Objective To preliminarily evaluate the safety and effectiveness of a novel non-implantable atrial shunt device based on radiofrequency ablation for the treatment of chronic heart failure(CHF).Methods This was a prospective single-arm study.From January 2023 to December 2023,five eligible CHF patients were consecutively enrolled at Beijing Anzhen Hospital,Capital Medical University,and underwent inter-atrial shunt using Shenzhen Betterway atrial shunt device.Pulmonary capillary wedge pressure(PCWP),right atrial pressure(RAP),pulmonary artery pressure(PAP),total pulmonary resistance(TPR),pulmonary vascular resistance(PVR),and pulmonary/systemic blood flow ratio(Qp/Qs)were measured using right heart catheterization before and immediately after procedure.Patients were followed up for 90 days,and echocardiography,right heart catheterization,and cardiac functional indicators were evaluated.The primary endpoint was procedural success.Secondary endpoints included clinical success,echocardiographic changes,6-minute walk distance(6MWD)changes,New York Heart Association(NYHA)class changes,Kansas city cardiomyopathy questionnaire(KCCQ)score changes,and amino-terminal probrain natriuretic peptide(NT-proBNP)level changes at 90 days.The safety endpoint was major cardiovascular and cerebrovascular adverse events and device-related adverse events.Results All five patients successfully achieved left-to-right atrial shunt.Compared with baseline,PCWP decreased significantly immediately after procedure in all five patients,with a procedural success rate of 100％.There were no significant changes in RAP,PAP,TPR,and PVR before and immediately after procedure.After 90 days follow-up,four patients had persistent left-to-right atrial shunt,and PCWP was significantly lower than baseline,with a clinical success rate of 80％.Compared with baseline,LVEF increased,left ventricular end-diastolic diameter decreased,and tricuspid annular plane systolic excursion and right ventricular fractional area change were not impaired in all five patients at 90 days.KCCQ scores and 6MWT improved,NT-proBNP decreased,and NYHA class did not change significantly.There were no deaths,rehospitalizations for heart failure,stroke-related adverse events,or device-related adverse events during the follow-up.Conclusions The novel non-implantable atrial shunt catheter can safely and effectively improve hemodynamic,echocardiographic,and cardiac functional indicators in patients with heart failure.However,larger-scale clinical studies are still needed to validate its long-term clinical effectiveness.

The threat of fungal diseases is increasingly rigorous. The clinically invasive fungal infections remain a main cause of morbidity and mortality in certain high-risk groups, especially in critical patients or immunocompromised patients. In drug therapy, the problems of off-target toxicity and antifungal drug resistance are still challenging. With the wide application of biomaterials and nanotechnology, more nanomedicine studies have been carried out on antifungal drugs, such as the amphotericin B liposome which greatly reduced the renal toxicity of drugs has been successfully marketed. For the unique physical and chemical properties, the nano-drug delivery system possessed great potential in improving the bioavailability, reducing the side effects of drugs, increasing the stability of drugs, and achieving cells or tissue-specificity through the modification. This review summarized the applications and limitations of antifungal drugs. Some nanomedicines were summarized in discussion oriented around the antifungal therapy, including liposomes, niosomes, lipid nanoparticles, polymer nanoparticles, microemulsion, dendrimers, inorganic nanocarriers. Nanotechnology and nano-drug delivery system provide promising strategies for the research and development of new formulations that can improve antifungal activity and possibly overcome antifungal drug resistance.

