ObjectiveInsomnia Disorder (ID) is associated with significant health burdens. First-line treatments are limited by accessibility or side effects, necessitating alternative approaches. rTMS, a noninvasive neuromodulation technique, has shown promise in treating various neuropsychiatric disorders by modulating cortical excitability. This comprehensive meta-analysis explores the effect of rTMS on ID and identifies possible factors that influence it.MethodsA comprehensive search of the Cochrane Library, Embase, Web of Science, PubMed, CNKI, and Wanfang databases identified RCTs evaluating the effects of rTMS on insomnia disorder. Data synthesis and subgroup analysis were performed via SMD, WMD, relative risk (RR), and 95% CI to evaluate the effects of rTMS and its influencing factors. The review protocol was prospectively registered in PROSPERO (CRD42024626833).ResultsNineteen studies contributed 23 trials involving 1,690 adult participants. The rTMS group demonstrated markedly improved sleep quality compared with sham rTMS recipients in individuals with insomnia disorder. (PSQI total scores; ISI; p < 0.001); (PSG (SE); p = 0.003). Combined rTMS and medication were more effective than medication alone. (PSQI total scores; p = 0.003). In the subgroup analysis, after excluding a study with high heterogeneity, the rTMS cohort showed greater improvement in sleep quality than the other treatment groups. (PSQI total scores; p = 0.03).ConclusionIndependent rTMS and rTMS-medication combinations significantly improve sleep patterns and rest quality in patients with Insomnia Disorder. The safety and efficacy of LF-rTMS are also significant. The duration of the disease, treatment duration, and stimulation site may influence the sleep quality of patients with ID.
The effects of unilateral deprivation amblyopia on fixation stability
IntroductionDeprivation amblyopia is a neurodevelopmental disorder caused by obstruction of the visual pathway due to congenital cataracts, ptosis or corneal opacities that occur during early visual development. Visual deficits persist into adulthood even though the obstruction (e.g. cataracts) have been removed early in life. The effects of deprivation amblyopia on oculomotor control have not been studied. The present study evaluates the effects of unilateral deprivation amblyopia resulting from congenital cataracts on fixation stability.MethodSeven adults with unilateral deprivation amblyopia and 18 adults with normal vision were tested during binocular and monocular viewing. A video-based eye tracker was used to record eye position of the viewing eye(s) (closed-loop condition with visual feedback) and the covered eye (open-loop condition with no visual feedback).ResultsFindings for the control group were consistent with previous studies. Fixation stability (eye position stability), evaluated using bivariate contour ellipse area (BCEA), microsaccade rate, amplitude and slow drift velocity, was best during binocular viewing, and significantly worse during open-loop monocular viewing. In comparison to the control group, patients had similar fellow eye fixation stability under binocular viewing, but fixation (eye position stability) was poorer under monocular closed-loop and open-loop viewing. Fixation stability was worst in the amblyopic eye in all viewing conditions.DiscussionOur findings demonstrate fixation stability deficits in adults with unilateral deprivation amblyopia, underscoring the lasting impact of early visual deprivation on oculomotor function.
