Shape-sensing Robotic-assisted Bronchoscopy (SS-RAB) in Sampling Peripheral Pulmonary Nodules: A Prospective, Multicenter Clinical Feasibility Study in China.

BACKGROUND: The ION system is a shape-sensing robotic-assisted bronchoscopy (SS-RAB) platform developed to biopsy peripheral pulmonary nodules (PPNs). There is a lack of data describing the use of this system in the Chinese population. The study aimed to assess the feasibility and safety of using SS-RAB to diagnose PPNs across multiple centers within China. METHODS: This prospective, multicenter study used SS-RAB in consecutive patients with solid or sub-solid PPNs 8 to 30 mm in largest diameter. Primary endpoints were diagnostic yield and the rates of procedure- or device-related complications. Radial endobronchial ultrasound (rEBUS) was to confirm lesion localization, followed by sampling, using the Flexision biopsy needle, biopsy forceps, and cytology brush. Subjects with nonmalignant index biopsy results were followed up to 6 months. RESULTS: A total of 90 PPNs were biopsied from 90 subjects across 3 centers using SS-RAB. The median nodule size was 19.4 mm (IQR: 19.3, 24.6) in the largest dimension. In all (100%) cases, the catheter successfully reached the target nodule with tissue samples obtained. The diagnostic yield was 87.8% with a sensitivity for malignancy of 87.7% (71/81). In a univariate analysis, nodule lobar location, presence of bronchus sign, and rEBUS view were associated with a diagnostic sample, but only rEBUS view showed an association in a multivariate analysis. The overall pneumothorax rate was 1.1% without pneumothorax requiring intervention, and there was no periprocedural bleeding. CONCLUSION: As an emerging technology in the Chinese population, SS-RAB can safely biopsy PPNs with strong diagnostic performance.

Non-invasive diagnosis of pulmonary nodules by circulating tumor DNA methylation: A prospective multicenter study.

BACKGROUND: With the popularization of computed tomography, more and more pulmonary nodules (PNs) are being detected. Risk stratification of PNs is essential for detecting early-stage lung cancer while minimizing the overdiagnosis of benign nodules. This study aimed to develop a circulating tumor DNA (ctDNA) methylation-based, non-invasive model for the risk stratification of PNs. METHODS: A blood-based assay ("LUNG-TRAC") was designed to include novel lung cancer ctDNA methylation markers identified from in-house reduced representative bisulfite sequencing data and known markers from the literature. A stratification model was trained based on 183 ctDNA samples derived from patients with benign or malignant PNs and validated in 62 patients. LUNG-TRAC was further single-blindly tested in a single- and multi-center cohort. RESULTS: The LUNG-TRAC model achieved an area under the curve (AUC) of 0.810 (sensitivity = 74.4 % and specificity = 73.7 %) in the validation set. Two test sets were used to evaluate the performance of LUNG-TRAC, with an AUC of 0.815 in the single-center test (N = 61; sensitivity = 67.5 % and specificity = 76.2 %) and 0.761 in the multi-center test (N = 95; sensitivity = 50.7 % and specificity = 80.8 %). The clinical utility of LUNG-TRAC was further assessed by comparing it to two established risk stratification models: the Mayo Clinic and Veteran Administration models. It outperformed both in the validation and the single-center test sets. CONCLUSION: The LUNG-TRAC model demonstrated accuracy and consistency in stratifying PNs for the risk of malignancy, suggesting its utility as a non-invasive diagnostic aid for early-stage peripheral lung cancer. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov (NCT03989219).

Chinese verbal fluency deficiency in temporal lobe epilepsy with and without hippocampal sclerosis: a multiscale study.

