Five novel nor-eremophilane-type sesquiterpenoids, peniroqueforins E-H and J (1-4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), along with four known compounds (6 and 10-12), were isolated and characterized from fungus Penicillium roqueforti (P. roqueforti). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC₅₀) value of paclitaxel (PTX) combined with 1 in SW620/Ad300 cells was 50.36 nmol·L^-1, which was 65-fold more potent than PTX alone (IC₅₀ 3.26 μmol·L^-1). Subsequent molecular docking studies revealed an affinity between compound 1 and P-glycoprotein (P-gp), suggesting that this nor-eremophilane-type sesquiterpenoid (1) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.
Penicillium/chemistry* ; Humans ; Sesquiterpenes/isolation & purification* ; Cell Line, Tumor ; Molecular Structure ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/pharmacology* ; Drug Resistance, Multiple/drug effects* ; Molecular Docking Simulation

Objective To investigate the quality and in vitro release behavior of the sirolimus self-microemulsion-mesoporous silicon sustained release tablets and provide a basis for further research and development of related preparations. Methods The hardness, brittleness and content uniformity of the sustained-release tablets were tested refer to Pharmacopoeia of the People’s Republic of China 2020. Different diameters （10, 11, 12 mm）, different hardness （50, 70, 90 N）, different speed （50, 75, 100 r/min）, different dissolution methods （pulp method, basket method） were investigated. The release conditions of the sustained-release tablets with different pH solution （distilled water solution and 0.4% SDS solution with pH of 1.2, 4.5 and 6.8, respectively） and the in vitro release conditions of the sustained-release tablets were observed. Results The hardness, brittleness and content uniformity of the self-made sustained-release tablets were qualified; different diameters and dissolution methods had no effect on the drug release behavior of the sustained-release tablets in vitro, while the different hardness, different rotational speed and the different pH release media had certain effects. Conclusion The sirolimus self-microemulsion-mesoporous silicon sustained release tablets had good sustained-release effect in vitro and was deserved to further study.

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

ObjectiveTo observe the clinical efficacy of Gandouling decoction combined with neuromuscular electrical stimulation （NMES） in the treatment of dysphagia in Wilson disease （WD） with combined phlegm and stasis. MethodsA total of 80 WD patients with dysphagia due to combined phlegm and stasis treated in the Department of Encephalopathy， the First Affiliated Hospital of Anhui University of Chinese Medicine were randomized into a control group and an observation group， with 40 patients in each group. In addition， 40 healthy volunteers were recruited as the normal group. The control group was treated with basic copper drainage combined with NMES. The observation group was treated with Gandouling Decoction on the basis of the therapy in the control group. Each course of treatment lasted for 8 days， and the patients were treated for a total of 4 courses. All subjects underwent video fluoroscopic swallowing study （VFSS） before and after treatment. During the examination， contrast agents with 4 different characters were used for the swallowing action， and the passing time was recorded. The TCM syndrome score， water swallow test score， standard swallowing assessment （SSA） score， and 24-h urinary copper level before and after treatment were analyzed. ResultsWhen performing VFSS， the passing time of contrast agents of different characters in the oral stage was longer in the WD group than in the normal group （P<0.01）， while it had no significant difference in the pharyngeal stage. After treatment， the passing time in the oral stage shortened in the control and observation groups （P<0.01）， and the observation group outperformed the control group （P<0.01）. After treatment， both the control and observation groups showed declines in TCM syndrome score and SSA score （P<0.01） and an increase in water swallow test score （P<0.01）， and the changes were more obvious in the observation group than in the control group （P<0.01）. In addition， the treatment in the control and observation groups elevated the 24-h urinary copper level （P<0.01）， and the elevation in the observation group was more obvious than that in the control group （P<0.01）. Neither group showed obvious adverse reaction. ConclusionGandouling decoction combined with NMES can significantly ameliorate dysphagia in WD patients with the syndrome of combined phlegm and stasis regarding the TCM syndrome score， water swallow test score， and SSA score， demonstrating definite clinical efficacy and high safety.

Objectives:To investigate the clinical characteristics of patients with idiopathic pulmonary arterial hypertension(IPAH)with cardiovascular comorbidities.Methods:A total of 150 patients with IPAH admitted to Fuwai Hospital,Chinese Academy of Medical Sciences from October 2014 to June 2024 were enrolled in this retrospective study.The clinical variables,cardiac structure and hemodynamic characteristics were analyzed and compared between IPAH patients with or without cardiovascular comorbidities.Results:The mean age of the 150 patients was(35.9±12.5)years,73.3%of whom were female.There were 88(58.7%)IPAH patients with cardiovascular comorbidities.Compared to those without cardiovascular comorbidities(n=62),patients with cardiovascular comorbidities were older([38.9±12.3]years vs.[31.7±11.9]years,P=0.001),and N-terminal pro-B-type natriuretic peptide level was higher(1 469.0[656.8,2 615.8]pg/ml vs.923.5[304.4,1 958.8]pg/ml,P=0.006).The hemodynamic examination indicated that patients with cardiovascular comorbidities were featured with higher mean right atrial pressure(6.0[3.3,9.0]mmHg[1 mmHg=0.133 kPa]vs.4.0[3.0,6.3]mmHg,P=0.006),but lower mixed venous oxygen saturation([67.0±7.0]%vs.[70.3±6.9]%,P=0.010)and cardiac index(2.4[1.9,2.9]L/[min·m2]vs.2.8[2.3,3.8]L/[min·m2],P=0.013).Among IPAH patients with cardiovascular comorbidities,compared to patients with 1 comorbidity,patients with≥2 comorbidities were older(51.0[40.0,63.3]years vs.35.0[29.3,43.8]years,P<0.001),left atrial anteroposterior diameter([35.6±4.8]mm vs.[30.4±4.4]mm,P<0.001)and left end-diastolic anteroposterior diameter([40.8±7.5]mm vs.[35.8±5.5]mm,P=0.006)were larger.In patients with cardiovascular comorbidities,hypertension was the most common comorbidity(48.9%).Conclusions:Patients with IPAH and cardiovascular comorbidities exhibit aging characteristics.A series of cardiovascular comorbidities,including hypertension,significantly impact the clinical features,cardiac structural parameters,and hemodynamic status of IPAH.The assessment and management of comorbidities in IPAH patients should be prioritized in the future clinical practice.

