Effects of cerebellar repetitive transcranial magnetic stimulation in the treatment of post-stroke dysphagia: a meta-analysis and systematic review of randomized controlled trials.

Introduction：This study aimed to comprehensively evaluate the therapeutic efficacy of cerebellar repetitive transcranial magnetic stimulation (rTMS) in the rehabilitation of post-stroke dysphagia (PSD). Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed, Cochrane Library, Embase, and Web of Science to identify relevant randomized controlled trials (RCTs) investigating the application of cerebellar rTMS in the treatment of PSD. Inclusion and exclusion criteria were rigorously applied during the screening process, and pertinent characteristics of the included RCTs were meticulously extracted. The I2 statistic was employed to assess heterogeneity, and meta-analysis was conducted using Stata 17 software. The Cochrane Risk of Bias 2 tool and Pedro scale were utilized to evaluate bias risk and literature quality. Results: Our analysis encompassed a total of 5 RCTs involving 673 patients with dysphagia who met the inclusion criteria. The findings indicated a significant positive impact of cerebellar rTMS when combined with traditional swallowing exercises on PSD, demonstrating superior efficacy compared to conventional swallowing exercises in isolation. Furthermore, the study revealed no statistically significant differences based on stimulation site (unilateral vs. bilateral cerebellum), stimulation mode (rTMS vs. intermittent theta-burst stimulation [iTBS]), and stimulation frequency (5Hz vs. 10Hz).

LncRNA pol-lnc78 as a ceRNA regulates antibacterial responses via suppression of pol-miR-n199-3p-mediated SARM down-regulation in Paralichthys olivaceus.

Long non-coding RNAs (lncRNAs) function as key modulators in mammalian immunity, particularly due to their involvement in lncRNA-mediated competitive endogenous RNA (ceRNA) crosstalk. Despite their recognized significance in mammals, research on lncRNAs in lower vertebrates remains limited. In the present study, we characterized the first immune-related lncRNA (pol-lnc78) in the teleost Japanese flounder ( Paralichthys olivaceus). Results indicated that pol-lnc78 acted as a ceRNA for pol-miR-n199-3p to target the sterile alpha and armadillo motif-containing protein (SARM), the fifth discovered member of the Toll/interleukin 1 (IL-1) receptor (TIR) adaptor family. This ceRNA network regulated the antibacterial responses of flounder via the Toll-like receptor (TLR) signaling pathway. Specifically, SARM acted as a negative regulator and exacerbated bacterial infection by inhibiting the expression of inflammatory cytokines IL-1ß and tumor necrosis factor-α (TNF-α). Pol-miR-n199-3p reduced SARM expression by specifically interacting with the 3' untranslated region (UTR), thereby promoting SARM-dependent inflammatory cytokine expression and protecting the host against bacterial dissemination. Furthermore, pol-lnc78 sponged pol-miR-n199-3p to ameliorate the inhibition of SARM expression. During infection, the negative regulators pol-lnc78 and SARM were significantly down-regulated, while pol-miR-n199-3p was significantly up-regulated, thus favoring host antibacterial defense. These findings provide novel insights into the mechanisms underlying fish immunity and open new horizons to better understand ceRNA crosstalk in lower vertebrates.

An overview of systematic reviews of acupuncture for neurodegenerative disease.

BACKGROUND: Acupuncture has been widely used in the treatment of neurodegenerative diseases and a large number of systematic reviews (SRs) have been published, but the results are controversial. Therefore, it is necessary to comprehensively summarize and objectively evaluate the clinical evidence of acupuncture for neurodegenerative diseases. OBJECTIVE: To evaluate the SRs that assess the efficacy and safety of acupuncture for neurodegenerative diseases. This overview is intended to provide evidence for clinical decision making by healthcare providers and policymakers and to provide evidence for clinical decision making by healthcare providers and policymakers and to provide recommendations for researchers to conduct high quality SRs and clinical studies. METHODS: We searched four Chinese databases (SinoMed, CNKI, Wanfang and VIP) and four international databases (Cochrane Library, Embase, PubMed and Web of Science) for SRs of acupuncture for neurodegenerative diseases. The search period ran from the beginning of the database to March 5, 2023. Literature screening and data extraction were performed independently by two individuals. Methodological quality, risk of bias and associated evidence levels were assessed for all SRs using AMSTER 2, ROBIS and GRADE tools. In addition, the RCT overlap between SRs was calculated by corrected coverage area (CCA). We also conducted quantitative synthesis or descriptive analysis of the relevant data. RESULTS: Finally, we identified 53 SRs (three were qualitative descriptions and fifty were meta-analyses). Under AMSTAR 2, only one SR was rated as moderate quality, six SRs as low quality and 46 SRs as very low quality. According to ROBIS, 33 SRs were rated as a high risk of bias and 20 as a low risk of bias. Cognitive functions in neurodegenerative diseases, activities of daily living and the motor and non-motor outcomes associated with PD were included to summary description. The pooled results show that acupuncture combined with conventional treatment may have an overall advantage over conventional treatment, but the quality of evidence is low. Specific adverse reactions/events were reported in 20 SRs. Common needle-related adverse events included pain, dizziness, bleeding, or subcutaneous hematoma. No severe adverse events were reported in any SRs. CONCLUSION: Evidence suggests that acupuncture is generally effective and relatively safe for cognitive function and activities of daily living in neurodegenerative diseases. In addition, acupuncture may have some benefits in improving motor and non-motor symptoms in patients with PD. However, high-quality RCTs and SRs are still needed to further clarify the efficacy and safety of acupuncture in treating neurodegenerative diseases.

