RNA sequencing identifies key genes involved in intramuscular fat deposition in chickens at different developmental stages.

BACKGROUND: Intramuscular fat (IMF) is an important factor in meat quality, and triglyceride (TG) and Phospholipids (PLIP), as the main components of IMF, are of great significance to the improvement of meat quality. RESULTS: In this study, we used 30 RNA sequences generated from the transcriptome of chicken breast muscle tissues at different developmental stages to construct a gene expression matrix to map RNA sequence reads to the chicken genome and identify the transcript of origin. We used weighted gene co-expression network analysis (WGCNA) and identified 27 co-expression modules, 10 of which were related to TG and PLIP. We identified 150 highly-connected hub genes related to TG and PLIP, respectively, which were found to be mainly enriched in the adipocytokine signaling pathway, MAPK signaling pathway, mTOR signaling pathway, FoxO signaling pathway, and TGF-beta signaling pathway. Additionally, using the BioMart database, we identified 134 and 145 candidate genes related to fat development in the TG-related module and PLIP-related module, respectively. Among them, RPS6KB1, BRCA1, CDK1, RPS3, PPARGC1A, ACSL1, NDUFAB1, NDUFA9, ATP5B and PRKAG2 were identified as candidate genes related to fat development and highly-connected hub genes in the module, suggesting that these ten genes may be important candidate genes affecting IMF deposition. CONCLUSIONS: RPS6KB1, BRCA1, CDK1, RPS3, PPARGC1A, ACSL1, NDUFAB1, NDUFA9, ATP5B and PRKAG2 may be important candidate genes affecting IMF deposition. The purpose of this study was to identify the co-expressed gene modules related to chicken IMF deposition using WGCNA and determine key genes related to IMF deposition, so as to lay a foundation for further research on the molecular regulation mechanism underlying chicken fat deposition.

DEAR model in overweight endometrial cancer patients undergoing fertility-sparing treatment: A randomized controlled trial.

OBJECTIVE: To evaluate the effects of DEAR weight management in overweight patients undergoing fertility-sparing treatment for endometrial cancer or atypical hyperplasia. METHODS: Women with endometrial cancer or atypical hyperplasia who received fertility-sparing treatment and had a body mass index of >25 kg/m2 were randomly allocated to the DEAR (DEAR weight management) and control (self weight management) groups. Body morphology and composition, glycolipid metabolism, and tumor outcomes were assessed in both groups before and at 3 and 6 months after intervention. RESULTS: Overall, 72 subjects were included (36 in each group). Following intervention, the DEAR group showed significantly lower median body weight (69.45 vs. 78.05), body mass index (26.19 vs. 29.15), lipid accumulation index (29.21 vs. 57.86), body fat mass (24.00 vs. 29.30), visceral fat area (112.5 vs. 133.3), and glycolipid metabolic indices (except high density lipoprotein) than the control group (P < 0.05) and showed a decreasing trend. The test group achieved significantly higher complete remission (88.46% vs. 57.14%; P < 0.05); the time to complete remission did not differ significantly (P > 0.05). CONCLUSIONS: DEAR weight management can improve the studied parameters and complete remission rates in this population. REGISTRATION: NCT06169449.

Retinoic acid released from self-assembling peptide activates cardiomyocyte proliferation and enhances repair of infarcted myocardium.

The limited cardiomyocyte proliferation is insufficient for repair of the myocardium. Therefore, activating cardiomyocyte proliferation might be a reasonable option for myocardial regeneration. Here, we investigated effect of retinoic acid (RA) on inducing adult cardiomyocyte proliferation and assessed efficacy of self-assembling peptide (SAP)-released RA in activating regeneration of the infarcted myocardium. Effect of RA on inducing cardiomyocyte proliferation was examined with the isolated cardiomyocytes. Expression of the cell cycle-associated genes and paracrine factors in the infarcted myocardium was examined at one week after treatment with SAP-carried RA. Cardiomyocyte proliferation, myocardial regeneration and improvement of cardiac function were assessed at four weeks after treatment. In the adult rat myocardium, expression of RA synthetase gene Raldh2 and RA concentration were decreased significantly. After treatment with RA, the proliferated cardiomyocytes were increased. The formulated SAP could sustainedly release RA. After treatment with SAP-carried RA, expression of the pro-proliferative genes in cell cycle and paracrine factors in the infarcted myocardium were up-regulated. Myocardial regeneration was enhanced, and cardiac function was improved significantly. These results demonstrate that RA can induce adult cardiomyocytes to proliferate effectively. The sustained release of RA with SAP is a promise strategy to enhance repair of the infarcted myocardium.

