N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

Objective:To explore the relationship between the expressions of P21,P27 and proliferating cell nuclear antigen(PCNA)in glomerular mesangial tissue and poor renal prognosis in patients with immunoglobulin A(IgA)nephropathy.Methods:A total of 145 patients with IgA nephropathy treated in Xiaogan Central Hospital from April 2017 to August 2019 were selected as the research object.The expressions of P21,P27 and PCNA in glomerular mesangial tissue were detected by immunohistochemistry.All patients were followed up for 24 months,and the prognosis were counted.The expressions of P21,P27 and PCNA in glomerular mesangial tissue of patients with different prognosis were compared and the influencing factors of poor prognosis in patients with IgA nephropathy were analyzed by Logistic regression analysis.Results:The expression rates of P21,P27 and PCNA positive cells in glomerular mesangial tissue of patients with IgA nephropathy were(38.69±6.83)%,(55.94±8.08)%,(33.47±5.72)%,respectively.The incidence rete of poor prognosis in patients with IgA nephropathy was 17.24%,and the expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of patients with poor prognosis were higher than those in good prognosis group(P<0.05),while the expression rate of P27 positive cells was lower than that in good prognosis group(P<0.05).Logistic multiple regression analysis showed that elevated diastolic blood pressure,increased 24 h proteinuria,mesangial cell proliferation,segmental glomerulosclerosis,renal tubular atrophy/interstitial fibrosis,crescentic body,increased expression rates of P21 and PCNA positive cells and decreased expression rate of P27 positive cells were all risk factors affecting the poor prognosis of patients with IgA nephropathy(P<0.05).Conclusion:There are positive expressions of P21,P27 and PCNA in glomerular mesangial tissue of IgA nephropathy.The expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of of patients with poor prognosis of IgA nephropathy are higher than those with good prognosis,while the expression rate of P27 protein positive cells is lower than those with good prognosis,which are risk factors for poor prognosis of patients with IgA nephropathy.

Rubus corchorifolius(Shanmei or mountain berry,2n=14)is widely distributed in China,and its fruits possess high nutritional and medicinal values.Here,we reported a high-quality chromosome-scale genome assembly of Shanmei,with contig size of 215.69 Mb and 26,696 genes.Genome comparison among Rosaceae species showed that Shanmei and Fupenzi(Rubus chingii Hu)were most closely related,followed by blackberry(Rubus occidentalis),and that environmental adaptation-related genes were expanded in the Shanmei genome.Further resequenc-ing of 101 samples of Shanmei collected from four regions in the provinces of Yunnan,Hunan,Jiangxi,and Sichuan in China revealed that among these samples,the Hunan population of Shanmei possessed the highest diversity and represented the more ancestral population.Moreover,the Yunnan population underwent strong selection based on the nucleotide diversity,linkage dise-quilibrium,and historical effective population size analyses.Furthermore,genes from candidate genomic regions that showed strong divergence were significantly enriched in the flavonoid biosyn-thesis and plant hormone signal transduction pathways,indicating the genetic basis of adaptation of Shanmei to the local environment.The high-quality assembled genome and the variome dataset of Shanmei provide valuable resources for breeding applications and for elucidating the genome evo-lution and ecological adaptation of Rubus species.

BACKGROUND: Decreased heart rate variability (HRV) is a predictor of autonomic system dysfunction, and is considered as a potential mechanism of increased risk of cardiovascular disease (CVD) induced by exposure to particulate matter less than 2.5 μm in diameter (PM METHODS: An updated systematic review and meta-analysis of panel studies till November 1, 2019 was conducted to evaluate the acute effect of exposure to ambient PM RESULTS: A total of 33 panel studies were included in our meta-analysis, with 16 studies conducted in North America, 12 studies in Asia, and 5 studies in Europe. The pooled results showed a 10 μg/m CONCLUSION Short-term exposure to PM
Adult ; Aged ; Aged, 80 and over ; Air Pollutants/analysis* ; Air Pollution/analysis* ; Female ; Heart Rate/drug effects* ; Humans ; Male ; Middle Aged ; Particulate Matter/analysis* ; Young Adult

