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 analyze the relationship between angiotensin type Ⅱ 1 receptor autoantibodies (AT1-AA),blood uric acid and urea nitrogen with hypertensive disorder complicating pregnancy (HDCP). Methods A total of 125 patients with HDCP diagnosed in the obstetrics department of Tianjin Municipal Bao-di District People's Hospital from August 2021 to February 2023 were randomly selected as the HDCP group, and 55 healthy pregnant women admitted to this hospital during the same period were selected as the control group.The HDCP group was divided into the gestational hypertension subgroup (n=77) and preeclampsia group (n=48) according to the degree of disease progression.The levels of serum uric acid,blood urea nitro-gen and AT1-AA were detected and compared between the HDCP group and control group and between the gestational hypertension subgroup and preeclampsia subgroup.Results There were no statistically significant differences in the age,gestational time,D-dimer,serum calcium and serum creatinine between the control group and the HDCP group (P>0.05).The levels of peripheral blood AT1-AA,serum uric acid and blood u-rea nitrogen in the HDCP group were higher than those in the control group,and the differences were statisti-cally significant (P<0.05).The levels of peripheral blood AT1-AA,serum uric acid and blood urea nitrogen in the preeclampsia subgroup were significantly higher than those in the gestational hypertension subgroup, and the differences were statistically significant (P<0.05).The Spearman rank correlation coefficient analysis showed that the levels of peripheral blood AT1-AA (r=0.301),serum uric acid (r=0.380) and blood urea nitrogen (r=0.257) levels were positively correlated with the severity degree of HDCP (P<0.01).The area under the curve (AUC) of AT1-AA,serum uric acid and blood urea nitrogen detection alone and combined de-tection in the diagnosis of HDCP were 0.680,0.714,0.647 and 0.725,and the corresponding Youden coeffi-cients were 0.368,0.380,0.306 and 0.439,indicating that the value of combined testing was higher than that of single item detection in the diagnosis of HDCP.Conclusion AT1-AA,serum uric acid and blood urea nitro-gen are correlated with the occurrence and development of HDCP,and the 3-item combined detection has high-er value.

Objective:To investigate the change of D-Dimer (D-D), cardiac troponin I (cTnI) and vasoactive-inotropic score (VIS) after Stanford type A aortic dissection (TAAD) and thier predictive effect on death outcome.Methods:120 patients with TAAD who were treated in the Affiliated Hospital of Jining Medical College from January 2019 to January 2022 were retrospectively selected and divided into death group ( n=17) and survival group ( n=103) according to the 28-day survival after operation. The difference of clinical data between the two groups was compared, and the influencing factors of postoperative death in TAAD patients were analyzed by logistic regression method. Results:The age, deep hypothermic circulatory arrest time, D-D and cTnI of the patients in the death group were (60.50±5.42)years old, (30.40±9.92)min, (15.65±5.52)g/L and (3.32±0.82)mg/L, respectively, which were significantly higher than those in the survival group (all P<0.05). The VIS score and change of VIS score in the death group at 24 hours after operation were (9.66±1.10)points and (4.50±0.91)points respectively, which were significantly higher than those in the survival group (all P<0.05). Logistic regression analysis showed that age, D-D, cTnI and change of VIS score were the influencing factors of death after TAAD (all P<0.05). The area under the receiver operating characteristic (ROC) curve predicted by the D-D, cTnI and change of VIS score for death in TAAD patients was 0.718, 0.691 and 0.789 respectively (all P<0.05). Conclusions:Postoperative death of TAAD patients is affected by their age, D-D, cTnI and change of VIS score. The D-D, cTnI and change of VIS score have certain application value in predicting postoperative death of patients.

Pigs are considered as ideal donors for xenotransplantation because they have many physiological and anatomical characteristics similar to human beings. However, antibody-mediated immunity, which includes both natural and induced antibody responses, is a major challenge for the success of pig-to-primate xenotransplantation. Various genetic modification methods help to tailor pigs to be appropriate donors for xenotransplantation. In this study, we applied transcription activator-like effector nuclease (TALEN) to knock out the porcine α-1, 3-galactosyltransferase gene GGTA1, which encodes Gal epitopes that induce hyperacute immune rejection in pig-to-human xenotransplantation. Meanwhile, human leukocyte antigen-G5 gene HLA-G5, which acts as an immunosuppressive factor, was co-transfected with TALEN into porcine fetal fibroblasts. The cell colonies of GGTA1 biallelic knockout with positive transgene for HLA-G5 were chosen as nuclear donors to generate genetic modified piglets through a single round of somatic cell nuclear transfer. As a result, we successfully obtained 20 modified piglets that were positive for GGTA1 knockout (GTKO) and half of them expressed the HLA-G5 protein. Gal epitopes on the cell membrane of GTKO/HLA-G5 piglets were completely absent. Western blotting and immunofluorescence showed that HLA-G5 was expressed in the modified piglets. Functionally, the fibroblasts from the GTKO/HLA-G5 piglets showed enhanced resistance to complement-mediated lysis ability compared with those from GTKO-only or wild-type pigs. These results indicate that the GTKO/HLA-G5 pigs could be a valuable donor model to facilitate laboratory studies and clinics for xenotransplantation.
Animals ; Animals, Genetically Modified ; Gene Knockout Techniques ; HLA Antigens ; Humans ; Nuclear Transfer Techniques ; Swine ; Transplantation, Heterologous

Postprandial hyperinsulinemic hypoglycemia (PHH) is one of the serious complications after bariatric surgery, it can lead life-threatening neuroglycopenic symptoms, such as seizures, disorientation, impairment of version and loss of consciousness without any premonitory. The presentation, prevalence, diagnosis, pathology and treatment are reviewed in this summary.

