Pooled analysis of NeoCARH and NeoCART trials: patient-reported outcomes in patients with early-stage breast cancer receiving platinum-based or anthracycline-based neoadjuvant chemotherapy.

PURPOSE: Anthracycline-based or platinum-based neoadjuvant chemotherapy belongs to the standard treatment for early-stage breast cancer (EBC) that is either triple-negative or human epidermal growth factor receptor 2 positive (HER2 +). Currently, there is a paucity of data comparing their impact on health-related quality of life (HRQoL). METHODS: Triple-negative or HER2 + EBC from our two prospective randomized controlled trials, neoCARH and neoCART, were divided into two groups based on the neoadjuvant chemotherapy regimens they received: anthracycline-based or platinum-based group. HRQoL was the exploratory endpoint in these two trials, which was assessed using the European Organization for Research and Treatment of Cancer Quality of Life-Core30 and Breast23 questionnaires. The primary variable of interest was the C30 summary score (C30-SumSc). Assessments were carried out at baseline, after neoadjuvant chemotherapy, and 1 year and 2 years after diagnosis. RESULTS: The mean questionnaires' compliance rate was 95.0%. After neoadjuvant chemotherapy, 210 patients had evaluable HRQoL data, the mean least square change from baseline for the platinum-based group was - 15.997 (95% confidence interval (CI): - 17.877 to - 14.117), and it was - 20.156 (95% CI: - 22.053 to - 18.258) for the anthracycline-based group (difference: 4.159, 95% CI: 1.462 to 6.855, P = 0.003, minimal important difference = 3). For the majority of the domains of interest assessed by the C30 and BR23 questionnaires, the platinum-based group demonstrated superior outcomes in comparison to the anthracycline-based group. CONCLUSION: Patients receiving platinum-based or anthracycline-based regimens both experienced worsened HRQoL after neoadjuvant chemotherapy; however, the former provided relatively better HRQoL compared with the latter. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT03140553. Registered 4 May 2017 (neoCARH). NCT03154749. Registered 16 May 2017 (neoCART).

Bis-piperidine alkaloids from the peels of Areca catechu.

Four new alkaloids, arecatines A-D (1-4), were isolated from the peels of Areca catechu. Compound 1 is an unusual piperidine-pyridine hybrid alkaloid, whereas compounds 2-4 feature bis-piperidine alkaloids. Their structures were elucidated by UV, IR, HRESIMS, and NMR spectra analysis. The molecular docking analysis indicated that compound 3 exhibited the best binding affinity with the GABAA receptor, indicating its potential anti-epilepsy activity.

Comparison of accelerated and standard infliximab induction regimens in acute severe ulcerative colitis using propensity score analysis: a retrospective multicenter study in China.

Background: The optimal regimen of infliximab salvage in acute severe ulcerative colitis (ASUC) patients remains controversial. This study aimed to compare accelerated and standard infliximab induction in Chinese ASUC patients, and to explore risk factors and concrete accelerated regimens for them. Methods: Data were retrospectively collected from steroid-refractory ASUC patients receiving infliximab as rescue therapy at seven tertiary centers across China. Outcomes including colectomy and clinical remission (Mayo score ≤ 2 and every subscore ≤ 1 at Day 14) rates were compared between patients receiving accelerated and standard infliximab induction using propensity score adjustment for potential confounders. The dose-response relationship was explored by plotting restricted cubic splines. Logistic regression and Cox proportional hazards regression analyses were performed to determine risk factors for adverse outcomes. A systematic review and meta-analysis was also performed. Results: A total of 76 patients were analysed: 29 received standard and 47 received accelerated induction. The accelerated group had a higher 90-day colectomy rate (17.8% vs 0%, P = 0.019) and lower clinical remission rate (27.7% vs 65.5%, P = 0.001). After adjusting for propensity score and institution, there was no significant difference in colectomy or clinical remission rates (both P > 0.05). Dose-effect curves showed decreased colectomy hazard with higher cumulative infliximab dosage within 5 days, with no improvement observed for increasing cumulative infliximab dosage within 28 days. Multivariate logistic regression analyses revealed C-reactive protein of >10 mg/L at infliximab initiation (odds ratio = 5.00, 95% confidence interval: 1.27-24.34) as an independent risk factor for no clinical remission. Meta-analysis also revealed no significant difference in colectomy rates at 3 months (P = 0.54). Conclusions: After adjusting for confounders, there were no significant differences in colectomy or clinical remission rates between accelerated and standard infliximab induction among ASUC patients. Early administration of an intensified dosage within 5 days may be beneficial. Elevated C-reactive protein at infliximab initiation indicated need for intensive treatment.