Objective: To explore the effect of moxibustion at Shenque (CV 8) on myocardial structure and function in exercise-induced fatigue rats. Methods: A 12-week treadmill running training was performed to create an exercise-induced fatigue rat model. Sixty eligible male specific-pathogen-free grade Sprague-Dawley rats were randomly divided into a blank group, a control group, a model group, a non-meridian non-acupoint group, a Zusanli (ST 36) group and a Shenque (CV 8) group, with 10 rats in each group. Rats in the blank group did not receive treadmill running training or moxibustion. Rats in the control group did not receive treadmill running training but received mild moxibustion at Shenque (CV 8). Rats in the model group received treadmill running training but no moxibustion. Rats in the non-meridian non-acupoint group, the Zusanli (ST 36) group and the Shenque (CV 8) group received moxibustion at the non-meridian non-acupoint points, Zusanli (ST 36) or Shenque (CV 8) immediately after each treadmill running training, 15 min each time, once a day for 5 consecutive days a week at a 2-day interval, 60 times of moxibustion in total. Left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVESd), left ventricular diastolic volume (LVDv), left ventricular systolic volume (LVSv), ejection fraction (EF), stroke volume (SV), early diastolic peak flow velocity of mitral valve (E) and late diastolic peak flow velocity of mitral valve (A) of each group before and after the last treadmill running training were measured. Blood was collected 6 h after the last treadmill running training, and serum C-reactive protein (CRP), myoglobin (Mb), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI) and cardiac troponin T (cTnT) levels were detected. Finally, the heart was separated, the heart mass (HM) was measured, the cTnT level of the myocardial tissue was detected, the ultrastructural changes of the left ventricular myocardium were observed by transmission electron microscope, the left ventricular fraction shortening (LVFS), E/A and heart mass index (HMI) were calculated. Results: Compared with the same group before treatment, the rat cardiac LVEDd, LVESd, LVDv, LVSv, SV, E and A were significantly increased (all P<0.01), and the rat LVFS, E/A and EF were significantly decreased (all P<0.01) in the model group and the non-meridian non-acupoint group after treatment; the rat cardiac SV, LVDv, LVSv, E and A were all increased (all P<0.01), while E/A and EF were decreased (all P<0.01) in the Zusanli (ST 36) group after treatment; the rat cardiac LVDv, E and A were significantly increased (P<0.01 or P<0.05), and E/A was significantly decreased (P<0.01) in the Shenque (CV 8) group after treatment. After treatment, compared with the blank group, the rat cardiac LVEDd, LVESd, SV, LVDv, LVSv, E, A, the serum CRP, Mb, CK-MB, cTnI, cTnT and HMI, and the myocardial cTnT were increased (all P<0.01), and the LVFS, E/A and EF were all reduced (all P<0.01) in the model group; compared with the model group and the non-meridian non-acupoint group, rats in the Zusanli (ST 36) group and the Shenque (CV 8) group showed decreased LVEDd, LVESd, SV, LVDv, LVSv, E, A, serum CRP, Mb, CK-MB, cTnI, cTnT and HMI, and myocardial cTnT (P<0.01 or P<0.05), along with increased LVFS, E/A and EF (all P<0.01); compared with the Zusanli (ST 36) group, Mb and A of the Shenque (CV 8) group were decreased (both P<0.01), while both E/A and EF were increased (P<0.01, P<0.05). Transmission electron microscopy examination showed that myofibrils in the blank group and the control group were neatly arranged with clear light and dark bands; the model group and the non-meridian non-acupoint group showed different degrees of myofibril disintegration and breakage, increased and aggregated mitochondria of different sizes, and increased electron density. The myofibrils in the Shenque (CV 8) group and Zusanli (ST 36) group were arranged neatly with clear light and dark bands, and compensatory hyperplasia of mitochondria. Conclusion: Moxibustion at Shenque (CV 8) and Zusanli (ST 36) both can effectively improve the occurrence of myocardial remodeling in exercise-induced fatigue rats, and the effect of moxibustion at Shenque (CV 8) is better in improving cardiac function.

OBJECTIVE: This work aims to investigate the effect of stripping of steep sheep maxillary sinus by using 0.012 or 0.014 model new-type memory elastic silk sleeve stripper and umbrella stripper. METHODS: Goats with sinus floor gradients of 60° to 90° were selected by computed tomography of sheep head. A total of 72 animal models were established and randomized into three groups (n=24): group A (0.012 model), B (0.014 model) and C (umbrella stripper). Alveolar and maxillary sinus mucosa were stripped after crowning, and stripping length was measured when the stripping limit was reached or mucosal perforation occurred. RESULTS: The average stripping length of mucosa in group A was 11.3 mm±4.6 mm, and three cases experienced perforation of sinus floor mucosa. The average stripping length of mucosa in group B was 17.5 mm±5.0 mm, and one case experienced perforation of sinus floor mucosa. The average stripping length of mucosa in group C was 4.2 mm±1.3 mm, and four cases experienced perforation of sinus floor mucosa. The difference among the three groups was statistically significant (P<0.01) according to variance analysis. Moreover, the comparison between any two means was also statistically significant according to Dunnett's T3 test (P<0.05). CONCLUSIONS The new-type memory elastic silk sleeve stripper effectively stripped steep maxillary sinus mucosa. The 0.014 model exhibited superior peeling effect and was relatively safe.
Animals ; Goats ; Maxillary Sinus ; Mucous Membrane ; Sheep ; Silk ; Sinus Floor Augmentation

ObjectiveTo evaluate the effect of ejaculatory duct dilation combined with seminal vesicle clysis in the treatment of refractory hematospermia.

METHODSUsing ureteroscopy, we treated 32 patients with refractory hematospermia by transurethral dilation of the ejaculatory duct combined with clysis of the seminal vesicle with diluent gentamicin.

