RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.

Objective To study the effect of the combinational use of miR-34a-functionalized Bio-Oss? bone pow-der with transglutaminase crosslinked gelatin(Col-Tgel)on the osteoblastic differentiation of bone marrow mesenchymal stem cells(BMSCs)and bone defect healing after irradiation.Methods The experiment was approved by the Animal Ethics Committee.BMSCs were isolated from the bone marrow of 2-week-old Sprague-Dawley(SD)rats and identified.After reaching 80%confluence,BMSCs were irradiated with 2 Gy of X-ray radiation to establish a radiation-damaged BMSC model for further experimentation.2.5 μL or 5 μL of Col-Tgel was mixed with 10 mg of Bio-Oss?(P)to prepare PG-2.5 and PG-5.The optimal proportion of Bio-Oss?(P)and Col-Tgel was determined through in vitro and in vivo experiments.Cy3-labeled agomiR-34a,agomiR-34a,or agomiR NC was mixed with lipofectamine 2000 and added to 10 mg of Bio-Oss?(P).The mixtures were lyophilized,and 2.5 μL Col-Tgel was added to each group of lyophilized Bio-Oss?/lipofectamine/miRNA complexes or to 10 mg of Bio-Oss? to obtain PG-Cy3-miR-34a,PG-miR-34a,PG-miR NC,and PG.Irradiated BMSCs were cocultured with PG-Cy3-miR-34a to evaluate cellular uptake of Cy3-agomiR-34a using confocal microscopy.Then,irradiated BMSCs were cocultured with PG-miR-34a,PG-miR NC,and PG.The expression of miR-34a was tested by RT-qPCR and cell proliferation was tested by CCK-8 assay.After 14 days of osteogenic induc-tion,the mRNA expression of Runt-related transcription factor 2(Runx2),alkaline phosphatase(ALP),and osteocalcin(OCN)was tested by RT-qPCR.The bilateral tibias of 8-week-old SD rats were irradiated with a single dose of 15 Gy of X-ray radiation.Three weeks later,tibial defects with a diameter of 3 mm and a depth of 2 mm were created 2-3 mm be-low the epiphyseal line in the tibial metaphysis.The composite bone substitute materials of PG-miR-34a,PG-miR NC,and PG were implanted into the defect area.Eight weeks after implantation,the tibias were harvested and evaluated for bone regeneration using micro-CT analysis and HE staining.Results The results demonstrated that 2 Gy irradiation adversely affected the osteogenic differentiation capacity of BMSCs,evidenced by the decreased ALP staining and num-ber of mineralized nodules stained with Alizarin red in the irradiated group compared to the non-irradiated group.The composite material consisting of 10 mg Bio-Oss? and 2.5 μL Col-Tgel exhibited good osteogenic induction capability and handling properties and was used for subsequent experiments.The PG-Cy3-miR-34a could deliver the loaded Cy3-agomiR-34a into irradiated BMSCs.PG-miR-34a enhanced the expression of miR-34a in irradiated BMSCs without af-fecting cell proliferation.PG-miR-34a significantly upregulated the expression of osteogenic-related genes,including Runx2,ALP,and OCN.In the experiment of bone defect healing in irradiated tibias,micro-CT analysis showed that PG-miR-34a group had a higher bone volume in the bone defect area compared to other groups.The HE staining results al-so confirmed that implantation of PG-miR-34a can promote the healing of bone defects in irradiated tibias.Conclu-sion The combinational use of miR-34a-functionalized Bio-Oss? bone powder with Col-Tgel could promote the osteo-genic differentiation of irradiated BMSCs and enhance bone regeneration in irradiated bone defects.