Acupuncture combined with Chinese herbal medicine in the treatment of perimenopausal insomnia: A systematic review and meta-analysis.

BACKGROUND: Perimenopausal insomnia (PMI) is a relatively common menopausal symptom that can cause serious problems for the women themselves and their families. Today, the world is facing the trend and challenges of an aging population. It is reported that about 1.5 million women worldwide enter menopause every year, with sleep disorder identified as a core symptom. The efficacy of acupuncture combined with traditional Chinese medicine for treating PMI has been recognized by patients and doctors. METHODS: We searched 8 databases to identify 15 randomized controlled trials evaluating the effects of acupuncture combined with traditional Chinese medicine on sleep in patients with PMI compared with Western medicine alone. Subsequently, data extraction and analysis were performed to assess the quality and risk of bias of the study method design, and a meta-analysis of the data was performed. RESULTS: This study included 15 randomized controlled trials involving 1188 patients with PMI. The results show that acupuncture combined with traditional Chinese medicine seems to be more effective than Western medicine in the treatment of PMI: efficiency (RR: 1.18; 95% CI: 1.08, 1.29; P = .001); the Pittsburgh Sleep Quality Index (PSQI) (WMD: -2.77; 95% CI: 4.15-1.39; P < .0001); follicle-stimulating hormone (FSH) (WMD: -31.45; 95% CI: 42.7-20.2; P < .001) and the Hamilton Anxiety Score (HAMA) (WMD: -2.62, 95% CI: -3.93, -1.32; P < .0001). Compared with western medicine, E2 (WMD: 5.07; 95% CI: 5.78-15.92; P = .36) and LH (WMD: -4.86; 95% CI: 11.5-1.78; P = .151) had no difference. CONCLUSION: The current analysis results show that acupuncture combined with Chinese medicine seems to have a more positive effect than western medicine alone in improving sleep and FSHF in PMI patients, but no difference has been found in improving E2 and LH. This study provides a basis for acupuncture combined with Chinese medicine to treat PMI. However, due to the higher risk of evaluation in included studies, more rigorous randomized controlled trials and higher quality studies are needed to validate included studies.

Effects of acupuncture on mental health of migraine patients: a systematic review and meta-analysis.

BACKGROUND: Migraine is a neurological disease characterized by moderate to severe headache and various neurological symptoms. It is often cause mood and anxiety disorders that can seriously affect quality of life. Acupuncture has been claimed to have a role in treating neuropsychiatric disorders and is becoming increasingly popular. However, it remains unclear whether current evidence is sufficient to support acupuncture in improving mental health in migraine patients. OBJECTIVES: This systematic review and meta-analysis aimed to investigate the effect of acupuncture on the management of pain and mood disorders in patients with migraine. METHODS: We searched PubMed, Cochrane Library, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI) and Wan Fang Data Knowledge Service Platform for reports, conferences and academic papers published before January 1, 2022. Randomized controlled trials (RCTs) including acupuncture, sham acupuncture and medication for migraine were included. Stata 16.0 software and Cochrane RoB2.0 were used for data processing and migration risk analysis. RESULT: Thirteen randomized controlled trials containing 1766 migraine patients were included in the present study, the results showed that compared with sham acupuncture and medication, acupuncture seemed to have advantage in improving SAS (WMD: -5.64;95% CI: -10.89, -0.39; p = 0.035) and SDS (WMD: -4.65; 95% CI: -9.25, -0.05; p = 0.048) in migraine patients. And it seems to be more effective in improving MH (SMD: 0.77; 95% CI: 0.19, 1.35; p = 0.009), VAS (SMD: -1.06; 95% CI: -1.73, -0.4; p = 0.002;) and MSQ (WMD: 4.76; 95% CI: 2.36, 7.15; p < 0.001) than sham acupuncture and medication. CONCLUSION: The present results suggest that, compared with Western medicine and sham acupuncture, acupuncture seems to be able to effectively improve anxiety and depression in migraine patients.And it may be more effective in improving SF36-mental health, VAS and MSQ than shame acupuncture or Western medicine. The results of this study need to be verified by higher quality RCTs.

