Construction of early warning classification of risk in bladder spasm and its intervention plans guided by the rate adjustment card of continuous bladder irrigation after transurethral resection of the prostate (TURP): development and usability study.

Background: Benign prostatic hyperplasia (BPH) is the most common benign disease causing voiding dysfunction in middle-aged and elderly men. the current "gold standard" for surgical treatment is transurethral resection of the prostate (TURP). Continuous bladder irrigation (CBI) is routinely given for 3 to 5 days after operation. However, this may induce bladder spasm. Bladder spasm not only brings physical and mental pain to patients, delaying the postoperative recovery process, but it also increases the medical economic burden. Therefore, it is important to take active measures to effectively warn and deal with bladder spasm. The color of the drainage fluid is an important indicator and requires close observation during CBI, as it can reflect real-time postoperative bleeding. When the color of drainage fluid is abnormal, effective measures should be undertaken. Grading nursing intervention divides patients into different conditions according to their possible changes, and then recommends targeted nursing intervention. Existing studies have formulated CBI programs from the perspective of quantifying the relationship between drainage fluid color and irrigation speed, but have yet to incorporate bladder spasm prevention and control levels or design corresponding grading nursing intervention programs according to different drainage fluid colors. This study aimed to construct the risk warning classification and intervention plan of bladder spasm under the guidance of CBI speed adjusting card after TURP. Methods: Based on the rate adjustment card of CBI after TURP, we formulated the first draft of an early warning classification of risk in bladder spasm and its intervention plans by combining methods suggested from a literature search with semi-structured interviews and results from 2 rounds of correspondence inquiries with 28 experts by the Delphi method. We further screened and revised grading standards and measures. Results: The positive coefficients of experts in 2 rounds of correspondence inquiries were both 100%, the authority coefficients were both 0.952, and the Kendall harmony coefficients were 0.238 and 0.326, respectively (P<0.01). In the second round of correspondence inquiries, the coefficient of variation of expert opinions was 0.000-0.154, and the coefficient of variation of all items was <0.25. Finally, a 3-level risk warning classification standard and 23 nursing measures for CBI complicated by bladder spasm was constructed. Conclusions: The early warning classification of risk in bladder spasm and its intervention plans guided by rate adjustment card of CBI after TURP are scientific and feasible, and can provide a basis and guidance for effective and standardized CBI in patients after TURP.

Effects of fermentation on the structures of yellow compounds in citrus pomace.

To enhance the stability and light resistance of the yellow compounds in citrus pomace, our study successfully isolated and purified five compounds using ultrasonic-assisted extraction and column chromatography. The identified compounds include methyl linoleate, (2-ethyl)hexyl phthalate, 1,3-distearoyl-2-oleoylglycerol, 6,6-ditetradecyl-6,7-dihydroxazepin-2(3H)-one, and n-octadeca-17-enoic acid. The monomers extracted from fresh pomace, compounds 1 and 2, exhibit structural similarities to flavonoids and carotenoids. In contrast, the polymers isolated from fermented pomace, compounds 3, 4, and 5, share structural units with the fresh pomace compounds, indicating the transformation to stable polymeric forms. This suggests that the microbial fermentation process not only enhances the value of citrus pomace, but also provides a promising pathway for the synthesis of natural antioxidant yellow pigments with far-reaching theoretical and practical significance.

Using Quercetin to Construct Molecularly Imprinting Polymer in the Preparation and Enrichment of Flavonol and Flavonoid Compounds.

