Efficacy of Repetitive Transcranial Magnetic Stimulation over the Supplementary Motor Area on Motor Function in Parkinson's Disease: A Meta-Analysis.

OBJECTIVES: The objective of this study was to assess the effect of repetitive transcranial magnetic stimulation (rTMS) on the supplementary motor area (SMA) in motor function in Parkinson's disease (PD) patients. METHOD: Databases searched included 5 databases from October 7,2022 to January 4, 2023. The Cochrane Bias Risk Assessment Tool was used for quality assessment. Standardized mean differences (SMDs) were calculated using a random-effects model. Outcome measure is the motor function examination of the motor part of Unified Parkinson's Disease Rating Scale (UPDRS-III). RESULTS: Seven studies totaling 374 patients were included. Meta-analysis showed that stimulation of SMA significantly improved motor function in PD patients compared with sham stimulation (SMD = -1.24; 95% CI, -2.24 to -0.24; P = 0.02; I 2 = 93%). Stimulation of the same target (SMA), subgroup analysis showed that high-frequency rTMS (HF-rTMS) is more effective than low-frequency rTMS (LF-rTMS) in improving motor function in PD (SMD = -1.39; 95% CI, -2.21 to -0.57; P = 0.04; I 2 = 77.2%). CONCLUSIONS: Overall, rTMS over SMA had a statistically significant improvement in motor function in PD patients, and HF-rTMS is statistically significantly more effective than LF-rTMS.

Can cerebellar theta-burst stimulation improve balance function and gait in stroke patients? A randomized controlled trial.

BACKGROUND: The cerebellum is a key structure involved in balance and motor control, and has become a new stimulation target in brain regulation technology. Interference theta-burst simulation (iTBS) is a novel simulation mode of repetitive transcranial magnetic simulation. However, the impact of cerebellar iTBS on balance function and gait in stroke patients is still unknown. AIM: The aim of this study was to determine whether cerebellar iTBS can improve function, particularly balance and gait, in patients with post-stroke hemiplegia. DESIGN: This study is a randomized, double-blind, sham controlled clinical trial. SETTING: The study was carried out at the Department of Rehabilitation Medicine in a general hospital. POPULATION: Patients with stroke with first unilateral lesions were enrolled in the study. METHODS: Thirty-six patients were randomly assigned to the cerebellar iTBS group or sham stimulation group. The cerebellar iTBS or pseudo stimulation site is the ipsilateral cerebellum on the paralyzed side, which is completed just before daily physical therapy. The study was conducted five times a week for two consecutive weeks. All patients were assessed before the intervention (T0) and at the end of 2 weeks of treatment (T1), respectively. The primary outcome was the Berg Balance Scale (BBS), while secondary outcome measures included the Fugl Meyer Lower Limb Assessment Scale (FMA-LE), timed up and go (TUG), Barthel Index (BI), and gait analysis. RESULTS: After 2 weeks of intervention, the BBS, FMA-LE, TUG, and BI score in both the iTBS group and the sham group were significantly improved compared to the baseline (all P<0.05). Also, there was a significant gait parameter improvement including the cadence, stride length, velocity, step length compared to the baseline (P<0.05) in the iTBS group, but only significant improvement in cadence was identified in the sham group (P<0.05). Intergroup comparison showed that the BBS (P<0.001), FMA-LE (P<0.001), and BI (P=0.002) in the iTBS group were significantly higher than those in the sham group, and the TUG in the iTBS was significantly lower than that in the sham group (P=0.002). In addition, there were significant differences in cadence (P=0.029), strip length (P=0.046), gain velocity (P=0.002), and step length of affected lower limb (P=0.024) between the iTBS group and the sham iTBS group. CONCLUSIONS: Physical therapy is able to improve the functional recovery in hemiplegic patients after stroke, but the cerebellar iTBS can facilitate and accelerate the recovery, particularly the balance function and gait. Cerebellar iTBS could be an efficient and facilitative treatment for patients with stroke. CLINICAL REHABILITATION IMPACT: Cerebellar iTBS provides a convenient and efficient treatment modality for functional recovery of patients with stroke, especially balance function and gait.

