The multifaceted mechanisms of Dihydrotanshinone I in the treatment of tumors.

The morbidity and mortality of malignant tumors are progressively rising on an annual basis. Traditional Chinese Medicine (TCM) holds promise as a possible therapeutic agent for the avoidance or therapy of malignant tumors. Salvia miltiorrhiza Bunge (Danshen), a traditional Asian functional food, has therapeutic characteristics in application for the treatment of malignant tumors. Dihydrotanshinone I (DHTS) is the principal lipophilic phenanthraquinone compound found in Salvia miltiorrhiza Bunge, whose anti-tumor effect has attracted widespread attention. The anti-tumor effects include inhibiting cancer cell proliferation, triggering apoptosis of tumor cells, inducing ferroptosis in tumor cells, inhibiting tumor cell invasion and metastasis, and improving drug resistance of tumor cells. In this paper, we summarized and analyzed the mechanisms and targets of anti-tumor effect of DHTS, providing new ideas and establishing a solid theoretical basis for the future advancement and clinical treatment of DHTS.

Research progress of traditional Chinese medicine in the treatment of allergic rhinitis.

Allergic rhinitis, one of the common diseases in otolaryngology, has shown an increasing incidence under the influence of various geographical, cultural and economic factors, making it a common and serious global public health problem. Modern medicine uses medication as the primary therapy for allergic rhinitis, but poor symptom control and easy relapse are the disadvantages of this treatment. However, Traditional Chinese medicine, with its long history, has treated allergic rhinitis by symptomatic treatment according to pattern differentiation with its unique insights and methods, which are effective and safe in numerous clinical studies. Therefore, this paper describes TCM decoction, acupuncture, moxibustion, acupoint application, catgut-embedding therapy and ear acupuncture in the treatment of AR. This study aims to provide more personalized and precise treatment for allergic rhinitis patients by investigating the mechanism of action, clinical research and development of traditional Chinese medicine treatments.

Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia Diagnosed Following Recurrent Epistaxis.

We present a rare case of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia (LPL/WM) diagnosed in a 65-year-old female initially presenting with recurrent bilateral epistaxis. Despite multiple cauterizations and a history of ineffective conventional treatments, comprehensive evaluations led to the diagnosis, underscoring the critical need for thorough investigation in persistent epistaxis cases, particularly when standard approaches fail. This case emphasizes the importance of considering indolent lymphomas in the differential diagnosis of recurrent epistaxis and showcases the diagnostic pathway leading to successful identification and treatment of a rare etiology. Laryngoscope, 2024.

Robust Osteoconductive ß-Tricalcium Phosphate/L-poly(lactic acid) Membrane via Orientation-Strengthening Technology.

L-poly(lactic acid) (PLLA) is a biodegradable material with multiple biomedical application potentials, especially as a membrane for guided bone regeneration. In terms of its low strength and poor osteogenic activity, improving these two properties is the key to resolve the limitations of PLLA for bone-associated applications. Herein, an orientation-strengthening technology (OST) was developed to reinforce PLLA's mechanical strength by introducing biocompatible ß-tricalcium phosphate (ß-TCP) to improve the crystallinity of PLLA, allowing for the formation of a highly oriented architecture to acquire an advanced membrane with high mechanical property. Furthermore, the addition of ß-TCP nanoparticles significantly promotes the osteogenic activity of the composites. The tensile strength of the membrane containing 5 wt % ß-TCP was 220 MPa, which was 4-folds that of the native polylactic acid fabricated via the conventional method. The oriented microstructure enhanced both the mechanical strength and the osteogenic activity of the material. The parallel grooves on the material surface are similar to the mineralized collagen fibers on the bone surface, which promoted the growth and differentiation of osteoblasts, with ß-TCP further contributing to the osteoconductive effect. The combination of ß-TCP and orientation-strengthening effect endows the material with higher mechanical properties and bioactivities, which provides an advanced manufacturing strategy for the preparation of PLLA-based materials for bone repair.

Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial.