Flavonol and flavonoid compounds are important natural compounds with various biomedical activities. Therefore, it is of great significance to develop a strategy for the specific extraction of flavonol and flavonoid compounds. Quercetin is a well-studied flavonoid possessing many health benefits. This compound is a versatile antioxidant known to possess protective abilities against body tissue injury induced by pathological situations and various drug toxicities. Although quercetin is widely distributed in many plants, its content generally is not very high. Therefore, the specific extraction of quercetin as well as other flavonol and flavonoid compounds has profound significance. In this work, the quercetin molecularly imprinting polymer (QMIP) was successfully prepared, in which a typical flavonol quercetin was selected as the template molecule. QMIP was synthesized by performing the surface molecular imprinting technology on the surface of NH2-MIL-101(Fe). Our study results showed that QMIP exhibited quick binding kinetic behavior, a high adsorption capacity (57.04[Formula: see text]mg/g), and the specific recognition ability toward quercetin compared with structurally distinct compounds (selective [Formula: see text]). The specific adsorption ability of quercetin by QMIP was further explained using computation simulation that molecules with non-planar 3D conformations hardly entered the molecularly imprinted cavities on QMIP. Finally, QMIP was successfully used for the specific extraction of quercetin and five other flavonol and flavonoid compounds in the crude extracts from Sapium sebiferum. This study proposes a new strategy to synthesize the molecularly imprinted polymer based on a single template for enriching and loading a certain class of active ingredients with similar core structures from variable botanicals.

MRI-based vertebral bone quality score as a novel bone status marker of patients with adolescent idiopathic scoliosis.

To investigate the application of MRI-based vertebral bone quality (VBQ) score in assessing bone mineral density (BMD) for patients with adolescent idiopathic scoliosis (AIS). We reviewed the data of AIS patients between January 2021 and October 2023 with MRI, whole-spine plain radiographs, quantitative computed tomography (QCT) and general information. VBQ score was calculated using T1-weighted MRI. Univariate analysis was applied to present the differences between variables of patients with normal BMD group (QCT Z-score > - 2.0) and low BMD group (QCT Z-score ≤ - 2.0). The correlation between VBQ score and QCT Z-score was analyzed with Pearson correlation test. A multivariate logistic regression model was used to determine the independent factors related to low BMD. Receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic performance of VBQ score in distinguishing low BMD. A total of 136 AIS patients (mean age was 14.84 ± 2.10 years) were included, of which 41 had low BMD. The low BMD group had a significantly higher VBQ score than that in normal group (3.48 ± 0.85 vs. 2.62 ± 0.62, P < 0.001). The VBQ score was significantly negative correlated with QCT Z score (r = - 0.454, P < 0.001). On multivariate analysis, VBQ score was independently associated with low BMD (OR: 4.134, 95% CI 2.136-8.000, P < 0.001). The area under the ROC curve indicated that the diagnostic accuracy of the VBQ score for predicting low BMD was 81%. A sensitivity of 65.9% with a specificity of 88.4% could be achieved for distinguishing low BMD by setting the VBQ score cutoff as 3.18. The novel VBQ score was a promising tool in distinguishing low BMD in patients with AIS and could be useful as opportunistic assessment for screening and complementary evaluation to QCT before surgery.

Wheat flour-derived amyloid fibrils for efficient removal of organic dyes from contaminated water.

Amyloid fibrils derived from different proteins have been proved as a promising material for adsorption of various pollutants from wastewater, which showed advantages of low cost and eco-friendliness. However, most of the amyloid fibrils derived from animal-based proteins with high environmental footprint, while more sustainable amyloid fibrils derived from plant materials are desirable. In this study, a plant-derived amyloid fibril was extracted from the commonly used wheat flour with a simple and scalable protein purification and fibrillization process. Interestingly, the amyloid fibrils showed good adsorption capacity towards typical organic dyes (Eosin Y (EY) and Congo red (CR)) from contaminated water. Adsorption kinetic analysis indicated the adsorption process to EY or CR by wheat flour amyloid well fitted with a pseudo-second-order model. The adsorption also followed a Langmuir isothermal model with adsorption capacities of 333 mg/g and 138 mg/g towards CR and EY, respectively. This work demonstrated the feasibility to utilize the plant-based amyloid fibril for organic dyes removal from contaminated water, which provided an affordable, sustainable and scalable tool for organic dyes removal from wastewater.

Pharmacokinetics, pharmacodynamics, and safety of frunexian in healthy Chinese volunteer adults: A randomized dose-escalation phase I study.