The correct thoughts and principles of diagnosis and treatment of chronic refractory wounds need to be formulated. Through the relevant domestic and international consensus and based on clinical experience, the Thoughts and principles of diagnosis and treatment of chronic refractory wounds in China is proposed. It is considered that in the diagnosis and treatment of chronic refractory wounds, in the case of fully understanding the patient′s medical history, the following thoughts and principles should be complied in order. (1) Pay attention to the cleanliness of the wound after being cleaned. (2) Reasonably perform debridement to avoid being " excessive" or " not thorough". (3) Reasonably perform examination, diagnosis, and differential diagnosis of pathogenic factors. (4) Treat according to etiology. (5) Find comorbidities and prevent adverse outcomes. (6) Select the correct wound treatment method reasonably and timely. When the conservative wound care treatment is considered, pay attention to embodying the concept of etiological treatment, treat the wound according to the principles of safety, phase, selectivity, and effectiveness, and make a reasonable choice of continuing conservative treatment or surgical treatment in time after completing the preparation of the wound bed. When surgical treatment is considered, pay attention to the selection of reasonable surgical method and donor site, pay attention to the healing rate of surgical wound site and the outcome of donor site, and give reasonable protection to the wound site after surgery. (7) Carry out rehabilitation treatment after wound healing and related health education.

Objective To investigate the effect of sevoflurane anesthesia on the expression of hippocampal apolipoprotein E (ApoE) mRNA of rats.Methods Sixty healthy male Sprague-Dawley rats,weighing 300-400 g,aged 15 weeks,were randomly divided into 2 groups (n=30 each) using a random number table:50％ oxygen group (group C) and 3.2％ sevoflurane group (group S).The rats in group C inhaled 50％ oxygen for 2 h,while those in group S inhaled 3.2％ sevoflurane in 50％ oxygen for 2 h.Morris water maze test was carried out before anesthesia and at 24 and 72 h after anesthesia.At 2,24 and 72 h after anesthesia,hippocampal specimens were obtained for determination of the expression of ApoE mRNA by RT-PCR.Results Compared with group C,no significant change was found in the escape latency,time of staying at the original platform quadrant,frequency of crossing the original platform,and swimming distance before and after anesthesia,and the expression of ApoE mRNA was up-regulated after anesthesia in group S.There was no significant difference in the escape latency,time of staying at the original platform quadrant,frequency of crossing the original platform,and swimming distance before and after anesthesia,and expression of ApoE mRNA at each time point after anesthesia between the two groups.Conclusion Cognitive dysfunction induced by sevoflurane has no relationship with the up-regulated expression of ApoE mRNA in the hippocampus of rats.

BACKGROUNDIn China, the prevalence of chronic kidney disease has increased significantly. Many studies shows that the spectrum of kidney disease had changed in recent years. We retrospectively analyzed the pathological types of renal biopsy and its spectrum change at the General Hospital of the Chinese People's Liberation Army from December 1987 to December 2012, in order to offer new supporting evidences for further specifying the distribution of renal pathological types in China.

METHODSAccording to the "Revised Protocol for the Histological Typing of Glomerulopathy" (WHO, 1995), pathological diagnosis of renal biopsy was classified, detection rate of each pathological type was summarized (i.e., percentage of total renal biopsy cases), study period was divided at an interval of 5 years, and age-stratified distribution change of main pathological types was analyzed.

RESULTSThe proportion of pathological types in 11 618 cases of renal biopsy was as follows: primary glomerulonephritis (PGN, 70.7%), secondary glomerulonephritis (SGN, 20.7%), tubular-interstitial nephropathy (4.0%), hereditary/rare nephropathy (0.3%), end-stage renal disease (0.9%), and unclassified renal disease (3.3%). Among PGN, there was IgA nephropathy (IgAN, 37.0%), membranous nephropathy (MN, 11.8%), mesangial proliferative glomerulonephritis (MsPGN, 8.9%), minimal change disease (MCD, 6.6%), and focal segmental glomerulosclerosis (3.9%). Among SGN there was lupus nephritis (LN, 5.5%), Henoch-Schönlein purpura glomerulonephritis (5.3%), hepatitis B virus-associated nephritis (HBVAN, 3.03%), diabetic nephropathy (2.2%), and hypertension/malignant hypertension-associated renal damage (1.9%). Pathological data were analyzed from 1987-1992 to 2008-2012 (after age adjustment). Detection rate of IgAN tended to rise (P < 0.001). Detection rates of MN and MCD rose significantly (P < 0.001), but detection rate of MsPGN dropped significantly (P < 0.001). Among SGN, detection rate of HBVAN tended to drop (P < 0.001).

CONCLUSIONIn China, PGN was the most common glomerulopathy (mostly IgAN), LN was the most common SGN, and detection rate of MN and MCD rose significantly.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; methods ; Child ; Child, Preschool ; China ; Female ; Glomerulonephritis, Membranous ; diagnosis ; Humans ; Kidney ; pathology ; Kidney Diseases ; diagnosis ; Male ; Middle Aged ; Young Adult

Objective Explore the safe nursing method of the plasma infusion for patients with extraordinarily severe burn in shock stage,ensure patients inputing plasma safely and timely,tide over shockstage smoothly.Method 68 patients with severe burn shock stage were randomly divided into experimental group and control group,both with 34 cases?The experimental group input plasma take regular blood transfusion methods and special nursing care,control group take usual care only.Result to take special nursing care for patients with severe burn in shockstage inputing plasma can reduce the incidence of adverse transfusion reactions,tide over shockstage smoothly,improve cure rates and reduce mortality?