Procyanidin B2 improves developmental capacity of bovine oocytes via promoting PPARγ/UCP1-mediated uncoupling lipid catabolism during in vitro maturation.

Metabolic balance is essential for oocyte maturation and acquisition of developmental capacity. Suboptimal conditions of in vitro cultures would lead to lipid accumulation and finally result in disrupted oocyte metabolism. However, the effect and mechanism underlying lipid catabolism in oocyte development remain elusive currently. In the present study, we observed enhanced developmental capacity in Procyanidin B2 (PCB2) treated oocytes during in vitro maturation. Meanwhile, reduced oxidative stress and declined apoptosis were found in oocytes after PCB2 treatment. Further studies confirmed that oocytes treated with PCB2 preferred to lipids catabolism, leading to a notable decrease in lipid accumulation. Subsequent analyses revealed that mitochondrial uncoupling was involved in lipid catabolism, and suppression of uncoupling protein 1 (UCP1) would abrogate the elevated lipid consumption mediated by PCB2. Notably, we identified peroxisome proliferator-activated receptor gamma (PPARγ) as a potential target of PCB2 by docking analysis. Subsequent mechanistic studies revealed that PCB2 improved oocyte development capacity and attenuated oxidative stress by activating PPARγ mediated mitochondrial uncoupling. Our findings identify that PCB2 intricately improves oocyte development capacity through targeted activation of the PPARγ/UCP1 pathway, fostering uncoupling lipid catabolism while concurrently mitigating oxidative stress.

Vitrification of Mammalian Oocytes: Recent Studies on Mitochondrial Dysfunction.

Vitrification of reproductive cells is definitely essential and integral in animal breeding, as well as in assisted reproduction. However, issues accompanied with this technology such as decreased oocyte competency and relatively low embryo survival rates appear to be a tough conundrum that has long perplexed us. As significant organelles in cell metabolism, mitochondria play pivotal roles in numerous pathways. Nonetheless, extensive evidence has demonstrated that vitrification can seriously impair mitochondrial function in mammalian oocytes. Thus, in this article, we summarize the current progress in oocyte vitrification and particularly outline the common mitochondrial abnormalities alongside subsequent injury cascades seen in mammalian oocytes following vitrification. Based on existing literature, we tentatively come up with the potential mechanisms related to mitochondrial dysfunction and generalize efficacious ways which have been recommended to restore mitochondrial function.

Clinico-pathological and gene features of 15 nemaline myopathy patients from a single Chinese neuromuscular center.

BACKGROUND: Nemaline myopathy, the most common of the congenital myopathies, is caused by various genetic mutations. In this study, we attempted to investigate the clinical features, muscle pathology and genetic features of 15 patients with nemaline myopathy. RESULTS: Among the 15 patients, there were 9 (60.00%) males and 6 (40.00%) females, and 9 (60.00%) of them came from three families respectively. The age of seeing a doctor ranged from 9 to 52 years old, the age of onset was from 5 to 23 years old, and the duration of disease ranged from 3 to 35 years. Ten out of the 15 patients had high arched palate and elongated face. Only one patient had mild respiratory muscle involvement and none had dysphagia. Muscle biopsies were performed in 9 out of the 15 patients. Pathologically, muscle fibers of different sizes, atrophic muscle fibers and compensatory hypertrophic fibers could be found, and occasionally degenerated and necrotic muscle fibers were observed. Different degrees of nemaline bodies aggregation could be seen in all 9 patients. The distribution of type I and type II muscle fibers were significantly abnormal in patients with nemaline myopathy caused by NEB gene, however, it was basically normal in patients with nemaline myopathy caused by TPM3 gene and ACTA1 gene. Electron microscopic analysis of 6 patients showed that nemaline bodies aggregated between myofibrils were found in 5(83.33%) cases, and most of them were located near the Z band, but no intranuclear rods were found. The gene analysis of 15 NM patients showed that three NM-related genes were harbored, including 11 (73.33%) patients with NEB, 3 (20.00%) patients with TPM3, and 1 (6.67%) patient with ACTA1, respectively. A total of 12 mutation sites were identified and included 10 (83.33%) mutations in exon and 2(16.67%) mutations in intron. CONCLUSIONS: The clinical phenotype of nemaline myopathy is highly heterogeneous. Muscle pathology shows that nemaline bodies aggregation is an important feature for the diagnosis of NM. NEB is the most frequent causative gene in this cohort. The splicing mutation, c.21522 + 3A > G may be the hotspot mutation of the NEB gene in Chinese NM patients.

Correlation between bilateral GFR in patients with localized renal cancer after partial nephrectomy.