The purpose of this study was to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of frunexian (formerly known as EP-7041 and HSK36273) injection, a small molecule inhibitor of activated coagulation factor XI (FXIa), in healthy Chinese adult volunteers. This study was a randomized, placebo- and positive-controlled, sequential, ascending-dose (0.3/0.6/1.0/1.5/2.25 mg/kg/h) study of 5-day continuous intravenous infusions of frunexian. Frunexian administration exhibited an acceptable safety profile with no bleeding events. Steady state was rapidly reached with a median time ranging from 1.02 to 1.50 h. The mean half-life ranged from 1.15 to 1.43 h. Frunexian plasma concentration at a steady state and area under the concentration-time curve exhibited dose-proportional increases. The dose-escalation study of frunexian demonstrated its progressively enhanced capacities to prolong activated partial thromboplastin time (aPTT) and inhibit FXIa activity. The correlations between PK and PD biomarkers (aPTT/baseline and FXI clotting activity/baseline) were described by the two Emax models, with the EC50 values of 8940 and 1300 ng/mL, respectively. Frunexian exhibits good safety and PK/PD properties, suggesting it is a promising candidate for anticoagulant drug.

Comparative analysis of four nutritional scores predicting the incidence of MACE in older adults with acute coronary syndromes after PCI.

To determine the most appropriate nutritional assessment tool for predicting the occurrence of major adverse cardiovascular events (MACE) within 1 year in elderly ACS patients undergoing PCI from four nutritional assessment tools including PNI, GNRI, CONUT, and BMI. Consecutive cases diagnosed with acute coronary syndrome (ACS) and underwent percutaneous coronary intervention (PCI) in the Department of Cardiovascular Medicine of the Air force characteristic medical center from 1 January 2020 to 1 April 2022 were retrospectively collected. The basic clinical characteristics and relevant test and examination indexes were collected uniformly, and the cases were divided into the MACE group (174 cases) and the non-MACE group (372 cases) according to whether a major adverse cardiovascular event (MACE) had occurred within 1 year. Predictive models were constructed to assess the nutritional status of patients with the Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Controlling nutritional status (CONUT) scores, and Body Mass Index (BMI), respectively, and to analyze their relationship with prognosis. The incremental value of the four nutritional assessment tools in predicting risk was compared using the Integrated Discriminant Improvement (IDI) and the net reclassification improvement (NRI). The predictive effect of each model on the occurrence of major adverse cardiovascular events (MACE) within 1 year in elderly ACS patients undergoing PCI was assessed using area under the ROC curve (AUC), calibration curves, decision analysis curves, and clinical impact curves; comparative analyses were performed. Among the four nutritional assessment tools, the area under the curve (AUC) was significantly higher for the PNI (AUC: 0.798, 95%CI 0.755-0.840 P < 0.001) and GNRI (AUC: 0.760, 95%CI 0.715-0.804 P < 0.001) than for the CONUT (AUC: 0.719,95%CI 0.673-0.765 P < 0.001) and BMI (AUC: 0.576, 95%CI 0.522-0.630 P < 0.001). The positive predictive value (PPV) of PNI: 67.67% was better than GNRI, CONUT, and BMI, and the negative predictive value (NPV): of 83.90% was better than CONUT and BMI and similar to the NPV of GNRI. The PNI, GNRI, and CONUT were compared with BMI, respectively. The PNI had the most significant improvement in the Integrated Discriminant Improvement Index (IDI) (IDI: 0.1732, P < 0.001); the PNI also had the most significant improvement in the Net Reclassification Index (NRI) (NRI: 0.8185, P < 0.001). In addition, of the four nutritional assessment tools used in this study, the PNI was more appropriate for predicting the occurrence of major adverse cardiovascular events (MACE) within 1 year in elderly ACS patients undergoing PCI.

Pharmacokinetics, pharmacodynamics and safety of LPM3480392 in two phase I clinical trials in healthy Chinese male subjects.

