Objective:To explore the role and possible mechanism of ACOT11 in renal fibrosis model mice.Methods:A mouse model of renal fibrosis was established by unilateral ureteral obstruction(UUO)(Sham group and UUO7 group),and the expression of ACOT11 in the kidneys of UUO induced fibrosis mouse models was detected by protein immunoblotting and real-time fluorescence quantitative PCR(qRT-PCR).Subsequently,immunohistochemistry,Masson staining,H&E staining,PAS staining,and other experimental methods were used to detect the expression levels of fibrosis biomarkers fibronectin,α-SMA,and COL-1 in the kidneys of control and experimental group mice.In addition,by constructing ACOT11 gene knockout model mice and using the gene knockout model mice to construct a renal fibrosis model,the expression levels of fibrosis biomarkers such as fibronectin,α-SMA,COL-1,as well as fibrosis mechanism pathway related indicators TGF-β and Smad2 in the kidneys of each group of mice were further detected.Results:The results of WB and qRT-PCR experiments showed that the expression of ACOT11 in the kidney tissue of UUO model mice was significantly reduced compared to the Sham group.After knocking out the ACOT11 gene,H&E staining,PAS staining,and Masson staining showed that pathological inflammatory reactions such as abnormal glomerular and tubular structures,inflammatory cell infiltration and interstitial fibrous tissue proliferation in mice were significantly aggravated compared to the control group,and the expression of fibrosis markers Fibronectin,α-SMA,and COL-1 was significantly higher than that of the control group.Conclusion:ACOT11 plays a protective role in mice with unilateral ureteral obstruction model.After ACOT11 gene knockout,the fibrosis biomarkers of the mouse kidney increases and the degree of fibrosis worsens.

AIM:To investigate the effects of electroacupuncture(EA)at"Qihai","Zhongji"and"Guanyuan"acupoints on urinary control function in rats with stress urinary incontinence(SUI)as well as to explore the mechanism of regulating ferroptosis.METHODS:A total of 50 Sprague-Dawley(SD)rats were randomly assigned to 5 groups.The rats in control(Con)group did not receive any treatment.The rats in model group was modeled for bilateral oophorectomy and vaginal dilation.The rats in EA group received EA treatment at"Qihai","Zhongji"and"Guanyuan"acupoints after modeling,while those in sham acupuncture(sham)group received EA treatment beside the specified acupoints after modeling.The rats in EA+solute carrier family 7 member 11(SLC7A11)inhibitor imidazole ketone erastin(IKE)group received an intraperitoneal injection of 50 mg/kg IKE and EA intervention after modeling.After the experiment,the uri-nary control indicators of leak point pressure(LPP),abdominal LPP(ALPP),and maximum bladder capacity(MBC)were measured for all rats.Hematoxylin-eosin(HE),Masson and Prussian blue staining was performed to observe the pathological changes and iron deposition in the urethral sphincter muscle.Enzyme-linked immunosorbent assay(ELISA)was performed to detect the mitochondrial functional indicators(mitochondrial membrane potential and ATP)and redox in-dicators:changes in the levels of reactive oxygen species(ROS),malondialdehyde(MDA),and glutathione(GSH).RT-qPCR,Western blot and immunofluorescence staining were performed to detect the expression of key iron death proteins.RESULTS:When compared with the Con group,the main urinary control indicators of MBC,LPP,and ALPP in the model group were significantly reduced(P<0.05),and the urethral sphincter fibers were broken and disordered,iron de-position was significant,and the proportion of muscle fibers was significantly reduced.The mitochondrial function indica-tors and GSH levels were significantly reduced(P<0.05),while the ROS intensity,Fe2+and MDA levels were significant-ly increased(P<0.05),the glutathione peroxidase 4(GPX4)and SLC7A11 mRNA protein expressions were significantly reduced(P<0.05),and the acyl-CoA synthetase long-chain family member 4(ACSL4)and transferrin receptor 1(TFR1)protein expressions were significantly increased(P<0.05).When compared with the model group,the main urinary con-trol indicators of the rats in the EA group were significantly improved(P<0.05).The urethral sphincter fibers breakage and disordered were attenuated,iron deposition was significantly reduced,and the proportion of muscle fibers was signifi-cantly increased.The mitochondrial function indicators and GSH levels were significantly increased(P<0.05),while the ROS intensity,Fe2+and MDA levels were significantly reduced(P<0.05).The mRNA and protein expressions of GPX4 and SLC7A11 were significantly increased(P<0.05),and the mRNA and protein expressions of ACSL4 and TFR1 were significantly reduced(P<0.05).When compared with the EA group,the above indicators in the EA+IKE group showed negative changes,and the difference was statistically significant(P<0.05).CONCLUSION:Treatment with EA at"Qi-hai","Zhongji"and"Guanyuan"acupoints improves urinary function in SUI,and the underlying mechanism may be relat-ed to ferroptosis mediated by the SLC7A11/GPX4 signaling pathway.

