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Semen Lepidii is the dried and mature seeds of the cruciferous plant of Descurainia Sophia or Lepidium Apetalum, being a widely-used traditional Chinese medicine for various pharmacological effects, such as antibacterial, antitumor, diuretic and improving immune function. However, the chemical components of Semen Ledidii from different regions have not been clear, limiting the further application of this herb medicine in clinic. Therefore, in this study, a method of ultra-performance liquid chromatography-electrostatic Orbital ion trap tandem mass spectrometry (UPLC-Orbitrap-MS/MS) was developed to identify the chemical components of the three Semen Lepidii, namely Descurainia Sophia 1 (DS1), Descurainia Sophia 2 (DS2) and Lepidium Apetalum (LA) from different regions, and to study the fragmentation pathways of the identified components. The methanol-water (70:30, V/V) extract of the three mashed powder samples was separated on an ACQUITY UPLC BEH C18 column (100 mm×2.1 mm×1.7 μm), and infused into high mass resolution Orbitrap mass spectrometer for analyzing under positive and negative ion modes. MS/MS data were acquired with a Full MS/dd-MS2 mode, and the chromatographic peaks were aligned and extracted by using Compound Discoverer (CD) software. Then, the accurate mass informations of the precursor and fragment ions were matched to the databases in the CD platform for identification of components in the samples, and studied the fragmentation pathways of identified compounds. A total of 39 compounds are identified in DS1, including alkaloids, flavonoids, cardiac glycosides, amides, organic acids, amino acids, and others. This method was used to analyze methanol-water extract of DS2 and LA, 37 compounds are identified in DS2, including 10 compounds which are not identified in DS1, and 42 compounds are identified in LA, including 7 compounds which are not identified in both DS1 and DS2. The results indicated that the chemical components of Semen Lepidii originated from different regions are remarkably different and may act as medicine in various ways. This study provides a fundamental for further studying the molecular mechanism of pharmacological effects of Semen Lepdii, which can promote its clinical application.

BackgroundThe current national burden of emergency general surgery (EGS) illnesses and the extent of surgeon involvement in the care of these patients remain largely unknown. To inform needs assessments, research, and education, we sought to: (1) translate previously developed International Classification of Diseases (ICD), 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes representing EGS conditions to ICD 10th Revision, CM (ICD-10-CM) codes and (2) determine the national burden of and assess surgeon involvement across EGS conditions.MethodsWe converted ICD-9-CM codes to candidate ICD-10-CM codes using General Equivalence Mappings then iteratively refined the code list. We used National Inpatient Sample 2016 to 2017 data to develop a national estimate of the burden of EGS disease. To evaluate surgeon involvement, using Wisconsin Hospital Association discharge data (January 1, 2016 to June 30, 2018), we selected adult urgent/emergent encounters with an EGS condition as the principal diagnosis. Surgeon involvement was defined as a surgeon being either the attending provider or procedural physician.ResultsFour hundred and eighty-five ICD-9-CM codes mapped to 1,696 ICD-10-CM codes. The final list contained 985 ICD-10-CM codes. Nationally, there were 2,977,843 adult patient encounters with an ICD-10-CM EGS diagnosis. Of 94,903 EGS patients in the Wisconsin Hospital Association data set, most encounters were inpatient as compared with observation (75,878 [80.0%] vs. 19,025 [20.0%]). There were 57,780 patients (60.9%) that underwent any procedure. Among all Wisconsin EGS patients, most had no surgeon involvement (64.9% [n = 61,616]). Of the seven most common EGS diagnoses, surgeon involvement was highest for appendicitis (96.0%) and biliary tract disease (77.1%). For the other five most common conditions (skin/soft tissue infections, gastrointestinal hemorrhage, intestinal obstruction/ileus, pancreatitis, diverticular disease), surgeons were involved in roughly 20% of patient care episodes.ConclusionSurgeon involvement for EGS conditions ranges from highly likely (appendicitis) to relatively unlikely (skin/soft tissue infections). The wide range in surgeon involvement underscores the importance of multidisciplinary collaboration in the care of EGS patients.Level of evidencePrognostic/epidemiological, Level III.

The neutralizing antibody is a potential therapeutic for the ongoing COVID-19 pandemic. As an antiviral agent, numerous mAbs recognize the epitopes that overlap with ACE2-binding sites in the SARS-CoV-2-RBD. Some studies have shown that residual changes on the spike protein can significantly decrease the efficiency of neutralizing antibodies. To address this issue, a therapeutic cocktail could be an effective countermeasure. In the present study, we isolated a fully human neutralizing antibody, JS026, from a convalescent patient. The comparative analysis revealed that JS026 binding to SARS-CoV-2-RBD mainly located between epitopes for class 2 and class 3 mAbs as opposed to that of class 1 (etesevimab) antibodies. A cocktail of etesevimab and JS026 increased neutralizing efficacy against both wild-type SARS-CoV-2 and the recent emergence of Alpha, Beta, Gamma, and Delta variants. JS026 and the cocktail reduced virus titers in the infected lungs of hACE2 transgenic mice and relieved pathological changes. These findings would benefit antibody-based therapeutic countermeasures in the treatment of COVID-19.