Drugs for acute postoperative pain and breakthrough cancer pain are still urgent in clinical. LPM3480392 is a G-protein-biased ligand at the µ-opioid receptor and showed potent analgesia in nonclinical studies. Two phase I studies of LPM3480392 were conducted in healthy Chinese male volunteers to explore its tolerability, pharmacokinetics and pharmacodynamics under single ascending doses (Study I 0.1-3.0 mg, 30 min) and different infusion times (Study II, 0.6-1.0 mg, 2-15 min). There was one serious adverse event (AE) observed in Study II, and the rest AEs were mild or moderate in severity and resolved by the end of the study. Plasma LPM3480392 maximum concentration (Cmax ) (under lower infusion rate) and area under the plasma concentration-time curve (AUCs) were generally increased with dose. Moreover, LPM3480392 at a dose of 0.6 mg under a 2 min infusion rate elicited effective analgesia as the peak effect within 10-30 min, which was measured by cold pain test and pupillometry. These findings suggest that LPM3480392 could be a potential treatment for acute pain management.

Association between whole blood essential trace elements and cognitive function in older adults.

BACKGROUND: Essential trace elements (ETEs) are essential nutrients for keeping the nervous system functioning. Associations between ETEs and cognitive function are still inconclusive and limited. OBJECTIVES: We aimed to investigate the individual and joint associations between ETEs and cognitive function among older adults. METHODS: A population (N = 2181) at an average age≥ 65 from Yiwu cohort in China was available for this study. Whole blood chromium (Cr), selenium (Se), manganese (Mn), and copper (Cu) concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), consisting of five specific cognitive domains: orientation, registry, attention and calculation, recall, and language and praxis. Linear regression, restricted cubic spline (RCS) analysis, and Bayesian kernel machine regression (BKMR) were used to analyze the individual and joint associations between ETEs and cognitive function. RESULTS: The association between Cr and MMSE score presented an inverted-U shape (Q3 versus Q1: ß = 0.774, 95 % CI: 0.297, 1.250; Q4 versus Q1: ß = 0.481, 95 % CI: 0.006, 0.956); and Cr was especially associated with the registry, recall, and language and praxis. Per IQR (36.32 µg/L) increase of Se was positively associated with the MMSE score (ß = 0.497, 95 % CI: 0.277, 0.717) and all five cognitive domains. The BKMR showed that the dose-response association between Se and cognitive function increased initially and then decreased with increasing Se concentration when fixed the other ETEs in median. ETEs mixture was positively associated with cognitive function, and Se (posterior inclusion probabilities, PIPs = 0.915) was the most important contributor within the ETEs mixture. CONCLUSIONS: The nonlinear association between Cr and cognitive function suggested further exploration of an appropriate concentration range for ETEs. A positive association between mixed ETEs and cognitive function is a reminder that their joint association should be considered. Further prospective studies or intervention studies are warranted to validate our findings in the future.

Association of image-defined risk factors with clinical features, tumor biology, and outcomes in neuroblastoma: a single-center retrospective study.

Image-defined risk factors (IDRF) in neuroblastoma have been developed to predict tumor resectability and surgical complications; however, the potential prognostic value of IDRF in neuroblastoma has been variably reported. Previous studies did not report the IDRF status separately from the International Neuroblastoma Risk Group (INRG) stage. Moreover, the association between IDRF and clinical and pathological factors has not been discussed further. In this retrospective study, we investigated the clinical and biological features of neuroblastoma at different INRG stages based on IDRF. Event-free survival (EFS) and overall survival (OS) related to the INRG stage were analyzed using log-rank tests, and the prognostic value of the IDRF number and type was also evaluated. Among 72 patients, 182 IDRF at diagnosis were found in 79.2%. The distribution of the INRG stages was 10 L1 (13.9.0%), 25 L2 (34.7%), and 37 M/MS (51.4%). Patients with stage M/Ms had a larger tumor volume, a higher percentage of age ≥ 18 months, elevated lactate dehydrogenase (LDH) level, elevated ferritin level, and a higher percentage of COG high-risk compared with stage L1 and L2 patients. EFS and OS were similar for stage L1 and L2 tumors but were significantly poorer for metastatic disease. However, EFS (P = 0.06) and OS (P = 0.07) were similar for IDRF-negative and positive neuroblastomas. Patients with stage M/Ms with IDRF-positive had poorer EFS (P = 0.001) and OS (P < 0.001) compared with patients in stage L2. An IDRF ≥ 4, vascular IDRF, and infiltrative IDRF of the tumor were significant indicators of poor prognosis.   Conclusion: Our study indicates that increasing the INRG stages based on IDRF is associated with various unfavorable clinical features of neuroblastoma. The principal determinant of survival in neuroblastoma is the presence of metastatic disease more than IDRF alone at diagnosis. Both the number and type of IDRF have important clinical significance in the protocol planning of neuroblastoma, rather than just considering the absence or presence of IDRF. What is Known: • The International Neuroblastoma Risk Group Staging System (INRGSS) now employs image-defined risk factors (IDRFs) to stratify and stage disease. • The presence of IDRF at diagnosis are associated with higher rates of operative complications and incomplete surgical resection. What is New: • The principal determinant of survival from neuroblastoma is the presence of metastatic disease at diagnosis, more than IDRF alone. • IDRF number and type should also be considered during the diagnosis and treatment planning of neuroblastoma, rather than just considering the absence or presence of IDRF.

