Tenovin 3 induces apoptosis and ferroptosis in EGFR 19del non small cell lung cancer cells.

Epidermal growth factor receptor (EGFR) exon 19 deletion is a major driver for the drug resistance of non-small cell lung cancer (NSCLC). Identification small inhibitor capable of selectively inhibiting EGFR-19del NSCLC is a desirable strategy to overcome drug resistance in NSCLC. This study aims to screen an inhibitor for EGFR exon 19 deletion cells and explore its underlying mechanism. High through-put screen was conducted to identify an inhibitor for EGFR-19del NSCLC cells. And tenovin-3 was identified as a selective inhibitor of PC9 cells, an EGFR-19del NSCLC cells. Tenovin-3 showed particular inhibition effect on PC9 cells proliferation through inducing apoptosis and ferroptosis. Mechanistically, tenovin-3 might induce the apoptosis and ferroptosis of PC9 cells through mitochondrial pathway, as indicated by the change of VDAC1 and cytochrome c (cyt c). And bioinformatics analyses showed that the expression levels of SLC7A11 and CPX4 were correlated with NSCLC patient's survival. Our findings provide evidences for tenovin-3 to be developed into a novel candidate agent for NSCLC with EGFR exon 19 deletion. Our study also suggests that inducing ferroptosis may be a therapeutic strategy for NSCLC with EGFR exon 19 deletion.

Efficacy of acupuncture (Jin's three-needle) on motor symptoms and anxiety in patients with Parkinson's disease: protocol for a multicentre, randomised, assessor-blinded clinical trial.

INTRODUCTION: Parkinson's disease (PD) has a significant impact on a substantial number of individuals in China. Notably, 31% of patients with PD also grapple with the additional burden of anxiety. This dual challenge of managing both PD and anxiety underscores the complexity of the condition and the diverse range of symptoms patients may experience. Considering the circumstances, the cost and potential drawbacks associated with traditional antiparkinsonian drugs become increasingly relevant. Acupuncture emerges as a significant non-pharmacological adjunct therapy. Offering a potentially safer and more cost-effective option, acupuncture addresses the pressing need for holistic and complementary treatments that may alleviate both the motor symptoms of PD and the accompanying anxiety. METHODS AND ANALYSIS: This is a multicentre, randomised controlled and assessor-blind trial. A total of 210 eligible patients with PD will be randomly assigned (1:1) to Jin's three-needle (JTN) acupuncture group or waitlist (WL) group. Patients in the JTN group will receive acupuncture therapy three times per week for 4 weeks. Patients in the WL group will maintain their original dosage of antiparkinsonian drugs and receive acupuncture therapy after the observation period. The primary outcome measure will be the Unified Parkinson's Disease Rating Scale score. The secondary outcome measures will be the scores of the Hoehn-Yahr Rating Scale, Unified Dyskinesia Rating Scale, Non-Motor Symptoms Scale, 39-item Parkinson's Disease Questionnaire, Parkinson Anxiety Scale, Hamilton Anxiety Scale, Hamilton Depression Scale, Zarit burden interview and the level of cortisol and adrenocorticotropic hormone. The evaluation will be executed at baseline, the end of the treatment and a follow-up period. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine (K[2023]014). All patients have to provide written, informed consent. The study will be disseminated through presentations in peer-reviewed international journals and at national and international conferences. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry; ChiCTR2300074675.

Efficacy of acupuncture for the treatment of Parkinson's disease-related constipation (PDC): A randomized controlled trial.