To test a Chinese character version of phonemic verbal fluency task in patients with temporal lobe epilepsy (TLE), and assess the verbal fluency deficiency pattern in TLE with and without hippocampal sclerosis. Thirty patients with TLE and hippocampal sclerosis (TLE-HS), 28 patients with TLE and without hippocampal sclerosis (TLE-NHS), and 29 demographically matched healthy controls (HC) participated in this cross-sectional study. Both sexes were enrolled. Participants finished a Chinese character verbal fluency (VFC) task during functional MRI. The activation/deactivation maps, functional connectivity, degree centrality, and community features of left frontal and temporal regions were compared. Neural network classification model was applied to differentiate TLE-HS and TLE-NHS using functional statistics. The VFC scores were correlated with semantic fluency in HC while correlated with phonemic fluency in TLE-NHS. Activation and deactivation deficiency was observed in TLE-HS and TLE-NHS (p < 0.001, k ≥ 10). Functional connectivity, degree centrality, and community features of anterior inferior temporal gyri were impaired in TLE-HS and retained or even enhanced in TLE-NHS (p < 0.05, FDR-corrected). The functional connectivity was correlated with phonemic fluency (p < 0.05, FDR-corrected). The neural network classification reached an area under curve = 0.90 in diagnosing hippocampal sclerosis. The VFC task is a Chinese phonemic verbal fluency task suitable for clinical application in TLE. During the VFC task, functional connectivity of phonemic circuits was impaired in TLE-HS and was enhanced in TLE-NHS, representing a compensative phonemic searching strategy applied by patients with TLE-NHS.Significance Statement Verbal fluency tasks are essential assessment for patients with epilepsy. However, the testing and applying of Chinese phonemic verbal fluency is at an initial stage. We tested a Chinses character verbal fluency task in Chinese with temporal lobe epilepsy, and depicted the functional alteration patterns in them. Our work provided a Chinese verbal fluency task suitable for clinical application. Our results highlighted the importance of left anterior inferior frontal gyrus in Chinese, and might have impact on the surgical protocol of Chinese patients with left TLE and promote further development of rehabilitative and therapeutic approaches for verbal fluency decline.

Tuina on knee pain and functional decline of lower limbs for patients with mild-to-moderate knee osteoarthritis in Shanghai: protocol for a multicentre, assessor-blinded, randomised controlled trial.

INTRODUCTION: Knee osteoarthritis (KOA) is one of the most common osteoarthritis, imposing substantial economic and medical burdens on both individuals and society. In China, Tuina has been selected as a complementary and alternative therapy to relieve knee pain and dysfunction symptoms. However, the current evidence is insufficient to support the efficacy of Tuina therapy in addressing knee pain and improving physical function. The trial aims to compare the effectiveness of Tuina with celecoxib, which is considered as the standard treatment, and to assess its potential as an alternative therapy through changes in outcome measures. METHODS AND ANALYSIS: A total of 360 KOA patients aged between 40 and 70 years and classified as Kellgren and Lawrence grades I-II will be recruited from eight subcentral hospitals. The participants will be randomly assigned to either the treatment group (Tuina, Biw) or the control group (celecoxib, Qd), with both groups undergoing a 4-week intervention phase followed by an 8-week follow-up phase. The primary outcome is the change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale at week 4 compared with baseline. Secondary outcomes including WOMAC stiffness and function subscales, WOMAC total score, 36-item Short-Form Health Survey, Timed Up and Go test, Short Physical Performance Battery, gait analysis parameters and pain medication records will be assessed at weeks 4, 8 and 12. Any adverse events that occur during the trial will be promptly recorded. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine (2023SHL-KY-16-01, 2023SHL-KY-16-02). Written informed consent will be obtained from all participants. Study results will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2300069416.

Role of mesenchymal stem cell-derived exosomes in the regeneration of different tissues.

Exosomes are nanovesicles with multiple components used in several applications. Mesenchymal stem cells (MSCs) are well known for their great potential in clinical applications. MSC-derived exosomes (MSC-Exos) have been shown to mediate tissue regeneration in various diseases, including neurological, autoimmune, and inflammatory diseases, cancer, ischemic heart disease, lung injury, and liver fibrosis. They can modulate the immune response by interacting with immune effector cells in the presence of anti-inflammatory compounds and are involved in intercellular communication through various types of cargo. This review summarizes the MSC-Exos-mediated tissue regeneration in various diseases, including neurological, cardiovascular, liver, kidney, articular cartilage, and oral tissue applications. In addition, we discuss the challenges and prospects of MSC-Exos in tissue regeneration.

Bilateral glymphatic dysfunction and its association with disease duration in unilateral temporal lobe epilepsy patients with hippocampal sclerosis.