Objective To observe the value of shear wave elastography(SWE)for evaluating therapeutic effect of ultrasound-guided drug injection for muscle injury.Methods Eighty patients with unilateral muscle injury were retrospectively included,including 40 cases underwent ultrasound-guided drug injection(group A)and 40 cases underwent electromagnetic wave physiotherapy plus external application of Yunnan Baiyao Gao(group B).Pain intensity was assessed using visual analogue scale(VAS)before treatment and 3 weeks after the final treatment,while the Young modulus(E)value of the injured muscle was measured before treatment and 1,2 and 3 weeks after final treatment,and the improvements of VAS scores and E values were compared between groups.Results The total effective rate in group A(35/40,87.50%)was higher than that in group B(21/40,52.50%;P＜0.05).Before treatment,no significant difference of VAS score was found between group A(8.07±0.83)and group B(7.88±0.85)(P＞0.05).After treatment,VAS scores decreased in both groups(both P＜0.05),which in group A(2.30±1.07)was more obviously than that in group B(4.80±0.82)(P＜0.05).After treatment,E values of injury muscles increased significantly in both groups(P＜0.05),while group A had a greater increase in overall magnitude and overall rate than group B(P＜0.05).Conclusion Ultrasound-guided drug injection therapy had significant therapeutic effect for muscle injuries,which could be dynamically monitored with SWE.

support the diagnosis.The treatment of PHCC is mainly based on surgery.Due to the characteristics of intact capsule,surgical resection is relatively easy and the cure rate is higher than that of ordinary hepatocellular carcinoma,and the postoperative survival rate is relatively ideal.For unresectable PHCC,palliative treatment based on transcatheter arterial chemoembolization can be used.This article reviews the progress on diagnosis and treatment of PHCC in order to provide reference for clinical practice.