RESULTSThe operation was successfully accomplished in 31 cases, with the mean operation time of 32 (26－47) minutes. The patients were followed up for 6－39 (mean 23.6) months. No complications, such as urinary incontinence and retrograde ejaculation, were found after operation. Hematospermia completely disappeared in 27 cases, was relieved in 1, and recurred in 3 after 3 months postoperatively. Those with erectile dysfunction or mental anxiety symptoms showed significantly decreased scores of IIEF-Erectile Function (IIEF-EF) and Self-Rating Anxiety Scale (SAS).

CONCLUSIONSEjaculatory duct dilation combined with seminal vesicle clysis under the ureteroscope, with its the advantages of high effectiveness and safety, minimal invasiveness, few complications, and easy operation, deserves general clinical application in the treatment of refractory hematospermia.

Dilatation ; Ejaculatory Ducts ; surgery ; Genital Diseases, Male ; Hemospermia ; surgery ; Humans ; Male ; Postoperative Period ; Recurrence ; Seminal Vesicles ; surgery ; Ureteroscopy

OBJECTIVETo explore the mechanism of miR-124 inhibiting the proliferative activity of prostate cancer PC3 cells.

METHODSLuciferase reporter gene assay was used to examine the specific binding ability of miR-124 to PKM2 mRNA 3'-UTR. After miR-124 was transfected mimic to PC3 cells, the expression levels of PKM2 mRNA and protein were detected by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot, respectively. The effects of miR-124 mimic and PKM2 siRNA on the proliferative activity of the PC3 cells were determined by MTT assay.

RESULTSThe expressions of PKM2 mRNA and protein were upregulated (5.12 +/- 0.35) times and (4.05 +/- 0.20) times respectively in the PC3 cells as compared with those in the RWPE-1 cells (P < 0.05). Luciferase reporter gene assay demonstrated that miR-124 targeted PKM2 3'-UTR. At 24 hours after transfection with miR-124 mimic, the PKM2 protein expression in the PC3 cells was downregulated (0.16 +/- 0.04) times (P < 0.05), while the PKM2 mRNA level was not changed significantly (P > 0.05), as compared with the control group. MTT assay showed that both miRNA-124 mimic and PKM2 siRNA could inhibit the proliferation of the PC3 cells, but the former exhibited a greater inhibitory effect than the latter. After transfection with miR-124 mimic and PKM2 siRNA, the cell growth rates were (66.20 +/- 5.10)% vs (82.10 +/- 6.35)% at 24 hours (P < 0.05) and (49.34 +/- 2.37)% vs (70.10 +/- 5.80)% at 48 hours (P < 0.05).

CONCLUSIONmiR-124 can suppress the proliferation of PC3 cells by regulating the PKM2 gene.

Carrier Proteins ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; genetics ; Humans ; Male ; Membrane Proteins ; genetics ; metabolism ; MicroRNAs ; genetics ; Prostatic Neoplasms ; genetics ; metabolism ; pathology ; Thyroid Hormones ; genetics ; metabolism ; Transfection

With the development of space life science, researches on ground-based microgravity simulation become more and more important for spaceflight to complement their limited missions. It is well known that bone marrow mesenchymal stem cells (BMSCs) are pluripotent, self-renewing cells with multi-lineage differentiation capacity on the ground, but their responses under microgravity and the underlying regulatory mechanisms are poorly understood. Ground-based microgravity simulation might affect cell proliferation, apoptosis and expression of surface molecules, and induce cytoskeletal reorganization, as well as alter the differentiation potential of BMSCs. In this review, how ground based microgravity simulation mediates BMSCs’ responses and its involved mechanisms are summarized to further understand the mechano-biological coupling in such process and provide theoretical references for space flight-induced pathophysiological alterations.

OBJECTIVETo evaluate the clinical efficacy of transrectal 125 I seeds implantation brachytherapy (BT) combined with intermittent hormonal therapy (IHT) in the treatment of locally advanced prostate cancer.

METHODSWe treated 27 patients with locally advanced prostate cancer by transrectal 125I seeds implantation BT combined with IHT, and dynamically observed the changes in the PSA level, prostate volume, maximum urinary flow rate (Qmax) and International Prostate Symptoms Score (IPSS).

