Efficacy of rTMS in treating functional impairment in post-stroke patients: a systematic review and meta-analysis.

BACKGROUND: Most stroke patients suffer from an imbalance in blood supply, which causes severe brain damage leading to functional deficits in motor, sensory, swallowing, cognitive, emotional, and speech functions. Repetitive transcranial magnetic stimulation (rTMS) is thought to restore functions impaired during the stroke process and improve the quality of life of stroke patients. However, the efficacy of rTMS in treating post-stroke function impairment varies significantly. Therefore, we conducted a meta-analysis of the number of patients with effective rTMS in treating post-stroke dysfunction. METHODS: The PubMed, Embase, and Cochrane Library databases were searched. Screening and full-text review were performed by three investigators. Single-group rate meta-analysis was performed on the extracted data using a random variable model. Then subgroup analyses were performed at the levels of stroke acuity (acute, chronic, or subacute); post-stroke symptoms (including upper and lower limb motor function, dysphagia, depression, aphasia); rTMS stimulation site (affected side, unaffected side); and whether or not it was a combination therapy. RESULTS: We obtained 8955 search records, and finally 33 studies (2682 patients) were included in the meta-analysis. The overall analysis found that effective strength (ES) of rTMS was 0.53. In addition, we found that the ES of rTMS from acute/subacute/chronic post-stroke was 0.69, 0.45, and 0.52. We also found that the ES of rTMS using high-frequency stimulation was 0.56, while the ES of rTMS using low-frequency stimulation was 0.53. From post-stroke symptoms, we found that the ES of rTMS in sensory aspects, upper limb functional aspects, swallowing function, and aphasia was 0.50, 0.52, 0.51, and 0.54. And from the site of rTMS stimulation, we found that the ES of rTMS applied to the affected side was 0.51, while the ES applied to the unaffected side was 0.54. What's more, we found that the ES of rTMS applied alone was 0.53, while the ES of rTMS applied in conjunction with other therapeutic modalities was 0.53. CONCLUSIONS: By comparing the results of the data, we recommend rTMS as a treatment option for rehabilitation of functional impairment in patients after stroke. We also recommend that rehabilitation physicians or clinicians use combination therapy as one of the options for patients.

Bidirectional Mendelian randomization analysis of the genetic association between primary lung cancer and colorectal cancer.

BACKGROUND: With the development and popularization of low-dose chest CT technology, the diagnosis and survival rates of patients with early lung cancer (LC) have significantly improved. The occurrence of colorectal cancer (CRC) as the second primary cancer (SPC) in primary lung cancer (PLC) survivors has become an essential factor affecting the prognosis of early LC. This study explored the potential association between PLC and CRC genetically, laying a foundation for developing SPC-CRC prevention strategies after primary early LC. METHODS: Based on a two-sample bidirectional Mendelian randomization (MR) design, this study systematically screened genetic instrumental variables (IVs) based on the genome-wide association studies (GWAS) of PLC and CRC, applied inverse variance weighted (IVW) as the main method to assess the incidence association between the two cancers, and used a variety of other MR methods for supplementary analysis. Finally, the Genetic Risk Scores (GRS) method was used for secondary analysis to verify the results robustness further. RESULTS: From LC to CRC forward MR analysis, 20 genetic IVs of overall LC, 15 genetic IVs of squamous cell lung carcinoma (LUSC), and 10 genetic IVs of adenocarcinoma of the lung (LUAD) were screened. In the reverse MR analysis from CRC to LC, 47 genetic IVs for overall CRC, 37 for colon cancer, and 25 for rectal cancer were screened. The IVW method and a variety of MR methods all found that overall LC and CRC were significantly associated at the genetic level. Subgroup analysis also showed that LUSC was associated with CRC. And the results of the GRS method were consistent with those of the main analysis, confirming the robustness of the study. Our MR study found an association between LC and CRC, with an increased risk of SPC-CRC following PLC, especially LUSC. Our study provides an essential basis for the precise prevention of SPC-CRC after PLC, suggesting that we should pay more attention to the population with a history of PLC in clinical work, and pay close attention to the incidence of SPC-CRC, and carry out intervention and treatment as soon as possible.

Cancer-testis non-coding RNA LEF1-AS1 regulates the nuclear translocation of PDCD5 and suppresses its interaction with p53 signaling: a novel target for immunotherapy in esophageal squamous cell carcinoma.

Despite the improvement of current classical treatment, the prognosis of esophageal squamous cell carcinoma (ESCC) remains poor. Immunotherapy, as a new treatment method, has revolutionized the therapy of various cancer types and created more attractive for ESCC. Cancer-testis genes (CTGs), because of its characteristic expression and immunomodulation property, are considered as the ideal targets for tumor immunotherapy. However, the ESCC-specific CTGs, especially long non-coding RNA (lncRNA), has not been elucidated. In the present study, a systematic strategy was adopted to screen ESCC-specific cancer-testis lncRNA (CT-lncRNA). Collectively, 447 genes were recognized as ESCC-specific CT-lncRNAs, in particularly LEF1-AS1 showed the most aberrantly expression and clinically associated with poor outcome. Functional assays revealed that H3K27 acetylation in LEF1-AS1 promoter might give rise to the activation of LEF1-AS1 during ESCC tumorigenesis. The activated LEF1-AS1 was predominantly localized in the cytoplasm implicated in regulation of apoptosis and proliferation capacities of ESCC cells in vitro and in vivo. Further mechanistic studies unveiled that LEF1-AS1 participated in ESCC by interacting with RNA binding protein PDCD5 through weakened its nuclear translocation binding to TP53, leading to p53 degradation and disruption the transcription of downstream genes. Taken together, our findings suggest that LEF1-AS1 acts as a CT-lncRNA and might be an ideal immunotherapeutic target for clinical intervention for ESCC.

