[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

Pinelliae Rhizoma (PR), known as Banxia in Chinese, Hange in Japanese, and Banha in Korean, is a renowned herbal medicine in East Asia derived from the dry tuber of Pinellia ternata (Thunb.) Breit. (PT). It is extensively utilized in dispensing granules, classical prescriptions, and herbal formulas to treat various conditions, including cough, infection, phlegm, nausea, asthma, and inflammation. Despite numerous studies on PR and its classical prescriptions over recent decades, a comprehensive synthesis of available evidence regarding its multifunctional roles and therapeutic potential is lacking. This review aims to address this gap by examining emerging evidence from metabonomics, preclinical studies, and clinical trials, while exploring potential trends and prospects for future research. A systematic literature search was conducted across six electronic databases, including PubMed, Web of Science, Scopus, ScienceDirect, Wanfang, and China National Knowledge Infrastructure, to identify relevant articles on PR published until March 2023. PR contains 107 compounds with diverse pharmacological activities, including anti-inflammatory, immune regulatory, anti-viral, anti-cancer, anti-asthma, antitussive and expectorant, antioxidant, anti-obesity, anti-atherosclerosis, anti-microbial, emetic and anti-emetic, anti-convulsant and anti-epileptic, sedative and hypnotic, learning and memory enhancement, and anti-depressant effects. Metabonomic studies suggest that raw PR may exhibit cardiotoxicity and pregnancy toxicity while showing no apparent hepatorenal toxicity. However, limited pharmacokinetic investigations on PR constrain its clinical translation. Furthermore, clinical safety data on PR is scarce, with only four clinical trials assessing its positive effects in pediatric epilepsy, nausea and vomiting, soft tissue injury, and chronic sinus tract. This review aims to enhance understanding of PR and provide valuable information and recommendations for further research and development of herbal medicine.
Humans ; Pinellia/chemistry* ; Animals ; Ethnopharmacology ; Drugs, Chinese Herbal/chemistry* ; Phytochemicals/chemistry* ; Rhizome/chemistry*

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Ganoderma lucidum is a mushroom widely used for its edible and medicinal properties. Primary bioactive constituents of G. lucidum are ganoderic triterpenoids (GTs), which exhibit important pharmacological activity. Abscisic acid (ABA), a plant hormone, is associated with plant growth, development, and stress responses. ABA can also affect the growth, metabolism, and physiological activities of different fungi and participates in the regulation of the tetracyclic triterpenes of some plants. Our findings indicated that ABA treatment promoted GT accumulation by regulating the gene expression levels (squalene synthase (sqs), 3-hydroxy-3-methylglutaryl-CoA reductase (hmgr), and lanosterol synthase (ls)), and also activated cytosolic Ca²⁺ channels. Furthermore, under ABA mediation, exogenous Ca²⁺ donors and inhibitors directly affected the cytosolic Ca²⁺ concentration and related gene expression in Ca²⁺ signaling. Our study also revealed that ABA-mediated cytosolic Ca²⁺ played a crucial regulatory role in GT biosynthesis, accompanied by antioxidant defense modulation with increasing superoxide dismutase (SOD) activity and ascorbate peroxidase (APX) activity, and the resistance ability of O₂^•- and glutathione (GSH) contents.
Reishi/metabolism* ; Triterpenes/metabolism* ; Abscisic Acid/metabolism* ; Antioxidants/metabolism*

The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62⁺ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62⁺ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.

Objective:To investigate the intention to obtain disease related information and its influencing factors among the elderly at their end-of-life stage.Methods:A cross-sectional survey was conducted among 414 elderly people aged ≥60 in 7 long-term residential care facilities and 15 communities in the central urban area of Fuzhou using the late-life care preference questionnaire from October 2016 to June 2017. Univariate analysis, multiple linear regression analysis and ordered multi-classification logistic regression analysis were used to identify information preference of the disease-related information and influencing factors among the elderly.Results:The level of disease-related information needs of the elderly was scored (17.1±4.9); 48.8% (202/414) preferred detailed or maximum information; 30.7% (127/414) wanted selective and partial information; 20.5% (85/414) did not want to know any information. Multiple linear regression analysis showed that age, education, and whether or not they had received or seen other life-sustaining treatments were the main factors affecting the level of disease-related information needs (standardized regression coefficients were -0.141, 0.116, 0.115, all P<0.05); ordered multi-classification logistic regression analysis showed that age (compared with 60-69 years old, 70-79 years old: OR=0.544, 95% CI: 0.310-0.957; 80-89 years old: OR=0.526, 95% CI: 0.289-0.956), education level (compared with primary school and below, college or above: OR=2.166, 95% CI: 1.093-4.290), main sources of living expenses (compared with other allowance, family support: OR=7.303, 95% CI: 1.157-46.108, pension: OR=9.288, 95% CI: 1.502-57.415; provident fund scheme/saving: OR=15.676, 95% CI: 2.122-115.793), whether or not they had received or seen other life-sustaining treatments (compared with yes, OR=1.985, 95% CI: 1.150-3.425) were the main factors affecting the level of disease-related information needs. Conclusions:Most of the elderly prefer to know disease-related information. Age, educational level, main sources of living expenses and whether or not they had received or seen other life-sustaining treatments are the main influencing factors.