Objective:To discuss the correlation of pathologic findings after radical prostatectomy and preoperative 18F-PSMA-1007 PET/CT parameters with the prognosis of patients with prostate cancer. Methods:A retrospective case series study was conducted. The clinicopathological data of 48 patients with prostate cancer who underwent radical prostatectomy in Shanxi Province Cancer Hospital between January 2019 and August 2023 were retrospectively analyzed. All patients underwent 18F-PSMA-1007 PET/CT imaging before surgery. The age, the preoperative serum total prostate-specific antigen (tPSA), prostate-specific antigen density (PSAD), prostate volume, tumor diameter, TNM staging, the pathologic data after radical prostatectomy [International Society of Urological Pathology (ISUP) grade, resection margin status, nerve invasion], and preoperative maximum standard uptake value (SUV max) were collected. The receiver operating characteristic (ROC) curves were used to evaluate the efficacy of PET/CT parameter SUV max in predicting tumor recurrence after prostate cancer surgery. The recurrence-free survival (RFS) was analyzed by using the Kaplan-Meier method and log-rank test was performed. Cox proportional risk model was used to analyze the factors influencing RFS after radical prostatectomy. Results:All 48 patients were acinar adenocarcinoma. The median level of the patients' serum tPSA was 19.16 (10.50, 30.99) ng/ml; the median prostate volume was 36.20 (31.83, 45.48) ml; the median tumor diameter was 2.80 (1.60, 4.00) cm; the median PSAD was 0.48 (0.31,1.02) ng·ml -1·cm -3. The primary SUV max of prostate cancer was 13.61 (8.10, 20.20) . Of the 48 patients, 1 case died of heart disease and 1 case died of COVID-19 within 3 to 6 months after surgery, and the rest 46 patients were analyzed for prognosis. Among 46 cases, 26 were in the ISUP low-grade group and 20 were in the high-grade group; 17 were positive and 29 were negative for nerve invasion; 7 were positive and 39 were negative for margin status. The median follow-up time was 18.5 (8-64) months. There were 30 recurrence-free patients and 16 recurrent patients by the follow-up in April 2024. The median RFS time was 15 months; and there were statistically significant differences in RSF among the ISUP high-grade and low-grade groups, preoperative SUV max ≥ 16.77 and < 16.77 groups, positive and negative resection margin groups (all P < 0.01). SUV max was positively correlated with ISUP pathological grade and tPSA level ( r value was 0.634, 0.584, respectively; both P < 0.01). The differences in preoperative serum tPSA level, PSAD, tumor diameter, and SUV max were statistically significant between the ISUP low-grade group and the high-grade group (all P < 0.01); the differences in preoperative serum tPSA, PSAD, and tumor diameter were statistically significant between the nerve invasion positive group and nerve invasion negative group (all P < 0.01); the differences in preoperative serum tPSA, PSAD, tumor diameter, and SUV max between patients with positive resection margins or not were not statistically significant (all P > 0.05). Multivariate Cox regression analysis showed that the tumor resection margin status (negativity vs. positivity: HR = 7.82,95% CI: 1.97-31.07, P < 0.01), ISUP pathological grade (low grade vs. high grade: HR = 4.34,95% CI:1.21-15.62, P < 0.05), and the preoperative SUV max (<16.77 vs. ≥ 16.77: HR = 4.18, 95% CI:1.36-12.85 , P < 0.05) were independent influencing factors for RFS in patients with prostate cancer after radical prostatectomy. Conclusions:Pathological grading after radical prostatectomy and the preoperative 18F-PSMA-1007 PET/CT parameters are associated with the prognosis of patients with prostate cancer.

This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs. Nevertheless, the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance, thereby substantially restricting their therapeutic utility. Consequently, there is an imperative need to expedite the discovery of novel antifungal agents. This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation. These emerging compounds exhibit unique benefits concerning their modes of action, antimicrobial spectra, and pharmacokinetic characteristics, potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens. It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.

Cardiovascular diseases (CVD) and their risk factors are exerting an increasingly significant impact on public health, and the incidence rate of CVD continues to rise. This article provides an interpretation of essentials from the newly published Annual Report on Cardiovascular Health and Diseases in China (2024), aiming to offer scientific evidence for CVD prevention, treatment, and the formulation of relevant policies.
China/epidemiology* ; Cardiovascular Diseases/prevention & control* ; Humans ; Risk Factors ; Incidence

On the basis of that the fluorescence wavelength of copper nanoclusters(CuNCs)could cover the entire visible region,multicolor fluorescent CuNCs/starch composites were prepared and applied in fingermark development.With L-glutathione as the reducing agent and protective ligand,blue emissive and orange emissive CuNCs solutions were obtained in alkaline solutions at 90℃and 25℃,respectively.With the aggregation-induced emission effect induced by ethanol as a poor solvent,the fluorescence of orange emissive CuNCs with a higher intensity was achieved in an ethanol-water solution.With ascorbic acid as the reducing agent and 3-mercaptopropionic acid as the protective agent,green emissive CuNCs solution was prepared in an acid solution.Particle morphologies,chemical compositions and optical properties of these three CuNCs above were investigated using physical characterization and spectroscopic analysis,indicating that well-dispersed CuNCs had excellent photoluminescent properties.These CuNCs solutions were combined with starch to form composite powders by simply drying.The influences of the type of CuNCs and the ratio of CuNCs to starch on the emission wavelength and fluorescence intensity of the products were studied.The obtained CuNCs/starch composites could emit blue,green and orange fluorescence under 365 nm ultraviolet light,respectively,which were suitable for fingermark development.Minutiae and partial level-3 features of latent fingermarks could be effectively developed.High-quality fluorescence fingermark images would be captured using appropriate optical filters to eliminate background interference of various substrates.