The rostral agranular insular cortex (RAIC) has been associated with pain modulation. Although the endogenous cannabinoid system (eCB) has been shown to regulate chronic pain, the roles of eCBs in the RAIC remain elusive under the neuropathic pain state. Neuropathic pain was induced in C57BL/6 mice by common peroneal nerve (CPN) ligation. The roles of the eCB were tested in the RAIC of ligated CPN C57BL/6J mice, glutamatergic, or GABAergic neuron cannabinoid receptor 1 (CB1R) knockdown mice with the whole-cell patch-clamp and pain behavioral methods. The E/I ratio (amplitude ratio between mEPSCs and mIPSCs) was significantly increased in layer V pyramidal neurons of the RAIC in CPN-ligated mice. Depolarization-induced suppression of inhibition but not depolarization-induced suppression of excitation in RAIC layer V pyramidal neurons were significantly increased in CPN-ligated mice. The analgesic effect of ACEA (a CB1R agonist) was alleviated along with bilateral dorsolateral funiculus lesions, with the administration of AM251 (a CB1R antagonist), and in CB1R knockdown mice in GABAergic neurons, but not glutamatergic neurons of the RAIC. Our results suggest that CB1R activation reinforces the function of the descending pain inhibitory pathway via reducing the inhibition of glutamatergic layer V neurons by GABAergic neurons in the RAIC to induce an analgesic effect in neuropathic pain.
Mice ; Animals ; Insular Cortex ; Peroneal Nerve ; Mice, Inbred C57BL ; Neuralgia ; GABAergic Neurons ; Analgesia ; Analgesics ; Receptors, Cannabinoid

Depressive disorder is manifested as emotional and physical abnormality. Theoretically, the governor vessel is distributed along the spine, related to the brain and communicated with five zang and six fu organs. It is the key meridian for understanding the various symptoms of depressive disorder. Depressive disorder is caused by dysfunction, stagnation or emptiness of the governor vessel, resulting in malnutrition of the brain. In clinical diagnosis and treatment, based on the theory of the governor vessel, the etiology and pathogenesis are analyzed in the patients with depressive disorder. In order to achieve harmonizing mutually the mental and physical conditions, acupuncture is delivered to adjust the spirit and physical state, moving cupping is to regulate the governor vessel, tuina manipulation is to promote meridians and collaterals and physical exercise is to coordinate the body and the spirit.
Humans ; Acupuncture Therapy/methods* ; Meridians ; Acupuncture ; Brain ; Depressive Disorder ; Acupuncture Points

Purpose: Despite the high prevalence of postdialysis fatigue (PDF) in maintenance hemodialysis patients, no meta-analysis on the prevalence and risk factors of PDF has yet been published. This study aimed to identify the prevalence of PDF and explore its related factors. Methods: PubMed, Embase, CENTRAL, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the four Chinese databases (National Knowledge Infrastructure [CNKI], Chinese Biomedical Literature database [SinoMed], Wanfang Digital Periodicals [WANFANG], and Chinese Science and Technology Periodicals [VIP] database) were searched from inception up to July 2022. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The articles were independently searched by two reviewers, and the relevant data were extracted. The Agency for Healthcare Research and Quality was used to assess the quality of the included studies. Results: Thirteen articles with 2,118 participants were included. The pooled prevalence was 60.0%. The meta-analysis results revealed that the ultrafiltration volume, mean arterial pressure after dialysis, and good sleep quality were potentially associated with PDF, whereas only good sleep quality (odds ratio 0.24, 95% confidence interval 0.19e0.30) was significantly associated with PDF. Conclusion PDF is common in maintenance hemodialysis patients, which is related to the ultrafiltration volume, sleep quality, and mean arterial pressure after dialysis. However, the mechanism underlying the risk factors and PDF remains unknown. Further research is warranted to investigate the risk factors, intervention, treatment, and mechanism in maintenance hemodialysis patients.

OBJECTIVE: To observe the clinical effect of electroacupuncture (EA) on aged insomnia, and explore its possible mechanism. METHODS: A total of 60 patients with aged insomnia were randomly divided into an EA group (30 cases) and a sham EA group (30 cases, 1 case dropped off). The patients in the EA group were treated with acupuncture at Baihui (GV 20), Yintang (GV 29), Shenmen (HT 7), Sanyinjiao (SP 6), Xinshu (BL 15) and Shenshu (BL 23), and EA was used at Baihui (GV 20) and Yintang (GV 29), with intermittent wave, 2 Hz in frequency. In the sham EA group, the acupoints and the EA connection acupoints were the same as those in the EA group, 2-3 mm in depth, but no current was connected. The intervention was given 30 min each time, once every other day, 3 times a week for 4 weeks in the both groups. Before and after treatment, the Pittsburgh sleep quality index (PSQI) and Montreal cognitive assessment (MoCA) scale were used to assess sleep quality and cognitive function, and serum melatonin (MT) and dopamine (DA) levels were detected. RESULTS: After treatment, the total score and sub-item scores of PSQI in the EA group were lower than those before treatment ( CONCLUSION Electroacupuncture can improve sleep quality and cognitive function in aged insomnia patients, and its mechanism may be related to regulating serum MT and DA levels.
Acupuncture Points ; Aged ; Dopamine ; Electroacupuncture ; Humans ; Melatonin ; Sleep Initiation and Maintenance Disorders/therapy*