Objective:To investigate the clinical effect of fingertip reconstruction using the toenail osteocutaneous flap without vascular anastomosis.Methods:From January 2015 to October 2020, the clinical data of patients with fingertip injuries were analyzed retrospectively, which were treated with the toenail osteocutaneous flap without vascular anastomosis in Chang’an Xin’an Hospital. The donor site was closed primarily or covered by a local flap. The appearance and function of the patients’ fingers were followed up. All cases were evaluated by the standard of thumb finger reconstruction function evaluation of the Chinese Medical Association of Hand Surgery. Appearance and function of nail bed after reconstruction was evaluated from four aspects.Results:A total of 11 cases (12 fingers) were enrolled, including eight males and three females. The average age was 35.6 years (range, 17-50 years). The etiologies included crush-related injury, cutting injury, mangled injury, and chemical corrosion injury. The injuries were found in thumb, index finger, middle finger, ring finger, or combined with multiple fingers. All fingertip defects were located distal to the nail root, including the defects distal to lunula in four cases, the defects distal to middle of the nail in five fingers , and the defects distal to 1/3 of the nail in three cases. Elective surgery was performed in 7 cases and emergency surgery in 4 cases. The defects ranged from 0.2 cm/0.5 cm/0.5 cm to 0.6 cm/0.8 cm/1.0 cm (phalanx/nail/finger pulp). The size of the toenail osteocutaneous flap ranged from 0.2 cm/0.5 cm/0.7 cm to 0.6 cm/0.8 cm/1.0 cm (phalanx/nail/flap). The defects length of the finger pulp were less than 1.0 cm. All reconstructed fingers survived, and the follow-up was 6-30 months (average, 12.5 months). The appearances of the reconstructed fingers were pulmp and ruddy, and the nails were flat. There was no dysfunction in the donor site. The average healing time of bone was 2.1 months (range, 1.5-3.0 months). According to the evaluation of index function, seven cases were excellent, four cases were good. The appearance and function of the nail bed were excellent in six fingers, good in five fingers, and poor in one finger.Conclusion:It is a simple and effective way to reconstruct the fingertip using the toenail osteocutaneous flap without vascular anastomosis.

A new electrochemical sensor for organophosphate pesticide(methyl-paraoxon)detection based on bifunctional cerium oxide(CeO2)nanozyme is here reported for the first time.Methyl-paraoxon was degraded into p-nitrophenol by using CeO2 with phosphatase mimicking activity.The CeO2 nanozyme-modified electrode was then synthesized to detect p-nitrophenol.Cyclic voltammetry was applied to investigate the electrochemical behavior of the modified electrode,which indicates that the signal enhancement effect may attribute to the coating of CeO2 nanozyme.The current research also studied and discussed the main parameters affecting the analytical signal,including accumulation potential,accumulation time,and pH.Under the optimum conditions,the present method provided a wider linear range from 0.1 to 100 μmol/L for methyl-paraoxon with a detection limit of 0.06 μmol/L.To validate the proof of concept,the electrochemical sensor was then successfully applied for the determination of methyl-paraoxon in three herb samples,i.e.,Coix lacryma-jobi,Adenophora stricta and Semen nelum-binis.Our findings may provide new insights into the application of bifunctional nanozyme in electro-chemical detection of organophosphorus pesticide.

Objective:To investigate the clinical effect of fingertip reconstruction using the toenail osteocutaneous flap without vascular anastomosis.Methods:From January 2015 to October 2020, the clinical data of patients with fingertip injuries were analyzed retrospectively, which were treated with the toenail osteocutaneous flap without vascular anastomosis in Chang’an Xin’an Hospital. The donor site was closed primarily or covered by a local flap. The appearance and function of the patients’ fingers were followed up. All cases were evaluated by the standard of thumb finger reconstruction function evaluation of the Chinese Medical Association of Hand Surgery. Appearance and function of nail bed after reconstruction was evaluated from four aspects.Results:A total of 11 cases (12 fingers) were enrolled, including eight males and three females. The average age was 35.6 years (range, 17-50 years). The etiologies included crush-related injury, cutting injury, mangled injury, and chemical corrosion injury. The injuries were found in thumb, index finger, middle finger, ring finger, or combined with multiple fingers. All fingertip defects were located distal to the nail root, including the defects distal to lunula in four cases, the defects distal to middle of the nail in five fingers , and the defects distal to 1/3 of the nail in three cases. Elective surgery was performed in 7 cases and emergency surgery in 4 cases. The defects ranged from 0.2 cm/0.5 cm/0.5 cm to 0.6 cm/0.8 cm/1.0 cm (phalanx/nail/finger pulp). The size of the toenail osteocutaneous flap ranged from 0.2 cm/0.5 cm/0.7 cm to 0.6 cm/0.8 cm/1.0 cm (phalanx/nail/flap). The defects length of the finger pulp were less than 1.0 cm. All reconstructed fingers survived, and the follow-up was 6-30 months (average, 12.5 months). The appearances of the reconstructed fingers were pulmp and ruddy, and the nails were flat. There was no dysfunction in the donor site. The average healing time of bone was 2.1 months (range, 1.5-3.0 months). According to the evaluation of index function, seven cases were excellent, four cases were good. The appearance and function of the nail bed were excellent in six fingers, good in five fingers, and poor in one finger.Conclusion:It is a simple and effective way to reconstruct the fingertip using the toenail osteocutaneous flap without vascular anastomosis.