Transcatheter aortic valve replacement (TAVR) has emerged as the standard treatment for severe aortic stenosis, demonstrating comparable efficacy to traditional surgery in low and intermediate-risk patients. However, the bioprosthetic valves utilized in TAVR have a limited lifespan, and bioprosthetic valve failure, including calcification, rupture or infection may develop, leading to poor clinical outcomes. Elevated blood pressure has been identified as a key factor in aortic valve calcification, and its role in bioprosthetic valve failure is gaining increasing attention. Hypertension may accelerate the calcification process and exacerbate valve failure due to increased mechanical stress on the valve, activation of the renin-angiotensin system, and enhanced thrombus formation. Furthermore, elevated blood pressure interacts with prosthesis mismatch and paravalvular leak, jointly affecting valve durability. This review explores the impact of elevated blood pressure on bioprosthetic valve calcification and failure after TAVR, and emphasizes the importance of blood pressure control, optimized preoperative assessment, and appropriate valve selection in reducing valve failures.
Humans ; Transcatheter Aortic Valve Replacement/adverse effects* ; Calcinosis/etiology* ; Bioprosthesis ; Heart Valve Prosthesis/adverse effects* ; Prosthesis Failure ; Aortic Valve Stenosis/surgery* ; Aortic Valve/surgery* ; Hypertension/physiopathology*

Loss-of-function variants of low-density lipoprotein receptor-related protein 5 (LRP5) can lead to reduced bone formation, culminating in diminished bone mass. Our previous study reported transcription factor osterix (SP7)‍-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration. However, the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown. In this study, we used mice with a conditional knockout (cKO) of LRP5 in mature osteoblasts, which presented decreased osteogenesis. The in vitro experimental results showed that SP7 could promote LRP5 expression, thereby upregulating the osteogenic markers such as alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2), and β‍-catenin (P<0.05). For the in vivo experiment, the SP7 overexpression virus was injected into a bone defect model of LRP5 cKO mice, resulting in increased bone mineral density (BMD) (P<0.001) and volumetric density (bone volume (BV)/total volume (TV)) (P<0.001), and decreased trabecular separation (Tb.‍Sp) (P<0.05). These data suggested that SP7 could ameliorate bone defect healing in LRP5 cKO mice. Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.
Animals ; Low Density Lipoprotein Receptor-Related Protein-5/metabolism* ; Osteoporosis/genetics* ; Mice ; Mice, Knockout ; Sp7 Transcription Factor/physiology* ; Osteogenesis ; Bone Density ; Osteoblasts/metabolism* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Mice, Inbred C57BL ; beta Catenin/metabolism*

COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

Objective:To assess the diagnostic performance of 68Ga-PSMA PET/CT and mpMRI in initial staging of prostate cancer. Methods:A retrospective analysis was conducted on patients with initial diagnosis of prostate cancer who underwent prostatectomy at Fudan University Shanghai Cancer Center from December 2021 to June 2023. All had biopsy-confirmed prostate cancer preoperatively and had not undergone any anti-tumor treatment. Prior to surgery, all patients underwent 68Ga-PSMA PET/CT and mpMRI scans. The surgical samples were processed by whole-mount slides pathology. Thirty patients were included, with a median age of 68 years (range 67-76 years). The preoperative median PSA level was 17.91 ng/ml (range 9.41-39.53 ng/ml). The median interval between the two examinations was 21.00 days (range 2.75-35.50 days). Based on the postoperative whole-mount slides pathology which was the gold standard, we compared the sensitivity and specificity of 68Ga-PSMA PET/CT and mpMRI in diagnosing extraprostatic extension, seminal vesicle invasion, and intraprostatic tumor lesion. Results:According to the postoperative pathology, among the 30 patients, 12 had extraprostatic extension (EPE), 8 had seminal vesicle invasion (SVI). Among the 50 lesions found before surgery, postoperative pathology showed that 38 of them were clinically significant prostate cancer lesions (76.0%, 38/50). Using whole-mount pathology, preoperative mpMRI, and 68Ga-PSMA PET/CT imaging for triple fusion comparison, the sensitivity and specificity of 68Ga-PSMA PET/CT in diagnosing EPE were 66.7% (8/12) and 88.9% (16/18), respectively. The sensitivity and specificity of mpMRI in diagnosing EPE were 50.0% (6/12) and 83.3% (15/18), respectively. In diagnosing SVI, the sensitivity and specificity of 68Ga-PSMA PET/CT were 50.0% (4/8) and 86.3% (19/22), respectively. The sensitivity and specificity of mpMRI were 75.0% (6/8) and 90.9% (20/22), respectively. When diagnosing clinically significant tumor lesions within the prostate, the sensitivity of 68Ga-PSMA PET/CT was 89.5% (34/38), which was significantly better than the mpMRI of 63.2% (24/38), with no significant difference in specificity. Conclusions:The sensitivity of 68Ga-PSMA PET/CT in diagnosing intraprostatic lesions was significantly higher than that of mpMRI, with no significant difference in specificity.

