Causal relationship between gut microbiota and intracranial hemorrhage: A two-sample Mendelian randomization study.

Patients with intracranial hemorrhage (ICH) usually have an imbalance in the gut microbiota (GM); however, whether this is a causal correlation remains unclear. This study used summary data from an open genome-wide association study to conduct double-sample Mendelian randomization (MR) to test the causal correlation between GM and ICH. First, we used a cutoff value of P < 10E-5 to select single nucleotide polymorphisms critical for each GM. Inverse variance weighted, weighted median, and MR-PRESSO methods were used to evaluate the strength of this causal association. Finally, functional maps and annotations from genome-wide association studies were used to determine the biological functions of the genes. MR analysis revealed that Rikenellaceae RC9 gut group was significantly positively correlated with ICH risk. For every unit increase in Rikenellaceae RC9 gut group, the relative risk of ICH increased by 34.4%(P = 4.62E-04). Rhodospirillales, Terrisporobacter, Veillonellaceae, Coprococcus 3, unknown genus, Alphaproteobacteria, and Allisonella groups were negatively correlated with the risk of ICH, while Anaerofilum, Eubacteriumbrachy group, Clostridia, Howardella, and Romboutsia were negatively correlated with the risk of ICH. Nonetheless, the specific role of single nucleotide polymorphisms gene enrichment requires further investigation. This study suggests the causal effect on ICH. The discovery of >10 GMs associated with ICH could be used to prevent and treat ICH.

Rebalancing SMAD7/SMAD3 Signaling Reduces Adhesion Formation during Flexor Tendon Healing.

Transforming growth factor-ß is a key factor in regulating adhesion formation during tendon healing. We investigated the effectiveness of SMAD family members, SMAD7 and SMAD3, in the TGF-ß/Smad signaling during flexor tendon repair. Mouse flexor toe deep tendon rupture anastomosis models were made. On days 3, 7, 14, 21, and 28, the expressions of smad7 and smad3 in flexor tendon tissues were detected by RT-qPCR and western blot. Furthermore, postoperative intraperitoneal injections of SMAD7 agonists or SMAD3 antagonists were given. The degree of tendon healing was evaluated by adhesion testing and biomechanical experiments. Hematoxylin and eosin (HE) staining was used to observe the pathological changes. Immunohistochemistry was used to evaluate the expressions of collagen III, SMAD3, and SMAD7. The mRNA levels of matrix metalloproteinases, Mmp2 and Mmp9, and scleraxis (SCX) in flexor tendon tissue were detected by RT-qPCR. Smad3 expression increased and Smad7 expression decreased in flexor tendon tissue after injury. In addition, the SMAD7 agonist blocked SMAD3 phosphorylation. SMAD7 agonist and SMAD3 antagonist both improved adhesion formation during flexor tendon healing, and decreased the expressions of collagen III, Mmp9, and SCX, while increasing Mmp2 expression. This study provides a possible theoretical basis for the SMAD7-SMAD3 signal cascade during flexor tendon adhesion healing.

Transcranial Magnetic Stimulation for Improving Dysphagia After Stroke: A Meta-Analysis of Randomized Controlled Trials.

Background: Rehabilitation of post-stroke dysphagia is an urgent clinical problem, and repetitive transcranial magnetic stimulation (rTMS) has been widely used in the study of post-stroke function. However, there is no reliable evidence-based medicine to support the effect of rTMS on post-stroke dysphagia. This review aims to evaluate the effectiveness and safety of rTMS on post-stroke dysphagia. Methods: English-language literature published before December 20, 2021, were searched in six electronic databases. Identified articles were screened, data were extracted, and the methodological quality of included trials was assessed. Meta-analysis was performed using RevMan 5.3 software. The GRADE method was used to assess the quality of the evidence. Results: A total of 10 studies with 246 patients were included. Meta-analysis showed that rTMS significantly improved overall swallowing function (standardized mean difference [SMD]-0.76, 95% confidence interval (CI)-1.07 to-0.46, p < 0.0001, n = 206; moderate-quality evidence), Penetration Aspiration Scale (PAS) (mean difference [MD]-1.03, 95% CI-1.51 to-0.55, p < 0.0001, n = 161; low-quality evidence) and Barthel index scale (BI) (MD 23.86, 95% CI 12.73 to 34.99, p < 0.0001, n = 136; moderate-quality evidence). Subgroup analyses revealed that (1) rTMS targeting the affected hemisphere and targeting both hemispheres significantly enhanced overall swallowing function and reduced aspiration. (2) Low-frequency rTMS significantly enhanced overall swallowing function and reduced aspiration, and there was no significant difference between high-frequency rTMS and control group in reducing aspiration (p = 0.09). (3) There was no statistical difference in the dropout rate (low-quality evidence) and adverse effects (moderate-quality evidence) between the rTMS group and the control group. Conclusion: rTMS improved overall swallowing function and activity of daily living ability and reduced aspiration in post-stroke patients with good acceptability and mild adverse effects.

TGF-ß3 regulates adhesion formation through the JNK/c-Jun pathway during flexor tendon healing.

BACKGROUND: The injured flexor tendon has poor healing ability, which is easy to cause tendon adhesion. It can affect the recovery of tendon function, which is still a long-term and difficult task for surgeons. Transforming growth factor ß (TGF-ß) has been widely considered to play an important role in flexor tendon repair in recent years. AIM: This work was to investigate the anti-adhesion and anti-inflammatory effects of TGF-ß3 on flexor digitorum longus (FDL) tendon repair rats. METHOD: Anastomosis models of tendon laceration in the flexion toes of rats were delivered with no treatment, vehicle, or TGF-ß3 -overexpressed adenovirus vector (ad-TGF-ß3) locally to the injured tendon area from day 3 to 8. Subsequently, the expression of TGF-ß3, TGF-ß1/2, Smad3, Smad7, JNK, phosphorylation (p)-JNK, c-Jun, and phosphorylation (p)-c-Jun were detected by western blot, the expression of Mmp9 and Mmp2 by RT-qPCR, the Range of motion (ROM) and gliding resistance by adhesion formation testing, the mechanical strength of tendon healing by biomechanical testing, the pathologic changes of flexor tendon tissues by HE staining, the expression of collagen type III by immunohistochemical staining, and the levels of IL-6, TNF-α, COX2 and IL-1ß in serum by ELISA, respectively. RESULTS: Rat models treated with no treatment showed a lower elevation of TGF-ß3 and Smad7 expression, and a higher elevation of TGF-ß1/2 and Smad3 expression, during day 14 to day 28. Besides, under the treatment of ad-TGF-ß3, a significantly increase was reflected in the expression of TGF-ß3 and Smad7, ROM, as well as mechanical strength of flexor tendon, whereas significantly reduction was shown in gliding resistance, the content of inflammatory cytokines, the ratio of p-JNK/JNK, p-c-Jun/c-Jun, as well as the expression of TGF-ß1/2, Smad3, Mmp9, and Mmp2 genes, as compared to those from vehicle treatment. Meanwhile, TGF-ß3 demonstrated a better pathologic recovery process with no obvious necrosis or fracture of collagen fibers. Besides, TGF-ß3 revealed a significant reduction of collagen type-III expression in the flexor tendon healing tissues. CONCLUSION: These findings suggested that TGF-ß3 effectively protected against flexor tendon injury via regulating adhesion formation.