Integrative Analysis of N6-methyladenosine RNA modifications related genes and their Influences on Immunoreaction or fibrosis in myocardial infarction.

Increasing studies have shown that N6-methyladenosine (m6A) modification plays an important role in cardiovascular diseases. In this study, we systematically investigated the regulatory mode of m6A genes in myocardial infarction (MI) by combining bioinformatics analysis of clinical samples with animal experiments. We utilized gene expression data of clinical samples from public databases to examine the expression of m6A genes in heart tissues and found a large difference between the healthy control group and MI group. Subsequently, we established an MI diagnosis model based on the differentially expressed m6A genes using the random forest method. Next, unsupervised clustering method was used to classify all MI samples into two clusters, and the differences in immune infiltration and gene expression between different clusters were compared. We found LRPPRC to be the predominant gene in m6A clustering, and it was negatively correlated with immunoreaction. Through GO enrichment analysis, we found that most differentially expressed genes between the two clusters were profibrotic. By means of WGCNA, we inferred that GJA4 might be a core molecule in the m6A regulatory network of MI. This study demonstrates that m6A regulators probably affects the immune-inflammatory response and fibrosis to regulate the process of MI, which provides a potential therapeutic target.

Therapeutic Effect of Tympanoplasty on Patients with Chronic Otitis Media with Tinnitus and Influencing Factors.

Objective: This research was conducted to investigate the therapeutic effects of tympanoplasty on patients with chronic otitis media with tinnitus and analyze the possible influencing factors for patient prognosis. Methods: This is a pre-post control group study, 86 patients with chronic otitis media were included as the subjects and enrolled into tinnitus group (n = 46) and the non-tinnitus group (n = 40). All patients underwent tympanoplasty under microscope or ear endoscopy. A tinnitus severity and efficacy assessment scale was employed for the evaluation of the severity of tinnitus among the subjects. In addition, tinnitus handicap inventory (THI) was utilized to evaluate disease alleviation. Results: Before treatment, the proportions of the patients with tinnitus at grades I, II, III, IV, and V amounted to 15.22%, 32.61%, 21.74%, 17.39%, and 13.04%, respectively, while they were 30.43%, 45.65%, 13.04%, 8.71%, and 2.17%, respectively 3 months after treatment (P < .05). THI scores for the patients in the tinnitus group before and 3 months after treatment amounted to 17.96 ± 3.66 and 16.21 ± 3.29, respectively (P < .05). After treatment, the air conduction (AC) and bone conduction (BC) thresholds and air-bone gap (ABG) of the two groups apparently declined (P < .05). No statistical significance was detected in the differences in disease classification, disease courses, and whether an electric drill was used among the patients between effective and invalid groups (P > .05). Conclusion: To some extent, tympanoplasty alleviated tinnitus among patients with chronic otitis media and promoted the restoration of hearing. Hence, it is worthy of application in clinical treatment.

Assessment of the effectiveness of the BOPPPS model combined with case-based learning on nursing residency education for newly recruited nurses in China: a mixed methods study.