The burden of cardiovascular disease attributable to high fasting plasma glucose：Findings from the global burden of disease study 2019.

AIM: High fasting plasma glucose (HFPG) is a key risk factor for cardiovascular disease (CVD). Few studies have evaluated the CVD burden attributable to HFPG globally. It is urgent to investigate the current epidemiological pattern and past trends of CVD attributable to HFPG. METHODS: We used the Global Burden of Disease Study (GBD) 2019 to describe the CVD burden attributable to HFPG in 2019 and evaluate temporal trends between 1990 and 2019. RESULTS: Global Disability-Adjusted Life Years (DALYs) cases and death cases of HFPG-related CVD were approximately 72,591,163 and 3,763,298 in 2019, with an increase of 107.4 % and 114.6 % compared with 1990, respectively. Despite the increases, the age-standardized DALYs rate (ASDAR) and age-standardized death rate (ASDR) of HFPG-related CVD contributed to 895.2 per 100,000 people and 48.4 per 100,000 people in 2019, with an estimated annual percentage change (EAPC) of -0.22 and -0.31, respectively, from 1990. The highest ASDAR and ASDR of HFPG-related CVD were in 2019 observed in the low-middle SDI (Socio-demographic Index) and middle-SDI regions. Low SDI and some low-middle SDI regions showed an increase in ASDAR and ASDR of HFPG-related CVD from 1990 to 2019. Males are more affected by HFPG-related CVD than females across all years. The CVD burden attributable to HFPG in the elderly are higher than those in the young in 2019. The main causes of the global CVD burden attributable to HFPG in 2019 were ischemic heart disease, stroke, and peripheral arterial disease. CONCLUSION: The CVD burden attributable to HFPG remains a serious public health challenge threatening human health worldwide. It is necessary to develop more targeted and specific strategies to reduce CVD burden attributable to HFPG, especially in males, elderly, and lower SDI regions.

Natural L-type calcium channels antagonists from Chinese medicine.

L-type calcium channels (LTCCs), the largest subfamily of voltage-gated calcium channels (VGCCs), are the main channels for Ca2+ influx during extracellular excitation. LTCCs are widely present in excitable cells, especially cardiac and cardiovascular smooth muscle cells, and participate in various Ca2+-dependent processes. LTCCs have been considered as worthy drug target for cardiovascular, neurological and psychological diseases for decades. Natural products from Traditional Chinese medicine (TCM) have shown the potential as new drugs for the treatment of LTCCs related diseases. In this review, the basic structure, function of LTCCs, and the related human diseases caused by structural or functional abnormalities of LTCCs, and the natural LTCCs antagonist and their potential usages were summarized.

Hovendulcisic acid A-D: four novel ceanothane-type triterpenoids from Hovenia dulcis stems with anticancer properties.

Sixteen ceanothane-type triterpenoids, including four new compounds-hovendulcisic acids A-D (1-4) -were purified from the stems of Hovenia dulcis Thunb. The structures of 1-4 were confirmed by comprehensive means including ECD and quantum chemical calculations. Putative biosynthetic pathways of 1-16 were proposed, and 3, 5, and 15 exhibited antitumor activity on A549 and MDA-MB-231 cells.

Copper-Catalyzed Asymmetric Kinugasa/Michael Addition Cascade Reactions for the Synthesis of Chiral Spiro ß-Lactams.

A mild copper-catalyzed asymmetric Kinugasa/Michael addition cascade process is developed. The reaction of α, ß-unsaturated ester-tethered propiolamides with nitrones provides an efficient protocol for the construction of functionalized chiral 2,6-diazaspiro[3.4]octane-1,5-dione products in satisfactory yields and with high enantio- and diastereoselectivities.

Two new chemical constituents from the aerial parts of Tripterygium wilfordii.

Tripterygium wilfordii has been historically employed as a conventional botanical insecticide and a plant of medicinal significance. A new dihydroagarofuran sesquiterpene (1) and a new acyclic compound (2), along with seven known compounds (3-9), have been isolated from the aerial parts of Tripterygium wilfordii. The identification of the structures of novel compounds were accomplished through comprehensive spectroscopic analyses, encompassing HRESIMS, NMR, UV, IR, and a comparative analysis with spectroscopic data from compounds previously characterised. In in-vitro bioassay, compound 8 exhibited significant inhibitory activity for NO release in LPS-induced RAW 264.7 cells, with an IC50 value of 15.7 µM.

A magnetic beads-based ligand fishing method for rapid discovery of monoterpene indoles as monoamine oxidase A inhibitors from Hunteria zeylanica.

