In this work,a fluorescent probe PIN was synthesized using indole-3-carbohydrazide and pyrenecarboxaldehyde as raw materials.PIN showed weak fluorescence emission in aqueous solution with acetonitrile volume fraction of 70％.However,when Cu2+was added to this aqueous solution of PIN,a new fluorescence emission peak appeared at 495 nm,and the intensity of this peak gradually increased with the increase of concentration of Cu2+,and also caused a significant change in the fluorescence color of the solution.In contrast,the addition of 15 kinds of other common metal ions did not cause such change.The detection limit of PIN for Cu2+was 78.7 nmol/L,which was much lower than the maximum permitting level of Cu2+in drinking water in hygienic standard for drinking water in China.Therefore,PIN was a highly selective and sensitive fluorescence-enhanced probe for Cu2+.Meanwhile,the addition of Cu2+could also cause a new absorption peak at 440 nm in the ultraviolet-visible absorption spectrum of the aqueous solution of PIN,and meanwhile the colorless PIN solution changed into yellow,exhibiting the performance of PIN as a colorimetric probe for Cu2+.By fitting with the Levenberg-Marquardt algorithm equation,the binding ratio of PIN to Cu2+was 2:1,and the binding constant was 3.42×1012 L2/mol2.In addition,the binding mode of PIN with Cu2+was explored by using proton nuclear magnetic resonance(1H NMR)titration experiments and density functional theory simulations.The results showed that the addition of Cu2+could cause the aggregation of PIN molecules to form excimers,thus showing highly selective recognition.Finally,PIN was made into a simple test strip,which could achieve rapid and convenient fluorescence detection of Cu2+in actual water samples.

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Aim To investigate the therapeutic effect of newly formulated Tadalafil tablets on liver fibrosis in mice induced by carbon tetrachloride(CCl4)and its impact on the activation of hepatic stellate cells(HSCs).Methods Liver fibrosis model was estab-lished by intraperitoneally injecting 20％CCl4 corn oil solution twice a week for eight weeks.After four weeks of modeling,the treatment group was administered ei-ther the newly formulated Tadalafil tablets(1.0 mg·kg-1)or the Cialis(2.5 mg·kg-1)via gavage for the remaining four weeks.We assessed the effects of Tadalafil on collagen deposition,tissue structural dam-age,and HSCs activation markers in the fibrotic liver of mice using serum biochemical analysis,histopathologi-cal staining,and Western blotting following the treat-ment period.LX-2 cells were cultured and treated with tadalafil after TGF β1 stimulation,and the effects of tadalafil on LX-2 cell activation were assessed via Western blot.Results Compared to the normal mice,the model group mice exhibited a significantly higher liver-specific index,increased liver function indicators,and notable hepatocyte necrosis.Additionally,liver lobules were damaged,accompanied by severe infiltra-tion of inflammatory cells.Both smooth muscle actin(α-SMA)and fibronectin(Fn)were elevated,serving as markers of HSCs activation.As a result of treatment with the newly formulated Tadalafil tablets,liver tissue damage was significantly reduced,transaminase levels decreased,necrosis and inflammatory cell infiltration were reduced,and collagen fiber deposition was allevia-ted,and α-SMA and Fn expression was reduced.It was worth noting that low-dose newly formulated Tadalafil tablets were found to be as effective as high-dose Cia-lis.In a cellular model,Tadalafil significantly inhibited the activation of LX-2 cells and reduced the expression of proteins related to cell activation.Conclusions The newly formulated Tadalafil tablets can significantly inhibit HSCs activation,reduce extracellular matrix(ECM)deposition,improve liver fibrosis and liver function damage caused by CCl4.This new formulation offers a significant advantage over Cialis in terms of ef-fectiveness,with a lower effective dose.