BACKGROUND: Expanding new nurse training and education is a priority for nursing educators as well as a critical initiative to stabilize the nursing workforce. Given that there is currently no standardized program for the training of new nurses in China, we investigated the effectiveness of the bridge-in, objective, pre-assessment, participatory learning, post-assessment, and summary model combined with case-based learning ((BOPPPS-CBL) for the standardized training of new nurses. METHODS: The mixed method approach with explanatory sequential (quantitative-qualitative) method was used. A questionnaire was used to compare the impact of the BOPPPS-CBL model and the Traditional Learning Model (TLM) on the core competencies of 185 new nurses for two years of standardized training. Quantitative data were analyzed using SPSS 22.0. Focus group interviews were used with four groups of new nurses and perceptions of BOPPPS-CBL training were recorded. Qualitative data were analyzed thematically. RESULTS: According to the quantitative data, more new nurses agreed that the BOPPPS-CBL model stimulated their learning and improved their core nursing competencies than the TLM. The BOPPPS-CBL group outperformed the TLM group on theoretical knowledge tests. Qualitative data revealed that 87.5% of new nurses agreed on the value of BOPPPS-CBL training, and three themes were extracted: (1) role promotion; (2) formation of new thinking to solve clinical problems; and (3) suggestions for improvement. CONCLUSION: BOPPPS-CBL training had a significant impact on improving new nurses' core competencies and promoting the transition of new nurses to clinical practice nurses in China. The study recommends BOPPPS-CBL training as an effective teaching model for the standardized training and education of new nurses.

Interventional Embolization of Unilateral Cavernous Sinus With ONXY Glue Combined With Coils for the Treatment of Bilateral Dural Arteriovenous Fistula.

PURPOSE: To summarize the clinical experience of unilateral sponge sinus embolization of cavernous sinus dural arteriovenous fistula (CS DAVF) via jugular vein access with ONXY gel and spring coil intervention. METHODS: The authors retrospectively analyzed the clinical data of 3 patients who were treated with unilateral cavernous sinus embolization for bilateral cavernous sinus dural arteriovenous fistula (CS DAVF) from October 2020 to May 2022 in our department by using transjugular vein access spring coil + ONXY gel interventional embolization. RESULTS: Immediate postoperative angiography suggested that the cavernous sinus fistula was completely embolized in all 3 patients, and cerebral angiography was carried out from 6 to 12 months after the operation and assessed using the Class grading method, and there was no recurrence in any of the 3 patients. CONCLUSIONS: Transvenous access ONXY adhesive combined with spring coil interventional embolization of unilateral cavernous sinus to cure bilateral cavernous sinus dural arteriovenous fistula is feasible, which can avoid the excessive use of spring coils and ONXY adhesive, and it is the key to the effective cure of DAVF in cavernous sinus area and to reduce the complication.

Identification, characterization and optimization of culture medium conditions for organic acid-producing lactic acid bacteria strains from Chinese fermented vegetables.

Lactic acid bacteria (LAB) are widely exploited in fermented foods and are gaining attention for novel uses due to their safety as biopreservatives. In this study, several organic acid-producing LAB strains were isolated from fermented vegetables for their potential application in fermentation. We identified nine novel strains belonging to four genera and five species, Lactobacillus plantarum PC1-1, YCI-2 (8), YC1-1-4B, YC1-4 (4), and YC2-9, Lactobacillus buchneri PC-C1, Pediococcus pentosaceus PC2-1 (F2), Weissella hellenica PC1A, and Enterococcus sp. YC2-6. Based on the results of organic acids, acidification, growth rate, antibiotic activity and antimicrobial inhibition, PC1-1, YC1-1-4B, PC2-1(F2), and PC-C1 showed exceptional biopreservative potential. Additionally, PC-C1, YC1-1-4B, and PC2-1(F2) recorded higher (p < 0.05) growth by utilizing lower concentrations of glucose (20 g/L) and soy peptone (10 g/L) as carbon and nitrogen sources in optimized culture conditions (pH 6, temperature 32 °C, and agitation speed 180 rpm) at 24hr and acidification until 72hr in batch fermentation, which suggests their application as starter cultures in industrial fermentation.

Acoustic effects of speaker sex, speech sample, and Mandarin tone on vowel production of post-stroke spastic dysarthria.

