NRG1-ErbB4 signaling in the medial amygdala controls mating motivation in adult male mice.

Motivation-driven mating is a basic affair for the maintenance of species. However, the underlying molecular mechanisms that control mating motivation are not fully understood. Here, we report that NRG1-ErbB4 signaling in the medial amygdala (MeA) is pivotal in regulating mating motivation. NRG1 expression in the MeA negatively correlates with the mating motivation levels in adult male mice. Local injection and knockdown of MeA NRG1 reduce and promote mating motivation, respectively. Consistently, knockdown of MeA ErbB4, a major receptor for NRG1, and genetic inactivation of its kinase both promote mating motivation. ErbB4 deletion decreases neuronal excitability, whereas chemogenetic manipulations of ErbB4-positive neuronal activities bidirectionally modulate mating motivation. We also identify that the effects of NRG1-ErbB4 signaling on neuronal excitability and mating motivation rely on hyperpolarization-activated cyclic nucleotide-gated channel 3. This study reveals a critical molecular mechanism for regulating mating motivation in adult male mice.

Association of hypoxia-inducible factor 1α expression with susceptibility to hepatitis B virus-related hepatocellular carcinoma: A meta-analysis.

Hypoxia-inducible factor 1α (HIF-1α) triggers tumorigenesis and progression in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Inconsistent findings have been reported on the influence of HIF-1α over-expression on the clinical outcomes of HBV-related HCC. This study aims to clarify the role of HIF-1α overexpression in the tumorigenesis and prognosis of HBV-induced HCC. Systematic and comprehensive search of online papers was carried out to elucidate the contribution of HIF-1α expression to susceptibility of HBV-induced HCC. STATA 12.0 software was utilized to analyze available data extracted from all eligible literature. Publication bias and sensitivity were comprehensively analyzed. A total of 23 published studies involving 2244 subjects were finally screened. The HIF-1α expression was remarkably upregulated in HBV-induced HCC tissues than in normal liver tissues, non-tumorous tissues, paraneoplastic tissues, and non-HBV HCC tissues. The high HIF-1α expression tended to be positively related to capsular infiltration (odds ratio (OR) 1.767; 95% confidence interval (CI) 1.058, 2.950). The HIF-1α expression was relevant to lymph node metastasis (OR 3.778; 95% CI 1.666, 8.568). High levels of HIF-1α expression tended to be closely implicated in portal vein invasion (OR 6.728, 95% CI 2.191, 20.656) but were irrelevant to alpha-fetoprotein, cirrhosis, Edmondson grading, tumor size, age, gender, and histological grade. Analysis of pooled data showed that HIF-1α was not statistically relevant to poor overall survival in HBV-related HCC. Our data provides compelling evidence that HIF-1α overexpression may imply a greater probability of invasion and metastasis in patients with HBV-induced HCC.

Effect of robotic-assisted gait training on gait and motor function in spinal cord injury: a protocol of a systematic review with meta-analysis.

INTRODUCTION: Robotic-assisted gait training (RAGT) has been reported to be effective in rehabilitating patients with spinal cord injury (SCI). However, studies on RAGT showed different results due to a varied number of samples. Thus, summarising studies based on robotic-related factors is critical for the accurate estimation of the effects of RAGT on SCI. This work aims to search for strong evidence showing that using RAGT is effective in treating SCI and analyse the deficiencies of current studies. METHODS AND ANALYSIS: The following publication databases were electronically searched in December 2022 without restrictions on publication year: MEDLINE, Cochrane Library, Web of Science, Embase, PubMed, the Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure. Various combinations of keywords, including 'motor disorders', 'robotics', 'robotic-assisted gait training', 'Spinal Cord Injuries', 'SCI' and 'gait analysis' were used as search terms. All articles on randomised controlled trials (excluding retrospective trials) using RAGT to treat SCI that were published in English and Chinese and met the inclusion criteria were included. Outcomes included motor function, and gait parameters included those assessed by using the instrumented gait assessment, the Berg Balance Scale, the 10-m walk speed test, the 6-min walk endurance test, the functional ambulation category scale, the Walking index of SCI and the American Spinal Injury Association assessment scale. Research selection, data extraction and quality assessment were conducted independently by two reviewers to ensure that all relevant studies were free from personal bias. In addition, the Cochrane risk-of-bias assessment tool was used to assess the risk of bias. Review Manager V.5.3 software was used to produce deviation risk maps and perform paired meta-analyses. ETHICS AND DISSEMINATION: Ethics approval is not required for systematic reviews and network meta-analyses. The results will be submitted to a peer-reviewed journal or presented at a conference. PROSPERO REGISTRATION NUMBER: CRD42022319555.

