MCF-7 cells were injected into the subcutaneous or tail vein of mice to observe lung metastasis and the number of subcutaneous tumors.Results Bioinformat-ics and IHC showed that the expression of PXMP4 in breast cancer tissues was significantly increased(P＜0.05),and the prognosis of breast cancer patients with high expression of PXMP4 was poor(P＜0.05).The clinicopathological analysis showed that the expression of PXMP4 was correlated with tumor grade and lymph node metastasis(P＜0.05).In vitro knock-down of PMXP4 inhibited the proliferation,invasion and EMT process of breast cancer cells(P＜0.05).Conversely,overex-pression of PXMP4 promoted the proliferation,invasion and EMT process of breast cancer cells(P＜0.05).In vivo,the number of lung metastases,the size of subcutaneous tumor,and the expression of Ki67 in tumor tissue were significantly de-creased after silenced PXMP4(P＜0.05).Conclusion PXMP4 is related to tumor grading and lymph node metastasis.PXMP4 promotes proliferation,invasion and EMT process of breast cancer cells.

Objective To construct and identify a patient-derived organoid model,and to investigate the sensitivity of chemotherapy drugs using this model.Methods Pancreatic cancer cells were obtained from the surgical specimens of two female patients with a confirmed diagnosis of pancreatic cancer after tumor tissue digestion,and then the cells were inoculated into a culture dish using matrigel for three-dimensional culture.Paraffin sections were prepared for HE staining and immunohistochemical staining and were compared with the parent tumor tissue to determine whether the histopathological features of the tumor in vivo were preserved.The pancreatic cancer organoids were treated with seven chemotherapy drugs at different concentrations;Cell Titer-Glo?3D reagent was used to measure cell viability,and the results of drug sensitivity were analyzed.Results Two patient-derived pancreatic cancer organoids were successfully constructed,and HE staining and immunohistochemical staining showed that the pancreatic cancer organoids had consistent histopathological features with the tumors of the corresponding patient.Both pancreatic cancer organoids were more sensitive to gemcitabine monotherapy and the combination of oxaliplatin+SN38+fluorouracil,and patient 1 was more sensitive than patient 2.There were individual differences in the response to drugs between the organoids from different patients.Conclusion The pancreatic cancer organoid model successfully constructed in this study can reflect the histological classification of parent pancreatic tumors and can be used for in vitro chemotherapy drug sensitivity test,which is expected to provide a reference for clinical medication.

Surgical technique of lung transplantation exerts significant impact on clinical prognosis of the recipients.Choosing an appropriate surgical incision determines the exposure of intraoperative visual field,which is the first step of surgical success and directly affects subsequent surgical procedures.Lung transplantation incision is usually considered as primary closure.Nevertheless,for patients with high-risk factors such as oversized lung allografts and primary graft failure after lung transplantation,primary closure cannot be achieved.Hence,delayed chest closure is an effective strategy.The selection of incisions and the adoption of delayed chest closure of lung transplantation exert profound impact upon perioperative prognosis,long-term quality of life and surgical complications of the recipients.Therefore,the development and research status of Clamshell incision,anterolateral incision,posterolateral incision and median sternal incision in lung transplantation were reviewed,highlighting the effect of incision patterns on clinical prognosis of lung transplantation and providing reference for the selection of incisions in clinical lung transplantation.

This paper reports the maternal and fetal outcomes of three twin pregnancies with chronic hypertension and obstructive sleep apnea-hypopnea syndrome (OSAHS) who were treated with continuous positive airway pressure (CPAP). All three women with twin pregnancies were diagnosed with chronic hypertension. Furthermore, symptoms such as snoring and apnea assisted the diagnosis of OSAHS through polysomnography monitoring. Case 1 was treated with CPAP at 28 gestational weeks. The blood pressure increased gradually after the first month of CPAP treatment, with an elevated urine protein concentration. At 34 gestational weeks, the pregnant woman underwent a cesarean section due to the development of hemolysis, elevated liver enzymes, and low platelet syndrome. Case 2 was treated with CPAP at 11 gestational weeks, with stable blood pressure throughout the pregnancy, and was delivered through cesarean section at 37 weeks of pregnancy. Case 3 started CPAP at 13 gestational weeks for four months, and increased blood pressure and urine protein were observed. Medication brought the blood pressure down, and urine protein became negative. At 32 gestational weeks, a cesarean section was performed because of premature rupture of the membrane. Her CPAP treatment continued till delivery with good maternal and infant outcomes. The treatment outcomes of the three cases suggest that CPAP may prolong the time of blood pressure rise among twin pregnancies where chronic hypertension and OSAHS coexist, which potentially reduces the occurrence of adverse maternal and infant outcomes.

