In Vivo Pharmacokinetic Study of Polygonatum cyrtonema Polysaccharide DPC1 after Oral and Intraperitoneal Administration.

(1) Background: Polygonatum cyrtonema is a medicinal plant, and its polysaccharides are used for immunomodulation and the treatment of hyperglycemia. Investigation of the tissue distribution and pharmacokinetics of P. cyrtonema polysaccharide can further elucidate its pharmacological mechanisms. (2) Methods: A fluorescence-labeling approach using rhodamine B (RhB) as a fluorescent molecular probe was used for the quantitative assessment of the polysaccharide from dried P. cyrtonema (DPC1) samples, and the pharmacokinetics and tissue distribution of DPC1 were evaluated in mice after intraperitoneal or oral administration. (3) Results: DPC1 was successfully labeled with RhB, showing degrees of fluorescence labeling at 0.453% and 0.568% as determined by the ultraviolet and enzyme marker methods, respectively. DPC1-RhB was rapidly absorbed into the bloodstream after oral and intraperitoneal administration. Pharmacokinetic characteristics showed that oral administration and intraperitoneal administration were consistent with the features of a two-compartment model. (4) Conclusion: After administration, DPC1-RhB was primarily distributed in the tissues of the heart, spleen, and lung, indicating that the drug has a targeted effect on these tissues. Overall, the findings provide a comprehensive reference for the in vivo distribution of DPC1, together with a foundation for further elucidation of its pharmacological mechanisms and the development and application of DPC1 formulations.

Composition of Polygonatum zanlanscianense Pamp. Steam and Leaf Phenolic Extract and Its Protective Mechanism on t-BHP-Induced Oxidative Damage of HepG2 Cells.

Plant phenolic compounds have attracted considerable attention because of their health benefits. This study aimed to investigate the composition and antioxidant activity of phenol extracts from Polygonatum zanlanscianense Pamp. steam and leaf (PPP). The FTIR, UPLC-Q-Obtrip-MS, and HPLC-DAD methods were used to analyze the composition of PPP, and 20 phenolic compounds were preliminarily identified. Among them, the contents of hyperin, astragalin, and diosmetin levels were the highest. Treatment with PPP can significantly reduce t-BHP-induced cell damage in HepG2 cells, reactive oxygen species (ROS) accumulation, and malondialdehyde (MDA) content. Meanwhile, the superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) activities can be increased. Moreover, PPP enhanced Nrf2 expression, which was consistent with that of heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and NAD(P)H quinone oxidoreductase-1 (NQO1), whereas the expression of Keap1, the Nrf2 inhibitor, was decreased. All findings indicate that PPP can serve as a natural bioactive substance for preventing oxidative stress.

Spectrum-Effect Relationships as an Effective Approach for Quality Control of Natural Products: A Review.

As natural products with biological activity, the quality of traditional Chinese medicines (TCM) is the key to their clinical application. Fingerprints based on the types and contents of chemical components in TCM are an internationally recognized quality evaluation method but ignore the correlation between chemical components and efficacy. Through chemometric methods, the fingerprints represented by the chemical components of TCM were correlated with its pharmacodynamic activity results to obtain the spectrum-effect relationships of TCM, which can reveal the pharmacodynamic components information related to the pharmacodynamic activity and solve the limitations of segmentation of chemical components and pharmacodynamic research in TCM. In the 20th anniversary of the proposed spectrum-effect relationships, this paper reviews its research progress in the field of TCM, including the establishment of fingerprints, pharmacodynamic evaluation methods, chemometric methods and their practical applications in the field of TCM. Furthermore, the new strategy of spectrum-effect relationships research in recent years was also discussed, and the application prospects of this technology were discussed.

Detection of Intracerebral Hemorrhage Using Low-Field, Portable Magnetic Resonance Imaging in Patients With Stroke.

