Acupuncture for the Treatment of Neuropsychiatric Symptoms in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Neuropsychiatric symptoms (NPSs) of Parkinson's disease (PD) have received increasing attention, but effective treatment options remain limited. Acupuncture may have clinical benefits for NPSs in PD patients, but high-quality evidence supporting this possibility still needs to be discovered. Therefore, we conducted a meta-analysis to evaluate the effect of acupuncture treatment on NPSs in PD patients. METHODS: Randomized controlled trials (RCTs) of acupuncture treatment for PD retrieved from the following electronic databases: PubMed, Embase, Cochrane Library, Web of Science, and Scopus, were used to evaluate NPSs of PD patients. The Cochrane Intervention System Evaluation Manual assessed the methodological quality. RESULTS: A total of 13 RCTs involving 719 patients were included. The results showed that compared with medication alone or sham acupuncture, acupuncture improved sleep quality in PD patients, with Parkinson's Disease Sleep Scale (PDSS) [standardized mean difference (SMD)= 0.48, 95% confidence interval (CI)= 0.242 to 0.793, P = 0.001]. The I scores and total scores on Unified Parkinson's Disease Rating Scale (UPDRS) indicated acupuncture treatment was effective (SMD=-0.66, 95%CI=-0.66 to -0.18, P = 0.042; SMD=-0.77, 95%CI=-1.31 to -0.23, P = 0.005). Results of the Epworth Sleepiness Scale (ESS) and Parkinson's Disease Questionnaire-39 (PDQ-39) showed no statistically significant differences (SMD=-0.27, 95%CI=-0.08 to 0.62, P = 0.128; SMD=-0.20, 95%CI=-0.42 to 0.01, P = 0.554). Anxiety and depression research had no significant differences due to the excessive inter-study bias. CONCLUSION: Acupuncture treatment can improve sleep quality, psychological and behavioral alterations, and the overall condition of PD patients. However, the study revealed no significant positive intervention effects on anxiety, depression, and quality of life, underscoring the necessity for continued research to elucidate these domains' intricacies and develop productive therapeutic approaches.

Combined Transcriptome and Metabolome Analysis of Smooth Muscle of Myostatin Knockout Cattle.

Myostatin (MSTN), a growth and differentiation factor, plays an important role in regulating skeletal muscle growth and development. MSTN knockout (MSTN-KO) leads to skeletal muscle hypertrophy and regulates metabolic homeostasis. Moreover, MSTN is also detected in smooth muscle. However, the effect of MSTN-KO on smooth muscle has not yet been reported. In this study, combined metabolome and transcriptome analyses were performed to investigate the metabolic and transcriptional profiling in esophageal smooth muscles of MSTN-KO Chinese Luxi Yellow cattle (n = 5, 24 months, average body weight 608.5 ± 17.62 kg) and wild-type (WT) Chinese Luxi Yellow cattle (n = 5, 24 months, average body weight 528.25 ± 11.03 kg). The transcriptome was sequenced using the Illumina Novaseq™ 6000 sequence platform. In total, 337 significantly up- and 129 significantly down-regulated genes were detected in the MSTN-KO cattle compared with the WT Chinese Luxi Yellow cattle. Functional enrichment analysis indicated that the DEGs were mainly enriched in 67 signaling pathways, including cell adhesion molecules, tight junction, and the cGMP-PKG signaling pathway. Metabolomics analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 130 differential metabolites between the groups, with 56 up-regulated and 74 down-regulated in MSTN knockout cattle compared with WT cattle. Differential metabolites were significantly enriched in 31 pathways, including glycerophospholipid metabolism, histidine metabolism, glutathione metabolism, and purine metabolism. Transcriptome and metabolome were combined to analyze the significant enrichment pathways, and there were three metabolically related pathways, including histidine metabolism, purine metabolism, and arginine and proline metabolism. These results provide important references for in-depth research on the effect of MSTN knockout on smooth muscle.

Loss of Myostatin Alters Mitochondrial Oxidative Phosphorylation, TCA Cycle Activity, and ATP Production in Skeletal Muscle.