[The Molecular Mechanism of LncRNA HOTAIR Regulating the Proliferation, Invasion and Migration of Lymphoma Cells through Target Gene miR-20a-5p].

OBJECTIVE: To investigate the effects of lncRNA HOTAIR on the proliferation, invasion and migration of lymphoma cells through target gene miR-20a-5p and its molecular mechanism. METHODS: After synthesizing HOTAIR siRNA and siRNA NC plasmids, they were transfected into lymphoma Raji cells, respectively. The expression of HOTAIR mRNA was detected by RT-qPCR. The proliferation, invasion and migration of lymphoma Raji cells were detected by CCK-8 assay, Transwell assay and cell scratch healing assay, respectively. The target gene of lncRNA HOTAIR was predicted by miRcode software, and the relationship between HOTAIR and target gene was analyzed by dual luciferase assay. After synthesis of miR-20a-5p inhibitor and inhibitor NC, Raji cells were transiently transfected. The expression of miR-20a-5p was detected by RT-qPCR, and the effects of down-regulation of miR-20a-5p on the proliferation, invasion and migration of Raji cells were analyzed. The overexpression plasmid of lncRNA HOTAIR and miR-20a-5p mimics were transfected into Raji cells simultaneously to analyze the proliferation, invasion and migration ability of Raji cells. After overexpression or down-regulation of miR-20a-5p, the expression of JAK/STAT3 signaling pathway related proteins was analyzed. RESULTS: HOTAIR expression in Raji cells was decreased after transfection of HOTAIR siRNA (P<0.01), and miR-20a-5p expression was also decreased after transfection of miR-20a-5p inhibitor (P<0.01). HOTAIR had a targeting and negative regulation relationship with miR-20a-5p (r=-0.826). Silencing HOTAIR promoted the expression of miR-20a-5p and inhibited the proliferation, invasion and migration of Raji cells. Down-regulation of miR-20a-5p expression promoted the proliferation, invasion and migration of Raji cells. Effect of HOTAIR overexpression on the proliferation, invasion and migration of Raji cells could be reversed by up-regulation of miR-20a-5p. Down-regulation of miR-20a-5p expression activated the intracellular JAK/STAT3 signaling pathway. CONCLUSION: HOTAIR affects the proliferation, invasion and migration of lymphoma cells by targeting miR-20a-5p, and its mechanism may be related to the activation of JAK/STAT3 signaling pathway.

Efficacy of Tai Chi on lower limb function of Parkinson's disease patients: A systematic review and meta-analysis.

Background: At present, the effect of Tai Chi (TC) on lower limb function in patients with Parkinson's disease (PD) is controversial. Therefore, we conducted a meta-analysis on the influence of TC on lower limb function in PD patients. Methods: According to the PRISMA guidelines, seven databases were searched. Randomized controlled trials (RCTS) were selected and screened according to inclusion and exclusion criteria. We assessed the quality of the studies using the Cochrane Risk of Bias tool and then extracted the characteristics of the included studies. The random effect model was adopted, and heterogeneity was measured by I 2 statistic. Results: A total of 441 articles were screened, and 10 high-quality RCTs were with a total of 532 patients with PD met Our inclusion criteria. Meta-analysis showed that compared To control groups TC improved several outcomes. TC significantly improved motor function (SMD = -0.70; 95% CI = -0.95, -0.45; p < 0.001; I 2 = 35%), although The results were not statistically significant for The subgroup analysis of TC duration (SMD = -0.70; 95% CI = -0.95, -0.45; p = 0.88; I 2 = 0%;). TC significantly improved balance function (SMD = 0.89; 95% CI = 0.51, 1.27; p < 0.001; I 2 = 54%), functional walking capacity (SMD = -1.24; 95% CI = -2.40, -0.09; p = 0.04; I 2 = 95%), and gait velocity (SMD = 0.48; 95% CI = -0.02, 0.94; p = 0.04; I 2 = 78%), But Did Not improve endurance (SMD = 0.31; 95% CI = -0.12, 0.75; p = 0.16; I 2 = 0%), step length (SMD = 0.01; 95% CI = -0.34, 0.37; p = 0.94; I 2 = 29%), and cadence (SMD = 0.06; 95% CI = -0.25, 0.36; p = 0.70; I 2 = 0%). Conclusion: TC has beneficial effects on motor function, balance function, functional walking ability, and gait velocity, but does not improve walking endurance, stride length, and cadence.

