This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

Objective Literature on cognitive prognoses in association with stroke-related and pre-stroke factors,are surprisingly meagre.Prognoses of patients with post stroke cognitive impairment(PSCI)to structured cognitive rehabilitation are not clearly understood.This study aimed to compare if the prognoses of stroke survicors after cognitive rehabilitation programme was associated with chronic cerebrovascular disease(CVD).Methods An eight-week non-pharmacological clinical programme was ran for patients with mild strokes to provide clinical support to stroke patients and collect longitudinal data on stroke prognoses.149 ischemic stroke survivors(age 63.6±9.66,64.4%males)underwent an eight-week structured group cognitive rehabilitation programme.Baseline,immediate post programme(Immediate-PP)and 6-month post programme(6-month-PP)global cognitive and quality of life outcomes were assessed by Montreal cognitive assessment(MoCA)and dementia-quality of life instrument(DemQOL).Regression analyses evaluated the influence of cognitive rehabilitation on outcomes.Results With every past stroke experienced by patients,they were less likely to demonstrate an improvement in MoCA score Immediate-PP(OR=2.17,95%CI:0.980-4.813,P=0.056).Patients with severe white matter hyperintensities were less likely to demonstrate an improvement in MoCA scores Immediate-PP compared to Baseline(OR=2.13,95%CI:1.04-4.38,P=0.039).Finally,patients with microhemorrhages in the deep region were less likely to demonstrate an improvement in MoCA at 6-month-PP(OR=19.93,95%CI:1.04-384,P=0.047).Conclusions Pre-stroke CVD is associated with poorer cognitive outcomes post cognitive rehabilitation.Our initial programme shows promising results-however further research into cognitive rehabilitation for stroke survivors with pre-stroke CVD is needed.The findings from our clinical rehabilitation programme will be useful guiding the design of a clinical trial.

Objective To investigate the distribution and antimicrobial susceptibility of clinically isolated bacteria from intensive care units(ICUs)in hospitals of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021.Methods According to China Antimicrobial Resistance Surveillance System,data of clinically isolated bacterial strains and antimicrobial susceptibility testing results of bacteria from ICUs reported by all member units of Hunan Province Antimicrobial Resistance Surveillance System were analyzed with WHONET 2022 software.Results From 2012 to 2021,the total number of bacteria isolated from ICUs of member units of the Hunan Province Antimi-crobial Resistance Surveillance System was 5 777-22 369,with Gram-negative bacteria accounting for 76.1％-78.0％annually.Staphylococcus aureus ranked first among isolated Gram-positive bacteria each year.The top 5 bacteria among Gram-negative bacteria were Acinetobacter baumannii,Klebsiella pneumoniae,Escherichia coli,Pseudo-monas aeruginosa,and Stenotrophomonas maltophilia.Detection rate of methicillin-resistant Staphylococcus aureus showed a downward trend year by year.No Staphylococcus spp.were found to be resistant to vancomycin,teico-planin and linezolid.Detection rates of vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Entero-coccus faecium were 0.6-1.1％and 0.6％-2.2％,respectively.Resistance rates of Escherichia coli and Kleb-siella pneumoniae to imipenem were 3.1％-5.7％and 7.7％-20.9％,respectively.Resistance rates of Pseudo-monasaeruginosa and Acinetobacter baumannii to imipenem were 24.6％-40.1％and 76.1％-80.9％,respective-ly.Detection rates of carbapenem-resistant Pseudomonas aeruginosa declined year by year.Acinetobacter baumannii maintained high susceptibility to polymyxin B,with resistance rate＜10％.Conclusion Antimicrobial resistance of bacteria from ICUs is serious.Carbapenem-resistant Enterobacteriales has an upward trend after 2019.It is nece-ssary to strengthen the surveillance of bacterial resistance and carry out multidisciplinary collaboration.

When skin injuries are healing, complex wound environments can be easily created, which can result in wound infection, excessive inflammation caused by neutrophil accumulation and inflammatory factors, and excessive reactive oxygen species, resulting in high levels of oxidative stress. As a result of these factors, cell membranes, proteins, DNA, etc. may become damaged, which adversely affects the repair function of normal cells around the wound, resulting in the formation of chronic wounds. The effectiveness of wound dressings as a treatment is well known. They can offer temporary skin damage protection, prevent or control wound infection, create an environment that is conducive to mending skin damage, and speed wound healing. Traditional dressings like gauze, cotton balls, and bandages, however, have the drawbacks of having no antimicrobial properties, having weak adhesive properties, having poor mechanical properties, being susceptible to inflammation, obstructing angiogenesis, needing frequent replacement, and being unable to create an environment that is conducive to wound healing. As an innovative bandage, self-assembled hydrogel has great water absorption, high water retention, superior biocompatibility, biodegradability and three-dimensional (3D) structure. With properties including hemostasis, antibacterial, anti-inflammatory, and antioxidant, the synthesized raw material itself and the loaded active compounds have a wide range of potential applications in the treatment of skin injuries and wound healing. This research begins by examining and discussing the mechanism of cross-linking in self-assembled hydrogels. The cross-linking modes include non-covalent consisting of physical interaction forces such as electrostatic interactions, π-stacking, van der Waals forces, hydrophobic interactions, and metal-ligand bonds, covalent cross-linking formed by dynamic covalent bonding such as disulfide bonding and Schiff bases. And hybrid cross-linking with mixed physical forces and dynamic covalent bonding. The next part describes the special structure and excellent functions of self-assembled hydrogels, which include an extracellular matrix-like structure, the removal of exogenous microorganisms, and the mitigation of inflammation and oxidative stress. It goes on to explain the benefits of using self-assembled hydrogels as dressings for skin injuries. These dressings are capable of controlling cell proliferation, loading active ingredients, achieving hemostasis and coagulation, hastening wound healing, and controlling the regeneration of the injured area. The development of self-assembly hydrogels as dressings is summarized in the last section. The transition from purely non-covalent or covalent cross-linking to hybrid cross-linking with multiple networks, from one-strategy action to multi-strategy synergy in exerting antimicrobial, anti-inflammatory, and antioxidant effects and from single-function to multi-functioning in a single product. Additionally, it is predicted that future developments in self-assembled hydrogels will focus on creating biomimetic gels with multi-strategy associations linkage from naturally self-assembling biomolecules peptides, lipids, proteins and polysaccharides; improving the properties and cross-linking of raw materials to enhance the storage capabilities of hydrogels and cross-linking techniques, realizing the recycling of hydrogels; conducting additional research and exploration into the cross-linking process of hydrogels; and realizing the gel’s controllable rate of degradation. Furthermore, combining 3D printing and 3D microscopic imaging technology to design and build one-to-one specialized gel dressings; using computer simulation and virtual reality to eliminate the time factor, resulting in self-assembled hydrogels that perfectly fit the ideal dressing.