Identification of a novel transthyretin mutation D39Y in a cardiac amyloidosis patient and its biochemical characterizations.

Hereditary transthyretin cardiac amyloidosis (hATTR-CA) is a rare autosomal dominantly inherited disease caused by mutations in the transthyretin (TTR) gene. TTR mutations often cause the instability of transthyretin, production of misfolded proteins, and ultimately excessive deposition of insoluble amyloid fibrils in the myocardium, thereby leading to cardiac dysfunction. Herein, we report a novel transthyretin D39Y mutation in a Chinese family. We characterized the kinetic and thermodynamic stabilities of D39Y mutant TTR, revealing that TTR D39Y mutant was less stable than WT TTR and more stable than amyloidogenic mutation TTR L55P. Meanwhile, the only FDA approved drug Tafamidis showed satisfactory inhibitory effect toward ATTR amyloid formation and strong binding affinity in test tube revealed by isothermal titration calorimetry. Finally, we measured the well-folded tetrameric TTR concentration in patient's and his descents' blood serum using a previously reported UPLC-based assay. Notably, the tetramer concentrations gradually increased from symptomatic D39Y gene carrier father, to asymptomatic D39Y gene carrier daughter, and further to wild type daughter, suggesting the decrease in functional tetrameric TTR concentration may serve as an indicator for disease age of onset in D39Y gene carriers. The study described a Chinese family with hATTR-CA due to the TTR variant D39Y with its destabilizing effect in both kinetic and thermodynamic stabilities.

Patients-associated compound etiology may have more severe acute pancreatitis: a retrospective cohort study.

Background: Currently, the concept of "a single cause results in acute pancreatitis (AP)" has been deeply incorporated into clinical practice, whereas the concept of "compound-etiology" has not attract considerable attention. This study aimed to explore the impact of the category of etiology on AP clinical outcomes. Methods: Patients with AP hospitalized within 72 h of symptom onset were retrospectively enrolled in this study from January 2014 to October 2019. AP etiology was classified into two main categories: single-etiology and compound-etiology category. The single-etiology category mainly includes biliary, hypertriglyceridemia (HTG), and alcohol. The compound-etiology category refers to AP with two or more causes, which mainly include dual-etiology and triple-etiology category, that is the biliary-HTG type, HTG-alcoholic type, and biliary-HTG-alcoholic type. The general information and clinical outcomes were reviewed and compared in AP patients with different etiologies. Results: Two hundred sixty-eight out of a total of 904 AP patients belonged to the compound-etiology category. Compared with the single-etiology category, the patients in the compound-etiology category were younger, more predominantly male, more likely to be obese (body mass index ≥30 kg/m2) and more likely to have pre-existing diabetes. The clinical outcomes were worse for patients with increasing complexity of etiology type, as shown by comparison of the incidence of any organ failure (P<0.001); persistent organ failure (POF) (P<0.001); intensive care unit need (P<0.001); local complications (P<0.001). AP with HTG had a higher rate of POF (P=0.032) and acute necrotic collection (P=0.013) than AP with biliary or alcohol involvement. When other etiologies simultaneously accompanied HTG-AP, the clinical outcomes were significantly worse than those in HTG-AP without other etiologies, particularly the biliary-HTG-alcoholic type. The compound-etiology category was independently associated with POF [odds ratio (OR): 2.47, 95% confidence interval (CI): 1.65-3.72, P<0.001]. Conclusions: These results highlight the importance of determining AP etiology and the prevalence of the "compound-type" etiology. The compound-etiology category should be recognized as a separate concept in AP etiology and deserve higher priority.