METTL5 serves as a diagnostic and prognostic biomarker in hepatocellular carcinoma by influencing the immune microenvironment.

Despite the abnormal expression of 18S rRNA m6A methyltransferase METTL5 being reported in some types of human malignancies, but its effect on hepatocellular carcinoma (HCC) remains to be unclear. This study aims to elucidate the influences of METTL5 on the carcinogenesis and progression of HCC. Expressions of METTL5 gene, transcript, protein, and promoter methylation in HCC were examined through multiple databases, c-BioPortal was used to confirm the genomic alterations of METTL5, the biological functions, target networks of kinases and microRNAs of METTL5, and its interactive differential genes were investigated through LinkedOmics. The possible correlation of METTL5 with the tumor-related infiltration of immune cells for HCC were explored comprehensively by using the online tools of TIMER and TISIDB. Expressions of METTL5 gene, mRNA, and protein were considerably overexpressed in HCC samples in comparison with healthy samples. The high methylation of the METTL5 promoter was observed in HCC tissues. Elevated METTL5 expression exhibited unfavorable survival outcomes in HCC patients. METTL5 expression were enriched in the signaling pathways of ribosome and oxidative phosphorylation, mismatch repair, and spliceosome through the involvement of several cancer-related kinases and miRNAs. The METTL5 expression has a positive correlation with the infiltration degree of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC. Marker genes of tumor immune-infiltrated cells have strong connection with METTL5. Furthermore, the upregulation of METTL5 was strongly correlated with the immune regulation of immunomodulators, chemokines, and chemokine receptors in the immune microenvironment. The oncogenesis and development of HCC are closely related to METTL5 expression, and the overexpression of METTL5 resulted in the poor survival outcome of HCC patients by regulating tumor immune microenvironment.

Effects of repetitive transcranial magnetic stimulation on motor function and language ability in cerebral palsy: A systematic review and meta-analysis.

Objective: This review was conducted to assess the quality of the evidence of effectiveness of repetitive transcranial magnetic stimulation (rTMS) in treating motor and language ability of cerebral palsy (CP). Method: Medline, Cochrane library, Web of Science, Embase, PubMed, and CNKI databases were searched up to July 2021 by two independent reviewers. Randomized controlled trials (RCTs) that were published in English and Chinese and met the following criteria were included. The population comprised patients who met the diagnostic criteria for CP. Intervention included the following: comparison about rTMS and sham rTMS or comparison about rTMS combine with other physical therapy and other physical therapy. Outcomes included motor function, as follows: gross motor function measure (GMFM), Gesell Development Diagnosis Scale, fine motor function measure (FMFM), Peabody developmental motor scale, and Modified Ashworth scale. For language ability, sign-significant relation (S-S) was included. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. Results: Finally, 29 studies were included in the meta-analysis. Results of evaluation using the Cochrane Collaborative Network Bias Risk Assessment Scale showed that 19 studies specifically explained randomization, among which two studies described allocation concealment, four studies blinded participants and persons and had low risk of bias, and six studies explained that the assessment of outcome measures was blinded. Significant improvements in motor function were observed. The GMFM of total score was determined by using the random-effect model [I2 = 88%; MD = -1.03; 95% CI (-1.35, -0.71); P < 0.0001] and FMFM was determined by using the fixed-effect model [P = 0.40 and I2 = 3%; SMDs = -0.48, 95% CI (-0.65, -0.30); P < 0.01]. For language ability, the language improvement rate was determined using a fixed-effect model [P = 0.88 and I2 = 0%; MD = 0.37, 95% CI (0.23, 0.57); P < 0.01]. According to the PEDro scale, 10 studies had low-quality, four studies had excellent quality, and the other studies had good quality. Using the GRADEpro GDT online tool, we included a total of 31 outcome indicators, as follows: 22 for low quality, seven for moderate quality, and two for very low quality. Conclusion: The rTMS could improve the motor function and language ability of patients with CP. However, rTMS prescriptions varied, and the studies had low sample sizes. Studies using rigorous and standard research designs about prescriptions and large samples are needed to collect sufficient evidence about the effectiveness of using rTMS to treat patients with CP.