OBJECTIVE: In this study, the diffusion tensor imaging along perivascular space analysis (DTI-ALPS) technique was utilized to evaluate the functional changes in the glymphatic system of the bilateral hemispheres in patients with unilateral temporal lobe epilepsy (TLE) accompanied by hippocampal sclerosis (HS). The aim was to gain insights into the alterations in the glymphatic system function in TLE patients. METHODS: A total of 61 unilateral TLE patients with HS and 53 healthy controls (HCs) from the Department of Neurosurgery at Xiangya Hospital were included in the study. All subjects underwent DTI using the same 3 T MR Scanner, and the DTI-ALPS index was calculated. Differences in the DTI-ALPS index between TLE patients and HCs were evaluated, along with the correlation between the DTI-ALPS index of TLE and clinical features of epilepsy. These features included age, age of onset, seizure duration, and neuropsychological scores. RESULTS: Compared to the bilateral means of the HCs, both the ipsilateral and contralateral DTI-ALPS index of the TLE patients were significantly decreased (TLE ipsilateral 1.41 ± 0.172 vs. HC bilateral mean: 1.49 ± 0.116, p = 0.006; TLE contralateral: 1.42 ± 0.158 vs. HC bilateral mean: 1.49 ± 0.116, p = 0.015). The ipsilateral DTI-ALPS index in TLE patients showed a significant negative correlation with disease duration (r = -0.352, p = 0.005). CONCLUSIONS: The present study suggests the presence of bilateral dysfunctions in the glymphatic system and also highlight a laterality feature in these dysfunctions. Additionally, the study found a significant negative correlation between the ipsilateral DTI-ALPS index and disease duration, underscoring the significance of early effective interventions and indicating potential for the development of innovative treatments targeting the glymphatic system.

T cell-mediated tumor killing sensitivity gene signature-based prognostic score for acute myeloid leukemia.

BACKGROUND AND OBJECTIVE: Acute myeloid leukemia (AML) is an aggressive, heterogenous hematopoetic malignancies with poor long-term prognosis. T-cell mediated tumor killing plays a key role in tumor immunity. Here, we explored the prognostic performance and functional significance of a T-cell mediated tumor killing sensitivity gene (GSTTK)-based prognostic score (TTKPI). METHODS: Publicly available transcriptomic data for AML were obtained from TCGA and NCBI-GEO. GSTTK were identified from the TISIDB database. Signature GSTTK for AML were identified by differential expression analysis, COX proportional hazards and LASSO regression analysis and a comprehensive TTKPI score was constructed. Prognostic performance of the TTKPI was examined using Kaplan-Meier survival analysis, Receiver operating curves, and nomogram analysis. Association of TTKPI with clinical phenotypes, tumor immune cell infiltration patterns, checkpoint expression patterns were analysed. Drug docking was used to identify important candidate drugs based on the TTKPI-component genes. RESULTS: From 401 differentially expressed GSTTK in AML, 24 genes were identified as signature genes and used to construct the TTKPI score. High-TTKPI risk score predicted worse survival and good prognostic accuracy with AUC values ranging from 75 to 96%. Higher TTKPI scores were associated with older age and cancer stage, which showed improved prognostic performance when combined with TTKPI. High TTKPI was associated with lower naïve CD4 T cell and follicular helper T cell infiltrates and higher M2 macrophages/monocyte infiltration. Distinct patterns of immune checkpoint expression corresponded with TTKPI score groups. Three agents; DB11791 (Capmatinib), DB12886 (GSK-1521498) and DB14773 (Lifirafenib) were identified as candidates for AML. CONCLUSION: A T-cell mediated killing sensitivity gene-based prognostic score TTKPI showed good accuracy in predicting survival in AML. TTKPI corresponded to functional and immunological features of the tumor microenvironment including checkpoint expression patterns and should be investigated for precision medicine approaches.

MiCOL6, MiCOL7A and MiCOL7B isolated from mango regulate flowering and stress response in transgenic Arabidopsis.

The CONSTANS/CONSTANS-Like (CO/COL) family has been shown to play important roles in flowering, stress tolerance, fruit development and ripening in higher plants. In this study, three COL genes, MiCOL6, MiCOL7A and MiCOL7B, which each contain only one CCT domain, were isolated from mango (Mangifera indica), and their functions were investigated. MiCOL7A and MiCOL7B were expressed mainly at 20 days after flowering (DAF), and all three genes were highly expressed during the flowering induction period. The expression levels of the three genes were affected by light conditions, but only MiCOL6 exhibited a clear circadian rhythm. Overexpression of MiCOL6 promoted earlier flowering, while overexpression of MiCOL7A or MiCOL7B delayed flowering compared to that in the control lines of Arabidopsis thaliana under long-day (LD) and short-day (SD) conditions. Overexpressing MiCOL6, MiCOL7A or MiCOL7B in transgenic plants increased superoxide dismutase (SOD) and proline levels, decreased malondialdehyde (MAD) levels, and improved survival under drought and salt stress. In addition, yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) analyses showed that the MiCOL6, MiCOL7A and MiCOL7B proteins interact with several stress- and flower-related proteins. This work demonstrates the functions of MiCOL6, MiCOL7A and MiCOL7B and provides a foundation for further research on the role of mango COL genes in flowering regulation and the abiotic stress response.

Potential of Thermal Ablation Combined with Immunotherapy in Peripheral Lung Tumors: A Review and Prospect.