OBJECTIVE: To explore the relationship between the residual glomerular filtration rate (GFR) on the operated side and the GFR on the contralateral side following partial nephrectomy (PN) in patients with localized renal cell carcinoma (RCC). MATERIALS AND METHODS: Following institutional review board approval, we conducted a retrospective analysis of clinical records from May 2018 to July 2023, involving 118 patients who underwent partial nephrectomy for unilateral localized kidney tumors (T1-T2). Glomerular filtration rate data were assessed using single photon emission computed tomography (SPECT)/computed tomography imaging [using 9mTc-DTPA (diethylenetriaminepentaacetic acid) renal dynamic imaging]. The independent determinants of postoperative renal function or renal function change were determined using linear regression analysis. In addition, the patient's demographic, clinical, and nephrometry characteristics were collected. RESULTS: A total of 58 patients were finally enrolled. The preoperative and postoperative GFR of bilateral kidneys showed a significant positive correlation. Postoperative GFR of the operated kidney was the independent predictor of GFR of contralateral kidney (p = 0.001). Tumor diameter (p = 0.036), age (p = 0.005), and postoperative GFR of the contralateral kidney (p = 0.001) were all independent predictors of postoperative GFR of the operated kidney. ΔGFR1 was the independent predictor of ΔGFR2. Results showed that a more pronounced postoperative decline in GFR on the operated side corresponded to a weaker compensatory capacity of the contralateral-side kidney. CONCLUSIONS: During the course of the surgical procedure, the active endeavor to safeguard the renal function of the operated kidney side holds paramount importance, which yields positive outcomes for postoperative kidney function on the contralateral side, consequently contributing to the overall preservation of renal function.

Leonurine improves bovine oocyte maturation and subsequent embryonic development by reducing oxidative stress and improving mitochondrial function.

It is acknowledged that excessive reactive oxygen species (ROS) level attributes greatly to the compromised developmental potential of oocytes matured in vitro. Although agents were applied to alleviate ROS levels, results were varied because of the distinct antioxidative activity and cell toxicity. Leonurine (LEO), extracted from the natural Chinese herb motherwort, is considered to be a potent free radical scavenger. Yet, it is undetermined whether LEO is benefit for oocyte development during in vitro maturation (IVM). In the present study, the effect of LEO on the quality of bovine oocyte as well as the underlying mechanism was investigated. We found that maturation rate (P < 0.01), subsequent blastocyst formation rate (P < 0.05), and the total blastocyst cell number (P < 0.05) after parthenogenetic activation were significantly increased in the group treated with 20 µM LEO. Moreover, a dramatic decline in ROS (P < 0.01), decreased lipid content (P < 0.01), elevated MMP level (P < 0.05), increased ATP content (P < 0.05), and reduced mitochondrial temperature (P < 0.01) were observed in oocytes treated with LEO. Furthermore, the expression level of anti-apoptotic protein BCL2 was significantly higher in LEO treated oocytes (P < 0.01), and the ratio of BAX/BCL2 was obvious decreased (P < 0.01). Finally, we found that LC3B intensity was significantly reduced (P < 0.05) while the rate of EdU positive nuclei was markedly increased (P < 0.05) in embryos derived from LEO-treated oocytes. Our results demonstrate that LEO exhibits a potent protective role in the acquisition of oocyte development capacity against oxidative stress during IVM, and provides a new solution for optimizing the in vitro culture system of bovine embryos.

Alleviating Pregastroscopy Anxiety Using Mobile Social Media Application.

Aim: The research aimed to study the effect of using WeChat (a mobile social media application) on pregastroscopy anxiety and the cooperation of patients with different coping styles. Methods: In order to decrease patients' pregastroscopy anxiety and improve the tolerance of unsedated gastroscopy, WeChat, a widely used mobile social media application, was applied to provide information prior to their endoscopic procedure. Two hundred and thirty patients who underwent initial unsedated gastroscopy in a large teaching hospital in China were classified into two groups based on their coping style: information seekers or information avoiders, using the Information Subscale of the Krantz Health Opinion Survey (KHOS-I). Each of the two groups was prospectively randomly assigned to either receiving the brochure information or conjunctive interactive WeChat-delivered information of gastroscopy. To measure the level of state anxiety, the State Anxiety Scale of Spielberg's State-Trait Anxiety Inventory questionnaire was used. State anxiety, blood pressure and heart rate were measured at enrollment, upon arrival, and before gastroscopy. Results: Information seekers and avoiders who received information from the brochure and the WeChat platform experienced significantly less state anxiety upon arrival and before gastroscopy. Furthermore, information seekers who received information from the conjunctive WeChat platform had lower frequency of retching, lower scores of nausea and bloating, and better tolerance. Information avoiders who received information from the conjunctive WeChat platform had lower frequency of retching, lower scores of discomfort while swallowing the scope and nausea, and better tolerance. However, we found the percentage of information seekers who preferred no WeChat-delivered pregastroscopy information is greater than WeChat-delivered information at the initial questionnaire. No significant difference was found in blood pressure or heart rate upon arrival and before gastroscopy. Conclusions: Although people preferred no WeChat-delivered pregastroscopy information, the provision of gastroscopy information through a mobile social media application, such as WeChat, could significantly reduce patients' pregastroscopy anxiety, lower the frequency of retching, reduce the scores of nausea and bloating, and improve tolerance for information seekers. In addition, it could lower the frequency of retching, reduce the scores of discomfort while swallowing the scope and its concurrent nausea, and improve tolerance for information avoiders.

