Small-molecule Molephantin induces apoptosis and mitophagy flux blockage through ROS production in glioblastoma.

Glioblastoma (GBM), one of the most malignant brain tumors in the world, has limited treatment options and a dismal survival rate. Effective and safe disease-modifying drugs for glioblastoma are urgently needed. Here, we identified a small molecule, Molephantin (EM-5), effectively penetrated the blood-brain barrier (BBB) and demonstrated notable antitumor effects against GBM with good safety profiles both in vitro and in vivo. Mechanistically, EM-5 not only inhibits the proliferation and invasion of GBM cells but also induces cell apoptosis through the reactive oxygen species (ROS)-mediated PI3K/Akt/mTOR pathway. Furthermore, EM-5 causes mitochondrial dysfunction and blocks mitophagy flux by impeding the fusion of mitophagosomes with lysosomes. It is noteworthy that EM-5 does not interfere with the initiation of autophagosome formation or lysosomal function. Additionally, the mitophagy flux blockage caused by EM-5 was driven by the accumulation of intracellular ROS. In vivo, EM-5 exhibited significant efficacy in suppressing tumor growth in a xenograft model. Collectively, our findings not only identified EM-5 as a promising, effective, and safe lead compound for treating GBM but also uncovered its underlying mechanisms from the perspective of apoptosis and mitophagy.

Immunotherapy for Ovarian Cancer: Disappointing or Promising?

Ovarian cancer, one of the deadliest malignancies, lacks effective treatment, despite advancements in surgical techniques and chemotherapy. Thus, new therapeutic approaches are imperative to improving treatment outcomes. Immunotherapy, which has demonstrated considerable success in managing various cancers, has already found its place in clinical practice. This review aims to provide an overview of ovarian tumor immunotherapy, including its basics, key strategies, and clinical research data supporting its potential. In particular, this discussion highlights promising strategies such as checkpoint inhibitors, vaccines, and pericyte transfer, both individually and in combination. However, the advancement of new immunotherapies necessitates large controlled randomized trials, which will undoubtedly shape the future of ovarian cancer treatment.

Longitudinal patterns of patient-reported sleep disturbances after surgery for lung cancer.

PURPOSE: The purpose of this study was to identify longitudinal heterogeneous trajectories of sleep status, adjusted for the effect of pain over time, among patients who had surgery for lung cancer and to quantify how disturbed sleep in the hospital affects functional recovery after discharge. METHODS: We included patients from a surgical cohort (CN-PRO-Lung 1). All patients reported symptoms using the MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) daily during postoperative hospitalization. Group-based dual trajectory modeling was used to investigate trajectories of disturbed sleep and pain during the first 7 days of postoperative hospitalization. Cox regression was used to compare the recovery of walking ability between the different sleep trajectories. RESULTS: Among 421 patients, disturbed sleep trajectories comprised low (31%), moderate (52%), and high (17%) groups. The surgical approach and number of chest tubes were associated with pain, and the number of chest tubes was also associated with sleep disturbances (OR = 1.99; 95% CI: 1.08-3.67). Recovery of walking ability after discharge was significantly slower in the high (median days = 16; 95% CI: 5-NA) and moderate disturbed sleep trajectory groups (median days = 5; 95%CI: 4-6) than in the low group (median days = 3; 95% CI: 3-4). CONCLUSION: Changes in disturbed sleep among patients with lung cancer followed three distinct trajectories over the first 7 days of hospitalization after surgery. Dual trajectory analyses highlighted the high concordance between specific trajectories of disturbed sleep and pain. Patients at high sleep disturbance and high levels of pain may benefit from appropriate interventions for both symptoms in combination with the patient's surgical approach and the number of chest tubes.

Undescribed matrine-type alkaloids from Sophora alopecuroides with anti-inflammatory activity.