Background: Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP. Methods: A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398. Findings: Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study. Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were -2.1 (95% CI -2.9, -1.4; p < 0.0001) and -0.9 (95% CI -1.4, -0.5; p < 0.0001), respectively. Sinus CT scan revealed that Lund-Mackay CT score (LS mean difference [95% CI] -7.6, [-9.4, -5.8]; p < 0.0001) and sinus volume occupied by disease (LS mean difference [95% CI] -37%, [-47%, -28%]; p < 0.0001) were significantly improved with CM310 compared with placebo. In addition, CM310 significantly relieved the daily symptoms of patients with CRSwNP and improved their quality of life reflected by the improvements in the TSS (-2.6 [95% CI -3.5, -1.6]), UPSIT (10.4 [95% CI 6.8, 14.0]) and SNOT-22 score (-19.1 [95% CI -29.8, -8.5]). Compared with placebo, CM310 administration significantly reduced type 2-related biomarkers including the serum TARC and total IgE, and tissue eosinophils. The most common adverse events were upper respiratory tract infection, blood cholesterol increased, and tinnitus, but none were considered drug-related. Interpretation: These findings support CM310 as an effective additional treatment option to the standard of care in patients with severe ECRSwNP. Funding: KeyMed Biosciences (Chengdu) Limited.

A Versatile Disorder-to-Order Technology to Upgrade Polymers into High-Performance Bioinspired Materials.

Biodegradable polymer as traditional material has been widely used in the medical and tissue engineering fields, but there is a great limitation as to its inferior mechanical performance for repairing load-bearing tissues. Thus, it is highly desirable to develop a novel technology to fabricate high-performance biodegradable polymers. Herein, inspired by the bone's superstructure, a versatile disorder-to-order technology (VDOT) is proposed to manufacture a high-strength and high-elastic modulus stereo-composite self-reinforced polymer fiber. The mean tensile strength (336.1 MPa) and elastic modulus (4.1 GPa) of the self-reinforced polylactic acid (PLA) fiber are 5.2 and 2.1 times their counterparts of the traditional PLA fiber prepared by the existing spinning method. Moreover, the polymer fibers have the best ability of strength retention during degradation. Interestingly, the fiber tensile strength is even higher than those of bone (200 MPa) and some medical metals (e.g., Al and Mg). Based on all-polymeric raw materials, the VDOT endows bioinspired polymers with improved strength, elastic modulus, and degradation-controlled mechanical maintenance, making it a versatile update technology for the massive industrial production of high-performance biomedical polymers.

Comparative analysis of three common imaging modalities for nasolabial cysts.

OBJECTIVE: To compare the clinical diagnostic value of ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI) for nasolabial cysts. METHODS: The clinical and imaging data of 20 patients with 21 nasolabial cysts confirmed surgically and histopathologically were retrospectively analyzed. RESULTS: The largest cyst was 3.4 × 2.7 × 2.3 cm, and the smallest cyst was 1.1 × 0.7 × 0.5 cm. All cysts were located in the soft tissue between the nasolabial fold and maxillary bone. USG showed sensitivity of 95%, accuracy of 95%, and a missed diagnosis rate of 5%; CT showed sensitivity of 80%, accuracy of 80%, and a missed diagnosis rate of 20%; and MRI showed sensitivity of 85%, accuracy of 85%, and a missed diagnosis rate of 15%. CONCLUSIONS: USG showed higher sensitivity and accuracy and a lower missed diagnosis rate than CT and MRI. Therefore, USG is worth popularizing on a large scale for the diagnosis of nasolabial cysts.

Fabrication of PLCL Block Polymer with Tunable Structure and Properties for Biomedical Application.

Biodegradable materials are pivotal in the biomedical field, where how to precisely control their structure and performance is critical for their translational application. In this study, poly(L-lactide-b-ε-caprolactone) block copolymers (bPLCL) with well-defined segment structure are obtained by a first synthesis of poly(ε-caprolactone) soft block, followed by ring opening polymerization of lactide to form poly(L-lactide acid)  hard block. The pre-polymerization allows for fabrication of bPLCL with the definite compositions of soft/hard segment while preserving the individual segment of their special soft or hard segment. These priorities make the bPLCL afford biodegradable polymer with better mechanical and biodegradable controllability than the random poly(L-lactide-co-ε-caprolactone) (rPLCL) synthesized via traditional one-pot polymerization. 10 mol% ε-caprolactone introduction can result in a formation of an elastic polymer with elongation at break of 286.15% ± 55.23%. Also, bPLCL preserves the unique crystalline structure of the soft and hard segments to present a more sustainable biodegradability than the rPLCL. The combinative merits make the pre-polymerization technique a promising strategy for a scalable production of PLCL materials for potential biomedical application.