Objective: To evaluate the efficacy of acupuncture in treating Parkinson's disease-related constipation (PDC). Materials and methods: This was a randomized, controlled trial in which patients, outcome assessors, and statisticians were all blinded. Seventy-eight eligible patients were randomly assigned to either the manual acupuncture (MA) or sham acupuncture (SA) groups and received 12 sessions of treatment over a 4-week period. Following treatment, patients were monitored until the eighth week. The primary outcome was the change in weekly complete spontaneous bowel movements (CSBMs) from baseline after treatment and follow-up. The Constipation Symptom and Efficacy Assessment Scale (CSEAS), the Patient-Assessment of Constipation Quality of Life questionnaire (PAC-QOL), and the Unified Parkinson's Disease Rating Scale (UPDRS) were used as secondary outcomes. Results: In the intention-to-treat analysis, 78 patients with PDC were included, with 71 completing the 4-week intervention and 4-week follow-up. When compared to the SA group, weekly CSBMs were significantly increased after treatment with the MA group (P < 0.001). Weekly CSBMs in the MA group were 3.36 [standard deviation (SD) 1.44] at baseline and increased to 4.62 (SD, 1.84) after treatment (week 4). The SA group's weekly CSBMs were 3.10 (SD, 1.45) at baseline and 3.03 (SD, 1.25) after treatment, with no significant change from baseline. The effect on weekly CSBMs improvement in the MA group lasted through the follow-up period (P < 0.001). Conclusion: Acupuncture was found to be effective and safe in treating PDC in this study, and the treatment effect lasted up to 4 weeks. Clinical trial registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR2200059979.

Effect of electroacupuncture for Pisa syndrome in Parkinson's disease: A case report.

BACKGROUND: Pisa syndrome (PS) refers to marked lateral flexion of the trunk with a Cobb angle greater than 10°, which is typically mobile and can be resolved by lying down. PS is one of the most common postural deformities secondary to Parkinson's disease (PD) and can aggravate scoliosis in the advanced stages of PD. CASE SUMMARY: Here, we present the case of a 53-year-old woman who presented with lateral curvature for 6 mo. Full spine X-ray films in the correct position showed that the thoracolumbar spine was bent to the right without any rotation of the vertebrae. The patient was diagnosed with Pisa syndrome. After receiving a month's treatment with electroacupuncture, the Cobb angle decreased from 18.14° to 13.41°. CONCLUSION: This case demonstrates that electroacupuncture can effectively improve Pisa syndrome secondary to PD with few side effects and a low risk of recurrence. Additionally, early accurate diagnosis and timely intervention are meaningful for the prognosis of PS.

Effectiveness of Acupuncture for Anxiety Among Patients With Parkinson Disease: A Randomized Clinical Trial.

Importance: One of the ordinary manifestations of Parkinson disease (PD) is anxiety, which remains untreated. Anxiety is closely associated with the accelerated progression of PD. Efficacy of acupuncture for anxiety has been reported. However, to date, there are no data on acupuncture's effectiveness on anxiety for patients with PD. Objective: To investigate the effect of acupuncture vs sham acupuncture for treating anxiety in patients with PD. Design, Setting, and Participants: This is randomized, double-blinded, clinical trial enrolled patients between June 20, 2021, and February 26, 2022. Final follow-up was April 15, 2022. Patients with Parkinson disease and anxiety were allocated randomly (1:1) to receive acupuncture or sham acupuncture for 8 weeks. Acupuncture operators, outcome measures evaluators, and statistical analysts were blinded to the grouping of patients. Patients were blinded to their own grouping during the study. This study took place in the Parkinson clinic of a hospital in China. Interventions: Real acupuncture or sham acupuncture for 8 weeks. Main Outcomes and Measures: Primary outcome was Hamilton Anxiety Scale (HAM-A) score. Secondary outcomes were scores on the Unified Parkinson Disease Rating Scale (UPDRS), 39-item Parkinson Disease Questionnaire (PDQ-39), and serum levels of the adrenocorticotropic hormone (ACTH) and cortisol (CORT). Results: Seventy eligible patients were enrolled, including 34 women (48.5%) and 36 men (51.4%). Sixty-four patients (91%) completed the intervention and the 8-week follow-up, including 30 women (46.9%) and 34 men (53.1%) with a mean (SD) age of 61.84 (8.47) years. At the end of treatment, the variation of HAM-A score was 0.22 (95% CI, -0.63 to 1.07; P = .62) between the real acupuncture and sham acupuncture groups. At the end of follow-up, the real acupuncture group had a significant 7.03-point greater (95% CI, 6.18 to 7.88; P < .001) reduction in HAM-A score compared with the sham acupuncture group. Four mild adverse reactions occurred during the study. Conclusions and Relevance: This study found acupuncture to be an effective treatment for anxiety in patients with PD. These findings suggest that acupuncture may enhance the wellbeing of patients who have Parkinson disease and anxiety. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2100047253.

