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*

Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia,which long-term loss of control can lead to complications of blood vessels of heart,renal and other multi-system,and even threaten the patient's life.Monitoring for blood glucose is crucial for adjusting treatment and preventing complications.Traditional invasive glucose monitoring technology requires frequent blood collection,which not only leads to significant pain in patients,but also poses the risk of infection at the puncture site,coupled with the reduced compliance brought about by cumbersome operation,which seriously restricts the effectiveness and continuity of blood glucose management.The non-invasive monitoring technique for blood glucose can enhance frequency of monitoring,and comfort level through optical method,biosensing method,etc.,which has key values in optimizing glycemic control,reducing risk of complications,and decreasing medical cost.It is becoming a hot point of research.This review summarized a noninvasive monitoring technique system included sample analysis method,optical method and physiological process-based method,which analyzed principles,advantages,and limitations of its development of each detection method.The review also concluded the challenges of noninvasive monitoring technique for blood glucose in some aspects included overcoming individual differences,enhancing precision of measurement,and improving accuracy and stability.In addition,it proposed some developing directions of noninvasive monitoring technique in future,such as continuous monitoring equipment with low cost,establishment of standardized database,and individual validation,so as to promote implementation of noninvasive monitoring technique for blood glucose,and realize accurate management for diabetes mellitus.

Objective:To analyze the risk factors for atrial high-rate episodes (AHRE) following cardiac resynchronization therapy (CRT) and construct a predictive model for the occurrence of AHRE.Methods:This was a case-control study. Patients who received CRT treatment for heart failure in the Second Affiliated Hospital of Second Affiliated Hospital of Army Military Medical University from January 2017 to December 2020 were selected and divided into AHRE group and non-AHRE group according to whether AHRE occurred during the follow-up period. Baseline clinical data were collected. Patients were followed up regularly after CRT or cardiac resynchronization therapy defibrillator (CRT-D) implantation until August 31, 2022. Logistic regression model was used to analyze the factors influencing the occurrence of AHRE in patients with heart failure treated with CRT, and a nomogram prediction model was established. The receiver operating characteristic (ROC) curve was used to evaluate the nomogram model, and the Hosmer-Lemeshow test was used to evaluate the consistency of the prediction model.Results:A total of 198 patients, aged (62±8) years, 138 (69.7%) males, were enrolled, of whom 52 (26.3%) patients developed AHRE (AHRE group) and 146 (73.7%) had no AHRE (non-AHRE group) during the follow-up period. Multivariate logistic regression analysis revealed that age, coronary heart disease, C-reactive protein, left atrial volume, and left ventricular ejection fraction (LVEF) were independent influencing factors of heart failure patients developing AHRE after CRT surgery (all P<0.05). A nomogram prediction model was constructed by combining 5 indicators: age, coronary heart disease, C-reactive protein, left atrial volume, and LVEF. In this model, a score of 4 was assigned for age ≥65 years, 4 for coronary heart disease, 4 for C-reactive protein ≥10 ng/ml, 20 for left atrial volume ≥35 ml, and 5 for LVEF ≤30%. The total score was obtained by accumulating the scores of each indicator, and the probability of heart failure patients developing AHRE after CRT surgery was predicted based on the total score. The area under the curve of the nomogram prediction model constructed in this study for predicting AHRE in heart failure patients after CRT surgery was 0.830 (95% CI: 0.795-0.866). The incidence of AHRE predicted by the model was basically consistent with the actual incidence of AHRE. The Hosmer-Lemeshow test indicated a good calibration of the model ( χ2=6.32, P=0.612). Conclusions:Age, coronary heart disease, C-reactive protein, left atrial volume, and LVEF are all independent risk factors for AHRE after CRT treatment. The nomogram prediction model based on the above factors can effectively predict the risk of AHRE in patients with heart failure after CRT, and the ROC curve and consistency test both show good prediction efficiency and consistency.

Objective To understand the distribution characteristics of fungi on object surface in hospital environ-ment,and provide reference for the scientific and precise formulation of environment control strategies based on fun-gal in clinic.Methods From December 7 to 23,2023,a total of 60 environmental specimens of 19 categories in 6 departments of a large tertiary first-class hospital were collected and divided into water-related environmental speci-men group,complete facade environmental specimen group,and sanitary ware environmental specimen group.18S rRNA sequencing was performed on specimens with fungi detected.Results Fungal detection rate of environmental specimens was 20.00％(12/60).Sink in the department of endocrinology had the highest fungal colony count(15 CFU/cm2),followed by the air outlet of air disinfection device in the department of thoracic surgery and the in-ternal part of a faucet in the department of endocrinology(both 10 CFU/cm2).The water-related environmental specimen group detected most diverse fungal genera(14 species),with high relative abundances of Aspergillus(100％),Meyerozyma(99.06％),Ophiocordyceps genus(95.63％),and Kodamaea(87.86％).The air outlet of air disinfection device was detected with a high abundance of Chaetomium(44.08％)and Corollospora(39.71％).There was no statistically significant difference in the α-diversity(Shannon and Simpson indices,P values of 0.661 and 0.568,respectively)and β-diversity(P=0.712)among the three environmental specimens.Conclusion Under the routine implementation of basic environmental cleaning and disinfection in medical institutions,fungi are in a low prevalence in the environment.However,moist surfaces and air disinfection device are prone to fungal colonization,and it is necessary to strengthen daily monitoring and take corresponding intervention measures to reduce the risk of infection.