Nomogram to predict the prognosis of patients with AFP-negative hepatocellular carcinoma undergoing chemotherapy: A SEER based study.

This study aimed to formulate reliable nomograms for predicting the outcomes of α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) patients after chemotherapy. HCC patients with normal AFP expression who received chemotherapy were screened and evaluated from the surveillance, epidemiology, and end results database. The prognostic factors for predicting outcomes of HCC patients undergoing chemotherapy were chosen by analyzing the results of Cox analyses. Then, a nomogram integrating the prognostic factors was established. The discrimination ability of the nomogram was evaluated with computation of area under the curve (AUC) and calibration curve. A total of 2424 patients with AFP-negative HCC undergoing chemotherapy were identified. The median overall survival (OS) for HCC patients undergoing chemotherapy was 33 months. Age, race, pathologic grade, N stage, M stage, surgery, and lung metastases were significantly linked to OS. These relevant factors were incorporated into the nomogram. AUC values of the prognostic nomogram for 3- and 5-year OS were 0.696 and 0.706 in the training groups, which were superior to those of the tumor node metastasis (TNM) stage (0.641 and 0.671) in training groups. The calibration curves indicated a high consistency between the predicted probability of nomograms and the actual observation. The validation groups produced AUC values of 0.674 and 0.736 for 3- and 5-year OS, which were superior to those of the TNM stage (0.601 and 0.637) in validation groups. The results revealed significantly unfavorable OS in the high-risk group (P < .001). Nomograms to accurately predict the OS for AFP-negative HCC patients after chemotherapy were established and exhibited a more accurate predication than the conventional TNM staging system.

Effects of rhythmic auditory stimulation on motor function and balance ability in stroke: A systematic review and meta-analysis of clinical randomized controlled studies.

Objective: Rhythmic auditory stimulation (RAS) belongs to neurologic music therapy, which has attracted clinical attention because of its efficacy in motor function after stroke. This study aimed to summarize the effectiveness of rhythmic auditory stimulation (RAS) for the treatment of motor function and balance ability in stroke through a systematic review and meta-analysis. Methods: All studies were retrieved from six databases. The effects of RAS on stroke were determined using the following indicators: motor function including step length, step cadence, velocity, Fugl-Meyer assessment (FMA); and balance ability including overall balance index (OBI) and Berg Balance Scale (BBS). The risk map of bias of the quality of the studies and the meta-analysis results of the indicators was prepared using RevMan 5.2 software. Results: A total of 1,363 abstracts were retrieved. Among them, 325 duplicate studies were eliminated, and 971 studies were excluded after reading the titles and abstracts. In addition, by downloading the full text for further reading and screening, 47 studies were excluded. A total of 22 studies were included in the systematic review, and 18 studies were included in the meta-analysis. Assessment of quality, based on the PEDro scale, two studies had low quality, three studies had excellent quality, and the other studies had good quality; based on the Cochrane Collaborative Network Bias Risk Assessment Scale. A total of 15 studies specifically explained the random methods used. Meanwhile, seven studies did not report random sequence generation. A total of 10 studies reported that the evaluation of experimental results was blinded. In the meta-analysis, the results of motor function [namely, velocity (SMD = 0.99, 95% CI (0.43, 1.55)), step length (SMD = 0.97, 95% CI (0.74, 1.20)), and step cadence (MD = 5.16, 95% CI (4.17, 6.14)), FMA (MD = 2.93, 95% CI (2.04, 3.83))], were statistically significant (P < 0.01). The results of balance ability [OBI (MD = -0.51, 95% CI (-0.86, -0.16)) and BBS (MD = 2.93, 95% CI (1.67, 4.20))], were also statistically significant (P < 0.01). Among all the outcome indicators, three indicators were included in more than 10 studies: these are step length, step cadence, and velocity. The results showed that the two sides of the funnel chart were asymmetrical, thus these results all showed heterogeneity. The GRADEpro GDT online tool was used to evaluate the quality of evidence for the outcome indicators in the included studies. Five outcome indicators were included, of which three were low-quality indicators and two were moderate-quality indicators. Conclusions: RAS could improve gait parameters, walking function, and balance ability of individuals with stroke. However, studies or samples of outcome indicators for balance ability of stroke patients is relatively insufficient, which also requires further research in the future. Systematic review registration: PROSPERO, identifier: CRD42021225102.