Efficacy of High-Frequency Repetitive Transcranial Magnetic Stimulation at 10 Hz in Fibromyalgia: A Systematic Review and Meta-analysis.

OBJECTIVE: The purpose of this review was to systematically assess the effectiveness of 10-Hz repetitive transcranial magnetic stimulation (rTMS) in fibromyalgia. DATA SOURCES: We searched PubMed, Cochrane Library, Embase, Web of Science, and Ovid databases as of November 6, 2021. STUDY SELECTION: The inclusion criteria for this review were randomized controlled trials of 10-Hz rTMS for fibromyalgia, exploring the effects of 10-Hz rTMS on pain, depression, and quality of life in patients with fibromyalgia. DATA EXTRACTION: Data extraction was performed independently by 2 evaluators according to predefined criteria, and the quality of the included literature was assessed using the Cochrane Bias Risk Assessment Tool. The measurement outcomes include visual analog scale, Hamilton Depression Rating Scale, and Fibromyalgia Impact Questionnaire, and so on. DATA SYNTHESIS: A total of 488 articles were screened, and the final 7 selected high-quality articles with 217 patients met our inclusion criteria. Analysis of the results showed that high-frequency transcranial magnetic stimulation at 10 Hz was significantly associated with reduced pain compared with sham stimulation in controls (standardized mean difference [SMD]=-0.72; 95% confidence interval [CI], -1.12 to -0.33; P<.001; I2=46%) and was able to improve quality of life (SMD=-0.70; 95% CI, -1.00 to -0.40; P<.001; I2=15%) but not improve depression (SMD=-0.23; 95% CI, -0.50 to 0.05; P=.11; I2=33%). In addition, a subgroup analysis of pain conducted based on stimulation at the primary motor cortex and dorsolateral prefrontal cortex showed no significant difference (SMD=-0.72; 95% CI, -1.12 to -0.33; P=.10; I2=62%). CONCLUSIONS: Overall, 10-Hz rTMS has a significant effect on analgesia and improved quality of life in patients with FMS but did not improve depression.

Mutation analysis of DC-SIGN promoter in chronic hepatitis B patients.

OBJECTIVE: To investigate whether there is mutation in DC-SIGN promoter region in patients with chronic hepatitis B (CHB) and healthy persons previously infected with hepatitis B virus (HBV) and to explore the relationship between the mutation in dendritic cell-specific intercellular adhension molecule-3-grabbing nonintegrin (DC-SIGN) promoter region and HBV. METHODS: The studied population was composed of two cohorts: 47 CHB patients and 20 healthy persons previously infected with HBV. The mutation in DC-SIGN promoter region was detected with PCR, single-stranded conformational polymorphism and heteroduplex analysis, cloning, sequencing and aligning the published DC-SIGN promoter sequence. RESULTS: The characteristic mutation within DC-SIGN promoter region in HBV infected individuals was observed. In the DC-SIGN promoter region, 4 hot spot mutations located in positions -139, -142, -222, and -336 were observed in the CHB patients, but only 1 spot mutation located in position -139 was observed in the healthy persons previously infected with HBV. The -336C which was absent in the healthy persons previously infected with HBV was shown in 11 CHB patients (23.40%). The -139T was far more frequent in the healthy persons previously infected with HBV (100%) than in the CHB patients (34.04%). CONCLUSION: In the DC-SIGN promoter region, -336C may be a genetic risk factor for developing CHB, but -139T may be associated with protection against HBV.