INTRODUCTION: Vowel production in dysarthria tends to be centralized, which is affected by many factors. This study examined the acoustic effects of speaker sex, tones, and speech samples (including sustained vowels, syllables, and sentences) and their interactions on vowel production in Mandarin speakers with post-stroke spastic dysarthria. METHODS: 28 patients with post-stroke spastic dysarthria (18 males, 10 females) and 21 healthy speakers (11 males and 10 females) with no significant difference in sex and age with dysarthria were recruited. They were asked to read sustained vowels /a, i, u/, 12 syllables and 12 sentences containing three vowels in four tones (ba, bá, bǎ, bà, bi, bí, bǐ, bì, pu, pú, pǔ, pù). Multiple spectral and temporal acoustic metrics were analyzed. RESULTS: Results showed that regardless of the speech samples or tones, vowel production was more centralized in dysarthria than healthy controls, manifested as the decrease in F1 range, F2 range, vowel space area (VSA), and vowel articulation index (VAI). A similar performance was observed for male speakers compared to females, and vowel duration in males was shorter than females. F1 range, F2 range, VSA, VAI, and vowel duration were significantly different across speech samples and tones, decreasing in the order of vowel-syllable-sentence and T3-T2-T1-T4, respectively. Interactions of group, speaker sex, speech sample, and tone were more sensitive in VAI and vowel duration. CONCLUSION: VAI and vowel duration were recommended as the prior metrics to the assessment of vowel production. Specific influencing factors (speaker sex, speech sample, and tone) of vowel production need to be considered by speech and language pathologists in the assessment and rehabilitation.

Bacterial biosynthesis of flavonoids: Overview, current biotechnology applications, challenges, and prospects.

Flavonoids are secondary metabolites present in plant organs and tissues. These natural metabolites are the most prevalent and display a wide range of beneficial physiological effects, making them usually intriguing in several scientific fields. Due to their safety for use and protective attributes, including antioxidant, anti-inflammatory, anticancer, and antimicrobial functions, flavonoids are broadly utilized in foods, pharmaceuticals, and nutraceuticals. However, conventional methods for producing flavonoids, such as plant extraction and chemical synthesis, entailed dangerous substances, and laborious procedures, with low product yield. Recent studies have documented the ability of microorganisms, such as fungi and bacteria, to synthesize adequate amounts of flavonoids. Bacterial biosynthesis of flavonoids from plant biomass is a viable and environmentally friendly technique for producing flavonoids on a larger scale and has recently received much attention. Still, only a few bacteria species, particularly Escherichia coli, have been extensively studied. The most recent developments in bacterial biosynthesis of flavonoids are reviewed and discussed in this article, including their various applications as natural food biocontrol agents. In addition, the challenges currently faced in bacterial flavonoid biosynthesis and possible solutions, including the application of modern biotechnology approaches for developing bacterial strains that could successfully produce flavonoids on an industrial scale, were elucidated.

InAs/GaAs quantum-dot lasers grown on on-axis Si (001) without dislocation filter layers.

InAs/GaAs quantum dot (QD) laser monolithically grown on silicon is one of the potential approaches to realizing silicon-based light sources. However, the mismatch between GaAs and Si generates a high density of threading dislocations (TDs) and antiphase boundaries (APBs), which trap carriers and adversely affect device performance. In this paper, we present a simple method to reduce the threading dislocation density (TDD) merely through GaAs buffer, eliminating the intricate dislocation filter layers (DFLs) as well as any intermediate buffer layers whose compositions are different from the target GaAs. An APB-free epitaxial 2.5 µm GaAs film was grown on exact Si (001) by metalorganic chemical vapor deposition (MOCVD) with a TDD of 9.4 × 106 cm-2. InAs/GaAs QDs with a density of 5.2 × 1010 cm-2 were grown on this GaAs/Si (001) virtual substrate by molecular beam epitaxy (MBE) system. The fabricated QD laser has achieved a single facet room temperature continuous-wave output power of 138 mW with a threshold current density of 397 A/cm2 and a lasing wavelength of 1306 nm. In this work, we propose a simplified method to fabricate high-power QD lasers, which is expected to promote the application of photonic integrated circuits.

Simultaneous determination of cordycepin and its metabolite 3'-deoxyinosine in rat whole blood by ultra-high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry and its application to accurate pharmacokinetic studies.