CD47KO/CRT dual-bioengineered cell membrane-coated nanovaccine combined with anti-PD-L1 antibody for boosting tumor immunotherapy.

Tumor vaccines trigger tumor-specific immune responses to prevent or treat tumors by activating the hosts' immune systems, and therefore, these vaccines have potential clinical applications. However, the low immunogenicity of the tumor antigen itself and the low efficiency of the vaccine delivery system hinder the efficacy of tumor vaccines that cannot produce high-efficiency and long-lasting antitumor immune effects. Here, we constructed a nanovaccine by integrating CD47KO/CRT dual-bioengineered B16F10 cancer cell membranes and the unmethylated cytosine-phosphate-guanine (CpG) adjuvant. Hyperbranched PEI25k was used to load unmethylated cytosine-phosphate-guanine (CpG) through electrostatic adsorption to prepare PEI25k/CpG nanoparticles (PEI25k/CpG-NPs). CD47KO/CRT dual-bioengineered cells were obtained by CRISPR-Cas9 gene editing technology, followed by the cell surface translocation of calreticulin (CRT) to induce immunogenic cell death (ICD) in vitro. Finally, the extracted cell membranes were coextruded with PEI25k/CpG-NPs to construct the CD47KO/CRT dual-bioengineered cancer cell membrane-coated nanoparticles (DBE@CCNPs). DBE@CCNPs could promote endocytosis of antigens and adjuvants in murine bone marrow derived dendritic cells (BMDCs) and induce their maturation and antigen cross-presentation. To avoid immune checkpoint molecule-induced T cell dysfunction, the immune checkpoint inhibitor, the anti-PD-L1 antibody, was introduced to boost tumor immunotherapy through a combination with the DBE@CCNPs nanovaccine. This combination therapy strategy can significantly alleviate tumor growth and may open up a potential strategy for clinical tumor immunotherapy.

Schwannoma in the Olfactory Groove: Two Case Reports.

The occurrence of an isolated schwannoma in the olfactory groove is extremely rare. We herein present 2 cases of schwannomas in the olfactory groove that were treated with endoscopic excision. In these 2 cases, the tumor originated in the cribriform plate and cerebrospinal fluid rhinorrhea occurred after tumor resection, which was repaired using tissue grafts.

An Integrated Analysis of Inflammatory Endotypes and Clinical Characteristics in Chronic Rhinosinusitis with Nasal Polyps.

Objective: Chronic rhinosinusitis with nasal polyps (CRSwNP) is mainly characterised by type 1 (T1), type 2 (T2) and type 3 (T3) inflammatory endotypes. However, correlations between inflammatory endotypes and clinical features in CRSwNP have not been demonstrated sufficiently. This study aimed to determine the endotype-phenotype associations in CRSwNP. Methods: Clinical data of 31 control subjects and 106 CRSwNP patients were analysed. Interferon (IFN)-γ (T1), Charcot-Leyden crystal galectin (CLC) (T2) and Interleukin (IL)-17A (T3) were used as biomarkers to identify the inflammatory endotypes. Results: The mRNA expression level of IFN-γ was positively correlated with IL-17A (r = 0.817; P < 0.0001). Headache/facial pain (P = 0.039) was associated with T1 endotype. Smell loss (P = 0.025) was associated with T2 endotype. Purulent rhinorrhea (P = 0.001) was associated with T3 endotype. Atopy (P = 0.030), asthma (P = 0.005) and recurrence (P = 0.022) were more frequent in T2 endotype. Total Symptom Scores (TSS) of T2 (P < 0.001) and T3 (P = 0.009) endotype were higher than non-T2 and non-T3, respectively. Sino Nasal Outcome Test-22 (SNOT-22) total scores of T3 (P = 0.054) endotype were higher than non-T3. Conclusion: Identifications of endotype-phenotype associations are useful in clinical diagnoses and targeted therapies for patients with CRSwNP.