Objective:To analysis the effects of alprostadil and yishen huashi particles on blood glucose,blood lipid,renal function and urinary podocyte proteins of patients with diabetic nephropathy.Methods:98 patients with diabetic nephropathy were selected and randomly divided into the control group and the experimental group with 49 cases in each group.The patients in the control group were treated with alprostadil,while the patients in the experimental group were treated with yishenhuashui particles on the basis of the control group.Then the curative effect,the levels of glycosylated hemoglobin (HbAlc),blood glucose (FPG),2 h postprandial blood glucose (2h PG),triglycerides (TG),total cholesterol (TC),high-density lipoprotein (HDL-C),low density lipoprotein (LDL-C),blood urea nitrogen (BUN),creatinine (Cr),β2 microglobulin (β2-MG),bladder inhibition (Cys-C) and urinary podocyte proteins (PCX) in the two groups were observed and compared between the two groups before and after the treatment.Results:The total effective rate of experimental group was higher than control group (P＜0.05).After treatment,there was no statistically significant difference about the HbA1c,FPG and 2 HPG between the two groups (P＞0.05).After the treatment,the levels ofTG,TC,LDL-C,BUN,Cr,β2 MG,Cys C,PCX and urinary nephrin/urine Cr of the experimental group were lower than those of the control group (P＜0.05).The HDL-C of experimental group was higher than that of the control group (P＜0.05).Conclusion:The curative is effect of alprostadil and yishen huashi particles in treatment diabetic nephropathy patients,can conducive to the improvement of blood glucose,blood lipid,renal function,reduce the concentration of urinary podocyte related proteins.

Objective To observe the short-term,long-term clinical results and complications in refractory juvenile idiopathic arthritis (JIA) treating with TNF-α inhibitors,and to compare 2 evaluation systems.Methods A retrospective review of 52 cases of patients with refractory JIA in Shenzhen Children's Hospital was performed.With reference to International Leagne of Associations for Rheumatology(ILAR)2001 diagnostic criteria,the patients were divided into 4 groups:26 polyarticular JIA patients,14 systemic JIA patients,9 oligoarticular JIA patients and 3 other types of patients.The children with JIA were based on the conventional treatment such as Methotrexate,combination of TNF-α inhibitors treatment.The short-term and long-term clinical outcomes were evaluated and compared with American College of Rheumatology (ACR) and Juvenile Arthritis Disease Activity Score (JADAS).Complications in each group were recorded.Results (1) Short-term outcome assessment:ACR 50 were achieved in 69.2％ of the polyarticular JIA,66.7％ in oligoarticular and 35.7％ in systemic JIA patients on the third month;and by the time of the sixth month it reached to 73.0％ in polyarticular JIA,77.7％ in oligoarticular JIA and 14.3％ in systemic JIA patients on the sixth month.Significant improvement of JADAS after the treatment was observed in each type of JIA,and the differences were statistically significant(all P ＜ 0.05).(2) Long-term outcome assessment:except for the cases missing follow-ups and withdrawal cases,46 patients were able to complete 2 years assessments:according to ACR,effective rate was 84.0％ in polyarticular JIA (21/25 cases),50.0％ in oligoarticular JIA (4/8 cases) and 7.7％ in systemic (1/13 cases) JIA patients;JADAS was significantly decreased in polyarticular JIA patients (76.0％,19/25cases) (P ＜ 0.05),while significant improvement was not observed in oligoarticular JIA and systemic JIA patients(P ＞ 0.05).(3) Complications of upper respiratory tract infection (23.0％,12 cases) and local reaction in injection site (7.6％,4 cases) were noticed.Higher risks of tuberculosis infection and malignancy were not observed.Conclusions (1) TNF-α inhibitors treatment showed a better short-term and long-term outcome in polyarticular and oligoarticular JIA patients,and it may also improve short-term outcome in systemic JIA but with poorer long-term outcome.(2)Two evaluated systems (ACR and JADAS) were well relative,but ACR was capable to compare clinical course between different types of JIA.(3) TNF-α inhibitors treatment was relatively safe with unremarkable adverse reactions.

Objective To detect the expression of human telomerase reverse transcriptase (hTERT ) and telomerase in hu‐man fetal gastric fibroblasts .Methods Human fetal gastric fibroblasts were isolated and cultured ,epithelial cells were exduded by CK‐18 immune staining .hTERT protein was determined by indirect immunofluorescence .Telomerase activity was analyzed using telomeric repeat amplification protocol assay (TRAP)while the same analysis in adult gastric fibroblast ,which as to be positive con‐trol .Results Cultured fibroblasts were CK‐18 negative .The positive hTERT immunostaining was detected in both cellular cyto‐plasm and nuclear compartments .Amplified telomeric repeats (about 170 bp) in human fetal gastric fibroblasts were longer than those (160 bp) in adult gastric fibroblasts .Conclusion hTERT and telomerase were expressed in human fetal gastric fibroblasts .