The feasibility for the development of road-rail medical vehicles was discussed.The gap between China's ground medical evacuation system and medical evacuation requirements was analyzed,and the limitations of the existing mobile medical units in China were introduced.The key points for developing road-rail medical vehicles were discussed.The road-rail medical vehicle would be an ideal tool for casualty treatment and rapid evacuation at war time and peace time,which could be a future development direction of the road-rail vehicle and medical train.[Chinese Medical Equipment Journal,2025,46(10):84-90]

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablet on pulmonary fi-brosis induced by paraquat(PQ)in rats,as well as its impact on histone acetylation levels in epithelial cells.Methods SD rats were randomly divided into four groups:the control group(control),the model group(PQ),the Tadalafil new tablet treatment group(N-Tad,1 mg·kg-1),and the positive control drug treatment group(Cialis,5 mg·kg-1).The model group and treatment group rats were intraperitoneally injected with PQ(30 mg·kg-1).Two hours after the initial treatment,the rats in the treatment group re-ceived N-Tad or Cialis via gavage,while the control and model groups were administered an equal volume of physiological saline by gavage once daily for 28 days.The weight gain rate and lung tissue index for each group of rats were calculated.Additionally,the effects of N-Tad treatment on lung tissue structural damage and collagen deposition in rats with PQ-in-duced pulmonary fibrosis were observed using HE stai-ning,Masson trichrome staining,and immunohisto-chemical techniques.By employing the Western blot technique,the effects of Tadalafil intervention on the expression of the epithelial marker E-cadherin(E-Cad),the stromal marker fibronectin(Fn),and the histone acetylation marker acetylated histones(Ac-his-tones)in A549 cells were observed.Results Com-pared to the control group,rats with PQ-induced pul-monary fibrosis exhibited a significant decrease in the rate of body weight growth,an increase in lung tissue index(P＜0.05),and a notable increase in the expression and distribution of the fibrosis marker alpha-smooth muscle actin(α-SMA)in lung tissue.The structure of the lung tissue was disrupted,accompanied by the deposition of interstitial collagen fibers.Both N-Tad and Cialis treatments could significantly enhance the rate of weight gain,decrease the lung tissue index,inhibit the expression of α-SMA,and reduce the depo-sition of interstitial collagen in the lung tissue of rats with pulmonary fibrosis.Notably,low-dose N-Tad treatment was comparable to high-dose Cialis treat-ment.At the cellular level,Tadalafil significantly in-hibited the high expression of Fn induced by transfor-ming growth factor beta 1(TGF-β1)in A549 cells.It also upregulated the expression of E-cadherin and sig-nificantly increased the levels of acetylated histones(P＜0.05).Conclusions N-Tad promotes histone acetylation in alveolar epithelial cells,significantly in-hibits epithelial-mesenchymal transition,increases E-cadherin expression,and improves lung tissue structur-al damage and collagen deposition caused by PQ.Ad-ditionally,it offers the advantage of a lower effective dose compared to Cialis,providing a new option for the treatment of pulmonary fibrosis.

Objective:To explore the possibility of using a inferior gluteal artery perforator flap (IGAPF) for breast reconstruction in the patient who did not have suitable donor site in back and abdomen.Methods:In November 2024, a 25-year-old unmarried and childless woman with right breast cancer received immediate right breast reconstruction by a right free IGAPF after modified right mastectomy in the Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Hainan Medical University. The locations of perforators were confirmed by both Multi-detector computed tomography angiography (MDCTA) and portable Doppler blood flow detector before surgery. The IGAPF was designed to take the inferior gluteal wrinkle as the lower edge, the axis of the flap was parallel to the inferior gluteal wrinkle, and the width of the flap was estimated where the incision could be directly closed. The size of right IGAPF was 6.0 cm×19.0 cm. Sharp dissection was performed between the sarcolemma and muscle fibres of gluteus, then the perforators were dissected along the direction of muscle fibres of gluteus. The vascular pedicle was kept at about 8.0 cm in length. The diameter of artery was about 2.0 mm and that for the veins was about 1.5 mm. End-to-end anastomoses with the right thoracodorsal artery and vein were successfully carried out. The donor site was directly closed, and it was hidden in the inferior gluteal wrinkle. Postoperative outpatient clinical review was made.Results:Pathological examination reported: an invasive carcinoma of right breast, axillary lymph node metastasis (2/10). The patient recovered well and the flap survived without any complication, i.e. ischemic necrosis, infection and haematoma. The patient was off-bed at 3 days and discharged at 13 days after surgery. At the 40 days of postoperative follow-up, the patient achieved a good recovery and the lower limb activity was not affected by the surgery. The patient was satisfied with the reconstructed breast and donor site recovery. The patient followed with scheduled chemotherapy and subsequent radiotherapy. The volume of reconstructed breast was smaller than the other breast, of which the patient was fully informed before the surgery.Conclusion:A free IGAPF provides an alternative donor sites for achieving a breast reconstruction due to the reliable pedicle vessels and invisible donor scars.