In this study, a novel magnetic bead-based ligand fishing method was developed for rapid discovery of monoterpene indoles as monoamine oxidase A inhibitors from natural products. In order to improve the screening efficiency, two different magnetic beads, i.e. amine and carboxyl terminated magnetic beads, were comprehensively compared in terms of their ability to immobilize monoamine oxidase A (MAOA), biocatalytic activity and specific adsorption rates for affinity ligands. Carboxyl terminated magnetic beads performed better for MAOA immobilization and demonstrated superior performance in ligand fishing. The MAOA immobilized magnetic beads were applied to screen novel monoamine oxidase inhibitors in an alkaloid-rich plant, Hunteria zeylanica. Twelve MAOA affinity ligands were screened out, and ten of them were identified as monoterpene indole alkaloids by HPLC-Obitrap-MS/MS. Among them, six ligands, namely geissoschizol, vobasinol, yohimbol, dihydrocorynanthenol, eburnamine and (+)-isoeburnamine which exhibited inhibitory activity against MAOA with low IC50 values. To further explore their inhibitory mechanism, enzyme kinetic analysis and molecular docking studies were conducted.

Triterpenoids from the Leaves of Diospyros digyna and Their PTP1B Inhibitory Activity.

Six new 2α-hydroxy ursane triterpenoids, 3α-cis-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (1), 3α-trans-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (2), 3α-trans-p-coumaroyloxy-2α-hydroxy-12-ursen-28-oic acid (3), 3ß-trans-p-coumaroyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (4), 3ß-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (5), and 3α-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (6), along with eleven known triterpenoids (7-17), were isolated from the leaves of Diospyros digyna. Their chemical structures were elucidated by comprehensive analysis of UV, IR, HRESIMS, and NMR spectra. All the isolated compounds were evaluated for their PTP1B inhibitory activity. 3ß-O-trans-feruloyl-2α-hydroxy-urs-12-en-28-oic acid (13) showed the best inhibition activity with an IC50 value of 10.32 ± 1.21 µM. The molecular docking study found that the binding affinity of compound 13 for PTP1B was comparable to that of oleanolic acid (positive control).

Improvement of Lung Function by Micronutrient Supplementation in Patients with COPD: A Systematic Review and Meta-Analysis.

BACKGROUND: A healthy, well-balanced diet plays an essential role in respiratory diseases. Since micronutrient deficiency is relatively common in patients with chronic obstructive pulmonary disease (COPD), micronutrient supplementation might have the beneficial health effects in those patients. This systematic review and meta-analysis aimed to demonstrate the impact of micronutrient supplementation on the lung function of patients with COPD. METHODS: The PubMed, Cochrane Library, and Web of Science databases were searched from their corresponding creation until February 2024. Search terms included 'chronic obstructive pulmonary disease', 'COPD', 'micronutrients', 'dietary supplements', 'vitamins', 'minerals', and 'randomized controlled trials'. Meta-analysis was performed to evaluate the effects of micronutrient supplementation alone or complex on lung function in patients with COPD. RESULTS: A total of 43 RCTs fulfilled the inclusion criteria of this study. Meta-analysis revealed that vitamin D supplementation could significantly improve FEV1% (WMDdifferences between baseline and post-intervention (de): 6.39, 95% CI: 4.59, 8.18, p < 0.01; WMDpost-intervention indicators (af): 7.55, 95% CI: 5.86, 9.24, p < 0.01) and FEV1/FVC% (WMDde: 6.88, 95%CI: 2.11, 11.65, WMDaf: 7.64, 95% CI: 3.18, 12.10, p < 0.001), decrease the odds of acute exacerbations, and improve the level of T-cell subsets, including CD3+%, CD4+%, CD8+%, and CD4+/CD8+% (all p < 0.01). The effects of compound nutrients intervention were effective in improving FEV1% (WMDde: 8.38, 95%CI: 1.89, 14.87, WMDaf: 7.07, 95%CI: -0.34, 14.48) and FEV1/FVC% (WMDde: 7.58, 95% CI: 4.86, 10.29, WMDaf: 6.00, 95% CI: 3.19, 8.81). However, vitamin C and vitamin E supplementation alone had no significant effects on lung function (p > 0.05). CONCLUSIONS: Micronutrient supplementation, such as vitamin D alone and compound nutrients, has improved effect on the lung function of patients with COPD. Therefore, proper supplementation with micronutrients would be beneficial to stabilize the condition and restore ventilation function for COPD patients.

Desquamative interstitial pneumonia: A case report.