TEAS, DHEA, CoQ10, and GH for poor ovarian response undergoing IVF-ET: a systematic review and network meta-analysis.

BACKGROUND: Assisted reproductive technology (ART) has brought good news to infertile patients, but how to improve the pregnancy outcome of poor ovarian response (POR) patients is still a serious challenge and the scientific evidence of some adjuvant therapies remains controversial. AIM: Based on previous evidence, the purpose of this systematic review and network meta-analysis was to evaluate the effects of DHEA, CoQ10, GH and TEAS on pregnancy outcomes in POR patients undergoing in vitro fertilization and embryo transplantation (IVF-ET). In addition, we aimed to determine the current optimal adjuvant treatment strategies for POR. METHODS: PubMed, Embase, The Cochrane Library and four databases in China (CNKI, Wanfang, VIP, SinoMed) were systematically searched up to July 30, 2022, with no restrictions on language. We included randomized controlled trials (RCTs) of adjuvant treatment strategies (DHEA, CoQ10, GH and TEAS) before IVF-ET to improve pregnancy outcomes in POR patients, while the control group received a controlled ovarian stimulation (COS) regimen only. This study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The surface under the cumulative ranking curve (SUCRA) was used to provide a pooled measure of cumulative ranking for each outcome. RESULTS: Sixteen RCTs (2323 women) with POR defined using the Bologna criteria were included in the network meta-analysis. Compared with the control group, CoQ10 (OR 2.22, 95% CI: 1.05 to 4.71) and DHEA (OR 1.92, 95% CI: 1.16 to 3.16) had obvious advantages in improving the clinical pregnancy rate. CoQ10 was the best in improving the live birth rate (OR 2.36, 95% CI: 1.07 to 5.38). DHEA increased the embryo implantation rate (OR 2.80, 95%CI: 1.41 to 5.57) and the high-quality embryo rate (OR 2.01, 95% CI: 1.07 to 3.78) and number of oocytes retrieved (WMD 1.63, 95% CI: 0.34 to 2.92) showed a greater advantage, with GH in second place. Several adjuvant treatment strategies had no significant effect on reducing the cycle canceling rate compared with the control group. TEAS was the least effective of the four adjuvant treatments in most pooled results, but the overall effect appeared to be better than that of the control group. CONCLUSION: Compared with COS regimen, the adjuvant use of CoQ10, DHEA and GH before IVF may have a better clinical effect on the pregnancy outcome of POR patients. TEAS needs careful consideration in improving the clinical pregnancy rate. Future large-scale RCTs with direct comparisons are needed to validate or update this conclusion. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022304723.

Continual learning with attentive recurrent neural networks for temporal data classification.

Continual learning is an emerging research branch of deep learning, which aims to learn a model for a series of tasks continually without forgetting knowledge obtained from previous tasks. Despite receiving a lot of attention in the research community, temporal-based continual learning techniques are still underutilized. In this paper, we address the problem of temporal-based continual learning by allowing a model to continuously learn on temporal data. To solve the catastrophic forgetting problem of learning temporal data in task incremental scenarios, in this research, we propose a novel method based on attentive recurrent neural networks, called Temporal Teacher Distillation (TTD). TTD solves the catastrophic forgetting problem in an attentive recurrent neural network based on three hypotheses, namely Rotation Hypothesis, Redundant Hypothesis, and Recover Hypothesis. Rotation Hypothesis and Redundant hypotheses could cause the attention shift phenomenon, which degrades the model performance on the learned tasks. Moreover, not considering the Recover Hypothesis increases extra memory usage in continuously training different tasks. Therefore, the proposed TTD based on the above hypotheses complements the inadequacy of the existing methods for temporal-based continual learning. For evaluating the performance of our proposed method in task incremental setting, we use a public dataset, WIreless Sensor Data Mining (WISDM), and a synthetic dataset, Split-QuickDraw-100. According to experimental results, the proposed TTD significantly outperforms state-of-the-art methods by up to 14.6% and 45.1% in terms of accuracy and forgetting measures, respectively. To the best of our knowledge, this is the first work that studies continual learning in real-world incremental categories for temporal data classification with attentive recurrent neural networks and provides the proper application-oriented scenario.