Objective:To establish tumor specific protein (SP70) targeted tumor cell enrichment technology and to assess applicational value of next-generation sequencing (NGS) analysis for enriched circulating tumor cell (CTC) in precision medicines of non-small cell lung cancer (NSCLC).Methods:The monoclonal antibody NJ001 was covalently coupled to the surface of magnetic beads to build targeted magnetic bead enrichment technology based on SP70. The limit of detection, coincidence rate, interference experiment, recovery test and clinical performance were evaluated. From March 2016 to August 2017, NGS analysis with or without pre-treatment of targeted enrichment for serous fluids of 43 NSCLC in the First Affiliated Hospital with Nanjing Medical University were compared (Kappa or Fisher exact test).Results:The CTC enrichment technology based on SP70 targeted immunomagnetic beads can specifically enrich tumor cells. The limit of detection was 10 4 SPC-A1 cells/L, and the coincidence rate, sensitivity and specificity were 100% (3/3). The endogenous interfering substances such as red blood cells, hemoglobin, white blood cells, epithelial cells and triglycerides had no interfering effects, as well as the exogenous interfering substances such as EDTA-K2, cefoxitin, carboplatin and paclitaxel. The recovery rate was 56.0% (56 000/100 000). A total of 30 gene mutations including 65 loci were found in 43 NSCLC under SP70 targeted enrichment, with a higher detection rate compared with unenrichment method [95.0% (19/20) vs 65.0% (13/20), χ 2=5.625, P=0.044]. Conclusion:In this study, SP70-targeted enriched CTC liquid biopsy method was established, with higher sensitivity and specificity of NGS detection than unenrichment method.

Objective:To investigate the clinical application and effect of the self-designed pedicled perforator flap combined with vacuum sealing drainage (VSD) for the repair of gluteal pressure ulcers.Methods:A retrospective study was performed on 15 patients with gluteal pressure ulcers who were treated with self-designed pedicled perforator flaps combined with VSD in Linyi People's Hospital from January 2020 to April 2023. The cohort included 9 males and 6 females, with ages ranging from 41 to 73 (57±16) years, and the duration of the disease ranged from 12 to 39 days. Following debridement surgery in conjunction with VSD treatment, the wounds were repaired with self-designed pedicled perforator flaps. In cases with larger donor areas, relay flaps were utilized. All wounds were closed in the first stage with VSD drainage for one week. Postoperative assessments focused on flap survival, wound healing, and patient follow-up.Results:Three cases were mixed pressure ulcers, 12 cases were ulcerative pressure ulcers, and the area of the base of the wound ranged from 3 cm × 5 cm to 10 cm × 15 cm. Among the cohort, 14 patients demonstrated favorable outcomes regarding flap survival and incision healing while one paraplegic patient experienced bleeding, subcutaneous congestion and poor incision healing after operation due to severe wound infection and poor fundamentals, and was discharged from the hospital after 10 days of healing post-operation with the flap clearing and repairing. The duration of the operation was (123±10) min, and the intraoperative blood loss was (87±5) ml. A total of 13 cases were followed up for 3 to 24 months with satisfactory results. The flaps demonstrated optimal hematologic performance, satisfactory appearance and texture, and no recurrence of ulcers.Conclusion:The combination of self-designed pedicled perforator flap with VSD is an effective method for repairing gluteal pressure ulcers with less intraoperative bleeding and shorter operative time.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.