Cordycepin from Cordyceps possesses excellent pharmacological properties, including anti-inflammation and anti-tumor effects, therefore representing a potential alternative medicine. However, doubts about the pharmacokinetic results of cordycepin had been raised in the previous study due to its rapid deamination. The organic solvent methanol was immediately added to terminate the degradation of cordycepin in anticoagulated blood samples and enable the accurate evaluation of pharmacokinetics in vivo. A sensitive and selective ultra-high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry method was developed and validated to simultaneously determine cordycepin and its deamination metabolite 3'-deoxyinosine using 2-chloroadenosine as an internal standard in rat whole blood. The calibration curves of cordycepin and 3'-deoxyinosine showed excellent linearity within the concentration range of 1.05-10 000.00 ng/ml with acceptable accuracy, precision, selectivity, recovery, matrix effect, and stability. This method was successfully applied to the pharmacokinetic study of cordycepin and its metabolite in rat blood. The effect of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride on the pharmacokinetics of cordycepin was investigated. In summary, the reliable pharmacokinetic parameters of cordycepin and its deamination metabolite 3'-deoxyinosine in rat blood were successfully elucidated. Erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride considerably prolonged the half-life of cordycepin in vivo.

Surgical outcomes of percutaneous endoscopic lumbar discectomy in obese adolescents with lumbar disc herniation.

In recent years, with improved living standards, adolescent obesity has been increasingly studied. The incidence of lumbar disc herniation (LDH) in obese adolescents is increasing yearly. No clinical studies have reported the use of percutaneous endoscopic lumbar discectomy (PELD) in obese adolescent lumbar disc herniation (ALDH) patients. This study evaluated the preliminary surgical outcomes of PELD in obese ALDH patients. Fifty-one ALDH patients underwent single-level PELD surgery between January 2014 and January 2020. Patients were divided into an obese group and a normal group. Patient characteristics and surgical variables were compared between the two groups. The VAS, ODI, and SF-36 scales were used preoperatively and postoperatively to evaluate the clinical efficacy. In this study, 19 patients were included in the obese group, and 28 were included in the normal group. There was no significant difference in age, sex, duration of low back pain, duration of leg pain, or operative level between the obese and normal groups preoperatively. The obese group had a longer operative time (OT) (101.9 ± 9.0 min vs. 84.3 ± 11.0 min, P < 0.001), more fluoroscopy exposures (41.0 ± 5.8 vs. 31.6 ± 7.0, P < 0.001) and a longer time to ambulation (29.9 ± 4.0 vs. 25.0 ± 2.9, p < 0.001) than the normal group. The groups did not significantly differ in complications. The VAS score for back and leg pain and the ODI and SF-36 score for functional status improved significantly postoperatively. The PELD procedure is a safe and feasible method for treating LDH in obese adolescents. Obese ALDH patients require a longer OT, more fluoroscopy exposures and a longer time to get out of bed than normal ALDH patients. However, PELD yields similar clinical outcomes in obese and normal ALDH patients.

Establishment of a Multi-parameter Evaluation Model for Risk of Aspiration in Dysphagia: A Pilot Study.

It's difficult for clinical bedside evaluations to accurately determine the occurrence of aspiration in patients. Although VFSS and FEES are the gold standards for clinical diagnosis of dysphagia, which are mainly used to evaluate people at high risk of dysphagia found by bedside screening, the operation is complicated and time-consuming. The aim of this pilot study was to present an objective measure based on a multi-parameter approach to screen for aspiration risk in patients with dysphagia. Objective evaluation techniques based on speech parameters were used to assess the oral motor function, vocal cord function, and voice changes before and after swallowing in 32 patients with dysphagia (16 low-risk aspiration group, 16 high-risk aspiration group). Student's t test combined with stepwise logistic regression were used to determine the optimal index. The best model consists of three parameters, and the equation is: logit(P) = - 3.824 - (0.504 × maximum phonation time) + (0.008 × second formant frequency of /u/) - 0.085 × (fundamental frequency difference before and after swallowing). An additional eight patients with dysphagia were randomly selected as the validation group of the model. When applied to validation, this model can accurately identify the risk of aspiration in 87.5% of patients, and the sensitivity is as high as 100%. Therefore, it has certain clinical practical value that may help clinicians to assess the risk of aspiration in patients with dysphagia, especially for silent aspiration.

Is CO2 laser microsurgery better than radiotherapy in early glottic cancer: a meta-analysis.