Effect of transcutaneous electrical acupoint stimulation on pregnancy outcomes in women with in vitro fertilization-embryo transfer: A systematic review and meta-analysis.

Objective: The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) on pregnancy outcomes in women undergoing in vitro fertilization-embryo transfer (IVF-ET), in order to provide evidence-based medical support. Methods: We searched the Cochrane Library, Embase, PubMed, Web of Science, SinoMed, and CNKI for relevant randomized controlled trials (RCTs) from inception to 31 May 2022, using the search terms "transcutaneous electrical acupoint stimulation," "TEAS," "in vitro fertilization-embryo transfer," "IVF-ET," "randomized controlled trial," and "clinical trials." The experimental group was treated with TEAS or combined with ovulation-inducing medication, and the control group was treated with mock TEAS (mTEAS), ovulation-inducing medication, or no intervention. The main outcome was the clinical pregnancy rate. Secondary outcomes were the embryo implantation rate, live birth rate, biochemical pregnancy rate, and number of oocytes retrieved. Stata15.1 software was used for data summary and analysis. Results: This review involved 15 RCTs and 4,281 participants. TEAS were superior to the control group for improving the clinical pregnancy rate [RR: 1.29, 95% CI: 1.19 to 1.40; p < 0.001; I2 = 23.0%], embryo implantation rate [RR: 1.43, 95% CI: 1.22 to 1.69; p < 0.001; I2 = 35.9%], live birth rate [RR: 1.33, 95% CI: 1.14 to 1.54; p < 0.001; I2 = 47.3%], and biochemical pregnancy rate [RR: 1.15, 95% CI: 1.05 to 1.26; p = 0.003; I2 = 49.1%], without significant heterogeneity. TEAS had no statistically significant effect on the number of oocytes retrieved as compared with the control group, and the heterogeneity was high [SMD: 0.34, 95% CI: -0.04 to 0.72; p = 0.081; I2 = 77.6%]. We performed subgroup analysis based on the sample size, interventions and intervention time-point. The results showed that the sample size had no effect on the results. There was no significant difference between TEAS and ovulation-inducing medication in the clinical pregnancy rate or the embryo implantation rate. In addition, TEAS did not significantly increase the embryo implantation rate or the live birth rate, compared with no intervention. In terms of safety, mild allergic symptoms were found in both the experimental group and the control group. Conclusion: In general, existing evidence supports the potential value of TEAS as an adjunctive treatment for improving pregnancy outcomes. High-quality, large-sample RCTs are needed to further support this conclusion. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=334892, identifier PROSPERO CRD42022334892.

Cytotoxic flavonoids from the leaves of Callicarpa nudiflora hook.

A new flavonoid glycoside, luteolin-3'-O-ß-D-6″-acetyl glucopyranoside (1), along with six known flavonoids, were isolated from the leaves of Callicarpa nudiflora Hook. The structures of the isolated compounds were established on the basis of extensive spectroscopic analyses. Compound 6 exhibited potent cytotoxicity and compounds 1 and 7 exhibited moderate cytotoxicity against human hepatocellular carcinoma SMMC-7721 cells.

Probiotics for constipation in Parkinson's: A systematic review and meta-analysis of randomized controlled trials.

Background: Parkinson's disease (PD)-related constipation may affects both disease occurrence and disease progression. Probiotics, as a potential therapeutic intervention, have attracted the attention of researchers, but the evidence of their efficacy and safety has not been systematically reviewed. Aim: A systematic review and meta-analysis of randomized controlled trials of probiotics in the treatment of PD constipation was conducted to determine the efficacy and safety of probiotics in the treatment of PD constipation. Methods: Four databases (The Cochrane Central Register of Controlled Trials, Embase, PubMed, and Web of Science) were searched from their establishment to June 1, 2022. We included randomized controlled trials of probiotics for the treatment of constipation in patients with PD, with probiotics in the experimental group and a placebo, another treatment, or no treatment in the control group. The primary outcome was the number of bowel movements per week. Secondary outcomes included nonmotor symptoms (NMS), gut transit time (GTT), abdominal pain, abdominal distention, constipation, and quality of life scores. Stata15.1 was used to generate a summary of the data and perform a descriptive analysis if necessary. The GRADE tool was used to assess the quality of the evidence and the Cochrane guidelines to assess the risk of bias for each study. Results: Finally, four qualified RCTs were included, comprising 287 participants. Compared with the control group, probiotics could effectively increase the frequency of defecation per week in PD patients (WMD = 1.02. 95%CI: 0.56-1.48, and P < 0.00001), but the heterogeneity was high, and the quality of the evidence was low. There was no significant difference in average stool consistency between patients with PD treated with probiotics and those given a placebo in (WMD = -0.08. 95%CI: -1.42-1.26, and P = 0.908). In addition, the results suggested that probiotics have no obvious effect on additional indicators of gastrointestinal dysfunction, such as GTT, abdominal pain, and abdominal distension, and there is insufficient evidence on their ability to improve NMS and Parkinson's disease Questionnaire 39 summary indices (PDQ39-SI). Safety issues should be carefully explained. Conclusion: There is insufficient evidence supporting the use of probiotics to treat constipation in patients with PD. Taking all the results together, probiotics have potential value in the treatment of PD-related constipation. Systematic Review Registration: PROSPERO CRD42022331325.