The safety and efficiency of fluoroless site-specific transseptal puncture guided by three-dimensional intracardiac echocardiography.

BACKGROUND: Although fluoroless transseptal puncture (TSP) guided by intracardiac echocardiography (ICE) has been used for many years, there are no reports of an accurate site-specific method for TSP in detail, especially about the safety and efficiency of the method. This study aimed to compare the efficacy and safety of TSP guided by three-dimensional ICE using a fluoroless site-specific method with that of the conventional fluoroless method in patients with atrial fibrillation (AF). METHODS: This prospective study included 60 patients with AF scheduled for radiofrequency ablation who were assigned to undergo modified fluoroless site-specific TSP (SS-ICE group, n = 30) or conventional fluoroless TSP (C-ICE group, n = 30). TSP was guided by three-dimensional ICE in both study groups. RESULTS: All fluoroless TSP were performed successfully in both groups. There were no significant differences in patient characteristics, Pre-TSP time (11.3 ± 1.7 min vs. 11.1 ± 1.6 min, P = 0.822) and TSP time (3.4 ± 0.9 min vs. 3.5 ± 1.1 min, P = 0.772) between the SS-ICE group and the C-ICE group. The distance between the actual traversing point and the presetting point in the fossa ovalis was less than 5 mm in 87% of patients (26/30, 3.1 ± 1.2 mm) in the SS-ICE group. There were no TSP-related complications in either group. CONCLUSION: SS-ICE method is a simple, safe, and effective approach for fluoroless site-specific TSP.

Association between antiplatelet medication and cerebral microbleeds in stroke-free population.

BACKGROUND: Cerebral microbleeds (CMBs) may increase the risk of future intracerebral hemorrhage and ischemic stroke. However, It is unclear whether antiplatelet medication is associated with CMBs. This study aimed to investigate the association between antiplatelet medication and CMBs in a community-based stroke-free population. METHODS: In this cross-sectional study, stroke-free participants aged 18-85 years were recruited from a community in Beijing, China. Demographic, clinical, and antiplatelet medication data were collected through a questionnaire, and all participants underwent blood tests and brain magnetic resonance imaging at 3.0T. The presence, count, and location of CMBs were evaluated using susceptibility-weighted imaging. The association between antiplatelet medication and the presence of CMBs was analyzed using multivariable logistic regression. The associations between antiplatelet medication and CMBs by location (lobar, deep brain or infratentorial, and mixed regions) were also analyzed using multinomial logistic regression. A linear regression analysis was conducted to determine the association between antiplatelet medication and the log-transformed number of CMBs. RESULTS: Of the 544 participants (mean age: 58.65 ± 13.66 years, 217 males), 119 participants (21.88%) had CMBs, and 64 participants (11.76%) used antiplatelet medication. Antiplatelet medication was found to be associated with CMBs at any location [odds ratio (OR) = 2.39, 95% CI: 1.24-4.58] and lobar region (OR = 2.83, 95% CI: 1.36-5.86), but not with the number of CMBs (ß = 0.14, 95% CI: -0.21-0.48). Among antiplatelet medications, aspirin use was found to be associated with any CMB (OR = 3.17, 95% CI: 1.49-6.72) and lobar CMBs (OR = 3.61, 95% CI: 1.57-8.26). CONCLUSIONS: Antiplatelet medication was associated with CMBs in stroke-free participants, particularly lobar CMBs. Among antiplatelet medications, aspirin use was associated with any CMB and lobar CMBs. Our findings suggest that it might be essential to optimize the management of antiplatelet medication in the stroke-free population with a higher burden of vascular risk factors to reduce the potential risk of CMBs.