Objective:To explore the impact of adverse childhood experience on self-injury behavior and the mediating role of self hating in adolescents.Methods:A cross-sectional survey was conducted in 6 high schools and 5 middle schools in Shandong Province from August 1 to December 31, 2022, using the adverse childhood experience questionnaire, self-hating scale and non-suicidal self-injury behavior rating questionnaire for adolescents. A total of 7 313 questionnaires were collected, of which 6 948 were valid. SPSS 22.0 software was used for Spearman correlation analysis, and biased-corrected non-parametric percentile Bootstrap method was used to test the significance of mediating effect.Results:(1) The scores of adverse childhood experience(4.0(2.0, 6.0)), self-hating (22.0 (13.0, 29.0)) and self-injury behavior (12.0 (7.0, 19.0)) in adolescents with self-injury behavior were higher than those without self-injury behavior(0(0, 2.0), 2.0(0, 9.0), 0(0, 1.0)), and the differences were statistically significant ( Z=-21.700, -22.654, -29.519, all P<0.001). (2) Adverse childhood experience was positively correlated with self-hating ( r=0.46, P<0.01) and self-injury behavior ( r=0.47, P<0.01). Self-hating was positively correlated with self-injury behavior ( r=0.51, P<0.01). (3) Adverse childhood experience directly predicted self-injury behavior with a direct effect of 0.163 (95% CI =0.127-0.200, P<0.01)and the effect size of 53.80%(0.163/0.303).Adverse childhood experiences indirectly predicted self-injury behavior through self-hating, with an indirect effect of 0.140 (95% CI=0.122-0.160, P<0.001) and the effect size of 46.20%(0.140/0.303).The total effect was 0.303 (95% CI=0.270-0.336, P<0.001). Conclusions:There is a close relationship between adverse childhood experiences, self-hating and self-injury behavior in adolescents. Adverse childhood experiences can directly predict self-injury behavior, and can also indirectly affect self-injury behavior through self-hating.

AIM:To evaluate the effect of astaxanthin(AST)on cognitive function of intestinal ischemia/re-perfusion(I/R)injury in rats and the role of autophagy.METHODS:Eight-week-old SPF-grade male Sprague-Dawley(SD)rats were randomly divided into sham group,I/R group,AST group and AST+3-methyladenine(3-MA)group,with 12 animals in each group.The superior mesenteric artery(SMA)of the rats in sham group was only exposed without clamping.The SMA in other 3 groups was clamped for 90 min,and then the arterial clamp was released to restore blood supply and perform reperfusion,thus establishing the intestinal I/R model.The rats in AST group were intraperitoneally in-jected with AST(45 mg·kg-1·d-1)3 d before modeling,and those in AST+3-MA group were intraperitoneally injected with AST(45 mg·kg-1·d-1)+3-MA(1.5 mg·kg-1·d-1)3 d before modeling.Morris water maze was used to evaluate the cogni-tive function of rats 48 h after surgery.Hematoxylin-eosin(HE)staining was used to evaluate intestinal tissue damage.Nissl staining of the frontal cortex was used to evaluate neuronal damage.The levels of interleukin-6(IL-6),IL-1β and tu-mor necrosis factor-α(TNF-α)in the frontal cortex and hippocampus were measured by ELISA kits.The protein levels of beclin-1,microtubule-associated protein 1 light chain 3(LC3)and P62 in the frontal cortex and hippocampus were detected by Western blot.RESULTS:Compared with sham group,the swimming distance of rats in I/R group was increased,with prolonged latency,elevated Chiu's score and decreased number of neurons(P<0.01),while the levels of IL-6,IL-1β and TNF-α in the frontal cortex and hippocampus were increased(P<0.01).Beclin-1 expression and LC3-II/LC3-I ratio in the frontal cortex and hippocampus were increased(P<0.05 or P<0.01).Compared with I/R group,the swimming distance and latency of rats in AST group were shortened,with decreased Chiu's score,increased neuronal number(P<0.01),de-creased IL-6,IL-1β and TNF-α levels in the frontal cortex and hippocampus(P<0.01),and increased beclin-1 expres-sion and decreased of P62 expression in the frontal cortex and hippocampus(P<0.05 or P<0.01).Compared with AST group,the swimming distance of rats in AST+3-MA group was increased,with prolonged latency,elevated Chiu's score,decreased number of neurons(P<0.05),increased levels of IL-6,IL-1β and TNF-α in the frontal cortex and hippocam-pus,and decreased beclin-1 expression and LC3-II/LC3-I ratio and increased P62 expression in the frontal cortex and hip-pocampus(P<0.01).CONCLUSION:Astaxanthin alleviates intestinal I/R-induced cognitive impairment in rats by pro-moting autophagy and inhibiting neuroinflammation.