A phytochemical investigation on the alkaloid fractions of Sophora alopecuroides L. led to the production of 11 undescribed matrine-type alkaloids, sophaloseedlines I-S (1-11), 12 known analogs (12-23), and an unexpected artificial matrine-derived Al(III) complex (24). The corresponding structures were elucidated by the interpretation of spectroscopic analyses, quantum chemical calculation, and six instances (1-4, 18, and 24), verified by X-ray crystallography. The biological activities screening demonstrated that none of the isolates exhibited cytotoxicity against four human cancer cell lines (HepG2, A549, THP-1, and MCF-7) and respiratory syncytial virus (RSV) at 50 µM, while moderate anti-inflammatory activity with IC50 value from 15.6 to 47.8 µM was observed. The key structure-activity relationships of those matrine-type alkaloids for anti-inflammatory effects have been summarized. In addition, the most potent 7-epi-sophoramine (19) and aluminum sophaloseedline T (24) could effectively inhibit the release of pro-inflammatory factors (TNF-α, IL-6, and IL-1ß), as well as the expression of iNOS and COX-2 proteins.

Patient adherence to therapy after switch to aflibercept from bevacizumab or ranibizumab for treatment-refractory neovascular age-related macular degeneration.

PURPOSE: Clinical trials have demonstrated that switching patients from intravitreal bevacizumab (IVB) or ranibizumab (IVR) to aflibercept (IVA) for treatment-refractory neovascular age-related macular degeneration (nAMD) can decrease the injection frequency. This study evaluated whether there was a difference in the rate of injections or nonadherent events after switching therapies. METHODS: The study comprised a retrospective, cross-sectional analysis of patients treated for nAMD from 2010 to 2018 who received ≥3 intravitreal injections of IVB/IVR prior to switching to IVA because of treatment-refractory nAMD. The treatment index, outcomes, and adherence to treatment were compared between both treatment regimens. RESULTS: Sixty-two patients (67 eyes) met inclusion criteria. There was no change in the treatment index (0.65 versus 0.66, P = 0.650) or the number of nonadherent events (33 versus 36, P = 0.760) after the switch from IVB/IVR to IVA. Central macular thickness (CMT) increased 7.7%±13.8% in eyes that had a nonadherent event (283±69 µm to 304±75 µm after resuming care, P = 0.039). There was no short-term impact on visual acuity (VA) for this subset of eyes (0.387±0.202 LogMAR versus 0.365±0.156 LogMAR, P = 0.636). Patients who had nonadherent events ended the study with similar VA compared with patients who had no treatment lapses (0.370±0.616 LogMAR versus 0.337±0.638 LogMAR, P = 0.843). CONCLUSION: Switching from IVB/ IVR to IVA for treatment-refractory nAMD in a real-world setting does not reduce the treatment index or increase adherence to treatment. Although there were short-term anatomical effects resulting from missed treatments, VA remained stable.

Development of a machine learning-based model for predicting risk of early postoperative recurrence of hepatocellular carcinoma.

BACKGROUND: Surgical resection is the primary treatment for hepatocellular carcinoma (HCC). However, studies indicate that nearly 70% of patients experience HCC recurrence within five years following hepatectomy. The earlier the recurrence, the worse the prognosis. Current studies on postoperative recurrence primarily rely on postoperative pathology and patient clinical data, which are lagging. Hence, developing a new pre-operative prediction model for postoperative recurrence is crucial for guiding individualized treatment of HCC patients and enhancing their prognosis. AIM: To identify key variables in pre-operative clinical and imaging data using machine learning algorithms to construct multiple risk prediction models for early postoperative recurrence of HCC. METHODS: The demographic and clinical data of 371 HCC patients were collected for this retrospective study. These data were randomly divided into training and test sets at a ratio of 8:2. The training set was analyzed, and key feature variables with predictive value for early HCC recurrence were selected to construct six different machine learning prediction models. Each model was evaluated, and the best-performing model was selected for interpreting the importance of each variable. Finally, an online calculator based on the model was generated for daily clinical practice. RESULTS: Following machine learning analysis, eight key feature variables (age, intratumoral arteries, alpha-fetoprotein, pre-operative blood glucose, number of tumors, glucose-to-lymphocyte ratio, liver cirrhosis, and pre-operative platelets) were selected to construct six different prediction models. The XGBoost model outperformed other models, with the area under the receiver operating characteristic curve in the training, validation, and test datasets being 0.993 (95% confidence interval: 0.982-1.000), 0.734 (0.601-0.867), and 0.706 (0.585-0.827), respectively. Calibration curve and decision curve analysis indicated that the XGBoost model also had good predictive performance and clinical application value. CONCLUSION: The XGBoost model exhibits superior performance and is a reliable tool for predicting early postoperative HCC recurrence. This model may guide surgical strategies and postoperative individualized medicine.