Exercise interventions for depressive symptoms in adults with lung and digestive cancer: a meta-analysis of randomized controlled trials
BackgroundDepressive symptoms are common among patients with cancer and can substantially impair quality of life, treatment adherence and overall well-being. Although exercise has been increasingly recognised as a promising non-pharmacological strategy for alleviating depression in oncology settings, existing evidence has focused predominantly on breast cancer, with limited attention to lung and digestive cancers. This meta-analysis aimed to evaluate the effects of exercise interventions on depressive symptoms in adults with lung and digestive cancer.MethodsA systematic search was conducted in PubMed, Web of Science, Embase, Cochrane Library and Scopus from database inception to March 2026. Randomized controlled trials investigating the effects of exercise interventions on depressive symptoms in adults with lung or digestive cancer were included. The primary outcome was depressive symptoms measured using validated instruments. Subgroup analyses were performed according to intervention format, exercise type and training frequency. Risk of bias was assessed using the Cochrane Risk of Bias tool version 1.ResultsEight randomized controlled trials were included in the meta-analysis. Baseline analysis showed no significant difference in depressive symptoms between the exercise and control groups before intervention. Post-intervention meta-analysis demonstrated that exercise significantly reduced depressive symptoms compared with control conditions (SMD = -0.45, P = 0.02), Although substantial heterogeneity was observed. Individually delivered programmes, walking-based exercise and moderate-frequency training (3–5 times per week) showed numerically larger effect estimates.ConclusionsExercise interventions may reduce depressive symptoms in adults with lung and digestive cancer and represent a promising adjunctive strategy for psychological care in these populations. Although subgroup differences were not statistically significant, certain intervention characteristics may be associated with greater benefit. Further large-scale, high-quality randomized trials are needed to confirm these findings and to establish the optimal exercise prescription for reducing depressive symptoms in adults with lung and digestive cancer.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420261336578.
Predictive value of antioxidant and thyroid function indicators for non-suicidal self-injury in adolescents with major depressive disorder
BackgroundNon-suicidal self-injury (NSSI) is highly prevalent in adolescents with major depressive disorder (MDD); however, its underlying pathophysiological mechanisms remain incompletely elucidated. Emerging evidence suggests a potential association between antioxidant markers, thyroid function parameters, and the occurrence of NSSI, although research in this domain remains limited. Accordingly, this study aimed to investigate the predictive efficacy of combining antioxidant and thyroid biomarkers with clinical symptoms for NSSI in adolescents with MDD.MethodsThis study recruited 162 adolescents with MDD between September 2022 and January 2026. Participants were stratified into groups based on the presence or absence of NSSI, in accordance with DSM-5 diagnostic criteria. Multidimensional scales were employed to assess the severity of depression, anxiety, perceived stress, and internet addiction (IA). Concurrently, blood samples were collected to measure bilirubin levels and thyroid function parameters. Stepwise logistic regression analysis was subsequently performed to identify independent risk factors associated with NSSI. Finally, receiver operating characteristic (ROC) curves were constructed to quantify the predictive performance of these identified independent factors.ResultsThe prevalence of NSSI in adolescents with MDD was 57.4%. Multivariate logistic regression analysis identified females (OR = 2.246, 95% CI = 1.032-4.888, P = 0.041), HAMD-17 score (OR = 1.183, 95% CI = 1.088-1.286, P < 0.001), indirect bilirubin (OR = 0.890, 95% CI = 0.797-0.995, P = 0.040), and TSH (OR = 2.060, 95% CI = 1.254-3.385, P = 0.004) as independent predictors of NSSI. Furthermore, ROC curve analysis further demonstrated that the four-item combination of sex, HAMD-17 score, indirect bilirubin, and TSH (AUC = 0.776, 95% CI = 0.701-0.850, P < 0.001) had a better ability to identify NSSI.ConclusionAdolescents with MDD, particularly females, represent a high-risk population for NSSI. Reduced levels of indirect bilirubin coupled with elevated TSH levels may constitute the underlying pathophysiological basis of NSSI and demonstrate significant clinical predictive value. In the future, targeted intervention strategies focusing on the antioxidant defense system and thyroid function may offer novel therapeutic avenues for the management of NSSI.