BACKGROUND: Lung tumors are prevalent malignancies associated with a high mortality rate, imposing significant medical and societal burdens. Although immunotherapy shows promise in improving survival, response rates are relatively modest. Thermal ablation can not only eliminate tumor cells directly but also enhance antitumor immunity response, thus manifesting a remarkable propensity to synergize with immunotherapy. SUMMARY: In this review, we provided a brief overview of the application of thermal ablation in peripheral lung tumors. We summarized the patient selection of thermal ablation. We highlighted the potential of thermal ablation to augment the antitumor immune response, offering a promising avenue for combined therapies. We summarized studies assessing the synergistic effects of thermal ablation and immunotherapy in preclinical and clinical settings. Lastly, we underscored the urgent issues that warrant in-depth exploration when applying thermal ablation and immunotherapy to lung tumor patients. KEY MESSAGES: This review emphasized the prospects of using thermal ablation combined with immunotherapy in patients with peripheral lung tumors. However, further research is needed to enhance and optimize this treatment strategy.

Association of preschool children behavior and emotional problems with the parenting behavior of both parents.

BACKGROUND: Parental behaviors are key in shaping children's psychological and behavioral development, crucial for early identification and prevention of mental health issues, reducing psychological trauma in childhood. AIM: To investigate the relationship between parenting behaviors and behavioral and emotional issues in preschool children. METHODS: From October 2017 to May 2018, 7 kindergartens in Ma'anshan City were selected to conduct a parent self-filled questionnaire - Health Development Survey of Preschool Children. Children's Strength and Difficulties Questionnaire (Parent Version) was applied to measures the children's behavioral and emotional performance. Parenting behavior was evaluated using the Parental Behavior Inventory. Binomial logistic regression model was used to analyze the association between the detection rate of preschool children's behavior and emotional problems and their parenting behaviors. RESULTS: High level of parental support/participation was negatively correlated with conduct problems, abnormal hyperactivity, abnormal total difficulty scores and abnormal prosocial behavior problems. High level of maternal support/participation was negatively correlated with abnormal emotional symptoms and abnormal peer interaction in children. High level of parental hostility/coercion was positively correlated with abnormal emotional symptoms, abnormal conduct problems, abnormal hyperactivity, abnormal peer interaction, and abnormal total difficulty scores in children (all P < 0.05). Moreover, paternal parenting behaviors had similarly effects on behavior and emotional problems of preschool children compared with maternal parenting behaviors (all P > 0.05), after calculating ratio of odds ratio values. CONCLUSION: Our study found that parenting behaviors are associated with behavioral and emotional issues in preschool children. Overall, the more supportive or involved the parents are, the fewer behavioral and emotional problems the children experience; conversely, the more hostile or controlling the parents are, the more behavioral and emotional problems the children face. Moreover, the impact of fathers' parenting behaviors on preschool children's behavior and emotions is no less significant than that of mothers' parenting behaviors.

Chinese expert consensus on cone-beam CT-guided diagnosis, localization and treatment for pulmonary nodules.

Cone-beam computed tomography (CBCT) system can provide real-time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Preoperative structural-functional coupling at the default mode network predicts surgical outcomes of temporal lobe epilepsy.

OBJECTIVE: Structural-functional coupling (SFC) has shown great promise in predicting postsurgical seizure recurrence in patients with temporal lobe epilepsy (TLE). In this study, we aimed to clarify the global alterations in SFC in TLE patients and predict their surgical outcomes using SFC features. METHODS: This study analyzed presurgical diffusion and functional magnetic resonance imaging data from 71 TLE patients and 48 healthy controls (HCs). TLE patients were categorized into seizure-free (SF) and non-seizure-free (nSF) groups based on postsurgical recurrence. Individual functional connectivity (FC), structural connectivity (SC), and SFC were quantified at the regional and modular levels. The data were compared between the TLE and HC groups as well as among the TLE, SF, and nSF groups. The features of SFC, SC, and FC were categorized into three datasets: the modular SFC dataset, regional SFC dataset, and SC/FC dataset. Each dataset was independently integrated into a cross-validated machine learning model to classify surgical outcomes. RESULTS: Compared with HCs, the visual and subcortical modules exhibited decoupling in TLE patients (p < .05). Multiple default mode network (DMN)-related SFCs were significantly higher in the nSF group than in the SF group (p < .05). Models trained using the modular SFC dataset demonstrated the highest predictive performance. The final prediction model achieved an area under the receiver operating characteristic curve of .893 with an overall accuracy of .887. SIGNIFICANCE: Presurgical hyper-SFC in the DMN was strongly associated with postoperative seizure recurrence. Furthermore, our results introduce a novel SFC-based machine learning model to precisely classify the surgical outcomes of TLE.