Bidirectional Mendelian randomization analysis investigating the genetic association between primary breast cancer and colorectal cancer.

Purpose: With the advancement in early diagnosis and treatment, the prognosis for individuals diagnosed with breast cancer (BC) has improved significantly. The prognosis of primary breast cancer (PBC) survivors can be significantly influenced by the occurrence of colorectal cancer (CRC) as a secondary primary cancer (SPC). The objective of this study is to explore the possible genetic association between PBC and CRC, aiming to lay a groundwork for the development of preventive strategies against SPC-CRC following BC surgery. Methods: We employed a bidirectional two-sample Mendelian randomization (MR) approach to thoroughly examine genetic instrumental variables (IVs) derived from genome-wide association studies (GWAS) conducted on PBC and CRC. And applied inverse variance weighted (IVW) and multiple other MR methods (weighted median, simple median, MR-PRESSO and MR-RAPS) to evaluate the association between the two cancers (PBC and CRC) at genetic level. Furthermore, the robustness of the findings was further confirmed through the utilization of the genetic risk score (GRS) method in a secondary analysis. Results: Forward MR analysis, a total of 179 BC genetic IVs, 25 estrogen receptor-negative (ER-) genetic IVs and 135 ER-positive (ER+) genetic IVs were screened. Reverse MR analysis, 179 genetic IVs of CRC, 25 genetic IVs of colon cancer, 135 genetic IVs of rectal cancer, 25 genetic IVs of left colon cancer and 135 genetic IVs of right colon cancer were screened. IVW and other MR methods found no significant genetic association between PBC and CRC (P > 0.05). Subgroup analysis also showed that ER- BC and ER+ BC were not correlated with the occurrence of CRC (P > 0.05). The findings of the secondary analysis using GRS were consistent with those obtained from the primary analysis, thereby confirming the robustness and reliability of this study. Conclusions: Our findings do not provide any evidence supporting the association between PBC and CRC at the genetic level. Further large-scale prospective studies are warranted to replicate our findings.

Smoking, alcohol consumption, diabetes, body mass index, and peptic ulcer risk: A two-sample Mendelian randomization study.

Background: Observational evidence has shown that smoking, alcohol consumption, type 2 diabetes, and body mass index (BMI) are risk factors for peptic ulcer disease (PUD), including gastric ulcer (GU) and duodenal ulcer (DU). However, the observed associations may be confounding factors. Herein, we use Mendelian randomization (MR) to examine causal associations such as smoking, alcohol, type 2 diabetes, BMI, and risks of PUD. Methods: We used 8,17,41,325,82, 231, and 616 identified genetic variants as proxies for age of smoking initiation (AgeSmk), smoking cessation (SmkCes, current/former), number of cigarettes smoked per day (CigDay), smoking status (SmkIni, ever/never), alcohol consumption, type 2 diabetes, and BMI to obtain unconfounded effect estimates on the GU and DU levels among 452,264 participants from the Gene ATLAS. The causal relationship was estimated by using inverse-variance weighted (IVW) as the main method. Sensitivity analysis includes Cochran's Q test, the MR-Egger test, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-robust adjusted profile score (MR-RAPS). In addition, secondary MR analysis was conducted within summary data using genetic risk scores (GRSs) as instrumental variables (IVs). Results: In our two-sample MR analyses, genetic predisposition to smoking (SmkInit) and BMI were associated with an increased risk of GU. The beta values were 0.0035 (95% CI, 0.0021, 0.0049, p = 1.56E-06) for smoking (SmkInit) and 0.0021 (95% CI, 0.0009, 0.0033, p = 0.0008) for BMI. Genetic predisposition to smoking (SmkInit) and higher genetically predicted BMI were associated with an increased risk of DU. The beta values of DU were 0.0029 (95% CI, 0.0017, 0.0041, p = 2.43E-06) for smoking (SmkInit) and 0.0018 (95% CI, 0.0007, 0.0029, p = 0.001) for BMI. No other causal association between smoking (AgeSmk, CigDay, and SmkCes), alcohol consumption, type 2 diabetes, and GU or DU was observed. Consistent results were obtained in sensitivity analyses. Furthermore, the GRS approach showed similar results in the several MR methods. Conclusion: These findings do not support a causal role of AgeSmk, CigDay, SmkCes, alcohol consumption, and type 2 diabetes in the development of GU and DU. However, it is confirmed that SmkInit and BMI have a causal part in the development of GU and DU.