Myostatin (MSTN) is an important negative regulator of skeletal muscle growth in animals. A lack of MSTN promotes lipolysis and glucose metabolism but inhibits oxidative phosphorylation (OXPHOS). Here, we aimed to investigate the possible mechanism of MSTN regulating the mitochondrial energy homeostasis of skeletal muscle. To this end, MSTN knockout mice were generated by the CRISPR/Cas9 technique. Expectedly, the MSTN null (Mstn-/-) mouse has a hypermuscular phenotype. The muscle metabolism of the Mstn-/- mice was detected by an enzyme-linked immunosorbent assay, indirect calorimetry, ChIP-qPCR, and RT-qPCR. The resting metabolic rate and body temperature of the Mstn-/- mice were significantly reduced. The loss of MSTN not only significantly inhibited the production of ATP by OXPHOS and decreased the activity of respiratory chain complexes, but also inhibited key rate-limiting enzymes related to the TCA cycle and significantly reduced the ratio of NADH/NAD+ in the Mstn-/- mice, which then greatly reduced the total amount of ATP. Further ChIP-qPCR results confirmed that the lack of MSTN inhibited both the TCA cycle and OXPHOS, resulting in decreased ATP production. The reason may be that Smad2/3 is not sufficiently bound to the promoter region of the rate-limiting enzymes Idh2 and Idh3a of the TCA cycle, thus affecting their transcription.

Sanfu herbal patch applied at acupoints in patients with bronchial asthma: statistical analysis plan for a randomised controlled trial.

BACKGROUND: Sanfu herbal patch (SHP) is widely used in the prevention and treatment of bronchial asthma in China, but its efficacy and mechanism of action are not completely clear. This trial aims to determine the efficacy of SHP and the underlying mechanism. METHODS/DESIGN: We will conduct a multi-centre parallel randomised controlled trial consisting of 72 participants with bronchial asthma recruited and randomly allocated at a ratio of 1:1 into two groups. The patients in one group will receive three courses of SHP treatment, and the patients in the other group will receive placebo treatment, with 24 weeks of follow-up evaluation for both groups. The primary outcome, i.e. forced expiratory volume in the first second (FEV1), which refers to the change in FEV1 from the beginning of the baseline to the end of 3 treatment sessions (TSs), will be assessed and compared via Student's t test or the Mann-Whitney U test. Other outcomes will include questionnaire surveys and laboratory indicators. Detailed and complete statistical analyses in a double-blinded fashion will be provided for evaluating this trial. DISCUSSION: The data we obtain will be examined based on the above statistical analysis, which will help to reduce the risk of external reporting bias and data-driven results. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), ChiCTR1900024616. Registered on 19 July 2019.

Association Between Serum Uric Acid and Intracranial Arterial Stenosis in a Korean Population: A Secondary Analysis Based on a Cross-Sectional Study.

Background and purpose: Intracranial arterial stenosis (ICAS) is a common cause of cerebrovascular disease. Studies have shown that the disease may be associated with elevated serum uric acid. However, the results remain inexact and controversial. To provide theoretical support for clinical practice, we assessed the relationship between uric acid and ICAS based on previous literature. Materials and Methods: A total of 1,011 samples were included in the secondary cross-sectional study we investigated. We evaluated the relationship between uric acid level and ICAS using multivariable logistic regression analysis. Results: The mean age of patients was 64.16 ± 9.13 years, and 35.51% (n = 359) were male in the study. One hundred and one (10%) of the included participants had ICAS. In the unadjusted model, uric acid level was positively associated with ICAS [odds ratio (OR) = 1.23, 95% confidence interval (CI): 1.07-1.42, p < 0.01]. After adjusting for potential confounders (sex, age, diabetes mellitus, coronary artery occlusive disease, hyperlipidemia, statin medication, hypertension, and fasting glucose), a positive relationship was observed between uric acid and ICAS (OR = 1.26, 95% CI: 1.08-1.47, p < 0.05). Conclusion: There was a positive relationship between uric acid levels and ICAS in neurologically healthy Korean participants.

Ultrasound-guided percutaneous microwave ablation of adenomyosis: a narrative review.