Choroid plexus mast cells drive tumor-associated hydrocephalus.

Tumor-associated hydrocephalus (TAH) is a common and lethal complication of brain metastases. Although other factors beyond mechanical obstructions have been suggested, the exact mechanisms are unknown. Using single-nucleus RNA sequencing and spatial transcriptomics, we find that a distinct population of mast cells locate in the choroid plexus and dramatically increase during TAH. Genetic fate tracing and intracranial mast-cell-specific tryptase knockout showed that choroid plexus mast cells (CPMCs) disrupt cilia of choroid plexus epithelia via the tryptase-PAR2-FoxJ1 pathway and consequently increase cerebrospinal fluid production. Mast cells are also found in the human choroid plexus. Levels of tryptase in cerebrospinal fluid are closely associated with clinical severity of TAH. BMS-262084, an inhibitor of tryptase, can cross the blood-brain barrier, inhibit TAH in vivo, and alleviate mast-cell-induced damage of epithelial cilia in a human pluripotent stem-cell-derived choroid plexus organoid model. Collectively, we uncover the function of CPMCs and provide an attractive therapy for TAH.

Bearing Capacity Performance and Optimal Design of a Novel Aluminum Alloy Arch Gusset Joint.

Current research on aluminum alloy gusset joints has neglected the influences of the angle between members and the curvature of the joint plate on joint performance. This study introduces the concept of the planar angle and establishes 16 joint models using ABAQUS finite element software with parameters such as the planar angle, arch angles, joint plate thickness, web thickness, and flange thickness. The load-bearing capacity of the novel aluminum alloy arch gusset joint is theoretically analyzed, and the concepts of strong and weak axes are proposed. The failure modes and significance of different parameters regarding the bearing capacity and initial stiffness of the joint under various parameters are summarized. The results indicate that the planar and arch angles significantly affect the bearing capacity, stiffness, and failure mode of the joint.

Targeting VCP potentiates immune checkpoint therapy for colorectal cancer.

Immune checkpoint blockade therapies are still ineffective for most patients with colorectal cancer (CRC). Immunogenic cell death (ICD) enables the release of key immunostimulatory signals to drive efficient anti-tumor immunity, which could be used to potentiate the effects of immune checkpoint inhibitors. Here, we showed that inhibition of valosin-containing protein (VCP) elicits ICD in CRC. Meanwhile, VCP inhibitor upregulates PD-L1 expression and compromises anti-tumor immunity in vivo. Mechanistically, VCP transcriptionally regulates PD-L1 expression in a JAK1-dependent manner. Combining VCP inhibitor with anti-PD1 remodels tumor immune microenvironment and reduces tumor growth in mouse models of CRC. Addition of oncolytic virus further augments the therapeutic activity of the combination regimen. Our study shows the molecular mechanism for regulating PD-L1 expression by VCP and suggests that inhibition of VCP has the potential to increase the efficacy of immunotherapy in CRC.

IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma.

IDH1 mutations frequently occur early in human glioma. While IDH1 mutation has been shown to promote gliomagenesis via DNA and histone methylation, little is known regarding its regulation in antiviral immunity. Here, we discover that IDH1 mutation inhibits virus-induced interferon (IFN) antiviral responses in glioma cells. Mechanistically, D2HG produced by mutant IDH1 enhances the binding of DNMT1 to IRF3/7 promoters such that IRF3/7 are downregulated, leading to impaired type I IFN response in glioma cells, which enhances the susceptibility of gliomas to viral infection. Furthermore, we identify DNMT1 as a potential biomarker predicting which IDH1mut gliomas are most likely to respond to oncolytic virus. Finally, both D2HG and ectopic mutant IDH1 can potentiate the replication and oncolytic efficacy of VSVΔ51 in female mouse models. These findings reveal a pivotal role for IDH1 mutation in regulating antiviral response and demonstrate that IDH1 mutation confers sensitivity to oncolytic virotherapy.