Two years of COVID-19: persistently reduced well-being and increases in global psychopathology during the pandemic in a representative Austrian population-sample within the COH-FIT study
IntroductionThe COVID-19 pandemic worsened well-being and mental health worldwide, but effects have diminished over time. However, prospective national data within representative samples remain scarce. We aimed to examine the change in well-being and psychopathology from pre-pandemic to intra-pandemic times in an Austrian representative general population sample, to identify vulnerable subgroups, and explore most effective coping strategies to mitigate the impact of COVID-19.MethodsData were collected in Austria as part of the Collaborative Outcomes Study on Health and Functioning During Infection Times (COH-FIT) survey, an international, multilingual, anonymous online survey assessing mental health indicators during COVID-19. Adults ≥18 years old participated through nationally representative sampling across three waves from 05/2020-04/2022. Outcomes included the WHO well-being index (WHO-5) and a global psychopathology score (‘P-score’), alongside 12 predefined risk factors and 16 coping strategies.ResultsAcross 4,148 adults, the mean WHO-5 well-being score decreased by 7.5 ± 17.7 points from the pre-pandemic baseline (73.2 ± 19.7) to the intra-pandemic average (65.7 ± 24.1) (p<.001). Participants with female sex, pre-existing mental or physical health conditions, and unemployment experienced greater declines. The proportion of individuals scoring <50, indicating depression, increased from 12.6% pre-pandemic baseline to 25.1% intra-pandemic, and the proportion scoring <29, indicating major depression, increased from 3.3% to 9.7% (both p<.001). The ‘P-score’ increased by 9.6 ± 15.0 points from 24.1 ± 19.5 pre-pandemic baseline to 33.7 ± 22.4 intra-pandemic (p<.001) with the same risk groups (except female sex). Although the greatest deterioration in both outcomes occurred during the mid-pandemic period (04/2021), neither well-being nor ‘P-score’ levels returned to pre-pandemic baseline values by 04/2022, nor to values from 05/2020 (Wave 1). Greater deterioration in WHO-5 and the P-score were associated with female sex, unemployment, pre-existing mental or physical disorders, and COVID-19 infection. The most commonly reported helpful coping strategies included internet use, physical activity, media consumption, social media and remote interaction, and meaningful hobbies.DiscussionCOVID-19 had a persistent negative impact on well-being and mental health in Austria. Vulnerable subgroups – including those with prior health conditions and unemployment – were particularly affected. The findings underscore the importance of implementing public health measures together with targeted interventions, preventive measures, and long-term psychosocial support, especially for risk populations.
The efficacy of acupuncture for depression-associated chronic pain: a systematic review and meta-analysis
ObjectiveThe comorbidity of pain and depression is prevalent, adding difficulty to the treatment of depression. This systematic review with meta-analysis aims to determine the efficacy and safety of acupuncture in treating depression-associated chronic pain (DACP).MethodsA comprehensive search was conducted across four international databases, namely PubMed, Embase, Web of Science, and the Cochrane Library, along with four regional databases, including Wanfang Data, CNKI, VIP database, and SinoMed, from inception to March 2025. The Cochrane Risk of Bias 2 tool was utilized to assess risk of bias in the included research articles, and the Grading of Recommendations Assessment, Development, and Evaluations system was employed to evaluate the certainty of evidence. Meta-regression analysis was performed to explore the influence of patient age and treatment duration on the study results, and sensitivity analysis was used to verify the stability of the results. The publication bias was evaluated when the number of included studies exceeded ten. All data analyses were completed using Stata15.1.ResultsTen randomized controlled trials involving 761 participants were included. Acupuncture combined with conventional medications was more effective than medication alone in improving depressive symptoms (standardized mean difference (SMD): -0.72; 95% confidence interval (CI): -0.91 to -0.53; P < 0.01) and reducing pain (SMD: -0.85; 95% CI: -1.36 to -0.34; P < 0.01). Head-to-head comparisons revealed that acupuncture is similar to medication in improving the Hamilton Depression Rating Scale scores (SMD: -0.05; 95% CI: -0.61 to 0.51; P > 0.05) and the Visual Analogue Scale scores (SMD: -0.33; 95% CI: -0.94 to 0.29; P > 0.05), suggesting no statistically significant difference between the two treatments. In contrast, acupuncture was associated with a better safety profile (relative risk: 0.40; 95% CI: 0.27 to 0.60). Further subgroup analysis found the advantage of a 4-week acupuncture treatment in improving depressive symptoms, while longer-term treatment tended to be more effective in relieving pain.ConclusionsAcupuncture appears to have comparable antidepressant and analgesic effects to conventional oral medications. When applied as an adjuvant therapy, acupuncture may enhance the clinical efficacy of monotherapy for DACP. Regarding treatment duration, a 4-week acupuncture intervention may be superior to a longer cycle (> 4 weeks) in alleviating depressive symptoms, while long-term acupuncture treatment may provide greater benefits in analgesia.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD420251026454.