Effects of the Prolong Life With Nine Turn-Method Qigong on Fatigue, Insomnia, Anxiety, and Gastrointestinal Disorders in Patients With Chronic Fatigue Syndrome: Protocol for a Randomized Controlled Trial.

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating multisystem disorder that can lead to various pathophysiological abnormalities and symptoms, including insomnia, gastrointestinal disorders, and anxiety. Due to the side effects of currently available drugs, there is a growing need for safe and effective nondrug therapies. The Prolong Life With Nine Turn (PLWNT) Qigong method is a system of mind-body exercise with restorative benefits that can alleviate the clinical symptoms of CFS and impart a significant inhibitory effect. Various studies have proven the treatment efficacy of PLWNT; however, the impact on insomnia, gastrointestinal disorders, and anxiety in patients with CFS has not yet been investigated. OBJECTIVE: This study aims to evaluate the efficacy and safety of the PLWNT method in terms of its effects on fatigue, insomnia, anxiety, and gastrointestinal symptoms in patients with CFS. METHODS: We will conduct a randomized, analyst-blinded, parallel-controlled trial with a 12-week intervention and 8-week follow-up. A total of 208 patients of age 20-60 years will be recruited. The patients will be randomly divided into a PLWNT Qigong exercise group (PLWNT Group) and a control group treated with cognitive behavioral therapy at a ratio of 1:1. Participants from the treatment groups will be taught by a highly qualified professor at the Shanghai University of Traditional Chinese Medicine once a week and will be supervised via web during the remaining 6 days at home, over 12 consecutive weeks. The primary outcome will be the Multidimensional Fatigue Inventory 20, while the secondary outcomes include the Pittsburgh Sleep Quality Index, Gastrointestinal Symptom Rating Scale, Hospital Anxiety and Depression Scale, functional magnetic resonance imaging, gut microbiota, and peripheral blood. RESULTS: The study was approved by the ethics committee of Shanghai Municipal Hospital of Traditional Chinese Medicine in March 2022 (Ethics Approval Number 2022SHL-KY-05). Recruitment started in July 2022. The intervention is scheduled to be completed in December 2024, and data collection will be completed by the end of January 2025. Over the 3-year recruitment period, 208 participants will be recruited. Data management is still in progress; therefore, data analysis has yet to be performed. CONCLUSIONS: This randomized trial will evaluate the effectiveness of the PLWNT method in relieving fatigue, insomnia, anxiety, and gastrointestinal symptoms in patients with CFS. If proven effective, it will provide a promising alternative intervention for patients with CFS. TRIAL REGISTRATION: China Clinical Trials Registry ChiCTR2200061229; https://www.chictr.org.cn/showproj.html?proj=162803. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/53347.

Transbronchial cryoablation in peripheral lung parenchyma with a novel thin cryoprobe and initial clinical testing.

BACKGROUND: Transbronchial cryoablation shows potential as a local therapy for inoperable peripheral lung cancer. However, its clinical application for peripheral pulmonary lesions has not been reported yet. METHODS: An improved cryoprobe with an 8-mm-long, 1.9-mm-wide cryotip was used. Initially, the safety and effectiveness of this cryoprobe were assessed in an in vivo porcine model. Transbronchial cryoablation with 2 or 3 freeze-thaw cycles (10 min or 15 min in each freezing time) was performed in 18 pigs under CT monitoring. Radiological and pathological examinations were performed to evaluate the extent of cryoablation. Subsequently, nine patients with stage IA peripheral lung cancer or metastases underwent transbronchial cryoablation with this cryoprobe under the guidance of navigation bronchoscopy and cone-beam CT. Technical success, safety and outcomes were assessed. RESULTS: 36 cryoablation procedures were performed successfully without any major complications in the porcine model. The extent of cryoablation increased with freezing time and the number of freeze-thaw cycles, which peaked at 24 hours and then gradually decreased. Pathological results showed a change from massive haemorrhage at 24 hours to fibrous hyperplasia with chronic inflammation after 4 weeks. In the clinical trial, 10 cryoablations were performed on 9 tumours with a technical success rate of 100%. One mild treatment-related complication occurred. Of the nine tumours, seven achieved complete ablation, while two exhibited incomplete ablation and subsequent local progression at 6 months. CONCLUSION: Our initial experience indicated that transbronchial cryoablation was a safe and feasible procedure for non-surgical peripheral stage IA lung cancer or pulmonary metastases. TRIAL REGISTRATION NUMBER: ChiCTR2200061544.