Objective:To evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

Objective:To investigate the correlation between serum prostaglandin E2 (PGE2), heat-shock protein 70 (HSP-70) and the severity of bleeding in patients with peptic ulcer bleeding (PUB).Methods:A total of 122 patients with peptic ulcer (PU) admitted to Chang'an Hospital from March 2021 to March 2024 were retrospectively collected and divided into simple PU group (50 cases) and PUB group (72 cases) according to whether PUB occurred. Serum levels of PGE2 and HSP-70 were determined by enzyme-linked immunosorbent assay (ELISA). Spearman test was used to analyze the correlation between serum PGE2, HSP-70 levels and bleeding severity in PUB patients. Logistic regression was used to analyze the risk factors of PUB, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum PGE2 and HSP-70 levels on the bleeding degree of PUB patients.Results:The proportion of non-steroidal anti-inflammatory drugsnon-ster (NSAID) used and Helicobacter pylori (Hp) infection, thromboplastin time (APTT) and prothrombin time (PT) in the PUB group were higher than those in the PU group: 42.00%(21/50) vs. 25.00%(18/72), 36.00%(18/50) vs. 58.33%(42/72), (28.78 ± 3.24) s vs. (26.72 ± 3.89) s, (13.14 ± 2.56) s vs. (11.26 ± 2.15) s, and the serum levels of PGE2 and HSP-70 were lower than those in the PU group: (174.25 ± 18.21) ng/L vs. (236.44 ± 24.52) ng/L, (0.78 ± 0.22) μg/L vs. (1.24 ± 0.38) μg/L, there were statistical significances ( P<0.05). The serum levels of PGE2 and HSP-70 in PUB patients decreased gradually with the severity of hemorrhage ( P<0.05). Spearman test showed that serum PGE2 and HSP-70 levels were negatively correlated with the severity of bleeding in PUB patients ( r = - 0.720, - 0.586, P<0.01). Logistic regression analysis showed that serum PGE2 and HSP-70 levels were protective factors for PUB ( P<0.05), while NSAID used, Hp infection, APTT and PT were risk factors for PUB ( P<0.05). ROC curve analysis results showed that the area under the curve of serum PGE2 and HSP-70 combined to predict the severity of bleeding in PUB patients was 0.935, which was higher than that predicted by the two indexes alone. Conclusions:The expression of serum PGE2 and HSP-70 are down regulated in PUB patients, and have correlated with the severity of bleeding. The joint detection of two indicators is more conductive to predicting the degree of bleeding in PUB patients.

Objective To evaluate the value of multimodal brain function monitoring using quantitative electroencephalography(QEEG)and transcranial Doppler(TCD)in predicting hematoma enlargement and prognosis in patients with acute hypertensive intracerebral hemorrhage.Methods A retrospective analysis was conducted on the clinical data of 120 patients with acute hypertensive intracerebral hemorrhage from October 2019 to October 2022.All patients underwent QEEG and TCD examinations within 24 hours of admission,and were divided into hematoma enlargement group(79 cases)and hematoma stabilization group(41 cases)based on whether the hema-toma had expanded.By comparing the parameter differences of QEEG and TCD between two groups,explore the correlation between these monitoring indicators and hematoma enlargement and patient prognosis.Results The patients in the hematoma enlargement group had a higher average age and a higher smoking rate.The initial neuro-logical damage in the hematoma enlargement group was more severe.The DAR and DTABR values of the hematoma enlargement group were significantly higher than those of the stable group at different time points after cerebral hemorrhage(P<0.05).Correlation analysis shows that DAR,DTABR,and P1 have significant positive correla-tions with hematoma enlargement,with DAR and DTABR showing particularly strong correlations(r values of 0.774 and 0.738,respectively,P<0.05),while P1 has relatively weak correlations(r=0.213,P<0.05).ROC curve analysis shows that DAR,DTABR,and P1 parameters have high sensitivity and specificity in predicting hematoma enlargement,with an AUC value of up to 0.970 for DAR.During the follow-up period,the MRS scores of the stable hematoma group were significantly better than those of the hematoma expansion group at all time points(P<0.05).Conclusion QEEG and TCD are helpful in early identification of high-risk patients,enabling more targeted treatment measures and improving clinical outcomes for patients.