Objective:To investigate the relationship of urinary 8-oxoguanosine(8-oxoGsn)with muscle mass, muscle strength, advanced glycation end products(AGEs), trace elements, heavy metals and other health-related indictors in different age groups of the Beijing area.Methods:A cross-sectional research was conducted.Healthy adults aged 25 to 93 years who sought health examination in the Health Examination Center of Beijing Hospital were recruited.Participants were divided into the young and middle-aged group and the elderly group with age 60 as the cutoff.Urinary 8-oxoGsn levels were detected by mass spectrometry and adjusted using urine creatinine values.Body composition was measured by multifrequency bioelectrical impedance analysis(BIA). Grip strength, 6-meter walking speed and 5-times sit to stand test were conducted by experienced team members.Skin autofluorescence was used to detect skin AGEs.A portable optical scanner was used to detect heavy metals and trace elements using reference points of the palm.Levels of fasting blood glucose, glycosylated hemoglobin, high-density lipoprotein and other common blood biochemical indicators were measured.Results:A total of 106 subjects were enrolled, including 68 in the young and middle-aged group and 38 in the elderly group.The proportion of patients with hypertension(14 ases or 36.8% vs.7 ases or 10.3%), systolic blood pressure[130(120, 140) vs.120(110, 126)mmHg], fasting blood glucose[5.7(5.2, 5.9)mmol/L vs.5.2(4.9, 5.5)mmol/L], glycosylated hemoglobin[6.0(5.7, 6.2)% vs.5.7(5.4, 5.9)%], 8-oxoGsn/Cre[1.9(1.4, 2.6) vs.1.3(1.0, 1.6)], AGEs(2.44±0.46 vs.2.01±0.29), 5-times sit to stand test scores[7.8(6.9, 9.8)s vs.6.0(5.0, 6.8)s], magnesium(31.4±7.2 vs.27.7±6.4), mercury(0.013±0.003 vs.0.008±0.003)and silver[0.011(0.010, 0.012) vs.0.010(0.009, 0.011)]were higher in the elderly group than in the young and middle-aged group, while grip strength[28.0(22.0, 35.1)kg vs.36.6(28.5, 49.1)kg], fat-free mass[44.9(37.5, 51.1)kg vs.53.3(42.4, 58.5)kg], trunk muscle mass[21.0(17.5, 23.9)kg vs.25(19.8, 27.4)kg], appendicular skeletal muscle mass[20.9(17.6, 23.9)kg vs.24.9(19.8, 27.3)kg], calcium[273.3(219.1, 480.0) vs.457.8(428.5, 489.1)], cobalt[0.029(0.027, 0.031) vs.0.031(0.028, 0.034)], selenium[1.44(0.93, 1.71) vs.1.61(1.53, 1.68)]and nickel[3.5(3.3, 4.0)*10 -3vs.3.8(3.6, 4.1)*10 -3]were lower in the elderly group than in the young and middle-aged group( P<0.05). Urinary 8-oxoGsn/Cre levels were positively correlated with age, time of 5-times sit to stand test, AGEs, fasting blood glucose, mercury and aluminum( rs=0.443, 0.292, 0.357, 0.205, 0.316 and 0.214, P<0.05), and negatively correlated with trunk muscle mass, appendicular skeletal muscle mass, fat-free mass, grip strength, silicon and manganese( rs=-0.334, -0.333, -0.332, -0.366, -0.246 and -0.234, P<0.05), with statistical significance. Conclusions:Increased urinary 8-oxoGsn/Cre levels are correlated with decreased muscle mass, poor physical function, accumulation of AGEs, decreased trace element levels and increased heavy metal levels.Therefore, 8-oxoGsn has the potential to be a broadly representative and sensitive indicator for health assessment.