Effect of polysaccharides on conformational changes and functional properties of protein-polyphenol binary complexes: A comparative study.

This study aimed to investigate the effect of different polysaccharides on the binding behavior and functional properties of soybean protein isolate (SPI)-quercetin (Que) complex. The binding behavior was assessed using multi-spectral technique with the Stern-Volmer equation, which confirmed the presence of static fluorescence quenching in Que and SPI. The addition of sodium alginate (SA) resulted in a reduction of the binding affinity between SPI and Que, while dextran (DX) exhibited some promoting effect. A slight blue shift was observed in amide I and amide II bands, indicating the presence of hydrophobic and electrostatic interactions. Circular dichroism spectra revealed the ordered structures transformed into a more disordered state when polysaccharides were added, leading to an increase in random coils (SA: 18.5 %, DX: 15.4 %). Docking and dynamic simulations demonstrated that SA displayed greater stability within the hydrophobic compartments of SPI than DX, increased rigidity and stability of the SPI structure in SPI-Que-SA complexes. Electrostatic forces played a significant role between SPI and SA, while van der Waals forces were the main driving forces in SPI-DX complexes. Overall, the introduction of SA led to a looser and stable structure of SPI-Que complexes, resulting in an improvement of their emulsifying, foaming, and antioxidant properties.

Using Clinician-Patient WeChat Group Communication Data to Identify Symptom Burdens in Patients With Uterine Fibroids Under Focused Ultrasound Ablation Surgery Treatment: Qualitative Study.

BACKGROUND: Unlike research project-based health data collection (questionnaires and interviews), social media platforms allow patients to freely discuss their health status and obtain peer support. Previous literature has pointed out that both public and private social platforms can serve as data sources for analysis. OBJECTIVE: This study aimed to use natural language processing (NLP) techniques to identify concerns regarding the postoperative quality of life and symptom burdens in patients with uterine fibroids after focused ultrasound ablation surgery. METHODS: Screenshots taken from clinician-patient WeChat groups were converted into free texts using image text recognition technology and used as the research object of this study. From 408 patients diagnosed with uterine fibroids in Chongqing Haifu Hospital between 2010 and 2020, we searched for symptom burdens in over 900,000 words of WeChat group chats. We first built a corpus of symptoms by manually coding 30% of the WeChat texts and then used regular expressions in Python to crawl symptom information from the remaining texts based on this corpus. We compared the results with a manual review (gold standard) of the same records. Finally, we analyzed the relationship between the population baseline data and conceptual symptoms; quantitative and qualitative results were examined. RESULTS: A total of 408 patients with uterine fibroids were included in the study; 190,000 words of free text were obtained after data cleaning. The mean age of the patients was 39.94 (SD 6.81) years, and their mean BMI was 22.18 (SD 2.78) kg/m2. The median reporting times of the 7 major symptoms were 21, 26, 57, 2, 18, 30, and 49 days. Logistic regression models identified preoperative menstrual duration (odds ratio [OR] 1.14, 95% CI 5.86-6.37; P=.009), age of menophania (OR -1.02 , 95% CI 11.96-13.47; P=.03), and the number (OR 2.34, 95% CI 1.45-1.83; P=.04) and size of fibroids (OR 0.12, 95% CI 2.43-3.51; P=.04) as significant risk factors for postoperative symptoms. CONCLUSIONS: Unstructured free texts from social media platforms extracted by NLP technology can be used for analysis. By extracting the conceptual information about patients' health-related quality of life, we can adopt personalized treatment for patients at different stages of recovery to improve their quality of life. Python-based text mining of free-text data can accurately extract symptom burden and save considerable time compared to manual review, maximizing the utility of the extant information in population-based electronic health records for comparative effectiveness research.

A Novel Aniline Derivative from Peganum harmala L. Promoted Apoptosis via Activating PI3K/AKT/mTOR-Mediated Autophagy in Non-Small Cell Lung Cancer Cells.