Clinical Study of Intraoperative Microelectrode Recordings during Awake and Asleep Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease: A Retrospective Cohort Study.

Our objective is to analyze the difference of microelectrode recording (MER) during awake and asleep subthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson's disease (PD) and the necessity of MER during "Asleep DBS" under general anesthesia (GA). The differences in MER, target accuracy, and prognosis under different anesthesia methods were analyzed. Additionally, the MER length was compared with the postoperative electrode length by electrode reconstruction and measurement. The MER length of two groups was 5.48 ± 1.39 mm in the local anesthesia (LA) group and 4.38 ± 1.43 mm in the GA group, with a statistical significance between the two groups (p < 0.01). The MER length of the LA group was longer than its postoperative electrode length (p < 0.01), however, there was no significant difference between the MER length and postoperative electrode length in the GA group (p = 0.61). There were also no significant differences in the postoperative electrode length, target accuracy, and postoperative primary and secondary outcome scores between the two groups (p > 0.05). These results demonstrate that "Asleep DBS" under GA is comparable to "Awake DBS" under LA. GA has influences on MER during surgery, but typical STN discharges can still be recorded. MER is not an unnecessary surgical procedure.

Chinese herbal medicine xuebijing injection for acute pancreatitis: An overview of systematic reviews.

Background: At present, a number of systematic reviews (SRs) on Xuebijing injection (a patent in China) in the treatment of acute pancreatitis (AP) or severe acute pancreatitis (SAP) have been published. However, the quality of evidence is uneven and has not been comprehensively evaluated. Aim: We evaluated the efficacy of Xuebijing injection for AP/SAP through an overview of SR, and to provide a scientific basis for its effectiveness and safety. Methods: We searched Cochrane Library, Embase, PubMed, SinoMed, CNKI, Wanfang, and VIP comprehensively. The retrieval period from inception to 30 November 2021, and the two reviewers independently complete the literature retrieval, data extraction and evaluation. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) and the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) were used to evaluate the methodological quality and reporting quality of the SRs, respectively. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to evaluate the quality grading of outcomes and the risk of bias in SRs was evaluated by ROBIS Tool. Finally, the RCTs involved in SRs were synthesized. Stata15.1 was used for quantitative analysis of total effectiveness rate, time until relief of abdominal pain, time until relief of abdominal distension, and serum amylase level. Results: Nine eligible SRs were included, including 92 RCTs and 6,837 participants. The quality of SRs was relatively good, and the manuscript structures were relatively complete. However, the methodological quality of SRs was low or critically low. RoB rated 5 SRs as low risk of bias and 4 SRs as high risk of bias. In GRADE, a total of 47 results were included in the 9 SRs, of which 5 results (10.64%) were moderate quality, 22 results (46.81%) were low quality, and 20 results (42.55%) were very low quality. The results of data synthesis showed that Xuebijing injection combined treatment increased the total effectiveness rate of AP patients (RR = 1.19, 95% CI 1.17-1.23, p < 0.0001), and there was no heterogeneity between studies (I2 = 0.0%, p = 0.589). Compared with the control group, Xuebijing injection group shortened the abdominal pain and distension relief time in AP patients (WMD = -1.69, 95% CI -1.88--1.50, p < 0.0001; WMD = -1.48, 95% CI -1.74--1.23, p < 0.0001), with high heterogeneity (I2 = 84.3%, p = 0.000; I2 = 72.2%, p = 0.000). Serum amylase level was also reduced (WMD = -2.06, 95% CI -2.47--1.64, p < 0.0001), with significant heterogeneity (I2 = 71.6%, p = 0.000). A total of one SR reported adverse drug reaction (ADR), no ADRs were observed in the control group. Conclusion: Although the quality of the evidence is not high, it can still reflect the clinical value of Xuebijing injection as an analgesic and anti-inflammatory traditional Chinese medicine in the treatment of AP/SAP. Therefore, future clinical studies should focus on the long-term efficacy and adverse reactions of drugs. Systematic Review Registration: (website), identifier (registration number).