Objective: To investigate the effect of insertion technique and electrode array type on the insertion force of electrode array, and to provide a basis for further optimizing electrode design and facilitating mini-invasive electrode insertion. Methods: Three types of electrode array from Nurotron (Standard Electrode, Slim-medium Electrode, Slim-long Electrode) were studied. from July 2019 to December 2019. These electrode arrays were inserted into the phantom models of the cochlea, manually or robot-assisted(medium speed and low speed). The real-time force during electrode array insertion was recorded by ATI Nano 17 Ti sensors and was analyzed by accessory software. Origin 2020b software was used for statistical processing. Results: The insertion force of all electrode arrays progressively increased with the insertion depth. With the manual technique, the peak force of slim-medium electrode insertion was significantly smaller than that of the standard electrode insertion((71.0±16.6) mN vs (140.9±52.7) mN, Z=3.683, P<0.01), and the peak force of the slim-long electrode insertion was between the peak force of standard electrode and slim-medium electrode(P>0.05). No difference was found in the force variation of insertion among the three electrodes(P>0.05). With medium-speed and low-speed robotic assistance, the peak force characteristics of three electrodes were similar to those with the manual technique, but the force variation of standard electrode insertion ((83.9±9.7) mN/s) at medium speed was significantly larger than that of the slim-long electrode insertion ((69.2±4.0)mN/s), and the force variation of the standard electrode insertion at low speed was significantly greater than the other two electrodes. For the same electrode, robot-assisted insertion presented significantly lower peak force and force variation than manual insertion for each type of electrode array. But there was no difference in the peak force and force variation between two-speed levels of robot assistance (P>0.05). Conclusions: The insertion force of the electrode array will be lower when a slim electrode array or robot technique is applied. Long electrode array might make manual insertion difficult or less precise. Robot assistance has advantage on force control during electrode array insertion.
Cochlea/surgery* ; Cochlear Implantation ; Cochlear Implants ; Electrodes, Implanted ; Humans ; Robotics

Aim To explore the mechanism of Fluspirilene inhibiting HCC through decreasing the expression of Akt.Methods The difference of mRNA was verified by the test of protein expression between Fluspirilenc treatment group and control group by HCC experiment in vivo and vitro, including Western blot, IHC after mRNA array.Results Akt expression was lower in Fluspirilene treatment group than that in control group by mRNA array.Protein expression of Akt, phosphorylate-CDK2 and phos- phorylate-Rb decreased massively in Fluspirilene treatment group in a concentration-dependent manner in HepG2 and Huh7 cells by Western blotting compared with those in control group.Declined expression of phosphorylate-Akt was proved in a concen- tration-dependent manner in xenograft tumor tissues in Fluspirilene treatment group compared with that in control group in IHC test.Conclusions Fluspirilene inhibits HCC by decreasing significantly the protein expression of Akt, phosphorylat-Akt, phos- phorylate-CDK2 and phosphorylate-Rb.

【Objective】 To establish and evaluate a nephelometric assay for the determination of immunoglobulin A (IgA) residues in human intravenous immunoglobulin(IVIG). 【Methods】 BN ProSpec^© automatic protein analyzer and its supporting immunoglobulin A determination kit (nephelometry) produced by German Siemens and the national standard of human IgA were used to establish the nephelometric assay to determine IgA residue in test products and verify the methodology. The test products include IVIG (pH4) prepared by low-temperature ethanol protein separation process and a novel IVIG prepared by chromatography. 【Results】 The average deviation of three calibration curves for IgA residues determination by the nephelometric assay were 1.08%, 0.95% and 1.54%,, and the three deviations of the quality control were 4.00%, -2.30% and -0.20%, respectively, which indicated good calibration and quality control. In the specificity test, the average recovery rates of IgA for reference substance 1 containing 100g/L maltose and reference substance 2 containing 20g/L glycine were 102.7% and 105.8%, respectively. The relative standard deviation (RSD) values of the repeatability tests of the two test products were 3.9% and 1.9%, and the RSD values of the intermediate precision test were 3.6% and 2.3%, respectively.The difference values at each time point in the durability test of test products′ storage time were all less than 10%, and the RSD values of the two test products in the durability test of kits of different batches were 2.8% and 2.2%, respectively. In the accuracy test, the average recovery rates of IVIG (pH4) added to the standard were 94.2%, 101.7% and 96.2%, respectively, and the average recovery rates of the novel IVIG added to the standard were 102.8%, 106.3% and 99.7%, respectively. The average recovery rate of the limit quantification test was 101.0%, and the RSD was 4.0%. 【Conclusion】 Nephelometric assay has the advantages of strong specificity, high precision and accuracy, good repeatability, simple and rapid operation, and automation, and can be used for the determination of IgA residue in IVIG (pH4) and novel IVIG products.