Aqueous-soluble components of sporoderm-removed Ganoderma lucidum spore powder promote ferroptosis in oral squamous cell carcinoma.

Objective: Ferroptosis is a novel cell death process which displays a promising role in cancer treatment. However, clinically available drugs targeting ferroptosis are rarely used, and yet there are no studies reporting on inducing ferroptosis via Chinese herbal extracts. Here we explored the tumor inhibition effects of Ganoderma lucidum (G. lucidum) on oral squamous cell carcinoma (OSCC). Specifically, we aimed to clarify the biological mechanism of components in the dietary, aqueous-soluble sporoderm-removed G. lucidum spore powder (A-GSP). Methods: Preliminary transcriptome analysis revealed the significant enrichment of the ferroptosis pathway. Cellular Fe2+, glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS) and lipid peroxide levels were measured to identify ferroptosis occurrence. Western blotting was used to measure ferroptosis-related proteins. Changes in mitochondria morphology and function were observed with transmission electron microscopy (TEM) and ATP detection assays. Ferroptosis inhibitor ferrostatin-1 was then used to verify the anti-tumor effects of A-GSP. Finally, nude mice xenograft models of oral cancer confirmed that A-GSP inhibited tumor growth. Results: A-GSP promoted ferroptosis in oral cancer cells by inducing Fe2+ influx, GSH depletion, as well as lipid peroxide and ROS accumulation. Ferroptosis-related proteins exhibited corresponding changes, particularly Acyl-coA synthetase long chain family member 4 (ACSL4) increase and glutathione peroxidase 4 (GPX4) decrease. A-GSP considerably lowered mitochondrial volume and ridge number, while significantly decreasing ATP production. Ferrostatin-1 reversed all of these A-GSP-induced changes. In vivo, A-GSP exerted a ferroptosis-mediated tumor-suppressing effect without observable adverse reactions. Conclusions: Our findings demonstrate the therapeutic potential of A-GSP for treating patients with OSCC by targeting ferroptosis.

Combined acupuncture-medicine anesthesia used in thyroid surgery: A systematic review and meta-analysis.

BACKGROUND: Combined acupuncture-medicine anesthesia (CAMA) is extensively used in thyroid surgery in China. We conducted a systematic review and meta-analysis to assess the efficacy and safety of CAMA. METHODS: We searched the China National Knowledge Infrastructure (CNKI), VIP database, WanFang database, PubMed, EMBASE, and the Cochrane Library for relevant literature. The term of literature was published before April 18, 2020, and there were no restrictions on publication language, region, or publication year. The inclusion criteria included a randomized controlled trial (RCT) of acupuncture combined with cervical plexus anesthesia. We used RevMan5.3 software for data analysis. If the chi-square test showed no significant heterogeneity (P > .10, I2 < 50%), we used the fixed-effect model to calculate risk ratio (RR) and mean difference. Otherwise, the random-effects model was used. RESULTS: Overall, 18 RCTs involving 1211 patients were included in the study. The anesthesia significant rate (ASR) in the transcutaneous electrical acupoint stimulation (TEAS) plus cervical plexus block anesthesia (CPBA) and electroacupuncture (EA) plus CPBA groups was significantly higher compared with the CPBA group (TEAS + CPBA: P < .001; EA + CPBA: P < .001). The pooled effect values of the intraoperative heart rate (HR) and mean arterial pressure (MAP) were significantly lower in both the TEAS + CPBA and EA + CPBA groups relative to the control group (HR: P = .05, P < .001; the MAP: P = .002, P < .001; respectively). Moreover, the postoperative adverse reaction was markedly lower in the experimental group than in the control group (RR = 0.30, P < .001), and there was no heterogeneity between the two groups (P = .71, I2 = 0%). CONCLUSION: Combined acupuncture-medicine anesthesia significantly increases the anesthesia significance rate, reduces the intraoperative heart rate, and blood pressure, and reduces the incidence of postoperative adverse reactions. However, more high-quality future studies should be conducted to validate the efficacy and safety of acupuncture combined anesthesia further.

Transcutaneous electrical acupoint stimulation for suspected laryngopharyngeal reflux disease.

PURPOSE: To determine the efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with proton pump inhibitor (PPI) therapy on symptoms and signs of patients with suspected laryngopharyngeal reflux disease (LPRD). METHODS: This was a prospective randomized controlled study. Seventy patients with reflux symptom index (RSI) > 13 and reflux finding score (RFS) > 7 were recruited and received PPI alone (control group) or TEAS combined with PPI (experimental group) for 12 weeks. Patients in the experimental group received TEAS at Tiantu (RN22), Renying (ST9), and Neiguan (PC6) once a day, five times a week. RSI, RFS, throat pain visual analog score (VAS), and LPR-health-related quality-of-life (LPR-HRQL) scores were evaluated at baseline and after 4 and 12 weeks. RESULTS: The decreases in total RSI and RFS, along with several subscores, were significantly higher in the experimental group than in the control group after 12 weeks (P < 0.05). The throat pain VAS and LPR-HRQL scores decreased significantly at 4 and 12 weeks after treatment in both groups, with significant differences between the groups (P < 0.001). No severe adverse events occurred, and the rates of adverse events were similar between the two groups. CONCLUSION: Compared with PPI alone, TEAS combined with PPI showed a significantly greater improvement in symptoms, signs, and quality of life in the treatment of LPRD without increasing the occurrence of adverse effects. Therefore, TEAS could serve as a useful and safe treatment method for LPRD. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100046755.