The choice between radiotherapy (RT) and CO2 laser surgery (CO2-LS) for early glottic cancer remains controversial. We systematically examined electronic databases in order to identify prospective trials comparing patients who had undergone CO2-LS or RT to treat early glottic cancer. Eleven studies involving 1053 patients were included. In the selected literature, the parameter setting of CO2 laser equipment can be summarized as wavelength 10.6 µm, superpulsed mode, continuous setting, power tailored on target structures (1-3 W for subtle resections and 4-15 W for cutting a larger tumor), and approximately 2080-3900 W/cm2 of laser energy. Using RevMan 5.3, we estimated pooled odds ratios (ORs) for dichotomous variables and pooled mean differences (MDs) for continuous variables, along with associated 95% confidence intervals (CIs). The heterogeneity in the treatment variables was measured using Higgins' inconsistency test and expressed as I2 values. The continuous variables were then depicted as histograms developed using PlotDigitizer 2.6.8. Compared to patients treated with CO2-LS, those treated with RT had better jitter (MD 1.27%, 95% CI 1.21 ~ 1.32, P < 0.001), and high scores on the "Grade (MD 6.54, 95% CI 5.31 ~ 7.76, P < 0.001), Breathiness (MD 9.08, 95% CI 4.02 ~ 14.13, P < 0.001), Asthenia (MD 2.13, 95% CI 0.29 ~ 3.98, P = 0.02), and Strain (MD 3.32, 95% CI 0.57 ~ 6.07, P = 0.02)" scale. Patients treated with CO2-LS had worse local control rates (OR 3.14, 95% CI 1.52 ~ 6.48, P = 0.002) while lower incidence of second primary tumor (OR 0.30, 95% CI 0.15 ~ 0.61, P < 0.001). It is hoped that retrospective analysis can provide suggestions for early glottis patients to choose personalized treatment.

Anti-Inflammatory Activities of Monoterpene and Sesquiterpene Glycosides from the Aqueous Extract of Artemisia annua L.

Artemisia annua L. is a Chinese medicinal herb, but the origin of its pharmacological properties, including its anti-inflammatory activity, remain unknown. In this study, five new monoterpene glycosides (1-5) and two new sesquiterpene glycosides (6 and 7) were isolated from the aqueous extract of the aerial parts of A. annua. The structures of these glycosides were determined using high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, electronic circular dichroism calculations, and chemical hydrolysis methods. The anti-inflammatory activities of the isolated compounds were evaluated by down-regulating interleukin-6 (IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Notably, all the new compounds significantly inhibited the expression of IL-6 in a dose-dependent manner.

[Effects of Xihuang Pills on proliferation and apoptosis of prostate cancer LNCaP cells based on AR/m TOR signaling pathway].

Based on the androgen receptor(AR)/mammalian target of rapamycin(mTOR)signaling pathway, the effects of Xihuang Pills-medicated serum on the proliferation and apoptosis of prostate cancer LNCaP cells were investigated. The drug-containing serum of SD rats was prepared by intragastric administration of Xihuang Pills suspension. The effects of low-, medium-, and high-dose Xihuang Pills-containing serum on the in vitro proliferation of LNCaP cells were detected by cell counting kit-8(CCK-8). Flow cytometry was used to detect the apoptosis level of LNCaP cells after intervention with different concentrations of Xihuang Pills. Protein expression of cleaved cysteinyl aspartate-specific proteinase caspase-3(cleaved caspase-3), B-cell lymphoma-2(Bcl-2), and AR as well as the phosphorylation level of mTOR protein were detected by Western blot. The results showed that compared with the blank serum, the drug-medicated serum could blunt the activity of LNCaP cells. Low-, medium-, and high-dose Xihuang Pills-containing serum could significantly increase the cell apoptosis rate, increase the expression of cleaved caspase-3 protein, decrease the expression of Bcl-2 protein, reduce the expression of AR protein, and down-regulate the level of phosphorylated mTOR(p-mTOR). To study the effect of Xihuang Pills on the growth of LNCaP cells in vivo, different doses of Xihuang Pills were used to intervene in the subcutaneous graft model in nude mice inoculated with LNCaP cells. The expression levels of AR, mTOR, p-mTOR, Bcl-2, and cleaved caspase-3 were detected by Western blot. The results showed that the volumes of subcutaneous graft tumor in the low-dose, medium-dose, and high-dose Xihuang Pills groups significantly decreased compared with that in the model group. The weight of subcutaneous transplanted tumor in each group with drug intervention was significantly lower than that in the model group. Compared with the model group, the low-dose, medium-dose, and high-dose Xihuang Pills groups showed increased cleaved caspase-3 protein expression, decreased Bcl-2 and AR protein expression, and reduced p-mTOR protein expression. Further experiments showed that AR agonist R1881 could block the anti-proliferation and pro-apoptotic effects of Xihuang Pills. The mechanism of Xihuang Pills against prostate cancer is related to the inhibition of the AR/mTOR signaling pathway, inhibition of LNCaP cell proliferation, and induction of apoptosis in cancer cells.

