Objective To investigate the efficacy of leaflet augmentation technique to repair the recurrent mitral valve (MV) regurgitation after mitral repair in children. Methods A retrospective analysis was conducted on the clinical data of children who underwent redo MV repair for recurrent regurgitation after initial MV repair, using a leaflet augmentation technique combined with a standardized repair strategy at Fuwai Hospital, Chinese Academy of Medical Sciences, from 2018 to 2022. The pathological features of the MV, key intraoperative procedures, and short- to mid-term follow-up outcomes were analyzed. Results A total of 24 patients (12 male, 12 female) were included, with a median age of 37.6 (range, 16.5–120.0) months. The mean interval from the initial surgery was (24.9±17.0) months. All children had severe mitral regurgitation preoperatively. The cardiopulmonary bypass time was (150.1±49.5) min, and the aortic cross-clamp time was (94.0±24.2) min. There were no early postoperative deaths. During a mean follow-up of (20.3±9.1) months, 3 (12.5%) patients developed moderate or severe mitral regurgitation (2 severe, 1 moderate). One (4.2%) patient died during follow-up, and one (4.2%) patient underwent a second MV reoperation. The left ventricular end-diastolic diameter was significantly reduced postoperatively compared to preoperatively [ (43.5±8.6) mm vs. (35.8±7.8)mm, P<0.001]. Conclusion The leaflet augmentation technique combined with a standardized repair strategy can achieve satisfactory short- to mid-term outcomes for the redo mitral repair after previous MV repair. It can be considered a safe and feasible technical option for cases with complex valvular lesions and severe pathological changes.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

Objective To explore the mechanism of Bushen Zhupai Decoction in treating ovarian fibrosis in polycystic ovary syndrome(PCOS)model rats based on IL-17/TRAF6/NF-κB signaling pathway.Methods Totally 60 SPF grade female SD rats were randomly divided into blank group,model group,Yousiyue group and TCM low-,medium-and high-dosage groups,with 10 rats in each group.The PCOS model was replicated by gavage of 1 mg/kg letrozole for 21 days.The Yousiyue group was given a 10 mg/kg solution of drospirenone ethinylestradiol tablets by gavage,TCM low-,medium-and high-dosage groups were given 8.82,17.64 and 35.28 g/kg of Bushen Zhupai Decoction by gavage,once a day for 28 consecutive days.HE and Masson staining were used to observe the morphology of ovarian tissue and ovarian fibrosis,the contents of serum IL-17,IL-18 and IL-1β were detected by ELISA,the mRNA expression of IL-17,TRAF6,NF-κB p65 and TGF-β1 in ovarian tissue were determined by RT-qPCR,the protein expression of TRAF6,NF-κB p65,TGF-β1,α-SMA,E-cadherin and the positive expression of IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA in ovarian tissue were detected by Western blot and immunohistochemical staining respectively.Results Compared with the blank group,the body mass,ovarian mass and ovarian index significantly increased of rats in model group,with follicular cystic dilation,thinning of granulosa cell layer,and significant increase in fibrosis positive range(P<0.01),the serum contents of IL-17,IL-18 and IL-1β significantly increased(P<0.01),the expressions of IL-17,TRAF6,NF-κB p65,TGF-β1 mRNA and IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA proteins significantly increased(P<0.01,P<0.05),the expression of E-cadherin protein significantly decreased(P<0.01).Compared with the model group,the ovarian index of rats in Yousiyue group and TCM medium-and high-dosage groups significantly decreased(P<0.01,P<0.05),the rats in TCM high-dosage group showed dominant follicles,increased thickness of granulosa cell layer,and significantly reduced fibrosis positive range(P<0.01),the serum contents of IL-17,IL-18 and IL-1β significantly decreased in Yousiyue group and TCM low-,medium-and high-dosage groups(P<0.01),the mRNA expressions of IL-17,TRAF6,NF-κB p65,TGF-β1,and the protein expressions of IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA in ovarian tissue significantly decreaed in TCM high-dosage group(P<0.01,P<0.05),the expression of E-cadherin protein significantly increased(P<0.01).Conclusion Bushen Zhupai Decoction can decrease the body mass,improve the ovarian index,decrease the expressions of inflammatory factors and improve the status of ovarian fibrosis in PCOS rats.The mechanism may be related to the regulation of IL-17/TRAF6/NF-κB signaling pathway.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective:To prepare ((2-(2-chlorophenyl)-3-(4-((2- 18F-fluoroethyl)oxy)phenyl)-5, 6, 7, 8-tetrahydrooxepino[3, 2-c]pyrazol-8-yl)amino)methanoic acid methyl ester ( 18F-JR-1001) and evaluate its binding affinity to the cannabinoid type 1 receptor (CB1R). Methods:18F-JR-1001 was synthesized using an integrated automated synthesis module, and its radiochemical yield (RCY) and molar activity were determined. Cell-specific uptake, lipid-water partition coefficient (log P), competitive binding assays, and in vitro stability tests were performed. Rimonabant-fed rat models (blocking group) with pre-occupied CB1R were established. Radioautography and microPET/CT imaging were conducted on both the blocking group and normal Sprague-Dawley (SD) rats to evaluate the brain uptake of 18F-JR-1001 and its blood-brain barrier (BBB) penetration capability. Results:The RCY of the synthetic 18F-JR-1001 after decay correction was (32.5±9.2)% ( n=10), with the molar activity of (194.6±67.3)GBq/μmol. Cell experiments demonstrated that 18F-JR-1001 exhibited specificity for CB1R, with log P of 3.40±0.11 ( n=3) and half-maximal inhibitory concentration of 0.975nmol/L. Within 3h at 37℃, the radiochemical purity of 18F-JR-1001 in physiological saline and blood remained above 92%, with no significant radioactive by-product peaks observed. Radioautography showed that the whole brain uptake of 18F-JR-1001 in the blocking group was 65.6% of that in normal SD rats. MicroPET/CT imaging showed that the mean whole brain uptake of 18F-JR-1001 in the blocking group was 0.4706, which was lower than that in normal SD rats (1.0561). Additionally, continuous scanning for 60min demonstrated that 18F-JR-1001 exhibited good BBB penetration capability. Conclusion:The synthesized 18F-JR-1001 meets the requirements of production and application, and is proved the potential as a CB1R-targeted tracer in the in vitro experiments, microPET/CT imaging and radioautography.