BACKGROUND: Neuroimaging is essential for detecting spontaneous, nontraumatic intracerebral hemorrhage (ICH). Recent data suggest ICH can be characterized using low-field magnetic resonance imaging (MRI). Our primary objective was to investigate the sensitivity and specificity of ICH on a 0.064T portable MRI (pMRI) scanner using a methodology that provided clinical information to inform rater interpretations. As a secondary aim, we investigated whether the incorporation of a deep learning (DL) reconstruction algorithm affected ICH detection. METHODS: The pMRI device was deployed at Yale New Haven Hospital to examine patients presenting with stroke symptoms from October 26, 2020 to February 21, 2022. Three raters independently evaluated pMRI examinations. Raters were provided the images alongside the patient's clinical information to simulate real-world context of use. Ground truth was the closest conventional computed tomography or 1.5/3T MRI. Sensitivity and specificity results were grouped by DL and non-DL software to investigate the effects of software advances. RESULTS: A total of 189 exams (38 ICH, 89 acute ischemic stroke, 8 subarachnoid hemorrhage, 3 primary intraventricular hemorrhage, 51 no intracranial abnormality) were evaluated. Exams were correctly classified as positive or negative for ICH in 185 of 189 cases (97.9% overall accuracy). ICH was correctly detected in 35 of 38 cases (92.1% sensitivity). Ischemic stroke and no intracranial abnormality cases were correctly identified as blood-negative in 139 of 140 cases (99.3% specificity). Non-DL scans had a sensitivity and specificity for ICH of 77.8% and 97.1%, respectively. DL scans had a sensitivity and specificity for ICH of 96.6% and 99.3%, respectively. CONCLUSIONS: These results demonstrate improvements in ICH detection accuracy on pMRI that may be attributed to the integration of clinical information in rater review and the incorporation of a DL-based algorithm. The use of pMRI holds promise in providing diagnostic neuroimaging for patients with ICH.

Acute and subacute neurovascular impact of cryptogenic air emboli.

Background: Cerebral air embolism is a rare cause of acute ischemic stroke that is becoming increasingly well-described in the literature. However, the mechanism and severity of this type of injury can vary, with ischemia typically emerging early in the course of care. To the best of our knowledge, delayed ischemia in this setting has not yet been described. Case Description: A stroke code was called for an unresponsive, hospitalized, 75-year-old man. A computerized tomography (CT) scan of the head revealed air within the right greater than left hemispheric cortical veins with loss of sulcation, concerning for developing ischemia, and CT angiography revealed absent opacification of the distal cortical vessels in the right anterior cerebral artery and middle cerebral artery territories. Magnetic resonance imaging (MRI) of the brain was obtained 5.75 h after the patient's last known well-showed small areas of subtle cortical diffusion restriction. Follow-up CT head within 24 h showed near-complete resolution of the air emboli after treatment with 100% fraction of inspired oxygen on mechanical ventilation. Subsequent MRI, performed 4 days after the initial event, showed extensive cortical diffusion restriction and cerebral edema crossing vascular territories. Conclusion: This case highlights that cerebral air emboli can cause delayed ischemia that may not be appreciated on initial imaging. As such, affected patients may require intensive neurocritical care management, close neurologic monitoring, and repeat imaging irrespective of initial radiographic findings.

In Search of the Optimal Antithrombotic Regimen for Intracerebral Hemorrhage Survivors with Atrial Fibrillation.

Spontaneous intracerebral hemorrhage (ICH) constitutes 10-15% of all strokes, and is a significant cause of mortality and morbidity. Survivors of ICH, especially those with atrial fibrillation (AF), are at risk for both recurrent hemorrhagic and ischemic cerebrovascular events. A conundrum in the field of vascular neurology, neurosurgery, and cardiology has been the decision to initiate or resume versus withhold anticoagulation in survivors of ICH with AF. To initiate anticoagulation would decrease the risk of ischemic stroke but may increase the risk of hemorrhage. To withhold anticoagulation maintains a lower risk of hemorrhage but does not decrease the risk of ischemic stroke. In this narrative review, we discuss the evidence for and against the use of antithrombotics in ICH survivors with AF, focusing on recently completed and ongoing clinical trials.

Recent advances in polysaccharides from edible and medicinal Polygonati rhizoma: From bench to market.

Although the increasing studies have corroborated the biological activities and great market utilization value of polysaccharide fractions derived from Polygonati rhizome, a well-known edible and medicinal plant, Polygonati rhizome polysaccharides (PRPs) still lack sufficient attention. Herein, we make attempt to systematically summarize recent advances in the extraction, purification, structural characteristics, biological activities, and commercial products of PRPs. Based on the detailed extraction and structural characteristics, the biological activities of PRPs including immune-regulation, anti-osteoporosis, anti-Alzheimer's disease, anti-diabetes and anti-atherosclerotic, are emphatically summarized, as well as the possible related mechanisms. Most importantly, about 365 kinds of commercial functional foods and over 500 patents related to PRPs as the main raw material were analyzed to explore the status quo and bottleneck for the development and utilization of PRPs. In conclusion, this review will benefit to bridge the gap between basic knowledge and market innovations, and facilitate the in-depth utilization of PRPs.

Laparoscopic "Shaving" for Infiltrative External Adenomyosis of Bowel Muscularis and Concomitant Deep Infiltrating Endometriosis.