Lenalidomide improves H2O2-induced PC12 cell injury by blocking the Notch signaling pathway.

Lenalidomide (LEN) has been reported to exert antitumor, anti-inflammatory, anti-angiogenic and immunomodulatory activities. However, the effects of LEN in spinal cord injury (SCI) are yet to be fully elucidated. The present study was conducted to identify whether LEN has a healing effect on SCI and to determine the underlying mechanism of action. The viability of H2O2-stimulated PC12 cells was detected using a Cell Counting Kit-8 assay. The viability of PC12 cells treated with LEN was examined with an MTT assay. The level of lactate dehydrogenase (LDH) was measured using an LDH assay kit, while the levels of the oxidative stress-related factors malondialdehyde, superoxide dismutase, glutathione peroxidase and catalase in PC12 cells were determined using commercial kits. Oxidative stress-related proteins were examined via western blotting. PC12 cell apoptosis was observed using a TUNEL assay, while apoptosis markers and Notch signaling-related proteins were examined via western blotting. The results of the present study demonstrated that H2O2 decreased PC12 cell viability in a dose-dependent manner. However, treatment with LEN significantly improved the viability of H2O2-stimulated PC12 cells and alleviated H2O2-induced cytotoxic injury. Additionally, LEN treatment inhibited the oxidative stress and apoptosis induced by H2O2 in PC12 cells. Notch signaling-related protein expression was downregulated after LEN treatment in H2O2-stimulated PC12 cells. In addition, a Notch agonist reversed the effects of LEN on H2O2-induced oxidative stress and PC12 cell apoptosis. In summary, it was demonstrated that LEN alleviated the H2O2-induced injury of PC12 cells by blocking the Notch signaling pathway, suggesting the value of applying LEN to the treatment of SCI.

Research Hotspots and Trends in Music Therapy Intervention for Patients With Dementia: A Bibliometrics and Visual Analysis of Papers Published From 2010 to 2021.

Background: As a serious public health problem, dementia has placed a heavy burden on society and families. Evidence suggests that the use of music therapy as a non-pharmacological intervention has certain advantages with respect to reducing the behavioral and psychological symptoms of dementia (BPSD) and improving the cognition and mental status of dementia patients. However, research trends and hotspots regarding music therapy intervention for dementia analysis have not been systematically studied via bibliometric analysis. Methods: We searched the Web of Science Core Collection (WoSCC) for texts published between January 1, 2010, and October 31, 2021, and visualized country, institution, journal, keyword co-occurrence, keyword emergence and keyword clustering. Results: A total of 217 articles from the WoSCC database were analyzed. In this research field, the annual number of publications has generally shown a slowly increasing trend, and the United States has the most publications and the most frequent cooperation among countries. University College London (UCL) has the most extensive influence among research institutions. Among articles, those published in the JOURNAL OF ALZHEIMER'S DISEASE were the most numerous, with 20 such articles being published, accounting for 9.22% (20/217) of the total. Comprehensive analysis of five clusters via biclustering shows that the research hotspots in this field during the past 11 years have mainly focused on the autobiographical memory, cognitive function, mental state and BPSD of dementia patients. Conclusion: This study conducted a bibliometric and visual analysis of relevant studies concerning music therapy intervention for dementia patients. Psychological problems faced by dementia patients and the topics of quality of life, individualized music therapy, the mental state of caregivers and other related topics may be important research directions in the future. Therefore, the question of how to develop standardized research protocols and identify unified efficacy evaluation indicators should be a focus of and difficulty for future research.

An Overview of Systematic Reviews of Moxibustion for Knee Osteoarthritis.