To investigate the association between obesity-related metabolic indices and the risk of knee osteoarthritis(KOA) in middle-aged and older Chinese adults(≥45 years) using data from the China Health and Retirement Longitudinal Study(CHARLS).

ObjectiveTo explore the key molecules regulated by norcantharidin (NCTD) in colon cancer treatment.MethodsWe used cell counting kit-8 and 5-ethnyl-2′-deoxyuridine/Hoechst staining assays to study the effects of NCTD on cell proliferation in colon cancer. Annexin V-fluorescein isothiocyanate/propidium iodide staining was used to evaluate apoptosis, whereas Transwell assays were conducted to evaluate migration and invasion. We performed RNA sequencing to analyze the changes in gene expression after treatment. Differential analysis was performed using differential expression sequencing 2 (Deseq2) in R. Cytoscape was used to construct a competing endogenous RNA (ceRNA) network and Gene Expression Omnibus (GEO) datasets were used to validate sine oculis homeobox homolog 4 (SIX4) expression in colon cancer tissues. Furthermore, the prognostic potential of SIX4 was evaluated using receiver-operating characteristic curves. We conducted an immune infiltration analysis to explore the SIX4 relationship with the immune microenvironment in colon cancer. Finally, SIX4 expression, pan-cancer prognosis, tumor mutation burden (TMB) correlations, microsatellite instability (MSI), and mismatch repair (MMR) were analyzed.ResultsNCTD inhibited colon cancer cell proliferation (P .0001), induced apoptosis (P = .0007), and suppressed the migration and invasion of colon cancer cells. The H19/miR-193b-3p/SIX4 axis was identified as the key ceRNA network involved in the anticancer activity of NCTD. SIX4 is highly expressed in colon cancer tissues, shortening patient survival and affecting immune infiltration. A pan-cancer analysis showed that SIX4 overexpression affects the survival of various cancers. Finally, we correlated SIX4 expression with TMB, MSI, and MMR expression.ConclusionNCTD inhibits the malignant behaviour of colon cancer cells. SIX4 is abnormally expressed in multiple tumor types, significantly affecting the overall survival of patients with cancer, and is a core regulatory target of NCTD in the treatment of colon cancer.

Human stem cell preparations and related products have been widely utilized in clinical trials and treatments for refractory diseases both domestically and internationally.Due to the complexity of the prepa-ration process for stem cell preparations,current microbial detection methods struggle to meet the safety testing requirements,particularly for release testing within medical institutions.Therefore,it is imperative to develop novel alternative methods to ensure the safe and timely clinical application of stem cell preparations.This article elaborates on the microbial testing procedures and relevant regulatory standards involved in stem cell preparations,covering aspects such as raw material selection,preparation processes,release testing,therapeutic application,and sample retention testing.The aim is to provide a foundation for microbial quality control in the clinical use of stem cell preparations.

Objective:To compare the effects of different appointment regimens on the daily waiting time, fixedness of treatment time and lateness rate of radiotherapy patients.Methods:Medical records of 5488 radiotherapy from 332 patients on the same linear accelerator in West China Hospital of Sichuan University from March to June 2022 were selected. Based on the radiotherapy information integration platform of MOSAIQ, all patients were randomly assigned to the morning class, afternoon class and evening class. Traditional manual appointment regimen was adopted for the morning class, 30 min appointment regimen for the afternoon class, and 15 min appointment regimen for the evening class, respectively. The differences in patient waiting time for treatment, fixedness of treatment time, and lateness rate under different appointment regimens were compared. The fixedness of treatment time and waiting time was determined by one-way ANOVA, and the 2×3 Chi-square test was adopted for the lateness rate. Results:The waiting time in the 15 min appointment, the 30 min appointment and manual appointment groups were (27.08 ± 17.21), (34.57± 19.12) and (41.50 ±20.94) min, respectively. There was statistical significance among three appointment regimens ( F=254.97, P<0.001). The waiting time was the shortest in the 15 min appointment group, followed by the 30 min appointment group, and the manual appointment group (all P<0.001 for two-group comparison). The fixedness of treatment time in the 15 min appointment, the 30 min appointment and the manual appointment groups were (15.60±7.87), (18.69±8.94) and (24.30±15.10) min, respectively. There was statistical significance among three groups ( F=25.23, P<0.001). Among them, the fixedness of treatment time in the 15 min appointment group was the highest, followed by the 30 min appointment group, and the manual appointment group (all P<0.001). The lateness rates in the 15 min appointment, the 30 min appointment and the manual appointment groups were 5.7%, 6.2% and 9.6%, respectively. The lateness rate in the manual appointment group was higher than those in the 15 min appointment and the 30 min appointment groups ( χ2=19.24、14.90, both P<0.001), but there was no statistical significance in the lateness rate between the 15 min appointment and 30min appointment groups ( χ2=0.39, P=0.535). Conclusion:In the clinical practice of conventional intensity-modulated radiotherapy technology carried out by conventional linear accelerator, the 15 min appointment regimen can shorten the waiting time for radiotherapy and improve the fixedness of daily radiotherapy time, which is worthy of clinical promotion.