AIM:To investigate the possible mech-anisms by observing the effects of sodium butyrate on the blood-brain barrier and cognitive function after intestinal ischemia/reperfusion in rats.METH-ODS:SD rats were randomly divided into 4 groups of 12 rats each,(1)sham-operated group(the Sham group);(2)intestinal ischemia/reperfusion group(the Ⅱ/R group);(3)intestinal ischemia/re-perfusion+sodium butyrate group(the NaB group):gavage of NaB 500 mg·kg-1·d-1 for 1 week before modeling;(4)intestinal ischemia/reperfusion+sodi-um butyrate+ITSA-1 group(the ITSA-1 group):NaB 500 mg·kg-1·d-1 gavage 1 week before modeling+IT-SA-1 0.5 mg/kg intraperitoneal injection in the first 5 d,3 d and 1 d.Intestinal mucosal injury was eval-uated by HE staining.Morris water maze test evalu-ated the cognitive function of rats.The microstruc-ture of the blood-brain barrier was observed by transmission electron microscope.The levels of in-flammatory cytokines IL-1β,IL-6,TNF-α,Claudin5,ZO-1,and MMP-9 in brain tissue were detected by ELISA.Western blotting detected Claudin5,ZO-1,CypA,and MMP-9 levels.RESULTS:Compared with the Sham group,Chiu's score in the Ⅱ/R group was increased(P<0.001).The swimming distance was increased(P<0.05),the proportion of the non-plat-form quadrant was increased(P<0.001),and the in-cubation period was prolonged(P<0.05).The micro-structure of the blood-brain barrier was changed under the transmission electron microscope.The inflammatory cytokines IL-1β,IL-6,and TNF-α were increased(P<0.001),the expressions of CypA and MMP-9 were increased(P<0.01),and the expres-sions of Claudin5 and ZO-1 were decreased(P<0.01,P<0.001).Compared with the Ⅱ/R group,neu-roinflammation,and blood-brain barrier damage were reduced,and cognitive function was im-proved in the Ⅱ/R+NaB group.The above injuries in group Ⅱ/R+NaB+ITSA-1 were similar to those in group Ⅱ/R.CONCLUSION:Sodium butyrate can ameliorate Ⅱ/R-induced neurocognitive dysfunction in rats by alleviating blood-brain barrier damage,possibly related to inhibiting the CypA/MMP-9 pathway.

Objective:To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis.Methods:The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software.Results:Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP.Conclusion:The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.

Objective:To explore the facilitators and barriers in implementing the orthokeratology lens-wearing education guidance program from the perspectives of children, their families, and medical and nursing staff.Methods:Based on phenomenological research, purposive sampling was used to select five medical workers, 18 children wearing orthokeratology lenses and family members from the Optometry Center of Peking University Third Hospital as interviewees for semi-structured interviews. Colaizzi's 7-step method was used to analyze interview data.Results:Two themes (facilitators and barriers) were extracted, among which facilitators included two sub-themes (strong demand for educational guidance, trust in medical and nursing staff), and barriers consisted of two sub-themes (patient factors, external support factors) .Conclusions:In promoting the educational guidance intervention program for wearing orthokeratology lenses, medical and nursing staff need to fully play the role of facilitators, analyze and solve barriers, and ultimately promote the smooth implementation of the intervention program.