Non-small cell lung cancer (NSCLC) is a common clinical malignant tumor with limited therapeutic drugs. Leading by cytotoxicity against NSCLC cell lines (A549 and PC9), bioactivity-guided isolation of components from Peganum harmala seeds led to the isolation of pegaharoline A (PA). PA was elucidated as a structurally novel aniline derivative, originating from tryptamine with a pyrrole ring cleaved and the degradation of carbon. Biological studies showed that PA significantly inhibited NSCLC cell proliferation, suppressed DNA synthesis, arrested the cell cycle, suppressed colony formation and HUVEC angiogenesis, and blocked cell invasion and migration. Molecular docking and surface plasmon resonance (SPR) demonstrated PA could bind with CD133, correspondingly decreased CD133 expression to activate autophagy via inhibiting the PI3K/AKT/mTOR pathway, and increased ROS levels, Bax, and cleaved caspase-3 to promote apoptosis. PA could also decrease p-cyclinD1 and p-Erk1/2 and block the EMT pathway to inhibit NSCLC cell growth, invasion, and migration. According to these results, PA could inhibit NSCLC cell growth by blocking PI3K/AKT/mTOR and EMT pathways. This study provides evidence that PA has a promising future as a candidate for developing drugs for treating NSCLC.

Recall Bias in the Assessment of Cough for Patients Discharged from Lung Surgery.

Purpose: This study aimed to evaluate the presence of recall bias when patients retrospectively report cough scores. Patients and Methods: Patients who underwent lung surgery between July 2021 and November 2021 were recruited for this study. We retrospectively assessed the severity of cough within the past 24 hours and the past 7 days using a 0-10 numerical rating scale. Recall bias was defined as the difference between the scores reported on the two assessments. Patients were grouped based on the longitudinal change in cough scores from pre-operation to 4 weeks after discharge using group-based trajectory models. Using generalized estimating equation to explore the factors influencing recall bias. Results: Overall, 199 patients were analyzed and demonstrated the three distinct trajectories of post-discharge cough: high (21.1%), medium (58.3%), and low (20.6%). Significant recall bias was found in week 2 for the high-trajectory patients (6.26 vs 5.10, P<0.01) and in week 3 for the medium-trajectory patients (2.88 vs 2.60, P=0.01). Among all recall bias, 41.8% were of underestimation, and 21.7% of overestimation. The high trajectory group (ß=1.14, P<0.01) and measurement interval (ß=0.36, P<0.01) were risk factors for underestimation, while post-discharge time (ß=-0.57, P<0.01) and measurement interval (ß=-0.13, P=0.02) were protective factors for overestimation. Conclusion: Retrospective assessment of post-discharge cough in patients who underwent lung surgery will introduce recall bias, with a tendency of underestimation. The high-trajectory group, interval time and post-discharge time are influencing factors of recall bias. For patients with severe cough at discharge, a shorter recall periods should be employed for monitoring, due to the large bias that results from a longer recall period.

Sophflarine A, a novel matrine-derived alkaloid from Sophora flavescens with therapeutic potential for non-small cell lung cancer through ROS-mediated pyroptosis and autophagy.