BACKGROUND: Currently, many systematic reviews (SRs) of moxibustion as a treatment of KOA have been published. However, the evidence of different SRs of moxibustion to treat KOA has not been comprehensively evaluated. AIM: This overview aimed to evaluate the existing results and provide scientific evidence of the effectiveness and safety of moxibustion in the treatment of KOA. METHODS: We conducted a comprehensive search of Embase, PubMed, Web of Science, Cochrane Library, SinoMed, CNKI, Wanfang, VIP, and other databases until October 31, 2021. A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2) was used to assess the methodological quality of SRs. Preferred Reporting Item for Systematic Reviews and Meta-Analyses was used to evaluate the reporting quality, and the risk of bias in SRs was evaluated by ROBIS Tool. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool to determine the strength of evidence and conducted a meta-analysis of the total effectiveness rate. RESULTS: Finally, 10 qualified SRs were included, including 57 randomized controlled trials and 5,149 participants. All SRs evaluated by AMASTAR-2 had more than one critical deficiency, so all SRs were rated as critically low. In the PRISMA checklist, the manuscript structures of the included SRs were relatively complete. Including four SRs with a low risk of bias and six with a high risk of bias using the ROBIS tool. In GRADE, two items (6.25%) were rated as high quality, three (9.37%) as medium quality, 17 (53.12%) as low quality and 10 (31.25%) as very low quality. A re-meta-analysis showed that moxibustion and moxibustion combined treatment improved the total effectiveness rate in knee osteoarthritis (risk ratio = 1.17, 95% confidence interval 1.13-1.21, P < 0.001 and risk ratio = 1.13, 95% CI: 1.04-1.23, P < 0.001), with low heterogeneity (I 2 = 36.3%, P = 0.020, and I 2 = 0.0%, P = 0.956). A total of eight SRs reported adverse events, and no serious adverse events occurred in the moxibustion group and control group. CONCLUSION: Moxibustion seems to be effective in treating KOA. Four SRs reported 10 common discomfort symptoms caused by moxibustion, and these adverse events can spontaneously subside, even can be avoided, therefore, moxibustion for KOA appears to be safe. However, the reliability of the results is reduced by the high risk of bias of the original studies and the low methodological quality of SRs. Therefore, future studies should pay more attention to the quality of the original study and the evidence quality of the SRs to provide more powerful and scientific evidence of the effectiveness and safety of moxibustion treatment of KOA.

Enriched environment for offspring improves learning and memory impairments induced by sevoflurane exposure during the second trimester of pregnancy.

Studies in animals indicate that sevoflurane exposure in the second trimester of pregnancy has harmful effects on the learning and memory of offspring. Whether an enriched environment can reverse the damage of sevoflurane exposure in the second trimester of pregnancy on the learning and memory of rat offspring remains unclear. In this study, rats at 14 days of pregnancy were exposed to 3.5% sevoflurane for 2 hours and their offspring were treated with an enriched environment for 20 successive days. We found that the enriched environment for offspring increased nestin and Ki67 levels in hippocampal tissue, increased hippocampal neurogenesis, inhibited glycogen synthase kinase 3ß activity, and increased the expression of cell proliferation-related ß-catenin and apoptosis-related Bcl-2, indicating that an enriched environment reduces sevoflurane-induced damage by increasing the proliferation of stem cells in the hippocampus. These findings suggest that an enriched environment can reverse the effects of sevoflurane inhaled by rats during the second trimester of pregnancy on learning and memory of offspring. This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University (approval No. 2018PS07K) on January 2, 2018.

Acupuncture for Relieving Abdominal Pain and Distension in Acute Pancreatitis: A Systematic Review and Meta-Analysis.

Background: Clinical evidence suggests that acupuncture is effective for relieving abdominal pain and distension in acute pancreatitis (AP). However, there is a lack of systematic reviews and meta-analyses that provide high-quality evidence of the efficacy and safety of acupuncture in this context. Aim: To assess the efficacy and safety of acupuncture for relieving abdominal pain and distension in AP. Methods: We searched the PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, VIP, and China Biomedical Literature databases. Randomized controlled trials of acupuncture plus routine treatment (RT) vs. RT alone or RT plus sham/placebo acupuncture were included. Primary outcomes included total effectiveness rate, VAS scores for abdominal pain and distension, and time until relief of abdominal pain and distension. Secondary outcomes included time until recovery of bowel sound, time until first defecation, length of hospital stay, and APACHE II score. Results: Nineteen eligible original studies (n = 1,503) were included. The results showed that acupuncture in combination with RT had a significant advantage in terms of increasing the total effectiveness rate [risk ratio: 1.15; 95% confidence interval (CI): 1.06-1.24; P = 0.001]. Acupuncture also reduced the VAS score for abdominal pain [weighted mean difference (WMD): -1.45; 95% CI: -1.71 to -1.19; P < 0.0001] and the VAS score for abdominal distension (WMD: -0.71; 95% CI: -1.04 to -0.37; P < 0.0001) in patients with AP. Other results also showed the efficacy of acupuncture. One study reported adverse events after acupuncture. Conclusion: Acupuncture in combination with RT has a better effect than RT alone for relieving abdominal pain and distension in AP. More rigorous studies are needed to confirm this result. Systematic Review Registration: PROSPERO CRD42019147503 (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=147503).

A Novel Eye Drop Formulation for Potential Treatment of Neovascular Age-Related Macular Degeneration.