OBJECTIVE: The purpose of the present review is to analyze and summarize the feasibility, effectiveness, and safety of ultrasound-guided percutaneous microwave ablation (MWA) for adenomyosis according to largest studies available in current literature, so as to provide a more robust foundation for its use in the treatment of patients with this condition. BACKGROUND: Adenomyosis is a common and frequently occurring gynecological disease. It can lead to clinical symptoms such as dysmenorrhea, menostaxis, menorrhagia, and anemia, and can seriously affect patients' quality of life. Treatments for adenomyosis include drug, minimally invasive, and surgical therapies. Among them, ultrasound-guided percutaneous microwave ablation has become a new hotspot in the minimally invasive treatment of adenomyosis in recent years, with its advantages of small trauma and a good therapeutic effect. METHODS: Relevant studies were retrieved from the CNKI (Chinese National Knowledge Infrastructure), CQVIP, Wanfang, PubMed, Web of Science, Cochrane Library, EMBASE, ClinicalTrials.gov, and Google Scholar databases. The retrieval time range was from January 2000 to June 2021. Chinese search terms included "adenomyosis", "microwave ablation", and "ultrasound". English search terms included "microwave ablation", "ultrasound", "(adenomyosis) OR (endometrioma) OR (adenomyoma)". CONCLUSIONS: Ultrasound-guided percutaneous microwave ablation therapy is a feasible, safe, and effective technique for the treatment of adenomyosis, and is worthy of clinical application and promotion.

The effectiveness and safety of Tuina for tension-type headache: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Tension-type headache (TTH) is one of the most common primary headache diseases in the world and has a serious negative impact on the physical and mental health of patients. Tuina is now widely used to treat tension-type headaches. This article aims to systematically review the evidence about the effectiveness of Tuina on the effectiveness rate, pain intensity, and impact of headache in individuals with TTH. METHODS: Eight databases for randomized controlled trials (RCTs) of Tuina were included in treatments for TTH. Cochrane Collaboration's tool was applied to evaluate the quality of the studies. Confidence in the effect estimates was determined with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. We use the software STATA 12.0 for meta-analysis and TSA software for test sequence analysis. RESULTS: Seven studies were included with a total sample of 1228 individuals. Meta-analysis results showed that Tuina was superior to drugs for improving the effectiveness rate (RR = 1.49, 95%CI: 1.25 to 1.77, p < 0.01, low evidence). A visual analog scale (VAS) score of Tuina was significantly lower than that of drugs (WMD = -0.738, 95% CI: -1.128 to -0.349, p < 0.01, moderate evidence). The trial sequential analysis showed that the effectiveness of Tuina for TTH was accurate. Adverse events were tolerable. CONCLUSION: Tuina has a certain effect in treating tension headache. However, due to the low level of methodological quality included in the article, this conclusion should be considered cautiously. More studies are necessary to strengthen the evidence regarding the effectiveness and safety of Tuina for subjects with TTH.

Transient Dux expression facilitates nuclear transfer and induced pluripotent stem cell reprogramming.

Cloned animals generated by somatic cell nuclear transfer (SCNT) have been reported for many years; however, SCNT is extremely inefficient, and zygotic genome activation (ZGA) is required for SCNT-mediated somatic cell reprogramming. To identify candidate factors that facilitate ZGA in SCNT-mediated reprogramming, we performed siRNA-repressor and mRNA-inducer screenings, which reveal Dux, Dppa2, and Dppa4 as key factors enhancing ZGA in SCNT. We show that direct injection of ZGA inducers has no significant effect on SCNT blastocyst formation; however, following the establishment of an inducible Dux transgenic mouse model, we demonstrate that transient overexpression of Dux not only improves SCNT efficiency but also increases that of chemically induced pluripotent stem cell reprogramming. Moreover, transcriptome profiling reveals that Dux-treated SCNT embryos are similar to fertilized embryos. Furthermore, transient overexpression of Dux combined with inactivation of DNA methyltransferases (Dnmts) further promotes the full embryonic development of SCNT-derived animals. These findings enhance our understanding of ZGA-regulator function in somatic reprogramming.