Deep infiltrating endometriosis (DIE) is a common finding in patients diagnosed with adenomyosis. Women commonly present with severe, incapacitating dysmenorrhea. We report a case of severe dysmenorrhea and lower abdominal tightness for 4 years, diagnosed with posterior adenomyosis. The patient underwent surgery and DIE involving the rectosigmoid and coexisting uterocervical adenomyosis infiltrating bowel muscularis successfully diagnosed and treated using laparoscopic "shaving" technique. Dysmenorrhea significantly resolved after surgery. Laparoscopic surgical "shaving" technique for external adenomyosis infiltrating Rectosigmoid muscularis is feasible, where uterine preservation is desired.

Prior Stroke and Age Predict Acute Ischemic Stroke Among Hospitalized COVID-19 Patients: A Derivation and Validation Study.

Objectives: Our objective was to identify characteristics associated with having an acute ischemic stroke (AIS) among hospitalized COVID-19 patients and the subset of these patients with a neurologic symptom. Materials and Methods: Our derivation cohort consisted of COVID-19 patients admitted to Yale-New Haven Health between January 3, 2020 and August 28, 2020 with and without AIS. We also studied a sub-cohort of hospitalized COVID-19 patients demonstrating a neurologic symptom with and without an AIS. Demographic, clinical, and laboratory results were compared between AIS and non-AIS patients in the full COVID-19 cohort and in the sub-cohort of COVID-19 patients with a neurologic symptom. Multivariable logistic regression models were built to predict ischemic stroke risk in these two COVID-19 cohorts. These 2 models were externally validated in COVID-19 patients hospitalized at a major health system in New York. We then compared the distribution of the resulting predictors in a non-COVID ischemic stroke control cohort. Results: A total of 1,827 patients were included in the derivation cohort (AIS N = 44; no AIS N = 1,783). Among all hospitalized COVID-19 patients, history of prior stroke and platelet count ≥ 200 × 1,000/µL at hospital presentation were independent predictors of AIS (derivation AUC 0.89, validation AUC 0.82), irrespective of COVID-19 severity. Among hospitalized COVID-19 patients with a neurologic symptom (N = 827), the risk of AIS was significantly higher among patients with a history of prior stroke and age <60 (derivation AUC 0.83, validation AUC 0.81). Notably, in a non-COVID ischemic stroke control cohort (N = 168), AIS patients were significantly older and less likely to have had a prior stroke, demonstrating the uniqueness of AIS patients with COVID-19. Conclusions: Hospitalized COVID-19 patients who demonstrate a neurologic symptom and have either a history of prior stroke or are of younger age are at higher risk of ischemic stroke.

Blood Pressure Management After Endovascular Thrombectomy.

Endovascular thrombectomy (EVT) has changed the landscape of acute stroke therapy and has become the standard of care for selected patients presenting with anterior circulation large-vessel occlusion (LVO) stroke. Despite successful reperfusion, many patients with LVO stroke do not regain functional independence. Particularly, patients presenting with extremes of blood pressure (BP) or hemodynamic variability are found to have a worse clinical recovery, suggesting blood pressure optimization as a potential neuroprotective strategy. Current guidelines acknowledge the lack of randomized trials to evaluate the optimal hemodynamic management during the immediate post-stroke period. Following reperfusion, lower blood pressure targets may be warranted to prevent reperfusion injury and promote penumbral recovery, but adequate BP targets adjusted to individual patient factors such as degree of reperfusion, infarct size, and overall hemodynamic status remain undefined. This narrative review outlines the physiological mechanisms of BP control after EVT and summarizes key observational studies and clinical trials evaluating post-EVT BP targets. It also discusses novel treatment strategies and areas of future research that could aid in the determination of the optimal post-EVT blood pressure.

Portable, bedside, low-field magnetic resonance imaging for evaluation of intracerebral hemorrhage.

Radiological examination of the brain is a critical determinant of stroke care pathways. Accessible neuroimaging is essential to detect the presence of intracerebral hemorrhage (ICH). Conventional magnetic resonance imaging (MRI) operates at high magnetic field strength (1.5-3 T), which requires an access-controlled environment, rendering MRI often inaccessible. We demonstrate the use of a low-field MRI (0.064 T) for ICH evaluation. Patients were imaged using conventional neuroimaging (non-contrast computerized tomography (CT) or 1.5/3 T MRI) and portable MRI (pMRI) at Yale New Haven Hospital from July 2018 to November 2020. Two board-certified neuroradiologists evaluated a total of 144 pMRI examinations (56 ICH, 48 acute ischemic stroke, 40 healthy controls) and one ICH imaging core lab researcher reviewed the cases of disagreement. Raters correctly detected ICH in 45 of 56 cases (80.4% sensitivity, 95%CI: [0.68-0.90]). Blood-negative cases were correctly identified in 85 of 88 cases (96.6% specificity, 95%CI: [0.90-0.99]). Manually segmented hematoma volumes and ABC/2 estimated volumes on pMRI correlate with conventional imaging volumes (ICC = 0.955, p = 1.69e-30 and ICC = 0.875, p = 1.66e-8, respectively). Hematoma volumes measured on pMRI correlate with NIH stroke scale (NIHSS) and clinical outcome (mRS) at discharge for manual and ABC/2 volumes. Low-field pMRI may be useful in bringing advanced MRI technology to resource-limited settings.