Controllable preparation of bioactive open porous microspheres for tissue engineering.

Biodegradable microspheres have been widely applied as cell carriers for tissue engineering and regenerative medicine. However, most cell carriers only have a simple planar structure and show poor biological activity and cell adherence, resulting in low cell density and unfavorable application effect. How to develop size-controllable microspheres with an open-porous structure remains a challenge, and is a key factor to extend their employment as cell/drug delivery vehicles to boost regeneration of tissues (e.g., bone). Herein, well-defined open porous microspheres of poly(lactic-co-glycolic acid) (PLGA with good biocompatibility approved by the Food and Drug Administration (FDA)) were developed by using a gas-assisted-emulsion and surface-alkalization-treatment technology (GEST). The gas-assisted-emulsion strategy enables the formation of microspheres with a large size of 200-300 µm, meanwhile, the microspheres have a large amount of micropores with diameter in the range of 10-60 µm. The following alkalization-treatment on the surface makes the microspheres form a good porous interconnectivity throughout both the surface and the interior of the microspheres. The good porous interconnectivity endows the microspheres with a highly open pore structure and a large specific surface area for nutrient exchange and cell attachment, thus promoting cell proliferation and nutrient transportation, promising their potential as an ideal cell carrier to increase cell density and bioactivity for cell therapy-based tissue engineering.

Bioactive Film-Guided Soft-Hard Interface Design Technology for Multi-Tissue Integrative Regeneration.

Control over soft-to-hard tissue interfaces is attracting intensive worldwide research efforts. Herein, a bioactive film-guided soft-hard interface design (SHID) for multi-tissue integrative regeneration is shown. Briefly, a soft bioactive film with good elasticity matchable to native ligament tissue, is incorporated with bone-mimic components (calcium phosphate cement, CPC) to partially endow the soft-film with hard-tissue mimicking feature. The hybrid film is elegantly compounded with a clinical artificial ligament to act as a buffer zone to bridge the soft (ligament) and hard tissues (bone). Moreover, the bioactive film-decorated ligament can be rolled into a 3D bio-instructive implant with spatial-controllable distribution of CPC bioactive motifs. CPC then promotes the recruitment and differentiation of endogenous cells in to the implant inside part, which enables a vascularized bone growth into the implant, and forms a structure mimicking the biological ligament-bone interface, thereby significantly improving osteointegration and biomechanical property. Thus, this special design provides an effective SHID-guided implant-bioactivation strategy unreached by the traditional manufacturing methods, enlightening a promising technology to develop an ideal SHID for translational use in the future.

Evaluation of efficacy and safety after replacement of methyl hydrogen with deuterium at methyl formate of Clopidogrel.

BACKGROUND AND PURPOSE: Despite being a first-line clinical drug, thienopyridines have many unsatisfactory aspects, including the low bioavailability of clopidogrel(CLP) and the high bleeding risk of prasugrel. We synthesized deuterium clopidogrel(D-CL, patented in China) to alleviate the deficiency of CLP in clinical, such as a slow onset, a greater influence of gene polymorphism, and a high frequency of drug-drug interaction. EXPERIMENTAL APPROACH: Molecular docking was used to analyze the affinity between D-CL and the P2Y12 receptor. The levels of active metabolites of D-CL were detected using HPLC/MS-MS and the activities of main metabolic enzymes were analyzed; Subsequently, platelet aggregation function, thrombus model were used to evaluate the pharmacodynamics of D-CL. Finally, the safety of D-CL were evaluated through examination of blood routine, PT, APTT, bleeding time, serological tests, liver pathological biopsy, liver cell apoptosis and detection of apoptosis-related proteins. KEY RESULTS: The introduction of deuterium made the binding of CLP to P2Y12 receptor more stable, improved the concentration of active metabolites, and substantially reduced the inhibition of major metabolic enzymes, including CYP2B6, CYP2C9, and CYP2C19, thereby, exerting better antiplatelet effects without increasing the risk of bleeding, along with a concomitant decrease in the apoptosis of hepatocytes.

The Impacts of Green Innovation Input and Channel Service in a Dual-Channel Value Chain.