Added value of systemic inflammation markers in predicting pulmonary infection in stroke patients: A retrospective study by machine learning analysis.

ABSTRACT: Exploring candidate markers to predict the clinical outcomes of pulmonary infection in stroke patients have a high unmet need. This study aimed to develop machine learning (ML)-based predictive models for pulmonary infection.Between January 2008 and April 2021, a retrospective analysis of 1397 stroke patients who had CT angiography from skull to diaphragm (including CT of the chest) within 24 hours of symptom onset. A total of 21 variables were included, and the prediction model of pulmonary infection was established by multiple ML-based algorithms. Risk factors for pulmonary infection were determined by the feature selection method. Area under the curve (AUC) and decision curve analysis were used to determine the model with the best resolution and to assess the net clinical benefits associated with the use of predictive models, respectively.A total of 889 cases were included in this study as a training group, while 508 cases were as a validation group. The feature selection indicated the top 6 predictors were procalcitonin, C-reactive protein, soluble interleukin-2 receptor, consciousness disorder, dysphagia, and invasive procedure. The AUCs of the 5 models ranged from 0.78 to 0.87 in the training cohort. When the ML-based models were applied to the validation set, the results also remained reconcilable, and the AUC was between 0.891 and 0.804. The decision curve analysis also showed performed better than positive line and negative line, indicating the favorable predictive performance and clinical values of the models.By incorporating clinical characteristics and systemic inflammation markers, it is feasible to develop ML-based models for the presence and consequences of signs of pulmonary infection in stroke patients, and the use of the model may be greatly beneficial to clinicians in risk stratification and management decisions.

Lateral position intubation followed by endoscopic ultrasound-guided angiotherapy in acute esophageal variceal rupture: A case report.

BACKGROUND: Massive esophageal variceal bleeding can be catastrophic, leading to high morbidity and mortality. Patients experiencing massive esophageal variceal bleeding are at high risk of aspiration and hemorrhagic shock in acute episodes. Intubation and bleeding control are the two essential steps for resuscitation of these patients. CASE SUMMARY: A 47-year-old male patient was admitted to our hospital with upper digestive tract bleeding. He was diagnosed with alcohol-induced liver cirrhosis and consequent esophagogastric varices. As he did not show a good response to somatostatin and Sengstaken-Blakemore tube placement, the patient was scheduled for endoscopic angiotherapy under anesthesia. Preoperative assessment showed an ASA physical status of III and Child-Pugh classification B. However, massive hemorrhage occurred just after induction of anesthesia.  Intubation by video-guided laryngoscopy in the lateral decubitus position was attempted twice and was successful. After that, an experienced endoscopic ultrasound (EUS) specialist performed angiotherapy and occluded the culprit vessel. An ultra-thin gastroscope was then inserted into the endotracheal tube to extract the blood observed in the lobar bronchi. The patient suffered hemorrhagic shock with an estimated blood loss of 1500 mL in 20 min and remained in the intensive care unit for two days. The patient was discharged from our hospital eight days later without major complications. CONCLUSION: Intubation in the lateral decubitus position and EUS-guided treatment can be life-saving procedures in patients with massive upper gastrointestinal hemorrhage.

Sinusoidal stimulation on afferent fibers modulates the firing pattern of downstream neurons in rat hippocampus.

Electrical stimulation in the brain is an emerging therapy for treating a wide range of neurological disorders. Although electrical pulses are commonly used in the clinic, other electrical waveforms such as sinusoidal-waves have been investigated to improve the therapeutic efficacy, to reduce the risk of tissue damage induced by stimulation, and to decrease the consumption of electrical energy. However, the effects of sinusoidal stimulation on neuronal activity are still unclear. In the present study, we investigated the neuronal responses to the stimulation of 50-Hz sinusoidal-waves applied on the afferent fibers of the neurons in the hippocampal CA1 region of Sprague-Dawley rat in vivo. Results show that the stimulation increased the firing rate of both pyramidal neurons and interneurons in the downstream region of stimulation. Also, the stimulation eliminated the original theta rhythms (2-5 Hz) in the single-unit activity of the two types of neurons and entrained these neurons to fire at the stimulation rhythm. These results provide new clues for the mechanisms of brain stimulation to suppress the pathological rhythms in the neuronal activity, and for the application of sinusoidal waveforms in brain stimulation therapy.