Hepatitis B virus X protein promotes proliferation and upregulates TGF-beta1 and CTGF in human hepatic stellate cell line, LX-2.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is a major cause of liver fibrosis, but the mechanisms underlying HBV-related fibrogenesis are still unknown. Although the roles of HBV X protein (HBx) remain poorly understood, it is thought to play an important role in the regulation of cellular growth and hepatocarcinogenesis. The aim of this study was to determine the role of HBx in liver fibrogenesis by studying the effect of HBx on the proliferation and expression of fibrosis-related molecules in the human hepatic stellate cell line, LX-2. METHODS: We established an in vitro co-culture system with LX-2 cells and a stable QSG7701-HBx cell line which had been transfected with the HBx gene. 3H-TdR incorporation and flow cytometry were used to determine the effects of HBx on the proliferation of LX-2 cells. Alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta1 (TGF-beta1), transforming growth factor-beta receptor II (TGF-betaRII), and connective tissue growth factor (CTGF) in LX-2 cells were analyzed by Western blotting. In addition, the expression levels of collagen type I (ColI) from the co-cultured media were measured by ELISA. RESULTS: 3H-TdR incorporation increased significantly in LX-2 cells co-cultured with QSG7701-HBx cells compared to those cultured with QSG7701-pcDNA3 and QSG7701 (non-tumorigenic human liver cell line). Cell cycle results revealed that HBx accelerated the progression of G1 to S in LX-2 cells. The expressions of alpha-SMA, TGF-beta1, TGF-betaRII, CTGF and ColI were significantly increased in the co-cultures of LX-2 cells with stable QSG7701-HBx cells. CONCLUSION: These results suggest that HBx may facilitate liver fibrosis by promoting hepatic stellate cell proliferation and upregulating the expression of fibrosis-related molecules.

[Polymorphism of hepatitis B virus x gene in hepatocellular carcinoma patients and the biological effects of HBx gene with deletion varations on QSG7701 cells].

OBJECTIVE: To investigate whether there were particular HBx gene mutations associated with hepatocellular carcinoma (HCC) development in patients. METHODS: The HBx genes were examined in 51 paraffin-embedded tumor tissue samples from patients with HCC and 25 serum samples from HBV carriers from southern China by nested polymerase chain reaction (PCR), single-stranded conformational polymorphism analysis, heteroduplex analysis and DNA sequencing. The HBx genes with deletion variations (HBx-d382, HBx-d431) from tumor tissues were cloned and transfected into QSG7701 cells. Then, the biological characteristics of the transfected cells were analyzed in nude mice by MTT assay, soft agar colony formation assay, flow cytometry and xenografting. RESULTS: Deletion mutation and point mutation were found in the HBx genes of HCC tumor tissues, and there were some differences between the HBx gene mutations in genotype B and those in genotype C. More mutations were found in genotype C than those in genotype B (t=-2.522, P < 0.05), but the deletion variations (HBx-d382, HBx-d431) were detected in genotype B HBV from HCC liver tissues. The HBx genes with deletion variations (HBx-d382, HBx-d431) were recombinant with pcDNA3 and transfected into QSG7701 cell lines successfully, which established four permanent transfected QSG7701 cell lines, including pcDNA3/HBx-d382/QSG7701, pcDNA3/HBx-d431/QSG7701, pcDNA3/HBx/QSG7701, and pcDNA3/QSG7701. pcDNA3/HBx-d382/QSG7701 and pcDNA3/HBx-d431/QSG7701 grew faster and had more potential colony formative activity than those of pcDNA3/QSG7701. Moreover, pcDNA3/HBx-d382/QSG7701 and pcDNA3/HBx-431/QSG7701 cells inoculated in nude mice produced tumors more rapidly than those of pcDNA3/HBx/QSG7701, and pcDNA3/QSG7701. The volumes of the tumors in nude mice were also obviously larger in pcDNA3/HBx-d382 and pcDNA3/HBx-d431 groups than those in pcDNA3/HBx/QSG7701 and pcDNA3/QSG7701 groups. CONCLUSION: Our results suggest that HBx gene mutations occur frequently in HCC tissues, and the deletion at nt382-400 of the HBx gene might play a role in carcinogenesis of HCC in southern China.