Structures of fructan and galactan from Polygonatum cyrtonema and their utilization by probiotic bacteria.

Polygonatum cyrtonema is a known tonic herb in Chinese Materia Medica, extensively consumed in China, but the structure and activity of its polysaccharide components remain to be clarified. Herein, two new polysaccharides (a fructan and a galactan) were purified from the dried and the processed P. cyrtonema rhizome, respectively. Structural analysis suggested that the fructan consisted of a (2 â†’ 6) linked ß-d-Fruf residues backbone with an internal α-d-Glcp residue and two (2 â†’ 1) linked ß-d-Fruf residues branches, and that the galactan was a (1 â†’ 4)-ß-d-galactan branched with a single ß-d-galactose at C-6 at about every nine residues in its main chain. The bioactive assay showed that the fructan and the galactan remarkably promoted growth of Bifidobacterium and Lactobacillus strains, indicating that they possess prebiotic activity. These findings may help expand the application of the polysaccharides from the tonic herb P. cyrtonema as functional ingredients in food products.

Cervical Cancer Surgery: Current State of Affairs.

Cervical cancer surgery has a history of more than 100-years whereby it has transitioned from the open approach to minimally invasive surgery (MIS). From the era of clinical exploration and practice, minimally invasive gynecologic surgeons have never ceased to explore new frontiers in the field of gynecologic surgery. MIS has fewer postoperative complications, including reduction of treatment-related morbidity and length of hospital stay than laparotomy; this forms the mainstay of treatment for early-stage cervical cancer. However, in November 2018, the New England Journal of Medicine had published two clinical studies on cervical cancer surgery (Laparoscopic Approach to Cervical Cancer [LACC]). Following these publications, laparoscopic surgery for early-stage cervical cancer has come under intense scrutiny and negative perceptions. Many studies began to explore the concept of standardized surgery for early-stage cervical cancer. In this article, we performed a review of the history of cervical cancer surgery, outlined the standardization of cervical cancer surgery, and analyzed the current state of affairs revolving around cervical cancer surgery in the post-LACC era.

Standardization and experience may influence the survival of laparoscopic radical hysterectomy for cervical cancer.

OBJECTIVE: Minimally invasive radical hysterectomy has been shown to be associated with poorer outcome in an influential prospective, randomized trial. However, many centers worldwide performing minimally invasive radical hysterectomy have data and experience that prove otherwise. We aim to review surgical and oncologic outcomes of patients operated by Laparoscopic Radical Hysterectomy in a tertiary hospital, by experienced surgeons and standardization in radicality, for cervical carcinoma Stage 1A1-1B1 from January 2009 to May 2014. MATERIALS & METHODS: Standardised surgical technique with Parametrium & Paracolpium resection approach was adopted by qualified and experienced Gynecologic/Gyne-Oncologic Endoscopic & Minimally Invasive Surgeons in performing Laparoscopic Radical Hysterectomy for Cervical Cancer stage 1A1-1B1 from January 2009-May 2014, involving 53 patients. Electronic Medical Record system (EMR) Of Chang Gung Memorial Hospital(Tertiary Referral Centre), Department of Obstetrics & Gynecology was accessed for surgical and oncologic outcomes. RESULTS: Fifty-Three patients operated from January 2009 to May 2014 were followed up for an average of 96.7 months with longest follow-up at 127 months. There were no cases of recurrence or death reported. 5 Year - Survival Rate and 5 Year Disease-Free Survival Rate were 100%. Two patients received post-operative pelvic radiation concurrent with chemotherapy using Cisplatin due to greater than 1/3 cervical stromal invasion. CONCLUSION: It is vital to standardize minimally invasive surgical techniques for early stage cervical cancer, with focus on adequate radicality and resection which may contribute to excellent survival outcomes. Further international multi-center randomized trial (Minimally Invasive Therapy Versus Open Radical Hysterectomy In Cervical Cancer) will provide justification for continued practice of MIS in early stage cervical cancer.