Purpose: Drug delivery to posterior ocular tissues via topical eye drop administration is arduous due to the unique anatomy and physiology of the eye. Therefore, treatments for posterior eye disease have to be administered via intravitreal injection or systemic route, both of which have their drawbacks. Herein, the objective of this work was to demonstrate that a specially designed eye drop formulation could effectively deliver small-molecule vascular endothelial growth factor (VEGF) inhibitor to posterior ocular tissues for antiangiogenic therapy. Methods: The unique eye drop formulation, termed ITRI AXN eye drops, was obtained from self-assembly of (2-hydroxypropyl)-ß-cyclodextrin with a VEGF tyrosine kinase inhibitor, a hydrophilic polymer, hypromellose, and a complex stabilizer, caffeine. In vivo ocular pharmacokinetics studies were performed with New Zealand White (NZW) rabbits and Non Human Primates (NHP). The antiangiogenesis effect was evaluated on the Long-Evans rat with laser-induced choroidal neovascularization and pigmented Dutch-Belted rabbits with VEGF-induced retinal neovascularization. Results: The successful drug transport from ocular surface to posterior ocular cavity was indicated by a drug biodistribution pattern in pharmacokinetic studies. Excellent drug exposure in the choroid and retina with the concentrations of 900- and 750-fold greater than drug IC50 0.5 hours post the eye drop administration (drug level: 0.8%) was observed on the NHP study. The obtained formulation also demonstrated a comparable antiangiogenic outcome with the intravitreal injection of anti-VEGF antibody on rat and rabbit disease models. Conclusions: Our eye drop formulation has demonstrated great promise in antiangiogenic therapy against retinal and choroidal neovascularization in animal models. The results suggest that the aim of this work can be successfully achieved by the novel eye drop formulation. Translational Relevance: The preclinical results provide evidence that ITRI AXN eye drops could effectively deliver therapeutics to the choroid and retina for antiangiogenic therapy.

Acupuncture for heart failure: a Bayesian network systematic review and meta-analysis protocol.

BACKGROUND: Heart failure (HF) is the final stage of cardiovascular disease development, and clinical studies on acupuncture for the treatment of HF are increasing. However, the efficacy and safety of these acupuncture methods are unclear. The purpose of this study is to conduct a meta-analysis of the relevant randomized controlled trials (RCTs) to explain their efficacy and safety through high-quality evidence. METHODS: The databases of the Cochrane Library, PubMed, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), Wan-fang, and VIP will be searched from inception date to June 2021. The search will not be restricted by language. This study will include RCTs of various acupuncture methods for HF. Study selection, data extraction, and research quality assessments will be conducted independently by two researchers. The primary outcome is the efficacy rate and heart function, the secondary outcomes are quality of life scores, rehospitalization, and adverse reactions/events. The software RevMan 5.3 and Aggregate Data Drug Information System (ADDIS) will be used for network meta-analysis (NMA). Risk of bias, meta-regression, subgroup analysis, and sensitivity analysis will be performed, and the quality of evidence will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. DISCUSSION: This study will confirm the efficacy and safety of acupuncture in improving the clinical symptoms and heart function of HF, or elucidate which method of acupuncture is better suited to this purpose.

Prognostic Value of an Immunohistochemical Signature in Patients With Head and Neck Mucosal Melanoma.

Purpose: We aimed to develop a prognostic immunohistochemistry (IHC) signature for patients with head and neck mucosal melanoma (MMHN). Methods: In total, 190 patients with nonmetastatic MMHN with complete clinical and pathological data before treatment were included in our retrospective study. Results: We extracted five IHC markers associated with overall survival (OS) and then constructed a signature in the training set (n=116) with the least absolute shrinkage and selection operator (LASSO) regression model. The validation set (n=74) was further built to confirm the prognostic significance of this classifier. We then divided patients into high- and low-risk groups according to the IHC score. In the training set, the 5-year OS rate was 22.0% (95% confidence interval [CI]: 11.2%- 43.2%) for the high-risk group and 54.1% (95% CI: 41.8%-69.9%) for the low-risk group (P<0.001), and in the validation set, the 5-year OS rate was 38.1% (95% CI: 17.9%-81.1%) for the high-risk group and 43.1% (95% CI: 30.0%-61.9%) for the low-risk group (P=0.26). Multivariable analysis revealed that IHC score, T stage, and primary tumor site were independent variables for predicting OS (all P<0.05). We developed a nomogram incorporating clinicopathological risk factors (primary site and T stage) and the IHC score to predict 3-, 5-, and 10-year OS. Conclusions: A nomogram was generated and confirmed to be of clinical value. Our IHC classifier integrating five IHC markers could help clinicians make decisions and determine optimal treatments for patients with MMHN.