ObjectiveThis study aims to observe the effect of sinomenine （SIN） on fatty acid binding protein 4 （FABP4） in synovial tissue of rats with osteoarthritis （OA） and investigate the therapeutic mechanism of SIN on OA， further providing new ideas for the management of osteoarthritis by traditional Chinese medicine （TCM）. MethodsAn OA rat model was constructed and randomly divided into a control group， an OA group， an OA + SIN-L group （50 mg·kg^-1）， an OA + SIN-M （100 mg·kg^-1）， an OA + SIN-H （200 mg·kg^-1）， and an OA + prednisone （PDN） group （5 mg·kg^-1）. Following surgical modeling for three weeks， an appropriate medication was administered for four weeks. During modeling and administration， a hot plate test was performed to detect the pain and swelling of the knee joints of the rats. The periarticular tissue was collected for arthropathological observation at the end of drug administration. The expression of cleaved Caspase-3， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and FABP4 in the synovial tissue of rats was detected by Western blot and real-time quantitative polymerase chain reaction （Real-time PCR）， and the expression and distribution of FABP4 protein in the synovial membrane were detected by immunofluorescence. ResultsCompared with those in the control group， the levels of inflammatory factors and FABP4 in the serum of rats in the OA group were significantly increased （P<0.05， P<0.01）， and joint swelling was significantly elevated （P<0.01）. The thermal pain threshold was significantly reduced （P<0.01）， and the expression of FABP4 protein and the fluorescence intensity were significantly increased （P<0.01）. The synovial tissue exhibited significantly increased inflammatory infiltration， proliferated fibroblasts， and an elevated apoptotic index （P<0.05， P<0.01）. Compared with those in the OA group， the serum lipid metabolism indexes of rats in the SIN administration group gradually returned to normal （P<0.05， P<0.01）， while the levels of inflammatory factors and FABP4 in the serum of rats in the SIN-administered group were significantly reduced （P<0.05， P<0.01）， and joint swelling was significantly decreased （P<0.05， P<0.01）. The thermal pain threshold was significantly elevated （P<0.05， P<0.01）， and the expression of FABP4 protein and fluorescence intensity in the synovial tissue were significantly decreased （P<0.05， P<0.01）. The synovial tissue displayed significantly reduced inflammatory infiltration and a decreased apoptotic index （P<0.05， P<0.01）. ConclusionThe therapeutic effect of SIN on OA may be related to the down-regulation of FABP4 expression， reduction of apoptosis， and inhibition of inflammatory factor expression.

The original version of this article (Yang et al., 2023) unfortunately contained a mistake. In Acknowledgments, the funding information for the Zhejiang Provincial Natural Science Foundation of China (No. LBY21H160001) was wrong. The correct funding should be the Zhejiang Health Science and Technology Project (No. 2022KY682), China.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

RNA-based gene therapy has been widely used for various diseases, and extensive studies have proved that suitable delivery routes greatly help the development of RNA therapeutics. Identifying a safe and effective delivery system is key to realizing RNA therapeutics' clinical translation. Inhalation is a non-invasive pulmonary delivery modality that can enhance the retention of therapeutic agents in the lungs with negligible toxicity, thereby improving patient compliance. Inhaled RNA therapeutics are increasingly becoming an area of focus for researchers; however, only several clinical trials have explored inhaled delivery of RNA for pulmonary diseases. This review presents an overview of recent advances in inhaled delivery systems for RNA therapeutics, including viral and nonviral systems, highlighting state of the art regarding inhalation in the messenger RNA (mRNA) field. We also summarize the applications of mRNA inhalants in infectious and other lung diseases. Simultaneously, the research progresses on small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), and different types of RNA are also discussed to provide new strategies for developing RNA inhalation therapy. Finally, we clarify the challenges inhaled RNA-based therapeutics face before their widespread adoption and provide insights to help advance this exciting field to the bedside.

Dental pulp-dentin complex defects remain a major unresolved problem in oral medicines. Clinical therapeutic methods including root canal therapy and vital pulp therapy are both considered as conservative strategies, which are incapable of repairing the pulp-dentin complex defects. Although biomaterial-based strategies show remarkable progress in antibacterial, anti-inflammatory, and pulp regeneration, the important modulatory effects of nerves within pulp cavity have been greatly overlooked, making it challenging to achieve functional pulp-dentin complex regeneration. In this study, we propose an injectable bioceramics-containing composite hydrogel in combination of Li-Ca-Si (LCS) bioceramics and gelatin methacrylate matrix with photo-crosslinking properties. Due to the sustained release of bioactive Li, Ca and Si ions from LCS, the composite hydrogels possess multiple functions of promoting the neurogenic differentiation of Schwann cells, odontogenic differentiation of dental pulp stem cells, and neurogenesis-odontogenesis couples in vitro. In addition, the in vivo results showed that LCS-containing composite hydrogel can significantly promote the pulp-dentin complex repair. More importantly, LCS bioceramics-containing composite hydrogel can induce the growth of nerve fibers, leading to the re-innervation of pulp tissues. Taken together, the study suggests that LCS bioceramics can induce the innervation of pulp-dentin complex repair, offering a referable strategy of designing multifunctional filling materials for functional periodontal tissue regeneration.
Dental Pulp/drug effects* ; Hydrogels/pharmacology* ; Animals ; Ceramics/pharmacology* ; Dentin/drug effects* ; Biocompatible Materials/pharmacology* ; Rats ; Gelatin ; Regeneration/drug effects* ; Cell Differentiation/drug effects* ; Injections ; Humans ; Odontogenesis/drug effects*