Effects of Rhythmic Auditory Stimulation on Gait and Motor Function in Parkinson's Disease: A Systematic Review and Meta-Analysis of Clinical Randomized Controlled Studies.

Objective: This study aimed to summarize the effectiveness of rhythmic auditory stimulation (RAS) for the treatment of gait and motor function in Parkinson's disease (PD) through a systematic review and meta-analysis. Methods: All studies were retrieved from eight databases. The effects of RAS on PD were determined using the following indicators: gait parameters including step length, stride width, step cadence, velocity, stride length; motor function including 6 min walk test (6MWT) and timed up-and-go test (TUGT); the Unified Parkinson's Disease Rating Scale (UPDRS); and the Berg Balance Scale (BBS). The risk map of bias of the quality of the studies and the meta-analysis results of the indicators was prepared with RevMan 5.2 software. Results: Twenty-one studies were included in the systematic review, and 14 studies were included in the meta-analysis. In the meta-analysis, the results of gait parameters, namely, velocity, step length, and stride length, were statistically significant (P < 0.05), whereas the results of cadence and stride width were not statistically significant (P ≧ 0.05). The results of 6MWT and TUGT for motor function as well as UPDRS-II, UPDRS-III, and BBS were statistically significant (P < 0.05). Conclusions: RAS could improve gait parameters, walking function, balance function, and daily living activities of individuals with PD. The application of RAS in conventional rehabilitation approaches can enhance motor performance in PD. Future studies should use a large sample size and a rigorous design to obtain strong conclusions about the advantages of RAS for the treatment of gait and motor function in PD.

Clinical Randomized Controlled Study of Acupuncture Treatment on Children with Autism Spectrum Disorder (ASD): A Systematic Review and Meta-Analysis.

This study aimed to summarize the effectiveness and safety of acupuncture in the treatment of autism spectrum disorder (ASD) through literature analysis and evaluation. All studies were retrieved from various databases as follows: English databases, such as PubMed, Cochrane Library, Ovid, and Web of Science, and Chinese databases, such as China National Knowledge Infrastructure (CNKI), WanFang Data (WF), and Technology Periodical Database (VIP). The Cochrane Collaboration's Bias Risk Assessment Scale was used to assess the studies' risk of bias. The effects of acupuncture treatment for ASD were determined using the following indicators: childhood autism rating scale (CARS), autism behavior check list (ABC), Reynell developmental language scale (RDLS), and functional independence measure of children (WeeFIM). The risk map of bias of these studies' quality and the meta-analysis results of the indicators was prepared with RevMan 5.2 software. Finally, 16 studies were included, five of which were in English and 11 were in Chinese. The 16 studies included 1332 patients. The CARS results for subgroup analysis were as follows: acupuncture subgroup (MD = -2.65, 95% CI (-3.22, -2.07)) and acupuncture plus massage subgroup (MD = -10.35, 95% CI (-11.34, -9.36)). The ABC results were as follows: (MD = -6.70, 95% CI (-9.10, -4.29)). The analysis results of sensory, relating, language, body and object use, and social/self-help in the subitems of ABC were as follows: sensory (MD = -2.67, 95% CI (-2.90, -2.44)), relating (MD = -3.28, 95% CI (-3.55, -3.02)), language (MD = -2.45, 95% CI (-2.73, -2.16)), body and object use (MD = -1.19, 95% CI (-1.38, -1.00)), and social/self-help (MD = -2.09, 95% CI (-2.30, -1.89)). For the analysis results of comprehension and expression ages in the subitems of RDLS, the comprehension age results were as follows: (MD = 0.08, 95% CI (-0.06, 0.22), P = 0.27). Those of expression age were as follows: (MD = 0.15, 95% CI (0.04, 0.26), P=0.009). The WeeFIM results were as follows: (MD = 3.70, 95% CI (2.38, 5.02)). This study suggested that acupuncture could effectively treat ASD. However, acupuncture methods and prescriptions at this stage remain heterogeneous, and acupuncture treatment operations require standardization. Studies using rigorous and standard research designs are needed to draw stronger conclusions about the advantages of using acupuncture to treat children and adolescents with ASD.