Robotic-assisted bronchoscopy for the diagnosis of peripheral pulmonary lesions: A systematic review and meta-analysis.

Robotic-assisted bronchoscopy (RAB) is a newly developed bronchoscopic technique for the diagnosis of peripheral pulmonary lesions (PPLs). The objective of this meta-analysis was to analyze the diagnostic yield and safety of RAB in patients with PPLs. Five databases (PubMed, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov) were searched from inception to April 2023. Two independent investigators screened retrieved articles, extracted data, and assessed the study quality. The pooled diagnostic yield and complication rate were estimated. Subgroup analysis was used to explore potential sources of heterogeneity. Publication bias was assessed using funnel plots and the Egger test. Sensitivity analysis was also conducted to assess the robustness of the synthesized results. A total of 725 lesions from 10 studies were included in this meta-analysis. No publication bias was found. Overall, RAB had a pooled diagnostic yield of 80.4% (95% CI: 75.7%-85.1%). Lesion size of >30 mm, presence of a bronchus sign, and a concentric radial endobronchial ultrasound view were associated with a statistically significantly higher diagnostic yield. Heterogeneity exploration showed that studies using cryoprobes reported better yields than those without cryoprobes (90.0%, 95% CI: 83.2%-94.7% vs. 79.0%, 95% CI: 75.8%-82.2%, p < 0.01). The pooled complication rate was 3.0% (95% CI: 1.6%-4.4%). In conclusion, RAB is an effective and safe technique for PPLs diagnosis. Further high-quality prospective studies still need to be conducted.

Cryoablation triggers type I interferon-dependent antitumor immunity and potentiates immunotherapy efficacy in lung cancer.

BACKGROUND: Cryoablation is a minimally invasive option for patients with medically inoperable non-small cell lung cancer (NSCLC) and can trigger abscopal immune-regulatory effects. However, it remains unclear how cryoablation affects the host-level immune response in NSCLC. In this study, we investigated the local and systemic immunological effects of cryoablation and the potential of combining cryoablation with programmed cell death protein 1 (PD-1) blockade to boost immunotherapy efficacy in NSCLC. METHODS: We first investigated systemic immunological effects induced by cryoablation in patients with early-stage NSCLC. Subsequently, we explored cryoablation-induced antitumor immunity and the underlying biological mechanisms using KP (Kras G12D/+, Tp53 -/-) mutant lung cancer cell allograft mouse models. Moreover, the synergistic efficacy of cryoablation and PD-1 blockade was explored in both mouse models and patients with unresectable NSCLC. RESULTS: We found that cryoablation significantly increased circulating CD8+ T cell subpopulations and proinflammatory cytokines in patients with early-stage NSCLC. In lung cancer cell allograft mouse models, we demonstrated that cryoablation resulted in abscopal growth inhibition of contralateral, non-ablated tumors. Integrated analysis of bulk, single-cell RNA and T cell receptor (TCR) sequencing data revealed that cryoablation reprogrammed the intratumoral immune microenvironment and increased CD8+ T cell infiltration with higher effector signature, interferon (IFN) response, and cytolytic activity. Mechanistically, cryoablation promoted antitumor effect through the STING-dependent type I IFN signaling pathway, and type I IFN signaling blockade attenuated this antitumor effect. We also found that the combination of PD-1 blockade with cryoablation further inhibited tumor growth compared with either treatment alone in an allograft mouse model. Moreover, the combination therapy induced notable tumor suppression and CD8+ T cell infiltration in patients with unresectable NSCLC. CONCLUSIONS: Our results provide mechanistic insights into how cryoablation triggers the antitumor immune effect in lung cancer, thereby potentiating programmed cell death ligand 1 (PD-L1)/PD-1 blockade efficacy in the clinical treatment of NSCLC.

Cone-Beam Computed Tomography-Guided Cryobiopsy Combined with Conventional Biopsy for Ground Glass Opacity-Predominant Pulmonary Nodules.