Abstract To investigate the curative effects of modified submucosal tunnel endoscopic resection(STER) and endoscopic submucosal resection(ESE) in the treatment of paracardial submucosal tumors. Eighty-four patients with paracardial submucosal tumors diagnosed through digestive endoscopy and endoscopic ultrasonography signed informed consent forms, and they were randomly divided into observation group(n=42) and control group(n=42) with the help of the table of random numbers. Patients in the control group received ESE treatment. Patients in the observation group received modified STER surgery.The operation time, average hospitalization time and treatment cost of patients in STER group were(61.32±32.01) min,(8.11±2.42) d and(21.7±3.4) thousand Chinese Yuan respectively, which were better than those in ESE group(87.63±34.09) min,(10.05±2.84) d and(25.9±3.9) thousand Chinese Yuan. The difference was statistically significant(P<0.05). The average number of titanium clips used in the observation group was(5.00±1.37), and in the control group the average number was(4.68±1.25). The difference was not statistically significant. In the STER group, there were 2 cases of intraoperative perforation and 1 case of delayed bleeding. In the ESE group, there were 4 cases of intraoperative perforation and 3 cases of intraoperative uncontrollable bleeding. The incidence of postoperative complications in the STER group was lower than that in the ESE group. The postoperative pathological examination revealed that in both groups the tumors were mostly stromal tumor and leiomyoma. A few of the patients were suffering from lipomas and schwannomas. There was no significant difference in terms of the pathological composition of the patients between the two groups.

Objective To develop a humidification fluid dropping joint for the breathing machine to solve the problems in humidification fluid retension,pipeline leakage,pipeline fixation and etc.Methods A Infusion extension tube was involved in with 10 cm length left at the injector end.A hole was made at the side wall of the L-shaped joint of the breathing machine,whose internal diameter equaled to the external diameter of the extension tube.The extension tube was put into the joint through the hole,and the depth of imbedded tube was within 4 and 6 cm.Sealing and fixation at the connection between the tube and hole were executed with 502 glue and short tourniquet.Results The humidification fluid dropping joint could be connected with infusion apparatus of the pump or the infusion extension tube of the micro pump,which behaved well in eliminating accumulated humidification fluid,sputum suction,humidification and facilitating mechanical ventilation.Conclusion The joint developed gains advantages in easy manufacture,reducing complications and increasing the dependence on artificial airway,and thus is worthy promoting clinically.