Acupuncture for Parkinson's disease: From theory to practice.

Advances in molecular biology and biochemistry have improved the treatment of Parkinson's disease (PD). There has been extensive evidence on the benefit of standard treatment (e.g., deep brain stimulation, levodopa, and dopamine agonists) and acupuncture for PD. This article aims to distill the similarities and differences in the treatment concepts between Chinese and Western medicine from the perspective of reinforcing the deficiency and purging the excess, summarize the latest evidence on the benefits of acupuncture for PD from theory to practice, and propose prospective treatment options for PD.

Efficacy of Acupuncture for Parkinson's Disease Anxiety: Two-Stage Protocol for a Randomized Controlled Clinical Trial.

Parkinson's disease anxiety (PDA) is a nonmotor symptom of Parkinson's disease (PD) that is often neglected. PDA poses a far-reaching challenge to the treatment of PD. Acupuncture could be successful in the treatment of PDA. However, the evidence for this is still limited. We propose a two-stage clinical trial. In stage 1, a total of 70 volunteers with PDA will be randomly assigned to either acupuncture (manual acupuncture) or control group (sham acupuncture) in a 1 : 1 ratio. Treatments will be performed for four weeks. The change in the Hamilton Rating Scale for Anxiety (HAMA) score from baseline to week 4 and week 12 will be the primary outcome. The levels of adrenocorticotropic hormone (ACTH), cortisol (CORT), serotonin (5-HT), and corticotropin-releasing factor (CRH) in the patients' serum and the scores on the Hoehn-Yahr Rating Scale and the Unified Parkinson's Disease Rating Scale (UPDRS) will all be considered among the secondary outcomes. Participants will be followed up until week 12. In stage 2, a total of 82 volunteers with PDA will be randomly assigned to either an acupuncture (manual acupuncture) or a control group (anti-Parkinson drugs only) in a 1 : 1 ratio. HAMA score will be the primary outcome. Universality, feasibility and cost effectiveness, Hoehn-Yahr Rating Scale, UPDRS, and serological indicators will be secondary outcomes. Participants will be followed up until week 4. The statistical analysis will include all the allocated individuals. The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine's Research Ethical Committee authorized this procedure, and the trial is registered with ChiCTR2100047253.

Prevalence, incidence and risk factors of strabismus in a Chinese population-based cohort of preschool children: the Nanjing Eye Study.

AIMS: To evaluate the prevalence, incidence and their related risk factors of strabismus among preschool children in China. METHODS: Children born between September 2011 and August 2012 in Yuhuatai District of Nanjing were invited to participate in the Nanjing Eye Study for a comprehensive eye examination annually since 2015. The data presented in this paper were obtained from 2015 to 2017, when these children grew from the age of 3 to 5 years. Eye examinations included visual acuity, anterior segment, posterior segment, refraction, and ocular alignment and motility. Risk factors were evaluated using univariable and multivariable logistic regression models for prevalent and incident strabismus. RESULTS: In 2015, a total of 2018 children (87.7% response rate) of 2300 eligible preschoolers completed the baseline eye examination when they were 3 years old. Among the 2018 participants, 50 had strabismus (prevalence rate, 2.48%). In multivariable analysis, prevalent strabismus was independently associated with parental strabismus history (OR=11.60, p<0.001), hyperopia (OR=6.22, p<0.001), prematurity (OR=3.07, p=0.01) and astigmatism (OR=2.15, p=0.04). Among 1766 children followed up for 2 years, 63 developed strabismus (annual incidence rate, 1.78%), of whom 57 had exotropia and 6 had esotropia. In multivariable analysis, incident strabismus was significantly associated with parental strabismus history (OR=5.55, p=0.04) and prematurity (OR=3.77, p<0.001). CONCLUSIONS: In this population-based cohort study, we found a higher incidence of strabismus and a higher exotropia:esotropia ratio than previous studies in preschool children. Parental strabismus history and prematurity were associated with a higher risk for both prevalent and incident strabismus.