[Clinical and genetic characteristics of children with primary dilated cardiomyopathy]. / å„¿ç«¥åŽŸå‘æ€§æ‰©å¼ åž‹å¿ƒè‚Œç— çš„ä¸´åºŠç‰¹å¾åŠé—ä¼ å­¦åˆ†æž.

OBJECTIVES: To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM). METHODS: A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data. RESULTS: Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade Ⅲ or Ⅳ, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05). CONCLUSIONS: There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.

Osteoblast MR deficiency protects against adverse ventricular remodeling after myocardial infarction.

RATIONALE: Mineralocorticoid receptor (MR) antagonists have been clinically used to treat heart failure. However, the underlying cellular and molecular mechanisms remain incompletely understood. METHODS AND RESULTS: Using osteoblast MR knockout (MRobko) mouse in combination with myocardial infarction (MI) model, we demonstrated that MR deficiency in osteoblasts significantly improved cardiac function, promoted myocardial healing, as well as attenuated cardiac hypertrophy, fibrosis and inflammatory response after MI. Gene expression profiling using RNA sequencing revealed suppressed expression of osteocalcin (OCN) in calvaria from MRobko mice compared to littermate control (MRfl/fl) mice with or without MI. Plasma levels of undercarboxylated OCN (ucOCN) were also markedly decreased in MRobko mice compared to MRfl/fl mice. Administration of ucOCN abolished the protective effects of osteoblast MR deficiency on infarcted hearts. Mechanistically, ucOCN treatment promoted proliferation and inflammatory cytokine secretion in macrophages. Spironolactone, an MR antagonist, significantly inhibited the expression and secretion of OCN in post-MI mice. More importantly, spironolactone decreased plasma levels of ucOCN and inflammatory cytokines in heart failure patients. CONCLUSIONS: MR deficiency in osteoblasts alleviates pathological ventricular remodeling after MI, likely through its regulation on OCN. Spironolactone may work through osteoblast MR/OCN axis to exert its therapeutic effects on pathological ventricular remodeling and heart failure in mice and human patients.

Mineralocorticoid receptor deficiency in Treg cells ameliorates DSS-induced colitis in a gut microbiota-dependent manner.

Mineralocorticoid receptor (MR) is a classic nuclear receptor and an effective drug target in the cardiovascular system. The function of MR in immune cells such as macrophages and T cells has been increasingly appreciated. The aim of this study was to investigate the function of Treg MR in the process of inflammatory bowel disease (IBD). We treated Treg MR-deficient (MRflox/flox Foxp3YFP-Cre , KO) mice and control (Foxp3YFP-Cre , WT) mice with dextran sodium sulphate (DSS) to induce colitis and found that the severity of DSS-induced colitis was markedly alleviated in Treg MR-deficient mice, accompanied by reduced production of inflammatory cytokines, and relieved infiltration of monocytes, neutrophils and interferon γ+ T cells in colon lamina propria. Faecal microbiota of mice with colitis was analysed by 16S rRNA gene sequencing and the composition of gut microbiota was vastly changed in Treg MR-deficient mice. Furthermore, depletion of gut microbiota by antibiotics abolished the protective effects of Treg MR deficiency and resulted in similar severity of DSS-induced colitis in WT and KO mice. Faecal microbiota transplantation from KO mice attenuated DSS-induced colitis characterized by alleviated inflammatory infiltration compared to that from WT mice. Hence, our study demonstrates that Treg MR deficiency protects against DSS-induced colitis by attenuation of colonic inflammatory infiltration. Gut microbiota is both sufficient and necessary for Treg MR deficiency to exert the beneficial effects.