Diffuse cystic lung diseases (DCLDs) are a group of heterogeneous lung diseases that are characterized by inflated spaces or cysts within the lung parenchyma. They also exhibit similar imaging characteristics and clinical manifestations compared with those of cystic lesions, such as pulmonary cavities, emphysema, bronchiectasis and honeycomb lung. The most common DCLDs encountered in the clinic include lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, Langerhans cell histiocytosis and lymphocytic interstitial pneumonia. In particular, accurate diagnosis of DCLDs in terms of the different lesions found is important, because their clinical courses, prognoses and treatment strategies vary widely. However, because DCLDs usually have overlapping clinical presentations, diagnosis typically requires a combination of clinical considerations that take into account characteristics of the cyst, its distribution, organ of origin and background parenchymal findings. The present report documents the case of a 73-year-old man diagnosed with desquamative interstitial pneumonia (DIP). The patient was admitted to the hospital due to chest tightness, shortness of breath and intermittent fever. The patient had been a smoker for >60 years and had stopped smoking for 6 months before being admitted. A transbronchial lung biopsy, bronchoscopy and alveolar lavage cytopathogen culture were performed to confirm the diagnosis of desquamative interstitial pneumonia (DIP). The patient was treated with hormonal therapy and advised to abstain from smoking. The diagnosis of DIP in comparison with other DCLDs was summarized for the purpose of providing a clinical basis for the accurate clinical diagnosis of DIP and the development of evidence-based practice guidelines.

The emerging role and clinical significance of circRNAs in papillary thyroid cancer.

Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy, and its global incidence has been gradually increasing. For advanced PTC, the mortality rates are also increasing yearly. Despite advancements in diagnosis and treatment, some advanced PTC exhibit aggressive behaviors, leading to a poor prognosis. CircRNAs are a class of non-coding RNAs characterized by a covalently closed loop structure. Their stability and abundance have positioned them as promising diagnostic and prognostic biomarkers. Numerous studies have identified dysregulated circRNAs in PTC tissues and cell lines, suggesting their involvement in PTC initiation and progression. In this review, we provide an overview of circRNAs and systematically discuss their role in PTC. CircRNAs affect cancer progression by regulating the Wnt/ß-catenin, PI3K/AKT, MAPK pathways, and others. Furthermore, circRNAs have been implicated in PTC metastasis and chemoresistance. We highlight their potential value as diagnostic markers, therapeutic targets, and prognostic indicators. In conclusion, circRNAs play a critical role in PTC, and dysregulated circRNAs influence multiple signaling pathways and cellular processes involved in tumorigenesis and metastasis. It represents a promising avenue for advancing the diagnosis, management, and treatment of PTC.

Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson's disease.

Parkinson's disease (PD) is a ubiquitous brain cell degeneration disease and presents a significant therapeutic challenge. By injecting 6-hydroxydopamine (6-OHDA) into the left medial forebrain bundle, rats were made to exhibit PD-like symptoms and treated by intranasal administration of a low-dose (2 × 105) or high-dose (1 × 106) human neural stem cells (hNSCs). Apomorphine-induced rotation test, stepping test, and open field test were implemented to evaluate the motor behavior and high-performance liquid chromatography was carried out to detect dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5-hydroxyindole-3-acetic acid in the striatum of rats. Animals injected with 6-OHDA showed significant motor function deficits and damaged dopaminergic system compared to the control group, which can be restored by hNSCs treatment. Treatment with hNSCs significantly increased the tyrosine hydroxylase-immunoreactive cell count in the substantia nigra of PD animals. Moreover, the levels of neurotransmitters exhibited a significant decline in the striatum tissue of animals injected with 6-OHDA when compared to that of the control group. However, transplantation of hNSCs significantly elevated the concentration of DA and DOPAC in the injured side of the striatum. Our study offered experimental evidence to support prospects of hNSCs for clinical application as a cell-based therapy for PD.

The Effect of Dexmedetomidine as a Local Anesthetic Adjuvant for Iliac Fascia Compartment Block on Postoperative Delirium in Elderly Patients Undergoing Elective Hip Surgery.