Inhibition of Fibroblast Activation in Uterine Leiomyoma by Components of Rhizoma Curcumae and Rhizoma Sparganii.

Background: The herbs Rhizoma Curcumae and Rhizoma Sparganii (RCRS) are often used in traditional Chinese medicine for the treatment of uterine leiomyoma (UL). The effectiveness of RCRS for the treatment of UL has been confirmed in our previous studies. Purpose: This study aimed to investigate the molecular mechanism by which RCRS inhibits the activation of fibroblast activation protein (FAP) and prevents UL in rats. Study Design and Methods: A Sprague Dawley (SD) rat model of UL was established via estrogen and progesterone load combined with external stimulation. Histological analyses, enzyme-linked immunosorbent assays, and western blotting were performed to evaluate the effect of RCRS on UL and elucidate its mechanism of action. Results: Our data showed that the treatment of SD rats with RCRS significantly reduced the expression of extracellular matrix component collagen, FAP, and transforming growth factor beta (a FAP-activating factor) and the phosphorylation of the cell proliferation pathway-related signaling factors AKT/MEK/ERK. Conclusion: Our results suggest that RCRS is effective in the prevention and treatment of UL in rats, and RCRS may exert its functions by inhibiting the activation of tumor-associated fibroblasts and cell proliferation and by improving the tumor extracellular matrix.

Huangyusang decoction for Type 2 diabetes: A protocol for systematic review and meta analysis.

BACKGROUND: Diabetes is a chronic metabolic disease characterized by elevated blood glucose levels due to insulin resistance and ß-cell dysfunction. In China, Huangyusang decoction (HYS) has been widely used to treat Type 2 diabetes. However, there is no systematic review found. In order to evaluate the efficacy and safety of HYS in the treatment of Type 2 diabetes, we need to conduct a meta-analysis and systematic evaluation. METHODS: We will enroll the randomized controlled trials (RCTs) evaluating the effectiveness and safety of HYS in the treatment of Type 2 diabetes. Data come mainly from 4 Chinese databases (CNKI, Wanfang, CBM, and VIP Database) and 4 English databases (PubMed, Embase, Cochrane Library, and Web of science). The enrollment of RCTs is from the starting date of database establishment till January 30, 2021. Fasting blood glucose is considered as the main indicator of the dyslipidemia, while the body mass index, glycated hemoglobin, fasting insulin, triglycerides, and cholesterol are regarded as the secondary indicators. There are safety indicators including liver enzyme and kidney function. The work such as selection of literature, data collection, quality evaluation of included literature, and assessment of publication bias will be conducted by 2 independent researchers. Meta-analysis will be performed by RevMan 5.0 software. RESULTS: This study will provide high-quality evidence for the effectiveness and safety of HYS in the treatment of type 2 diabetes. CONCLUSION: The results of the study will help us determine whether HYS can effectively treat type 2 diabetes. ETHICS AND DISSEMINATION: This study does not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/AXBRV.

Bi-directional association between epilepsy and dementia: The Framingham Heart Study.

OBJECTIVE: To assess the risk of incident epilepsy among participants with prevalent dementia and the risk of incident dementia among participants with prevalent epilepsy in the Framingham Heart Study (FHS). METHODS: We analyzed prospectively collected data in the Original and Offspring FHS cohorts. To determine the risk of developing epilepsy among participants with dementia and the risk of developing dementia among participants with epilepsy, we used separate, nested, case-control designs and matched each case to 3 age-, sex- and FHS cohort-matched controls. We used Cox proportional hazards regression analysis, adjusting for sex and age. In secondary analysis, we investigated the role of education level and APOE ε4 allele status in modifying the association between epilepsy and dementia. RESULTS: A total of 4,906 participants had information on epilepsy and dementia and dementia follow-up after age 65. Among 660 participants with dementia and 1,980 dementia-free controls, there were 58 incident epilepsy cases during follow-up. Analysis comparing epilepsy risk among dementia cases vs controls yielded a hazard ratio (HR) of 1.82 (95% confidence interval 1.05-3.16, p = 0.034). Among 43 participants with epilepsy and 129 epilepsy-free controls, there were 51 incident dementia cases. Analysis comparing dementia risk among epilepsy cases vs controls yielded a HR of 1.99 (1.11-3.57, p = 0.021). In this group, among participants with any post-high school education, prevalent epilepsy was associated with a nearly 5-fold risk for developing dementia (HR 4.67 [1.82-12.01], p = 0.001) compared to controls of the same educational attainment. CONCLUSIONS: There is a bi-directional association between epilepsy and dementia. with either condition carrying a nearly 2-fold risk of developing the other when compared to controls.