INTRODUCTION: Cryobiopsy (CB) using a 1.1-mm cryoprobe under fluoroscopic guidance is feasible and safe for diagnosis of ground glass opacity (GGO) lesions. However, the efficacy of CB combined with cone-beam CT (CBCT) for GGO-predominant pulmonary nodules remains elusive. METHODS: We retrospectively studied patients who underwent CB combined with conventional biopsy under CBCT guidance for GGO-predominant pulmonary nodules with a consolidation-to-tumour ratio <50.0%. RESULTS: A total of 32 patients with GGO-predominant pulmonary nodules were enrolled: 17 pure GGOs and 15 mixed GGOs. The mean lesion diameter was 15.81 ± 5.52 mm and the overall diagnostic yield was 71.9%. Seven lesions were diagnosed by CB alone, which increased the diagnostic outcomes by 21.9%. Diagnostic yields for CB, forceps biopsy (FB), brushing, and guide sheath flushing were 65.6%, 46.9%, 15.6%, and 14.3%, respectively. Univariate analysis revealed that positive computed tomography (CT) bronchus sign (p = 0.035), positive CBCT sign (p < 0.01), and CB-first biopsy sequence (p = 0.036) were significant predictive factors for higher diagnostic yield. Specimens obtained by CB had larger mean sample size (p < 0.01), lower blood cell area (p < 0.01), and fewer crush artefacts (p < 0.01) than specimens from FB. No severe bleeding or other complications occurred. CONCLUSION: CB using a 1.1-mm cryoprobe under CBCT guidance increased diagnostic yield for GGO-predominant pulmonary nodules based on conventional biopsy. Further, it provided larger and nearly intact samples compared with forceps.

Effect of Tuina Combined with Chinese Herbal Compress on Primary Dysmenorrhea with Cold Coagulation and Blood Stasis Syndrome: A Study Protocol for a Randomized Controlled Trial.

INDRODUCTION: Primary dysmenorrhea (PD) is a very common issue in young women that reduces the quality of women's lives. Both Western medicine and traditional Chinese medicine (TCM) provide several ways to treat PD; however, TCM treatment exhibits fewer side effects for the patient. Tuina massage and Chinese herbal compresses are considered forms of external TCM therapy that have been widely used to treat PD, especially in China. Therefore, to provide the most effective and safe treatment for PD, we combined Tuina and Chinese herbal compresses together in this observational study. METHODS: A randomized controlled trial (RCT) consisting of 114 participants from the Shanghai University of Traditional Chinese Medicine who meet inclusion criteria will be divided into two groups in a 1:1 allocation ratio. The intervention group will receive Tuina combined with Chinese herbal compress therapy, while the control group will only receive Chinese herbal compress therapy. The treatment will be given 3 days before menstruation (once per day, 3 times per menstrual cycle). The primary outcome will be measured with the Visual Analog Scale (VAS). The secondary outcomes will be measured by the Dysmenorrhea Symptom Score, the Chinese Medical Dysmenorrhea Symptom Score, the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), and the pain threshold at Guanyuan (CV4). CONCLUSION: This study will be the first RCT that will entail the combination of Tuina and Chinese herbal compresses to treat PD in the category of cold coagulation and blood stasis syndrome. If the results demonstrate that Tuina combined with a Chinese herbal compress is effective, we posit that this study will provide evidence-based references for a potential alternative treatment to treat PD in the future.Die primäre Dysmenorrhoe (PD) ist ein Problem, das bei jungen Frauen sehr häufig auftritt und ihre Lebensqualität beeinträchtigt. Sowohl die westliche Medizin als auch die traditionelle chinesische Medizin (TCM) bieten verschiedene Therapiemöglichkeiten zur Behandlung der PD, allerdings ist die TCM mit weniger Nebenwirkungen für die Patientin verbunden. Tuina-Massage und chinesische Kräuterkompressen gelten als Formen der äußerlichen TCM-Therapie, die besonders in China zur Behandlung der PD weit verbreitet sind. Daher haben wir in dieser Beobachtungsstudie Tuina und chinesische Kräuterkompressen kombiniert, um eine möglichst wirksame und sichere Behandlung der PD bereitzustellen.Es handelt sich um eine randomisierte kontrollierte Studie (randomized controlled trial, RCT), bei der 114 Teilnehmerinnen der Shanghai University of Traditional Chinese Medicine, die die Einschlusskriterien erfüllen, im Verhältnis 1:1 in zwei Gruppen aufgeteilt werden. Die Interventionsgruppe erhält Tuina in Kombination mit chinesischen Kräuterkompressen, während die Kontrollgruppe nur eine Behandlung mit chinesischen Kräuterkompressen erhält. Die Behandlung erfolgt drei Tage vor der Menstruation (einmal täglich, dreimal pro Menstruationszyklus). Das primäre Zielkriterium wird anhand der visuellen Analogskala (VAS) gemessen. Die sekundären Zielkriterien werden mithilfe des Dysmenorrhoe-Symptom-Scores, des chinesischen medizinischen Dysmenorrhoe-Symptom-Scores, der Self-rating Anxiety Scale (SAS), der Self-rating Depression Scale (SDS) und der Schmerzschwelle am Guanyuan-Akupunkturpunkt (CV4) ermittelt.Diese Studie ist die erste randomisierte kontrollierte Studie, die die Kombination von Tuina und chinesischen Kräuterkompressen zur Behandlung von PD in der Kategorie Kältekoagulation und Blutstauungssyndrom untersucht. Sollten die Ergebnisse zeigen, dass Tuina in Kombination mit chinesischen Kräuterkompressen wirksam ist, erwarten wir, dass diese Studie evidenzbasierte Belege für eine mögliche alternative Behandlung von PD in der Zukunft liefern wird.