Melatonin restores the pluripotency of long-term-cultured embryonic stem cells through melatonin receptor-dependent m6A RNA regulation.

N6-methyladenosine (m6A) methylation is the most common and abundant modification on mammalian messenger RNA (mRNA) and regulates the pluripotency of embryonic stem cells (ESCs). Research has shown that melatonin plays a fundamental role in DNA and histone modifications. However, the effect of melatonin on RNA modification is unknown. Here, for the first time, we investigated the effect of melatonin on m6A modifications in long-term-cultured ESCs. Pluripotency studies indicated that 10 µmol/L melatonin sufficiently maintained ESCs with stemness features over 45 passages (more than 90 days). Notably, treatment of ESCs with melatonin led to a significant decrease in the nuclear presence of m6A methyltransferase complex and decreased global m6A modification. Depletion of melatonin receptor 1 (MT1) by CRISPR/Cas9 significantly reduced the effects of melatonin on ESC pluripotency and m6A modification. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that melatonin promotes stabilization of core pluripotency factors, such as Nanog, Sox2, Klf4, and c-Myc, by preventing m6A-dependent mRNA decay. Using cell signaling pathway profiling systems, melatonin was shown to regulate m6A modification predominantly through the MT1-JAK2/STAT3-Zfp217 signal axis. This study reveals a new dimension regarding melatonin regulation of gene expression at the RNA level.

Generation of Fad2 and Fad3 transgenic mice that produce n-6 and n-3 polyunsaturated fatty acids.

Linoleic acid (18 : 2, n-6) and α-linolenic acid (18 : 3, n-3) are polyunsaturated fatty acids (PUFAs), which are essential for mammalian health, development and growth. However, the majority of mammals, including humans, are incapable of synthesizing n-6 and n-3 PUFAs. Mammals must obtain n-6 and n-3 PUFAs from their diet. Fatty acid desaturase (Fad) plays a critical role in plant PUFA biosynthesis. Therefore, we generated plant-derived Fad3 single and Fad2-Fad3 double transgenic mice. Compared with wild-type mice, we found that PUFA levels were greatly increased in the single and double transgenic mice by measuring PUFA levels. Moreover, the concentration of n-6 and n-3 PUFAs in the Fad2-Fad3 double transgenic mice were greater than in the Fad3 single transgenic mice. These results demonstrate that the plant-derived Fad2 and Fad3 genes can be expressed in mammals. To clarify the mechanism for Fad2 and Fad3 genes in transgenic mice, we measured the PUFAs synthesis-related genes. Compared with wild-type mice, these Fad transgenic mice have their own n-3 and n-6 PUFAs biosynthetic pathways. Thus, we have established a simple and efficient method for in vivo synthesis of PUFAs.

Inhibiting repressive epigenetic modification promotes telomere rejuvenation in somatic cell reprogramming.

The efficiency of somatic cell nuclear transfer (SCNT) reprogramming is extremely low in terms of production of cloned animals. Here, we found that telomere rejuvenation is a critical event for SCNT reprogramming. Through small-molecule screening, we identified that melatonin significantly improved the in vitro and in vivo developmental competence of SCNT-derived embryos. Through use of embryonic biopsy, single-cell RNA sequencing, and quantitative FISH experiments, we revealed that melatonin not only attenuated the zygotic genome activation defect but also facilitated telomere elongation in the SCNT embryos. Further investigation indicated that melatonin inhibited heterochromatic epigenetic modification related to gene silencing including DNA methylation and histone H3 lysine 9 trimethylation. In addition, melatonin could increase the level of activation markers such as acetylated histone H3. This is the first study to characterize melatonin-treatment and telomere rejuvenation in SCNT-mediated reprogramming. Moreover, combinational use of melatonin-treated donor embryos and pseudopregnant recipients achieved synergistic enhancement of the production of cloned animals.-Yang, L., Liu, X., Song, L., Su, G., Di, A., Bai, C., Wei, Z., Li, G. Inhibiting repressive epigenetic modification promotes telomere rejuvenation in somatic cell reprogramming.