This paper constructs a dual-channel value chain composed of one altruistic manufacturer and one altruistic retailer, where the manufacturer makes green innovation input for green products and sells its green products to its customers through both the direct channel and the traditional channel, the retailer provides channel service for customers and sells green products through the traditional channel. We consider two scenarios in which the manufacturer and the retailer make decentralized and centralized decisions, respectively. We develop two dynamic game models for the two scenarios and analyze the dynamic behaviors of the two dynamic game models using bifurcation diagram, LLE (largest Lyapunov exponent) and attraction of basin, etc. We find that the stability region in decentralized decision model is greater than that of centralized decision, and narrow with increase of service value, green innovation input. In the decentralized decision model, the stability of the system decreases with the altruistic behavior increasing. With the price adjustment speed increasing, the dual-channel green value chain system enters into chaotic state through flip bifurcation or N-S bifurcation. In the stable state, the manufacturer and the retailer can obtain the maximum utility with the appropriate value of green innovation input. In the chaotic state, the utilities of the manufacturer and retailer are greatly affected and significantly reduced. This study will provide good guidance for sustainable development decision-making of dual-channel green value chain.

Photovoltaic Array Fault Diagnosis Based on Gaussian Kernel Fuzzy C-Means Clustering Algorithm.

In the fault diagnosis process of a photovoltaic (PV) array, it is difficult to discriminate single faults and compound faults with similar signatures. Furthermore, the data collected in the actual field experiment also contains strong noise, which leads to the decline of diagnostic accuracy. In order to solve these problems, a new eigenvector composed of the normalized PV voltage, the normalized PV current and the fill factor is constructed and proposed to characterize the common faults, such as open circuit, short circuit and compound faults in the PV array. The combination of these three feature characteristics can reduce the interference of external meteorological conditions in the fault identification. In order to obtain the new eigenvectors, a multi-sensory system for fault diagnosis in a PV array, combined with a data-mining solution for the classification of the operational state of the PV array, is needed. The selected sensors are temperature sensors, irradiance sensors, voltage sensors and current sensors. Taking account of the complexity of the fault data in the PV array, the Kernel Fuzzy C-means clustering method is adopted to identify these fault types. Gaussian Kernel Fuzzy C-means clustering method (GKFCM) shows good clustering performance for classifying the complex datasets, thus the classification accuracy can be effectively improved in the recognition process. This algorithm is divided into the training and testing phases. In the training phase, the feature vectors of 8 different fault types are clustered to obtain the training core points. According to the minimum Euclidean Distances between the training core points and new fault data, the new fault datasets can be identified into the corresponding classes in the fault classification stage. This strategy can not only diagnose single faults, but also identify compound fault conditions. Finally, the simulation and field experiment demonstrated that the algorithm can effectively diagnose the 8 common faults in photovoltaic arrays.

[Filtering method of power frequency interference in ECG signals].

Electrocardiogram (ECG) signals are susceptible to be disturbed by 50 Hz power frequency in the process of acquisition and conversion. This paper puts forward the improved Levkov algorithm combined with the antisymmetry of sine wave and the characteristic of not--easily mutation of the sine wave amplitude. The improved and the original algorithms were compared with signal to noise ratio (SNR), root mean square error (RMSE) and coincidence of the signals. Based on the experimental comparison, it was concluded that the improved algorithm had better filte-ring functions, because it not only highly coincided with ECG, but also retained certain details of ECG.

[Continuous ECG recording for freely moving patients].

As more and more people are becoming aged in China and many of them tend to suffer from chronic cardiac problems, the long-term dynamic cardiac monitoring for freely moving patients becomes essential. A new design for continuous ECG recording on the freely moving patients at home and/or at work is proposed here. It is miniature in size, using digital technologies of the low gain amplifier, the high resolution analog to digital converter and the real-time digital filter that features > 100dB input signal dynamic range (ISDR), > 100dB common-mode rejection ratio (CMRR), and < 5microV (RMS) internal noise. The device works continuously more than 24 hours with a pair of AAA batteries, and is capable of storing the recorded data into a storage card. The preliminary tests showed that the P-QRS-T waveforms were captured and displayed smoothly in resting, walking, and activities, making the device useful in monitoring and analyzing for the patients on the move.