Trial of transcutaneous electrical acupoint stimulation in laryngopharyngeal reflux disease: study protocol for a randomized controlled trial.

BACKGROUND: Patients with persistent globus sensation, throat clearing, chronic cough, hoarseness, and other throat symptoms account for a large proportion of patients in ears, nose, and throat clinics. Laryngopharyngeal reflux disease (LPRD) is increasingly valued by otolaryngologists. Transcutaneous electrical acupoint stimulation (TEAS) is possibly a new method for the treatment of LPRD. This trial aims to determine whether TEAS combined with proton pump inhibitor (PPI) is better than PPI alone in the treatment of LPRD. METHODS: This prospective randomized controlled trial will be implemented in a tertiary hospital in China. Seventy patients diagnosed with LPRD will be randomly assigned to the TEAS + PPI group (intervention group) or PPI group (control group), at a ratio of 1:1. In addition to using PPI, the intervention group will receive TEAS at four groups of acupoints, and each group will be treated for 15 min, once for 60 min, five times a week, for 12 weeks, 60 times. The main outcome will be changes in the Reflux Symptom Index scores at 4, 12, and 24 weeks after treatment. The secondary outcomes will include changes in the reflux finding score, Laryngopharyngeal Reflux-Health-related Quality of Life score, and throat pain visual analog scale score. DISCUSSION: This trial will explore the feasibility of TEAS combined with PPI for the treatment of LPRD and provide potential evidence for its effectiveness and safety. The results of this study will be published in a peer-reviewed journal. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046755 . Registered on May 28, 2021.

Tumor necrosis factor α accelerates Hep-2 cells proliferation by suppressing TRPP2 expression.

TRPP2, a Ca2+-permeable non-selective cation channel, has been shown to negatively regulate cell cycle, but the mechanism underlying this regulation is unknown. Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine extensively involved in immune system regulation, cell proliferation and cell survival. However, the effects and mechanisms for the role of TNF-α in laryngeal cancer remain unclear. Here, we demonstrated using western blot analyses and intracellular Ca2+ concentration measurements that TNF-α treatment suppressed both TRPP2 expression and ATP-induced Ca2+ release in a laryngeal cancer cell line (Hep-2). Knockdown of TRPP2 by a specific siRNA significantly decreased ATP-induced Ca2+ release and abolished the effect of TNF-α on the ATP-induced Ca2+ release. TNF-α treatment also enhanced Hep-2 cell proliferation and growth, as determined using cell counting and flow cytometry cell cycle assays. Moreover, TNF-α treatment down-regulated phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK) and phosphorylated eukaryotic translation initiation factor (p-eIF2α) expression levels, without affecting PERK and eIF2α expression levels in Hep-2 cells. We concluded that suppressing TRPP2 expression and TRPP2-mediated Ca2+ signaling may be one mechanism underlying TNF-α-enhanced Hep-2 cell proliferation. These results offer new insights into the mechanisms of TNF-α-mediated laryngeal cancer cell proliferation, and provide evidences showing a potential role of TNF-α in the development of laryngeal cancer.

The contribution of matched envelope dynamic range to the binaural benefits in simulated bilateral electric hearing.

PURPOSE: This study examined the effects of envelope dynamic-range mismatch on the intelligibility of Mandarin speech in noise by simulated bilateral electric hearing. METHOD: Noise-vocoded Mandarin speech, corrupted by speech-shaped noise at 5 and 0 dB signal-to-noise ratios, was presented unilaterally or bilaterally to 10 normal-hearing listeners for recognition. For unilateral conditions, the right ear was presented with the 8-channel noise-vocoded stimuli generated using a 15-dB envelope dynamic range (DR). To simulate the envelope DR mismatch between the 2 ears, the left ear was presented with the 8-channel noise-vocoded stimuli generated using a 5-, 10-, or 15-dB envelope DR, respectively. RESULTS: Significant binaural summation benefits for Mandarin speech recognition were observed only with matched envelope DR between the 2 ears. With reduced DR, the performance of tone identification was more consistent in the steady-state speech-shaped noise than that of sentence recognition. CONCLUSIONS: Consistent with previous findings, the present results suggest that Mandarin speech-perception performance of bilateral electric listening in noise is affected by the difference of envelope DR between the 2 implanted ears, and the binaural summation benefits are maximized when DR mismatch is minimized between the 2 implanted ears.