BACKGROUND: Novel compounds and more efficient treatment options are urgently needed for the treatment of non-small cell lung cancer (NSCLC). The decoction of Sophora flavescens has been used to treat NSCLC in the clinic, and matrine-type alkaloids are generally considered to be the key pharmacodynamic material basis. But the previous study showed that common matrine-type alkaloids exhibit significant cytotoxicity only when at concentrations close to the millimolar (mM) level. The key antitumor alkaloids in S. flavescens seem to have not yet been revealed. PURPOSE: The aim of this study was to screen water-soluble matrine alkaloid with novel skeleton and enhanced activity from S. flavescens, and to reveal the pharmacological mechanism of its therapeutic effect on NSCLC. METHODS: Alkaloid was obtained from S. flavescens by chromatographic separation methods. The structure of alkaloid was determined by spectroscopic methods, and single-crystal X-ray diffraction. The mechanism of anti-NSCLC in vitro with cellular models was evaluated by MTT assay, western blotting, cell migration and invasion assay, plate colony-formation assay, tube formation assay, immunohistochemistry assay, hematoxylin and eosin staining. The antitumor efficacy in vivo was test in NSCLC xenograft models. RESULTS: A novel water-soluble matrine-derived alkaloid incorporating 6/8/6/6 tetracyclic ring system, named sophflarine A (SFA), was isolated from the roots of S. flavescens. SFA had significantly enhanced cytotoxicity compared with the common matrine-type alkaloids, having an IC50 value of 11.3 µM in A549 and 11.5 µM in H820 cells at 48 h. Mechanistically, SFA promoted NSCLC cell death by inducing pyroptosis via activating the NLRP3/caspase-1/GSDMD signaling pathway, and inhibited cancer cell proliferation by increasing the ROS production to activate autophagy via blocking the PI3K/AKT/mTOR signaling pathway. Additionally, SFA also inhibited NSCLC cell migration and invasion by suppressing EMT pathway, and inhibited cancer cell colony formation and human umbilical vein endothelial cell angiogenesis. In concordance with the above results, SFA treatment blocked tumor growth in an A549 cell-bearing orthotopic mouse model. CONCLUSION: This study revealed a potential therapeutic mechanism of a novel matrine-derived alkaloid, which not only described a rational explanation for the clinical utilization of S. flavescens, but also provided a potential candidate compound for NSCLC treatment.

Anti-inflammatory sesquiterpene polyol esters from the stem and branch of Tripterygium wilfordii.

The stem and branch extract of Tripterygium wilfordii (Celastraceae) afforded seven new dihydroagarofuran sesquiterpene polyesters [tripterysines A-G (1-7)] and eight known ones (8-15). The chemical structures of these new compounds were established based on combinational analysis of HR-ESI-MS and NMR techniques. The absolute configurations of tripterysines A-C (1-3) and E-G (5-7) were determined by X-ray crystallographic analysis and circular dichroism spectra. All the compounds were screened for their inhibitory effect on inflammation through determining their inhibitory effect on nitric oxide production in LPS-induced RAW 264.7 cells and the secretion of inflammatory cytokines TNF-α and IL-6 in LPS-induced BV2 macrophages. Compound 9 exhibited significant inhibitory activity on NO production with an IC50 value of 8.77 µmol·L-1. Moreover, compound 7 showed the strongest inhibitory effect with the secretion of IL-6 at 27.36%.

Risk stratification and molecular heterogeneity of endometrial cancer and expression profile of TIM-3: A retrospective cohort study.

OBJECTIVE: The present study aimed to implement ProMisE classification and risk grouping on a retrospective cohort of 628 patients with endometrial cancer (EC) and determine the molecular heterogeneity across subtypes and subgroups, as well as to investigate the potential beneficiary for TIM-3 checkpoint inhibition in ECs. METHODS: Protein expressions of p53, MMR, TIM-3 and CD8 were measured by immunohistochemistry, and massively parallel sequencing was conducted for 128 cancer-related genes. Patients were categorized into four ProMisE subtypes: MMR-deficient (MMRd), POLE-ultramutated (POLEmut), p53-wild type (p53wt), and p53-abnormal (p53abn), and were subjected to risk classification. RESULTS: 43 (6.9%) patients belonged to POLEmut, 118 (18.8%) to MMRd, 69 (11%) to p53abn, and 398 (63.3%) to p53wt. Compared to the 2016 stratification system, the 2021 ESGO/ESTRO/ESP risk stratification integrated with molecular classification revealed that 11 patients (11/628, 1.8%) were upgraded due to the p53abn signature, whereas 23 patients (23/628, 3.7%) were downgraded due to the POLEmut signature. JAK1 and RAD50 mutations showed higher frequencies in patients with aggressive phenotypes. RAD51B mutation was significantly related to poor RFS of the p53wt subtype but not of the other three molecular subgroups. TIM-3 expression was detected in 30.9% immune cells (ICs) and 29.0% tumor cells (TCs) in ECs, respectively. It was frequently expressed in POLEmut and MMRd ECs as compared to that in the other two molecular subtypes in TCs and ICs. CONCLUSIONS: Our study revealed the molecular heterogeneity across subtypes and subgroups. The new risk stratification system changed the risk grouping of some patients due to the integration of molecular features. RAD51B mutation can further stratify the recurrence risk in the p53wt subtype. Patients with MMRd or POLEmut may benefit most from immunotherapy against TIM-3.