Objective To analyze the virulence genes and molecular typing of non-O1/non-O139 Vibio cholerae in bloodstream infection,and to provide the scientific basis for its diagnosis,treatment, prevention and controls.Methods Five Vibio cholerae strains were obtained from blood samples of five inpatients with sepsis in Ruian People ’s Hospital from 2012 to 2015 . Morphological examination, biochemical identification,drug sensitivity test and multilocus sequence typing (MLST)classification analysis of strains were conducted.Totally 17 virulence genes were detected by PCR amplification.Results These five suspected Vibrio cholerae isolates were confirmed as non-O1/non-O139 Vibrio cholerae . Drug susceptibility test showed that all the strains were sensitive to tetracycline,ciprofloxacin,piperacillin and tazobactam, meropenem, amikacin and gentamicin; one strain was resistant to trimethoprim/sulfamethoxazole;all were resistant to ampicillin.MLST analysis showed that all strains were new sequence types (ST),belonging to ST268,ST269,ST267,ST270 and ST271 ,and two novel alleles of RY03(mdh:60 and pyrC:86)were discovered.Virulence genes testing showed that the five strains were divided into 4 virulence genotypes:RY02 and RY04 (hlyA + toxR + hap + rtxA + nanH + vasH + vasA +vasK + ),RY01 (hlyA +toxR +hap +rtxA +nanH +vasH -vasA +vasK - ),RY03 (hlyA +toxR +hap +rtxA +nanH - vasH + vasA + vasK + ) and RY05 (hlyA + toxR + hap + rtxA + nanH + vasH - vasA - vasK - ). Conclusions Non-O1/non-O139 Vibrio cholerae can cause human bloodstream infection in immunocompromised patients.The pathogenic factors may be related to the virulence genes of hlyA, toxR,hap ,rtxA and T6SS.

OBJECTIVE: To investigate the effect of the integration pattern of hospital-community on the grade-based management for hypertension in elders.
 METHODS: We randomly chosen 218 (male, n=121; female, n=97) primary senile hypertension patients from a Community Health Service Center of District in Changsha City, from June, 2013 to December, 2013. Based on the risky factors, the subjects were divided into three groups and every group received grade-based management on blood pressure with a integration pattern of hospital-community for six months. According to the HILL-BONE high blood pressure compliance scale and the self- designed blood pressure monitoring form, we assessed the effect of compliance and blood pressure control on senile hypertension patient. 
 RESULTS: Hypertension treatment rate for the elders ranged from 22.9% to 88.1% (P<0.01). The levels of blood pressure of the subjects were significantly decreased compared with baseline. The level of diastolic blood pressure in the low, average, high and very high-risk group was decreased by 17, 20 and 23 mmHg, respectively (P<0.01). The level of systolic blood in the low, average, high and very high-risk group was decreased by 6, 5 and 7 mmHg, respectively (P<0.01). The compliance rate of HILL-BONE hypertension rose from 54.5% to 87.4% (P<0.01).
 CONCLUSION The integration pattern of hospital-community with the grade-based management for hypertension significantly improved the senile hypertension control rate and compliance of drug treatment. The rational for drug usage rate rose obviously. The integration pattern of hospital-community with the grade-based management for elders deserves to spread.
Aged ; Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Community Health Services ; Delivery of Health Care, Integrated ; Disease Management ; Female ; Humans ; Hypertension ; therapy ; Male ; Patient Compliance ; Risk Factors ; Systole

AIM:To analyze circulating miR-141 in the serum as a non-invasive biomarker in the patients with prostate cancer ( PCa) and benign prostate hyperplasia ( BPH) , and healthy individuals.METHODS: A total of 75 pa-tients with PCa, 52 with BPH and 40 healthy individuals were enrolled into this study.Total RNA was isolated from the se-rum samples and the circulating levels of miR-141 were determined using quantitative real-time polymerase chain reaction. RESULTS:The serum levels of miR-141 were significantly higher in the patients with PCa compared to the patients with BPH and the healthy controls (P<0.01).The level of miR-141 in PCa group obviously differed from that in BPH group and healthy control group with high diagnosis performance, with areas under the curve of 0.785 and 0.801, respectively. No statistically significant difference of the serum miR-141 levels between the patients with BPH and healthy individuals was observed (P>0.05).The serum miR-141 level was also found to be related to Gleason score, clinical stage and bone me-tastasis status of the patients with PCa (P<0.05), and the patients with higher Gleason scores had higher serum miR-141 levels.No relationship was detected between miRNA-141 level and the patient’ s age, biochemistry recurrence and serum prostate-specific antigen level (P>0.05 for all comparisons).CONCLUSION: Circulating miR-141 could serve as a non-invasive biomarker for prostate cancer diagnosis, staging and prognosis prediction.