Discovery of molluscicidal and cercaricidal activities of 3-substituted quinazolinone derivatives by a scaffold hopping approach using a pseudo-ring based on the intramolecular hydrogen bond formation.

Discovery of novel topological agents against Oncomelania hupensis snails and cercariae remains a significant challenge in current Schistosomiasis control. A pseudo-ring formed from salicylanilide by an intramolecular hydrogen bond led to the discovery of 3-substituted quinazolinone derivatives which showed a potent molluscicidal and cercaricidal activities.

Design, synthesis, and cercaricidal activity of novel high-efficient, low-toxic self-spreading PEG-N-salicylanilide derivatives against cercariae larvae of Schistosome Japonicum floating on the water surface.

Novel cercaricides of PEG-N-salicylanilide derivatives that could self-spread and float on the water surface were designed and synthesized according to the particular habit of cercariae larvae of Schistosome japonicum. The structures of the cercaricides were characterized by the infrared spectra (IR), magnetic resonance ((1) H NMR), and mass spectrum (MS). The images of the floating cercaricides on the water surface were investigated by the Brewster angle microscopy (BAM). When the cercaricides were dropped on the water surface, they could spread along the air-water interface automatically and form thin membranes floating on the water surface immediately. The lethality rate of cercariae for 5a and 6a was more than 90% in 120 min at a surface concentration of 0.008 mg/cm(2) . The non-ionic surfactant-cercaricides not only showed strong cercaricidal activities against the cercariae larvae but also exhibited low toxicities, which offered an effective and environment-friendly approach for the reduction of population infection rate and the realization of schistosome control.

Chronic hydrocephalus after aneurysmal subarachnoid space hemorrhage.

To discuss predisposing factors of chronic hydrocephalus after aneurysmal subarachnoid space hemorrhage (aSAH). Clinical data of treating 32 patients with chronic hydrocephalus after aSAH through operations was retrospectively analyzed and processed. The incidence rate of chronic hydrocephalus of patients with an age above 60 years, Hunt-Hess III-IV level, posterior circulation aneurysm and anterior communicating aneurysm, hemorrhage twice or more and ventricle hematocele is prominently higher than patients with an age below 60 years, Hunt-Hess I-II level, aneurysms on other parts, one hemorrhage and no ventricle hematocele (P < 0.05). An age above 60 years, Hunt-Hess III-IV level, posterior circulation aneurysm and anterior communicating aneurysm, hemorrhage twice or more and ventricle hematocele are predisposing factors of chronic hydrocephalus after aSAH.

Genetic influence on baroreflex sensitivity in normotensive young men.

BACKGROUND: The dysfunction of baroreflex plays an important role in the pathogenesis of essential hypertension. Recent studies suggest that approximately 40% of the variation in baroreflex sensitivity (BRS) may be accounted for by genetic factors. However, only a few such genetic polymorphisms have been explicitly identified. METHODS: A total of 182 normotensive young men were included in the study. They were tested for the occurrence of genotypes involving nine polymorphisms in six genes that have a role in the regulation of the cardiovascular system. BRS was calculated from the spontaneous fluctuation of systolic blood pressure (SBP) and heart interval, using a sequence method. RESULTS: BRS was negatively correlated with body mass index (BMI), SBP, and family history of hypertension. Univariate analysis revealed that BRS is significantly associated with three of the polymorphisms studied. At the polymorphism T-786C in the endothelial nitric oxide (NO) synthase (eNOS) gene, the subjects with TT genotype had lower BRS than subjects carrying either the TC or the CC genotype. At the polymorphism of C-344T in the aldosterone synthase gene (CYP11B2), subjects with the TT genotype had higher BRS as compared to those with CC. At the polymorphism of T-58C in the bradykinin B2 receptor (B2R) gene, subjects with CC genotype had lower BRS as compared to subjects with TT. A multivariable linear regression analysis indicated that 16% of the BRS variation could be explained by these three polymorphisms. CONCLUSIONS: Baroreflex function plays an important role in regulating blood pressure, both in the short term and in the long term. Three polymorphisms that are associated with the variation in BRS were identified in the eNOS, CYP11B2, and B2R genes, respectively; overall, they accounted for 16% of the BRS variation.