Polymorphism analyses of hepatitis B virus X gene in hepatocellular carcinoma patients from southern China.

Chronic hepatitis B virus (HBV) infection is one of the major causes of hepatocellular carcinoma (HCC), and the HBV X (HBx) gene plays a critical role in the molecular pathogenesis of HBV-related HCC. We have investigated whether there are particular HBx gene mutations associated with HCC in patients from southern China. The HBx gene was examined in 51 paraffin-embedded tumor tissue samples from patients with HCC and 25 serum samples from the HBV carrier by nested polymerase chain reaction (PCR), single-stranded conformational polymorphism and heteroduplex analysis. The HBx genes with potentially important mutations from tumor tissue samples were cloned, sequenced and aligned with the published HBx gene sequence. HBV genotypes in tumor tissue samples were analyzed by nested PCR. Analyses of HBx gene polymorphism showed that 31.3% of HBx gene fragments in tumor tissue samples had a special pattern. A common deletion at nt 382-400 of the HBx gene accompanied by 29 point mutations was detected in four randomly selected tumor tissue samples with this pattern which caused a frame-shift in the HBx open reading frame with a new stop codon at nt 1818, resulting in an HBx polypeptide chain truncated at the C end in these cases. Among the four randomly selected samples, three were HBV genotype B, and one was not detected by our present assay. In another tumor tissue sample, amplification of the full-length HBx gene yielded a shorter fragment. Sequencing of this fragment revealed a 264 bp deletion between nt 1577 and 1840 of the HBV gene. These results suggest that HBx gene mutation occurs frequently in HCC samples, and the deletion at nt 382-400 of the HBx gene might play a role in carcinogenesis of HCC in southern China.

[Serum high-sensitivity C-reaction protein and heart fatty acid binding protein level and cardiac accidents in patients with unstable angina pectoris].

OBJECTIVE: To investigate the relationship between serum high-sensitivity C-reaction protein (hs-CRP) and heart fatty acid binding protein (h-FABP) on cardiac accidents in patients with unstable angina pectoris (UAP). METHOD: Serum levels of hs-CRP, h-FABP, cardiac troponin-I (cTn-I) and creatine kinase MB isoenzyme (CK-MB) were measured and cardiac accidents within 2 weeks after the test were observed in 74 patients (male 45) with stable AP (SAP) and 56 patients (male 29) with UAP. RESULTS: The incidence of cardiac accidents was significantly higher in UAP group (26.8%) than that in SAP group (10.53%, P < 0.001). Serum hs-CRP [(7.64 +/- 2.18) mg/L vs. (1.78 +/- 0.62) mg/L, P < 0.001], h-FABP [(16.46 +/- 5.28) microg/L vs. (3.15 +/- 2.61) microg/L, P < 0.001] and cTn-I [(1.28 +/- 0.43) microg/L vs. (0.67 +/- 0.09) microg/L, P < 0.001] levels were also significantly higher in UAP group than those in SAP group. The serum hs-CRP and h-FABP levels for patients with cardiac accidents in the SAP group were (6.32 +/- 2.06) microg/L and (8.76 +/- 3.83) microg/L respectively, which were higher than those for the patients having no cardiac accidents in the control (P < 0.01). The serum hs-CRP, h-FABP, cTn-I and CK-MB levels in patients with cardiac accidents were significantly higher than those in patients without cardiac accidents in both SAP and UAP groups. CONCLUSION: Measuring traditional parameters for myocardial damage (cTn-I and CK-MB) in combination with hs-CRP and h-FABP is valuable for predicting the risk of recent cardiac accidents for AP patients.