Objective:To analyze the risk factors for atrial high-rate episodes (AHRE) following cardiac resynchronization therapy (CRT) and construct a predictive model for the occurrence of AHRE.Methods:This was a case-control study. Patients who received CRT treatment for heart failure in the Second Affiliated Hospital of Second Affiliated Hospital of Army Military Medical University from January 2017 to December 2020 were selected and divided into AHRE group and non-AHRE group according to whether AHRE occurred during the follow-up period. Baseline clinical data were collected. Patients were followed up regularly after CRT or cardiac resynchronization therapy defibrillator (CRT-D) implantation until August 31, 2022. Logistic regression model was used to analyze the factors influencing the occurrence of AHRE in patients with heart failure treated with CRT, and a nomogram prediction model was established. The receiver operating characteristic (ROC) curve was used to evaluate the nomogram model, and the Hosmer-Lemeshow test was used to evaluate the consistency of the prediction model.Results:A total of 198 patients, aged (62±8) years, 138 (69.7%) males, were enrolled, of whom 52 (26.3%) patients developed AHRE (AHRE group) and 146 (73.7%) had no AHRE (non-AHRE group) during the follow-up period. Multivariate logistic regression analysis revealed that age, coronary heart disease, C-reactive protein, left atrial volume, and left ventricular ejection fraction (LVEF) were independent influencing factors of heart failure patients developing AHRE after CRT surgery (all P<0.05). A nomogram prediction model was constructed by combining 5 indicators: age, coronary heart disease, C-reactive protein, left atrial volume, and LVEF. In this model, a score of 4 was assigned for age ≥65 years, 4 for coronary heart disease, 4 for C-reactive protein ≥10 ng/ml, 20 for left atrial volume ≥35 ml, and 5 for LVEF ≤30%. The total score was obtained by accumulating the scores of each indicator, and the probability of heart failure patients developing AHRE after CRT surgery was predicted based on the total score. The area under the curve of the nomogram prediction model constructed in this study for predicting AHRE in heart failure patients after CRT surgery was 0.830 (95% CI: 0.795-0.866). The incidence of AHRE predicted by the model was basically consistent with the actual incidence of AHRE. The Hosmer-Lemeshow test indicated a good calibration of the model ( χ2=6.32, P=0.612). Conclusions:Age, coronary heart disease, C-reactive protein, left atrial volume, and LVEF are all independent risk factors for AHRE after CRT treatment. The nomogram prediction model based on the above factors can effectively predict the risk of AHRE in patients with heart failure after CRT, and the ROC curve and consistency test both show good prediction efficiency and consistency.

Objective:To investigate the correlation between serum prostaglandin E2 (PGE2), heat-shock protein 70 (HSP-70) and the severity of bleeding in patients with peptic ulcer bleeding (PUB).Methods:A total of 122 patients with peptic ulcer (PU) admitted to Chang'an Hospital from March 2021 to March 2024 were retrospectively collected and divided into simple PU group (50 cases) and PUB group (72 cases) according to whether PUB occurred. Serum levels of PGE2 and HSP-70 were determined by enzyme-linked immunosorbent assay (ELISA). Spearman test was used to analyze the correlation between serum PGE2, HSP-70 levels and bleeding severity in PUB patients. Logistic regression was used to analyze the risk factors of PUB, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum PGE2 and HSP-70 levels on the bleeding degree of PUB patients.Results:The proportion of non-steroidal anti-inflammatory drugsnon-ster (NSAID) used and Helicobacter pylori (Hp) infection, thromboplastin time (APTT) and prothrombin time (PT) in the PUB group were higher than those in the PU group: 42.00%(21/50) vs. 25.00%(18/72), 36.00%(18/50) vs. 58.33%(42/72), (28.78 ± 3.24) s vs. (26.72 ± 3.89) s, (13.14 ± 2.56) s vs. (11.26 ± 2.15) s, and the serum levels of PGE2 and HSP-70 were lower than those in the PU group: (174.25 ± 18.21) ng/L vs. (236.44 ± 24.52) ng/L, (0.78 ± 0.22) μg/L vs. (1.24 ± 0.38) μg/L, there were statistical significances ( P<0.05). The serum levels of PGE2 and HSP-70 in PUB patients decreased gradually with the severity of hemorrhage ( P<0.05). Spearman test showed that serum PGE2 and HSP-70 levels were negatively correlated with the severity of bleeding in PUB patients ( r = - 0.720, - 0.586, P<0.01). Logistic regression analysis showed that serum PGE2 and HSP-70 levels were protective factors for PUB ( P<0.05), while NSAID used, Hp infection, APTT and PT were risk factors for PUB ( P<0.05). ROC curve analysis results showed that the area under the curve of serum PGE2 and HSP-70 combined to predict the severity of bleeding in PUB patients was 0.935, which was higher than that predicted by the two indexes alone. Conclusions:The expression of serum PGE2 and HSP-70 are down regulated in PUB patients, and have correlated with the severity of bleeding. The joint detection of two indicators is more conductive to predicting the degree of bleeding in PUB patients.