RESULTSAll the implantation procedures were completed smoothly, lasting 20 to 35 minutes, with 40 to 58 seeds implanted. At 6 months after implantation, the PSA level was < 0.2 microg/L in all the patients (< 0.1 microg/L in 19 cases), the prostate volume was significantly reduced (P < 0.05), and Qmax and IPSS remarkably improved (P < 0.05). At 3 years after implantation, 19 cases were in the first cycle and the other 8 in the third cycle of IHT, of which 2 progressed to androgen-independent prostate cancer, and another 2 developed early bone metastasis. The rates of 3-year biochemically and clinically progression-free survival were 70.3% and 85.2%, respectively, and the rate of therapeutic effectiveness was 92.6%. No severe complications occurred in any of the cases.

CONCLUSIONTransrectal 125I seeds implantation BT combined with IHT is a safe and minimally invasive procedure for locally advanced prostate cancer, which can effectively retard its clinical progression with no such complications as severe urethral, rectal or erectile dysfunction.

Aged ; Brachytherapy ; Combined Modality Therapy ; Hormones ; therapeutic use ; Humans ; Iodine Radioisotopes ; administration & dosage ; therapeutic use ; Male ; Prostatic Neoplasms ; radiotherapy ; therapy ; Treatment Outcome

Culturing cells on planar substrate in vitro is a conventional cell biology method. However, each type of physiological tissues has its specific three-dimensional micro-structure, which provides various micro environment to regulate such biological processes as cell proliferation and differentiation. To date, a growing body of researches on the impacts of substrate micro-topography on cellular responses has been documented in the literature. It is found that micro-topograhical substrate can manipulate cell spreading, migrating, orientating, cytoskeleton remodeling, and stem cell differentiation, which are crucial to ex vivo tissue construction and surface modification of medical implanting materials. This review discusses the recent progresses of the effects of substrate micro-topography on cellular responses and the underlying mechanisms of mechano-biological coupling.

BACKGROUNDTechnetium-99m or (99m)Tc is widely used for labeling peptide in nuclear medicine. Somatostatin and its analog can inhibit tumor cell growth after binding with its receptor. This research was to study the preclinical effect of a new (99m)Tc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide, indirect (99m)Tc labeling of depreotide using HYNIC as a bifunctional chelator.

METHODSThe cyclopeptide, cyclo-[(N-Me) Phe-Tyr-D-Trp-Lys-Val-Hcy], the linear peptide, and [ClCH(2)-CO×b-Dap-Lys- Cys-Lys×amide] were synthesized by Fmoc solid-phase synthesis. The cyclopeptide and the linear peptide were linked by liquid-phase synthesis. The product depreotide was isolated and purified by high performance liquid chromatography and was confirmed by mass spectrography. Depreotide was labeled with (99m)Tc through a direct labeling method, using HYNIC as a bifunctional chelator. Paper chromatography method was used to calculate the labeling rate, and through the comparative analysis selected the best mark conditions. The new (99m)Tc-HYNIC-depreotide was tested by high-performance liquid chromatography (HPLC). The internalization and externalization rates of the new (99m)Tc-HYNIC-depreotide were studied in A549 cells. Furthermore, biodistribution of the radiopeptide was studied in nude mice, bearing tumors from human lung carcinoma cells SPC-A1.

RESULTSThe molecular of synthesize depreotide was 1358, and the purity of it was 95.29%. The labeling efficiency of (99m)Tc-HYNIC-depreotide was highest at pH 6.0 and 15°C, about (70.95 ± 0.84)%. The labeling rate of the new (99m)Tc-HYNIC-depreotide rose to a peak of (20.75 ± 0.48)% at 60 minutes in A549 cells at 37°C and decreased slightly later, while it elevated gradually during the time course at 4°C and 25°C. The internalization rate of the new (99m)Tc-HYNIC-depreotide at 37°C increased gradually and reached the peak of 84.4% in 120 minutes, while the externalization rate of the new (99m)Tc-HYNIC-depreotide was always less than 20%. In mice bearing the experimental SPC-A1 tumor, the new (99m)Tc-HYNIC-depreotide demonstrated a high tumor uptake of (4.05 ± 0.04)% ID/g at 1.5 hpi and remained high ((2.51 ± 0.06)% ID/g) at 4 hpi. The tumor-to-lung activity concentration ratio (T/Lu) was very high for the new (99m)Tc-HYNIC-depreotide at all time points. So did the tumor-to-muscle activity (T/Mu) and tumor-to-blood activity concentration ratios (T/Bl).

CONCLUSIONThe findings suggested that the new (99m)Tc-HYNIC-depreotide might be a promising candidate radiopharmaceutical for imaging somatostatin receptor positive lung cancer.

Animals ; Cell Line, Tumor ; Humans ; Hydrazines ; chemistry ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Mice, Nude ; Nicotinic Acids ; chemistry ; Receptors, Somatostatin ; metabolism ; Technetium ; chemistry