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

The intensive care unit (ICU) is a highly equipment-intensive area with a wide variety of medical devices, and the accuracy and timeliness of medical equipment data collection are highly demanded. The integration of the Internet of Things (IoT) into ICU medical devices is of great significance for enhancing the quality of medical care and nursing, as well as for the advancement of digital and intelligent ICUs. This study focuses on the construction of the IOT for ICU medical devices and proposes innovative solutions, including the overall architecture design, devices connection, data collection, data standardization, platform construction and application implementation. The overall architecture was designed according to the perception layer, network layer, platform layer and application layer; three modes of device connection and data acquisition were proposed; data standardization based on Integrating the Healthcare Enterprise-Patient Care Device (IHE-PCD) was proposed. This study was practically verified in the Chinese People's Liberation Army General Hospital, a total of 122 devices in four ICU wards were connected to the IoT, storing 21.76 billion data items, with a data volume of 12.5 TB, which solved the problem of difficult systematic medical equipment data collection and data integration in ICUs. The remarkable results achieved proved the feasibility and reliability of this study. The research results of this paper provide a solution reference for the construction of hospital ICU IoT, offer more abundant data for medical big data analysis research, which can support the improvement of ICU medical services and promote the development of ICU to digitalization and intelligence.
Intensive Care Units ; Internet of Things ; Humans ; Internet ; Data Collection

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

OBJECTIVES: To explore the efficacy and adverse reactions of nusinersen combined with risdiplam in the treatment of spinal muscular atrophy (SMA). METHODS: A retrospective analysis was conducted on the clinical data of 10 pediatric SMA patients treated with nusinersen combined with risdiplam at the Children's Medical Center of Xiangya Hospital, Central South University. RESULTS: Among the 10 SMA patients, there were 4 with type I, 4 with type II, and 2 with type III. Nine patients initially received nusinersen monotherapy, while 1 patient received nusinersen combined with risdiplam. The median duration of combination therapy with nusinersen and risdiplam for the 10 patients was 10.5 months (range: 0.5-20.0 months), with 6 patients undergoing combination therapy for more than 6 months, showing improvements in motor and/or respiratory function. The remaining 4 patients had combination treatment durations of 0.5, 1.0, 1.3, and 4.0 months, respectively, with no significant overall improvement. After combined treatment, 5 patients experienced skin hyperpigmentation, 2 had lumbar puncture site pain, 1 experienced vomiting, 1 had increased sputum production, and 1 had reduced total sleep time. All adverse reactions were mild and did not require medical intervention. CONCLUSIONS Nusinersen combined with risdiplam demonstrates efficacy in the treatment of SMA, and no significant adverse reactions have been observed.
Humans ; Oligonucleotides/adverse effects* ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Infant ; Muscular Atrophy, Spinal/drug therapy* ; Drug Therapy, Combination ; Child ; Azo Compounds ; Pyrimidines

OBJECTIVE: To analyze the gene mutation characteristics and survival time of patients with newly diagnosed acute myeloid leukemia (AML) based on next-generation sequencing(NGS) gene detection. METHODS: A retrospective analysis was conducted on the clinical data of 92 patients with AML (non APL) admitted to our hospital from January 2018 to May 2022. AML related genes tested were using NGS, the mutation characteristics and survival time of AML patients were analyzed. RESULTS: Among the 92 patients, 41 were males and 51 were females. A total of 38 types of gene mutations were detected. Six-two patients carried at least one gere mutation, while no gene mutations were detected in 30 patients. In the group with favourable prognosis (n =14), the frequencies of higher gene mutations were NRAS, KIT (21.43%, n =3), KRAS (14.29%, n =2). In the group with intermediate prognosis (n =64), the gene mutation frequencies from high to low were DNMT3A (18.75%, n =12), NPM1 (17.19%, n =11), IDH2, FLT3-ITD, CEBPA (12.50%, n =8), TET2 (10.94%, n =7). In the poor prognosis group (n =14), ASXL1, TP53, EZH2, NRAS had higher gene mutation frequency than others(14.29 %, n =2 ). Statistical analysis revealed that KIT had a relative hotspot of mutations in the intermediate-risk group, and DNMT3A had a relative hotspot of mutations in the high-risk group (P < 0.05). The correlation analysis of genes with high mutation rates in different prognostic groups, such as NRAS, KIT, IDH2, DNMT3A, NPM1, and FLT3-ITD, with prognosis found that KIT was a factor affecting OS (P < 0.05), while no significant differences were observed for the others(P >0.05). CONCLUSION The frequency of gene mutations is high in AML patients, 67.4% of the patients carried at least one gene mutation. The mutation frequency varies among different genes in patients with different karyotypes, and there are obvious dominant mutations. KIT and DNMT3A can be used as factors for evaluating the prognosis of AML.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Nucleophosmin ; Mutation ; Prognosis ; Retrospective Studies ; Male ; Female ; High-Throughput Nucleotide Sequencing ; Middle Aged ; DNA Methyltransferase 3A ; Adult ; Aged ; Survival Analysis ; Proto-Oncogene Proteins c-kit/genetics*