Development of a Patient-Reported Symptom Item Bank for Patients with Hepatobiliary or Pancreatic Malignancies: A Systematic Review.

Background: Patients with hepatobiliary or pancreatic cancers often experience severe symptoms, resulting in a sharp decline in functioning, poor quality of life, and increased mortality risk. Early and effective management of symptoms allows a better quality of life and reduced mortality, depending on the selection of appropriate assessment of specific symptoms for a defined purpose. We aimed to develop a symptom measurement item bank for hepatobiliary or pancreatic cancers. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was applied to organize this systematic review. The articles validated patient-reported outcome measures (PROMs) for hepatobiliary or pancreatic cancer and published before December 2021 were retrieved from the Web of Science, PubMed, Embase databases and Cochrane Library. Items from the existing PROMs were selected and classified into different patient-reported symptoms based on the concepts and specific underlying constructs of the objects measured. Results: Sixteen unique PROMs were identified across the 29 eligible studies included in our analysis. Items from the literature review (14 PROMs with 421 items for which information was obtained) were selected and classified. As a result of this study, we developed a symptom item bank with 40 patient-reported symptoms and 229 assessment items for hepatobiliary or pancreatic cancer, and fatigue, pain and nausea were the most common symptom items. Conclusion: We developed an item bank to assess the patient-reported symptoms of hepatobiliary or pancreatic cancer. This item bank could allow researchers to select appropriate measures of symptom and provide a basis for the development of a single-item symptom-measurement system.

Undescribed phloroglucinol derivatives with antiviral activities from Dryopteris atrata (Wall. Ex Kunze) Ching.

Nine undescribed phloroglucinol derivatives (dryatraols A-I) with five different backbones and three known dimeric acylphloroglucinols were isolated from the rhizome of Dryopteris atrata (Wall. Ex Kunze) Ching (Dryopteridaceae). Dryatraol A contains an unprecedented carbon skeleton-a butyrylphloroglucinol and a rulepidanol-type sesquiterpene are linked via a furan ring to form a 6/5/6/6 ring system. Dryatraols B and C are the first examples of monomeric phloroglucinols coupled with the aristolane-type sesquiterpene through the C-C bond. Dryatraol D features a rare spiro [benzofuran-2',5″-furan] backbone. Dryatraols E-I are five undescribed adducts with a butyrylphloroglucinol or filicinic acid incorporated into the germacrene-type sesquiterpene via a pyran ring. These undescribed structures were determined by comprehensively analysing the spectroscopic data, X-ray diffraction results, and electronic circular dichroism calculations. The result of in vitro antiviral activity evaluation indicated that dryatraol C displayed the strongest antiviral effect against both respiratory syncytial virus and influenza A virus (H1N1), with IC50 values of 11.9 µM and 5.5 µM, respectively. Dryatraols F-H exhibited considerable inhibitory activity against herpes simplex virus type 1 (HSV-1), with IC50 values ranging from 2.6 to 6.3 µM. Analysis of the inhibitory mechanism using a time-of-addition assay revealed that dryatraol G may inhibit the replication of HSV-1 by interfering with the late stage of the viral life cycle.

Three new compounds isolated from the whole plants of Salsola collina pall.

One new alkaloid, 6, 7-dimethoxyisoquinoline-N-oxide (1), one new benzofuran derivative, 3,7-dimethyl-6-acetyl-8-benzofuranol (2) and one new lignan, salsolains A (3), along with seven known compounds (4-10), were isolated from the whole plant of Salsola collina Pall. Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HR-ESI-MS, 1 D and 2 D NMR), and their absolute configurations were determined by the X-ray crystallography and ECD calculation. The activities of compounds 1-10 against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were assessed, especially, compound 5 (50 µM) exhibited the most significant anti-inflammatory activity with the secretion levels of IL-6 and TNF-α at 3.87% and 4.03%, respectively.