Clonidine ameliorates cerebral ischemia-reperfusion injury by up-regulating the GluN3 subunits of NMDA receptor.

This study aimed to investigate the protective effects of the alpha-2 adrenergic receptor (α2-AR) agonist, clonidine, on the cerebral ischemia-reperfusion (I/R) injury and elaborate the underlying mechanisms. Cerebral I/R model was established by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 4 h in adult male SD rats. Saline, clonidine and yohimbine (an α2-AR antagonist) were intraperitoneally administered each day for one week before surgery. Neurological deficit was evaluated just before decapitation. TTC staining was applied for correlation of cerebral infarction volume. HE staining was performed to observe the neuron morphology. Immunohistochemical staining was performed to detect the localization and expression of GluN3 proteins. Western blot analysis also was used to detect the expression levels of GluN3 proteins. Our data showed that clonidine ameliorated neurological deficit and reduced the cerebral infarction volume of the rats with cerebral I/R. It is worth noting that treatment with clonidine up-regulated the protein expression of GluN3 in the rats with the cerebral I/R, especially in the cell membrane. Moreover, clonidine also up-regulated the transposition from cytoplasm to cell membrane of GluN3 after cerebral I/R. In addition, yohimbine abolished the neuroprotective effects of clonidine. The results indicated that clonidine played a protective role in cerebral I/R injury through regulation of the protein expression of GluN3 subunits of N-methyl-D-aspartate (NMDA) receptor.

Bone Mineral Density Assessment by Quantitative Computed Tomography in Glucocorticoid-Treated Boys With Duchenne Muscular Dystrophy: A Linear Mixed-Effects Modeling Approach.

Objective: Boys with Duchenne muscular dystrophy (DMD) are at risk of bone damage and low bone mineral density (BMD). The aim of the study is to examine lumbar BMD values measured by QCT and identify the factors associated with BMD loss using a multilevel mixed-effects model. Methods: Lumbar BMD was evaluated by quantitative computed tomography (QCT) at diagnosis, 1 and 2 years follow up in patients with DMD who were treated with GC. Demographic data, functional activity scores (FMSs), laboratory parameters and steroid use were recorded. A multilevel mixed-effects model was used to analyze BMD loss. Results: Nineteen patients with DMD who had a total of sixty complete records between January 2018 and October 2021 were retrospectively analyzed. At baseline, 15.8% of patients (3/19) had low lumbar BMD (Z score ≤ -2), and the mean BMD Z score on QCT was -0.85 (SD 1.32). The mean BMD Z score at 1 and 2 years postbaseline decreased to -1.56 (SD 1.62) and -2.02 (SD 1.36), respectively. In our model, BMD Z score loss was associated with age (ß=-0.358, p=0.0003) and FMS (ß=-0.454, p=0.031). Cumulative GC exposure and serum levels of calcium, phosphorus, 25(OH)-vitamin D and creatinine kinase did not independently predict BMD loss. Conclusions: This study demonstrates that in DMD patients, lumbar BMD decreased gradually and progressively. Age and FMS are the main contributors to BMD loss in boys with DMD. Early recognition of risk factors associated with BMD loss may facilitate the development of strategies to optimize bone health.

Changes in Schlemm's canal, trabecular meshwork, and relevant parameters in the early stage after SMILE of myopia patients.

AIM: To observe the changes in Schlemm's canal (SC), trabecular meshwork (TM), and anterior chamber relevant parameters after small incision lenticule extraction (SMILE) of myopia patients. METHODS: A total of 58 eyes from 30 patients who underwent SMILE were divided into a low and moderate myopia group (group A, 32 eyes) and a high myopia group (group B, 26 eyes). The diameter and area of the SC, the width and thickness of TM obtained by CIRRUS HD-OCT5000, and the related anterior chamber parameters obtained by Pentacam anterior segment analysis system, accommodation amplitude (AMP) were observed pre- and postoperatively. The preoperative intraocular pressure (IOP) and postoperative correction of intraocular pressure (IOPcc) were measured. RESULTS: The diameter and area of the SC in the two groups were significantly increased postoperatively (all P<0.01). The TM width of the patients in the two groups were increased at 1mo after surgery (both P<0.01), but the TM thickness did not change (P>0.05). The corneal curvature, central anterior chamber depth, and anterior chamber volume decreased after SMILE surgery (all P<0.01). There was a weak negative correlation between the SC area change and AMP change in group A (r=-0.362, P<0.01). The postoperative IOP decreased after correction by Shah formula (P<0.05). CONCLUSION: SC and TM in myopia patients change in the early postoperative stage of SMILE and the IOP is decline.