Lophatheri Herba (Danzhuye in Chinese) is derived from the dried stems and leaves of Lophatherum gracile and has a long history of use as a medicinal and food source. Flavonoids and phenolic acids are the main active ingredients in Lophatheri Herba, which produce diuretic, anti-inflammatory, and antipyretic effects. Flavonoid glycosides and hydroxybenzoic acids are respectively the main structure in 44 flavonoids and 16 phenolic acids obtained from Lophatheri Herba. Modern pharmacological studies have found that the main chemical constituents of Lophatheri Herba play important roles in anti-inflammatory, cardioprotective, hepatoprotective and hypoglycaemic effects. Studies have demonstrated that flavonoid monomers, for example, luteolin, isoorientin, luteolin-7-O-β-D-glucoside and apigenin are more effective in exerting the above pharmacological effects. In addition, Lophatheri Herba is used in different food products as the main ingredient or as an accessory. This review describes Lophatheri Herba in terms of its chemical composition, pharmacological effects and efficacy, food development and applications, and clinical utility, and discusses the problems facing its use. This study provides valuable ideas and a scientific basis for the future development and use of L. gracile.

Acute ischemic stroke (AIS) is a cerebrovascular disease characterized by high morbidity, disability, and mortality, posing a significant threat to human health. Endovascular treatment has now been established as a key method for AIS management, in which stent retrievers that can mechanically remove blood clots play a key role in this technique. In recent years, stent retrievers have evolved in complexity and functionality to improve the ability of clot removing and surgical safety. However, the present instruments still have limitations on treatment efficiency, vascular adaptability, and operational precision, posing an urgent need for innovation in the design of stent retrievers. This paper systematically reviewed the structural features and working principles of AIS stent retrievers from the perspective of efficacy evaluation metrics, historical development, recent advancements in stent retrieval technology, and future prospects.
Humans ; Ischemic Stroke/surgery* ; Stents ; Endovascular Procedures/methods* ; Thrombectomy/methods* ; Device Removal/methods*

Objective To investigate the effect of Yiqi Jiedu Recipe(YQ)on the proliferation,migration,and invasion of nasopharyngeal carcinoma cells,and to explore its mechanisms of action on proliferation,migration,and invasion through the TGF-β1/SMAD3 signaling pathway.Methods(1)The 5-8F cells were divided into four groups:solvent control group,YQ 0.5 mg·mL-1 group,YQ 1.0 mg·mL-1 group,and 5-fluorouracil 2 μg·mL-1 group.Cell proliferation was monitored using real-time cell analysis(RTCA).Wound healing experiment was conducted to assess cell migration.After 24 hours of drug intervention,transwell assay was employed to measure cell invasion.The protein expression levels of β-catenin,E-cadherin,N-cadherin,TGF-β1,and SMAD3 in the cells were evaluated using the Western Blot method.(2)The 5-8F cells were divided into five groups:solvent control group,TGF-β1 10 ng·mL-1 group,TGF-β1 10 ng·mL-1+YQ 1.0 mg·mL-1 group,YQ 1.0 mg·mL-1 group,and LY3200882 10 μmol·L-1 group.Cell proliferation was monitored using RTCA.Wound healing experiment was conducted to assess cell migration.After 24 hours of drug intervention,transwell assay was employed to measure cell invasion.The protein expression levels of β-catenin,E-cadherin,N-cadherin,TGF-β1,and SMAD3 in the cells were evaluated using Western Blot.(3)The nude mice were randomly assigned into the model group,YQ group,and 5-fluorouracil group.Subcutaneous injection of 5-8F cell suspension was performed to establish the xenograft nude mouse model of nasopharyngeal carcinoma.After the tumors reached a certain size,the 5-fluorouracil group received intraperitoneal injection of 5-Fu once every 2 days,while the other groups were orally administered corresponding drugs once a day for three consecutive weeks.Tumor volume was measured every 3 days.Western Blot was conducted to assess the protein expression levels of β-catenin,E-cadherin,and N-cadherin in the tissues of each group.Results Compared with the solvent control group,the proliferation curves of 5-8F cells in the YQ(0.5 mg·mL-1,1.0 mg·mL-1)groups showed a decrease.The migration and invasion abilities of the cells were both reduced(P＜0.05,P＜0.01).Additionally,the expression of E-cadherin protein significantly increased(P＜0.01),while the protein expression of β-catenin,N-cadherin,TGF-β1,and SMAD3 all decreased(P＜0.05,P＜0.01).Compared with the model group,the transplanted tumor volume of nasopharyngeal carcinoma in the YQ group significantly decreased(P＜0.05).Furthermore,the protein expression of β-catenin and N-cadherin in the transplanted tissues of the YQ group was significantly downregulated(P＜0.05,P＜0.01),while the expression of E-cadherin protein was significantly upregulated(P＜0.01).After the addition of the activator and inhibitor of TGF-β1 signaling pathway,compared with the YQ 1.0 mg·mL-1 group,the TGF-β1 10 ng·mL-1+YQ 1.0 mg·mL-1 group showed a significant increase in the expression of TGF-β1,SMAD3,β-catenin,and N-cadherin proteins(P＜0.05,P＜0.01)and obvious enhancement of the abilities of cell proliferation,migration,and invasion(P＜0.01).Conclusion Yiqi Jiedu Recipe can inhibit the proliferation,migration,and invasion by regulating the TGF-β1/SMAD3 signaling pathway.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.