Wearable low-level laser therapy (laser acupuncture) versus manual acupuncture for chronic insomnia: protocol for a randomized, assessor-blinded, superiority trial
BackgroundChronic insomnia is a prevalent and disabling condition associated with impaired daytime functioning, psychiatric comorbidity, and autonomic dysregulation. Although cognitive behavioral therapy for insomnia (CBT-I) is recommended as the first-line treatment, access is limited. Acupuncture has demonstrated therapeutic benefits for insomnia but requires trained practitioners and repeated clinic visits. Low-level laser therapy (LLLT), an acupoint-targeted form of photobiomodulation that is also referred to as laser acupuncture when applied to acupuncture points, offers a non-invasive and standardized modality that may serve as a practical alternative.MethodsThis single-center, parallel-group, assessor-blinded, superiority randomized controlled trial will compare wearable LLLT with manual acupuncture in 106 adults with chronic insomnia. Participants aged 18–65 years who meet DSM-5 criteria for chronic insomnia and have an Insomnia Severity Index (ISI) score between 8 and 21 will be randomly allocated (1:1) to the LLLT group or acupuncture group. Both interventions will target bilateral HT7, PC6 and SP6 (six acupoints in total) for 30 minutes per session, three times per week, over two weeks (six sessions total). In the LLLT group, 650-nm laser irradiation will be delivered simultaneously to all six acupoints. The primary outcome is the change in ISI score from baseline to week 2. Secondary outcomes include sleep quality (Pittsburgh Sleep Quality Index, PSQI), fatigue (Fatigue Severity Scale, FSS), depressive symptoms (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalized Anxiety Disorder-7, GAD-7) and heart rate variability (HRV) indices. The ISI will be assessed at baseline, post-treatment (week 2), and follow-up (week 6). Secondary outcomes, including PSQI, FSS, PHQ-9, GAD-7, and HRV indices, will be assessed at baseline and week 2. Analyses will follow the intention-to-treat principle using analysis of covariance and prespecified longitudinal or repeated-measures models where appropriate.DiscussionThis trial will provide comparative evidence on the short-term efficacy and safety of wearable LLLT versus manual acupuncture for chronic insomnia. By directly comparing an established acupuncture protocol with a non-invasive intervention that has potential for future home-based implementation, the study aims to clarify the clinical value of LLLT as a less invasive alternative within the framework of complementary and integrative sleep medicine.Clinical trial registrationhttps://itmctr.ccebtcm.org.cn/Home/ProjectView?pid=d0e46c39-0647-4cbd-ba40-e2b02830fd28, identifier ITMCTR2025000977.
Decoding the origins of cellular self-organization for engineered biology
Nature Biotechnology, Published online: 01 June 2026; doi:10.1038/s41587-026-03161-w
This Perspective positions cellular self-organization as a foundational principle for the origin of multicellular life and discusses how decoding this concept with stem cell-based models will advance biological engineering.
Selection of human hematopoietic stem cells bearing the intended functional edit by transient AND-gate reporters
Nature Biotechnology, Published online: 01 June 2026; doi:10.1038/s41587-026-03142-z
Selection increases the purity of blood stem cells bearing targeted homologous recombination.
Downplaying toxicities in cancer drug trials is not acceptable
Nature Medicine, Published online: 01 June 2026; doi:10.1038/s41591-026-04463-x
As a physician I want to treat the patient, not just the tumor.