Pharmacokinetic and Bioequivalence Evaluation of 2 Tadalafil Tablets in Healthy Male Chinese Subjects Under Fasting and Fed Conditions.

Tadalafil is an effective, reversible, and competitive phosphodiesterase 5 inhibitor mainly used to treat erectile dysfunction. This study investigated the bioequivalence of generic and marketed formulations of 10-mg tadalafil tablets under fasted and fed conditions. This open-label, randomized, single-dose, 2-period crossover study included 53 healthy Chinese men (aged 20-43 years). Plasma samples were collected from 0.5 hours before treatment to 72 hours after each dose and analyzed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Pharmacokinetic parameters were calculated using noncompartmental analysis. Safety assessments were performed throughout the study. For the fasted state, the 90% confidence intervals of the geometric mean ratios between the generic and marketed formulations were 86.1% to 99.1% for the maximum plasma concentration and 88.4% to 100.3% for the area under the plasma concentration-time curve from time 0 to infinity, and the corresponding values under the fed state were and 99.9% to 108.4% and 95.7% to 104.3%, respectively. All data were within the accepted bioequivalence range of 80% to 125%. After consuming high-fat, high-calorie meals in the fed condition, the time to the maximum plasma concentration was similar between the formulations, and area under the plasma concentration-time curve from time 0 to infinity and maximum plasma concentration were 10.2% and 6.55% higher, respectively, for the marketed formulation. Thus, food had no clinically relevant effect on tadalafil exposure following a single oral dose in healthy Chinese men. No serious adverse reactions were reported. These results indicated that the analyzed generic and marketed tadalafil tablets were bioequivalent with similar safety profiles.

Efficacy and safety of prophylactic abdominal aortic balloon occlusion versus internal iliac arterial balloon occlusion for placenta accreta spectrum disorder: A systematic review and meta-analysis.

PURPOSE: To assess the efficacy and safety of abdominal aortic (AA) balloon occlusion versus internal iliac arteries (IIA) balloon occlusion in patients with placenta accreta spectrum (PAS) disorders. METHODS: Databases of Embase, PubMed, Web of Science and Cochrane Library were systematically searched from inception to May 2020. The relevant literature was screened and the quality was assessed. RevMan software 5.3 was used to analyze the data. RESULTS: Six studies involving 239 patients in AA occlusion and 281 patients in IIA occlusion were included. The results demonstrated that the intraoperative hemorrhage volume (MD - 410.61 ml, 95% CI -779.74 to -41.47 ml, p < 0.001), balloon dilatation duration (MD -5.34 min, 95% CI -9.91 to -0.77 min, p = 0.02) and fetus radiation dose (MD-20.81 mGy, 95% CI -31.84 to -9.78 mGy, p < 0.001) were significantly less in AA occlusion compared to IIA occlusion. There was no significant difference in the rate of lower extremity thrombosis between AA occlusion and IIA occlusion (OR 0.21, 95% CI 0.02 to 2.21, p = 0.19); similarly, no significant differences were found in blood transfusion volume (MD -344.50 ml, 95% CI -735.74 to 46.74 ml, p = 0.08), the rate of hysterectomy (OR 0.99, 95% CI 0.22 to 4.44, p = 0.99) and other outcome variables. CONCLUSION: The available data demonstrated AA occlusion was more effective in reducing intraoperative hemorrhage volume and fetus radiation dose compared with IIA occlusion in patients with PAS disorders. Larger studies or randomized controlled trials are needed to further assert this evidence.