Effect of Baduanjin Qigong on Sleep Quality and Hyperarousal State in Adults With Chronic Insomnia: Protocol for a Randomized Controlled Trial.

BACKGROUND: Chronic insomnia (CI) is a mind-body disease that is commonly defined as a state of having disturbed daytime activities due to poor nighttime sleep quality. Baduanjin qigong (BDJQG) is widely used for CI in China. However, there is little scientific evidence to evaluate its effects on the hyperarousal state, which is closely associated with improved sleep quality. OBJECTIVE: The objective of the trial is to assess the therapeutic effects of BDJQG on sleep quality in patients with CI. METHODS: A randomized controlled trial will be conducted on 86 patients, who will be divided into a BDJQG group and a cognitive behavioral therapy for insomnia group at a ratio of 1:1. Interventions in both groups will be given to the participants 7 times a week for 8 weeks, and the participants will be followed up for 4 weeks. The primary outcome is the change in the Pittsburgh Sleep Quality Index from baseline to week 8. The secondary outcomes are the changes in the Hyperarousal Scale, Insomnia Severity Index, Fatigue Scale-14, wrist actigraphy, salivary cortisol level, and functional magnetic resonance imaging from baseline to week 8. All main analyses will be carried out on the basis of the intention-to-treat principle. RESULTS: This study was funded from January 2023. As of the submission of the manuscript, there were 86 participants. Data collection began in April 2023 and will end in January 2024. Data analysis is expected to begin in January 2024, with the publication of results expected in February 2024. CONCLUSIONS: This study will present data concerning the clinical effects of BDJQG on CI. The results will help to demonstrate whether BDJQG is an effective therapy for improving sleep quality in association with a decreased hyperarousal level as a possible underlying mechanism. This study will provide much-needed knowledge for complementary and alternative therapy for patients with CI. TRIAL REGISTRATION: China Clinical Registration Agency ChiCTR2300069241; https://chictr.org.cn/bin/project/ChiCTR2300069241. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/53501.

Structural-functional coupling abnormalities in temporal lobe epilepsy.

Background: Nowadays, researchers are using advanced multimodal neuroimaging techniques to construct the brain network connectome to elucidate the complex relationship among the networks of brain functions and structure. The objective of this study was to evaluate the coupling of structural connectivity (SC) and functional connectivity (FC) in the entire brain of healthy controls (HCs), and to investigate modifications in SC-FC coupling in individuals suffering from temporal lobe epilepsy (TLE). Methods: We evaluated 65 patients with TLE matched for age and gender with 48 healthy controls. The SC-FC coupling between regions was determined, based on which whole-brain nodes were clustered. Differences in the coupling among the three groups of nodes were compared. To further validate the results obtained, the within-cluster coupling indices of the three groups were compared to determine the inter-group differences. Results: Nodes were divided into five clusters. Cluster 1 was primarily located in the limbic system (n = 9/27), whereas cluster 5 was mainly within the visual network (n = 12/29). By comparing average cluster SC-FC coupling in each cluster of the three groups, we identified marked discrepancies within the three cohorts in Cluster 3 (p = 0.001), Cluster 4 (p < 0.001), and Cluster 5 (p < 0.001). Post-hoc analysis revealed that the SC-FC coupling strengths in LTLE and RTLE were significantly lower than that in HCs in Cluster 3 (PL = 0.001/PR = 0.003), Cluster 4 (PL = 0.001/PR < 0.001), and Cluster 5 (PL < 0.001/PR < 0.001). We also observed that the within-cluster SC-FC coupling in cluster 5 of left- and right TLE was significantly lower than in HCs (PL = 0.0001, PR = 0.0005). Conclusion: The SC and FC are inconsistently coupled across the brain with spatial heterogeneity. In the fifth cluster with the highest degree of coupling in HCs, the average SC-FC coupling index of individuals with TLE was notably less than that of HCs, manifesting that brain regions with high coupling may be more delicate and prone to pathological disruption.