Identification of potential biomarkers of peripheral blood mononuclear cell in hepatocellular carcinoma using bioinformatic analysis: A protocol for systematic review and meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the cause of an overwhelming number of cancer-related deaths across the world. Developing precise and noninvasive biomarkers is critical for diagnosing HCC. Our research was designed to explore potentially useful biomarkers of host peripheral blood mononuclear cell (PBMC) in HCC by integrating comprehensive bioinformatic analysis. METHODS: Gene expression data of PBMC in both healthy individuals and patients with HCC were extracted from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs). The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to annotate the function of DEGs. Protein-protein interaction analysis was performed to screen the hub genes from DEGs. cBioportal database analysis was performed to assess the prognostic significance of hub genes. The Cancer Cell Line Encyclopedia (CCLE) and The Human Protein Atlas (HPA) database analyses were performed to confirm the expression levels of the hub genes in HCC cells and tissue. RESULTS: A total of 95 DEGs were screened. Results of the GO analysis revealed that DEGs were primarily involved in platelet degranulation, cytoplasm, and protein binding. Results of the KEGG analysis indicated that DEGs were primarily enriched in focal adhesion. Five genes, namely, myosin light chain kinase (MYLK), interleukin 1 beta (IL1B), phospholipase D1 (PLD1), cortactin (CTTN), and moesin (MSN), were identified as hub genes. A search in the CCLE and HPA database showed that the expression levels of these hub genes were remarkably increased in the HCC samples. Survival analysis revealed that the overexpression of MYLK, IL1B, and PLD1 may have a significant effect on HCC survival. The aberrant high expression levels of MYLK, IL1B, and PLD1 strongly indicated worse prognosis in patients with HCC. CONCLUSIONS: The identified hub genes may be closely linked with HCC tumorigenicity and may act as potentially useful biomarkers for the prognostic prediction of HCC in PBMC samples.

Association of RASSF1A hypermethylation with risk of HBV/HCV-induced hepatocellular carcinoma: A meta-analysis.

BACKGROUND: Researchers have discovered a large number of DNA methylation patterns in human cancer. These cancer-specific methylation patterns can provide information for the diagnosis, treatment, and prognosis of cancer. Methylation studies can find new biomarkers based on epigenetic analysis and apply these biomarkers to clinical oncology. Many studies on the association between RAASF1A methylation status and susceptibility to hepatitis B virus (HBV)/hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) have reached controversial conclusions. Hence, the current review comprehensively assessed the correlation between Ras association domain family 1A (RASSF1A) methylation and the risk of the HCV/HBV-induced HCC. METHODS: The appropriated publications were extracted in EMBASE, PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure databases using STATA 5.0 software. The odds ratios (ORs) with 95 % confidence interval (95 % CI) of RASSF1A methylation were computed. RESULTS: A total of 1015 HBV/HCV-related HCC samples, 124 non-HBV/HCV-related HCC (NBNC-HCC) samples, and 1225 nontumorous controls were extracted and examined in this research. The frequency of the methylated RASSF1A in the HBV/HCV-related tumor cases displayed a significantly increased OR compared with the overall nontumor samples (OR = 19.372, 95 % CI = 11.060-33.931, P = 0.000). The frequency of the methylated RASSF1A in HBV/HCV-related neoplasm cases displayed a significantly increased OR compared with the non-HBV/HCV-related neoplasm (NBNC-neoplasm) samples (OR = 2.150, 95 % CI = 1.398-3.308, P = 0.000). Compared with normal, chronic hepatitis B or C, cirrhosis, and paracancerous samples, the pooled OR of the RASSF1A promoter methylation in the HBV/HCV-induced HCC samples was 62.785(95 % CI = 35.224-111.909), 25.07 (95 % CI = 13.85-45.36), 6.89 (95 % CI = 3.33-14.264) and 9.02 (95 % CI = 0.91-89.80), respectively. The rate of RASSF1A hypermethylation was robustly correlated with tumor size and vascular invasion, and the pooled OR was 0.346 (95 % CI = 0.210 - 0.569) and 0.081 (95 % CI = 0.022 - 0.303), respectively. CONCLUSION: Results showed robust associations between RASSF1A gene methylation in promoter region and enhanced HBV/HCV-related HCC susceptibility, thereby revealing that RASSF1A methylation status may serve as an important indicator for HCC oncogenesis.