INTRODUCTION: We analyzed the effect of dexmedetomidine (DEX) as a local anesthetic adjuvant on postoperative delirium (POD) in elderly patients undergoing elective hip surgery. METHODS: In this study, 120 patients undergoing hip surgery were enrolled and randomly assigned to two groups: fascia iliaca compartment block with DEX + ropivacaine (the Y group, n = 60) and fascia iliaca compartment block with ropivacaine (the R group, n = 60). The primary outcomes: presence of delirium during the postanesthesia care unit (PACU) period and on the first day (D1), the second day (D2), and the third day (D3) after surgery. The secondary outcomes: preoperative and postoperative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), occurrence of insomnia on the preoperative day, day of operation, D1 and D2; HR values of patients in both groups before iliac fascia block (T1), 30 min after iliac fascia block (T2), at surgical incision (T3), 20 min after incision (T4), when they were transferred out of the operating room (T5) and after leaving the recovery room (T6) at each time point; VAS for T1, PACU, D1, D2; the number of patients requiring remedial analgesics within 24 h after blockade and related complications between the two groups. RESULTS: A total of 97 patients were included in the final analysis, with 11 and 12 patients withdrawing from the R and Y groups, respectively. The overall incidence of POD and its incidence in the PACU and ward were all lesser in the Y group than in the R group (p < 0.05). Additionally, fewer cases required remedial analgesia during the PACU period, and more vasoactive drugs were used for maintaining circulatory system stability in the Y group as compared to the R group (p < 0.05). At the same time, the incidence of intraoperative and postoperative bradycardia in the Y group was higher than that in the R group, accompanied by lower postoperative CRP and ESR (all p < 0.05). CONCLUSION: Ultrasound-guided high fascia iliaca compartment block with a combination of ropivacaine and DEX can reduce the incidence of POD, the use of intraoperative opioids and postoperative remedial analgesics, and postoperative inflammation in elderly patients who have undergone hip surgery, indicating that this method could be beneficial in the prevention and treatment of POD.

Cryo-EM structures of amyloid-ß and tau filaments in Down syndrome.

Adult individuals with Down syndrome (DS) develop Alzheimer disease (AD). Whether there is a difference between AD in DS and AD regarding the structure of amyloid-ß (Aß) and tau filaments is unknown. Here we report the structure of Aß and tau filaments from two DS brains. We found two Aß40 filaments (types IIIa and IIIb) that differ from those previously reported in sporadic AD and two types of Aß42 filaments (I and II) identical to those found in sporadic and familial AD. Tau filaments (paired helical filaments and straight filaments) were identical to those in AD, supporting the notion of a common mechanism through which amyloids trigger aggregation of tau. This knowledge is important for understanding AD in DS and assessing whether adults with DS could be included in AD clinical trials.

Identification and Genome Characterization of a Novel Virus within the Genus Totivirus from Chinese Bayberry (Myrica rubra).

Chinese bayberry (Myrica rubra) is an economically significant fruit tree native to eastern Asia and widely planted in south-central China. However, studies about the viruses infecting M. rubra remain largely lacking. In the present study, we employed the metatranscriptomic method to identify viruses in M. rubra leaves exhibiting yellowing and irregular margin symptoms collected in Fuzhou, a city located in China's Fujian province in the year 2022. As a consequence, a novel member of the genus Totivirus was identified and tentatively named "Myrica rubra associated totivirus 1" (MRaTV1). The genome sequencing of MRaTV1 was determined by overlapping reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). The two deduced proteins encoded by MRaTV1 have the highest amino acid (aa) sequence identity to the coat protein (CP) and RNA-dependent RNA polymerase (RdRP) of Panax notoginseng virus A (PNVA), a member of the genus Totivirus within the family Totiviridae, at 49.7% and 61.7%, respectively. According to the results of the phylogenetic tree and the species demarcation criteria of the International Committee on Taxonomy of Viruses (ICTV) for the genus Totivirus, MRaTV1 is considered a new member of the genus Totivirus.

Iron-modified biochar effectively mitigates arsenic-cadmium pollution in paddy fields: A meta-analysis.

The escalating problem of compound arsenic (As) and cadmium (Cd) contamination in agricultural soils necessitates the urgency for effective remediation strategies. This is compounded by the opposing geochemical behaviors of As and Cd in soil, and the efficacy of biochar treatment remains unclear. This pioneering study integrated 3780 observation pairs referred from 92 peer-reviewed articles to investigate the impact of iron-modified biochar on As and Cd responses across diverse soil environments. Regarding the treatments, 1) biochar significantly decreased the exchangeable and acid-soluble fraction of As (AsF1, 20.9%) and Cd (CdF1, 24.0%) in paddy fields; 2) iron-modified biochar significantly decreased AsF1 (32.0%) and CdF1 (27.4%); 3) iron-modified biochar in paddy fields contributed to the morphological changes in As and Cd, mainly characterized by a decrease in AsF1 (36.5%) and CdF1 (36.3%) and an increase in the reducible fraction of As (19.7%) and Cd (39.2%); and 4) iron-modified biochar in paddy fields increased As (43.1%) and Cd (53.7%) concentrations in the iron plaque on root surfaces. We conclude that iron-modified biochar treatment of paddy fields is promising in remediating As and Cd contamination by promoting the formation of iron plaque.