Strophanthidin (SPTD), one of the cardiac glycosides, is refined from traditional Chinese medicines such as Semen Lepidii and Antiaris toxicaria, and was initially used for the treatment of heart failure disease in clinic. Recently, SPTD has been shown to be a potential anticancer agent, but the underlying mechanism of action is poorly understood. Herein, we explored the molecular mechanism by which SPTD exerts anticancer effects in A549 human lung adenocarcinoma cells by means of mass spectrometry-based quantitative proteomics in combination with bioinformatics analysis. We revealed that SPTD promoted the expression of tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAIL-R2, or DR5) in A549 cells to activate caspase 3/6/8, in particular caspase 3. Consequently, the activated caspases elevated the expression level of apoptotic chromatin condensation inducer in the nucleus (ACIN1) and prelamin-A/C (LMNA), ultimately inducing apoptosis via cooperation with the SPTD-induced overexpressed barrier-to-autointegration factor 1 (Banf1). Moreover, the SPTD-induced DEPs interacted with each other to downregulate the p38 MAPK/ERK signaling, contributing to the SPTD inhibition of the growth of A549 cells. Additionally, the downregulation of collagen COL1A5 by SPTD was another anticancer benefit of SPTD through the modulation of the cell microenvironment.

Abstract Background Frail patients with chronic obstructive pulmonary disease (COPD) face a higher risk of adverse outcomes, but there is no clear consensus on which frailty measures are most suitable for COPD patients. Herein we evaluated the ability of frailty measurements in predicting 1-year acute exacerbation, hospitalization, and mortality in older patients with COPD. Methods A total of 302 patients [median age: 86 years (IQR: 80–90), 22.2% female] were admitted to the Department of Geriatric Medicine were prospectively enrolled in this study. Frailty status was assessed using the Fried Frailty Phenotype (FFP), Clinical Frailty Scale (CFS), Frailty Index of Accumulative Deficits (FI-CD), and Short Physical Performance Battery (SPPB). Cox proportional hazard regression and Poisson regression were used to evaluating the association of the adverse outcomes with frailty as assessed using the four instruments. The discrimination accuracy of these tools in predicting the 1-year all-cause mortality was also compared. Results Prevalence of frailty ranged from 51% (using FFP) to 64.2% (using CFS). The four frail instruments were associated with 1-year mortality. After an average follow-up time of 2.18 years (IQR: 1.56–2.62 years), frailty as defined by four instruments (except for FI-CD), was associated with death [FFP: Hazard ratio (HR) = 3.11, 95% confidence interval (CI) 1.30–7.44; CFS: HR = 3.68, 95% CI 1.03–13.16; SPPB: HR = 3.74, 95% CI 1.39–10.06). Frailty was also associated with acute exacerbation (using FFP) and hospitalization (using FFP, CFS, and FI-CD). Frail showed a moderate predictive ability [area under the curve ranging (AUC) 0.70–0.80] and a high negative predictive value (0.98–0.99) for 1-year mortality. Conclusions With the four different frailty assessment tools, frailty was associated with poor prognosis in older patients with stable COPD. The FFP, CFS, FI-CD, and SPPB instruments showed similar performance in predicting 1-year mortality.

ObjectiveThe present study aimed to predict myocardial ischemia in coronary heart disease (CHD) patients based on the radiologic features of coronary computed tomography angiography (CCTA) combined with clinical factors.MethodsThe imaging and clinical data of 110 patients who underwent CCTA scan before DSA or FFR examination in Changzhou Second People’s Hospital, Nanjing Medical University (90 patients), and The First Affiliated Hospital of Soochow University (20 patients) from March 2018 to January 2022 were retrospectively analyzed. According to the digital subtraction angiography (DSA) and fractional flow reserve (FFR) results, all patients were assigned to myocardial ischemia (n = 58) and normal myocardial blood supply (n = 52) groups. All patients were further categorized into training (n = 64) and internal validation (n = 26) sets at a ratio of 7:3, and the patients from second site were used as external validation. Clinical indicators of patients were collected, the left ventricular myocardium were segmented from CCTA images using CQK software, and the radiomics features were extracted using pyradiomics software. Independent prediction models and combined prediction models were established. The predictive performance of the model was assessed by calibration curve analysis, receiver operating characteristic (ROC) curve and decision curve analysis.ResultsThe combined model consisted of one important clinical factor and eight selected radiomic features. The area under the ROC curve (AUC) of radiomic model was 0.826 in training set, and 0.744 in the internal validation set. For the combined model, the AUCs were 0.873, 0.810, 0.800 in the training, internal validation, and external validation sets, respectively. The calibration curves demonstrated that the probability of myocardial ischemia predicted by the combined model was in good agreement with the observed values in both training and validation sets. The decision curve was within the threshold range of 0.1–1, and the clinical value of nomogram was higher than that of clinical model.ConclusionThe radiomic characteristics of CCTA combined with clinical factors have a good clinical value in predicting myocardial ischemia in CHD patients.

Polycystic ovary syndrome (PCOS) and periodontal disease (PDD) share common risk factors. The bidirectional interaction between PCOS and PDD has been reported, but until now, the underlying molecular mechanisms remain unclear. Endocrine disorders including hyperandrogenism (HA) and insulin resistance (IR) in PCOS disturb the oral microbial composition and increase the abundance of periodontal pathogens. Additionally, PCOS has a detrimental effect on the periodontal supportive tissues, including gingiva, periodontal ligament, and alveolar bone. Systemic low-grade inflammation status, especially obesity, persistent immune imbalance, and oxidative stress induced by PCOS exacerbate the progression of PDD. Simultaneously, PDD might increase the risk of PCOS through disturbing the gut microbiota composition and inducing low-grade inflammation and oxidative stress. In addition, genetic or epigenetic predisposition and lower socioeconomic status are the common risk factors for both diseases. In this review, we will present the latest evidence of the bidirectional association between PCOS and PDD from epidemiological, mechanistic, and interventional studies. A deep understanding on their bidirectional association will be beneficial to provide novel strategies for the treatment of PCOS and PDD.