Objective To investigate efficacy and effect on liver function of the experimental therapy with balloon catheter to block the main artery temporarily and then pressurize chemoembolization to treat hypovascular liver cancer. Methods Eighty patients with hypovascular liver cancer requiring interventional therapy were randomly divided into two groups.The experimental group was treated with the new therapy and the control group was treated with traditional therapy. The lipiodol-filling status and maximum diameter of the tumor was analyzed for a midterm outcome,and the change of AFP and liver function were evaluated.Mann-Whitney test was used for data between two groups,Friedman test was used for data of each group,and Spearman nonparameter relevant analysis was used for efficacy indexes.Results ( 1 ) All Patients have confirmed diagnosis of hypocvascular liver cancer and got balanced baseline. ( 2 ) Lipiodol-filling status:the clinical efficacy and benefit rates of patients from experimental group were higher than that from control group and showed statistically significant difference in 1,3,12 months (Z =-2.135,- 2.939,- 2.686 ; P =0.034,0.004,0.007 ),but no statistically significant difference in 6 month ( Z =- 1.170,P =0.242 ).The status of lipiodol-filling of experimental group ( x2 =2.593,P =0.459 ) was more stable than control group ( x2 =10.886,P =0.012).(3) Maximum diameter of the tumor:the clinical efficacy and benefit rates of patients from experimental group were higher than that from control group and showed statistically significant difference in 3,12 months ( Z =- 2.734,- 2.733 ; P =0.006,0.006),but no statistically significant difference in 1,6 month ( Z =- 1.692,- 1.895 ;P =0.091,0.058). But neither of two groups showed statistically significant difference in change of maximum diameter of the tumor ( x2 =5.500,P =0.139 ; x2 =6.509,P =0.089 ).Relation between lipiodol-filling and maximum diameter showed positive correlation in 3 month ( r =0.257,P =0.035 ). (4) Stratified analysis was used for data of AFP according to AFP value before therapy,and two groups showed no statistically significant difference for patients belonging to 20-1000 μg/L by Pearson Chi-square test. (5)Two groups showed no statistically significant difference for data of liver function before therapy and in 1,3,6months ( Z =- 1.073,- 1.314,-0.518,-0.549;P=0.308,0.189,0.604,0.583).Conclusions According to the midterm result of this experiment,the experimental therapy increased lipiodol-filling and decreased maximum diameter of the tumor significantly in 3 and 12 months correspondingly,but no significant difference was observed in AFP and liver function between groups yet. So the long-term efficacy and its influence to lung metastasis and survival rate need further research.

Objective To investigate the effect of dexmedetomidine on median effective target effect-site concentration ( EC50) of sufentanil inhibiting body movement evoked by skin incision in patients undergoing bilateral subtotal thyroidectomy. Methods Thirty-nine ASA I or II patients of both sexes aged 20-64 yr with a body mass index of 20-25 kg/m2 undergoing bilateral subtotal thyroidectomy were randomly divided into 2 groups: control group (group C) and dexmedetomidine group (group D). The patients were premedicated with intramuscular phenobarbital 0.1 g and scopolamine 0.3 mg. In group D dexmedetomidine 0.6 μg/kg was injected iv over 10 min at S min before induction of anesthesia. Anesthesia was induced with target-controlled infusion (TCI) of propofol and sufentanil. The target plasma concentration of propofol was set at 3.0 μg/ml which was maintained until the end of operation. TCI of sufentanil was started at 10 min after initiation of propofol TCI. The initial target effect-site concentration was set at 0.20 ng/ml and decreased/increased by 20% in the next patient according to whether the patient's body moved or not within 1 min after skin incision. Laryngeal mask airway was inserted at 3 min after initiation of sufentanil TCI. Spontaneous breathing was maintained. Skin incision was made at 10 min after initiation of sufentanil TCI. The EC50 and 95% confidence interval (CI) of sufentanil inhibiting skin incision-evoked body movement were calculated with sequential method. Results EC50, of sufentanil was 0.1148 ng/ml (95% CI 0.1055-0.1249 ng/ml) in group D and 0.1454 ng/ml (95% CI 0.1339-0.1580 ng/ml) in group C, and was significantly lower in group D than in group C. Conclusion Dexmedetomidine 0.6 μg/kg infused iv before operation can reduce the EC50 of sufentanil inhibiting body movement evoked by skin incision in patients undergoing bilateral subtotal thyroidectomy.

OBJECTIVE To discuss the prevention and control measures for nosocomial transmission of Mycobacterium tuberculosis.METHODS The status of hospital-acquired tuberculosis and influencing factors on nosocomial transmission of M.tuberculosis at home and abroad were analyzed.Then prevention and control measures for nosocomial tuberculosis were brought forward.RESULTS To prevent and control of nosocomial transmission of M.tuberculosis,it was necessary to strengthen personnel management and environmental monitoring,control the direction of air flow in hospitals,strengthen respiratory protection of health care workers and management of tuberculosis patients.CONCLUSIONS To prevent and control M.tuberculosis hospital infections,comprehensive prevention and control measures are needed.