Objective:To explore the influencing factors of hemodialysis (HD) initiation in non-diabetic kidney disease (NDKD) patients with predialysis arteriovenous fistula (AVF) creation.Methods:This was a single-center prospective cohort study. The NDKD patients undergoing predialysis AVF creation were enrolled at the First Affiliated Hospital of Xi'an Jiaotong University from 2015 to 2018. According to the estimated glomerular filtration rate (eGFR, the Chronic Kidney Disease Epidemiology Collaboration equation) and age, patients were divided into different subgroups, eGFR: group 1 [eGFR<10 ml·min -1·(1.73 m 2) -1], group 2 [ eGFR between 10 to 15 ml·min -1·(1.73 m 2) -1], and group 3 [eGFR > 15 ml·min -1·(1.73 m 2) -1]; age: age ≥65 years group and age <65 years group. The primary outcome was defined as the initiation of HD within 1 year after AVF surgery. The second outcome was the use of AVF access at the time of HD initiation. Cox proportional hazard regression was performed to identify which demographic and clinical factors were associated with the initiation of HD after AVF surgery. Logistic regression analysis was performed to investigate factors associated with AVF use at the initiation of HD. Results:A total of 220 patients were enrolled, with age of (48.1±16.2) years, of which 143(65.0%) were males. Overall, the clinical parameters of eGFR, cystatin C, serum albumin, 24h-Urine protein, serum phosphorus were as follows respectively, 7.7 (6.6,9.2) ml·min -1·(1.73 m 2) -1, (3.93±1.12) mg/L, (36.0±4.0) g/L, (2.22±1.36) g, (1.71±0.53) mmol/L. The proportion of patients initiating HD within 6 months ( Fisher=6.832, P=0.020) and the level of hemoglobin ( F=3.112, P=0.047) were higher in group 3 compared to the other two eGFR groups. While the median time interval between AVF creation and HD initiation ( H=6.295, P=0.043) was shorter in group 1. In age <65 years group, the level of serum albumin ( t=2.076, P=0.039), triglyceride ( t=1.995, P=0.048) were higher compared with age ≥65 years group; interestingly, the proportion of patients initiated HD within 3 months ( χ2=4.033, P=0.045) and 6 months ( χ2=5.012, P=0.025) were lower in age <65 years group. The median time interval between AVF creation and HD initiation among these patients was 84 (49,174) days. The patients initiating HD within 3 months, 6 months, and 1 year after AVF creation were 112 (50.9%), 152 (69.1%), and 202 (91.8%), respectively. Multivariate Cox regression analysis indicated that higher cystatin C level ( HR=1.283, 95% CI 1.121-1.469, P<0.001) was associated with earlier HD initiation within 1 year of AVF surgery in NDKD patients. AVF usage was accomplished in 64.3% of patients who initiated HD within 90 days, the ratio was 100.0% in those initiated HD between 91 to 180 days, and 88.0% in those ≥181 days after AVF surgery. No factor was independently associated with AVF use at HD initiation identified by multivariate logistic regression analyses in patients with NDKD. Conclusion:Serum cystatin C level is associated with HD initiation within 1 year of the predialysis AVF creation in NDKD patients.

Purpose::Although traditional craniotomy (TC) surgery has failed to show benefits for the functional outcome of intracerebral hemorrhage (ICH). However, a minimally invasive hematoma removal plan to avoid white matter fiber damage may be a safer and more feasible surgical approach, which may improve the prognosis of ICH. We conducted a historical cohort study on the use of multimodal image fusion-assisted neuroendoscopic surgery (MINS) for the treatment of ICH, and compared its safety and effectiveness with traditional methods.Methods::This is a historical cohort study involving 241 patients with cerebral hemorrhage. Divided into MINS group and TC group based on surgical methods. Multimodal images (CT skull, CT angiography, and white matter fiber of MRI diffusion-tensor imaging) were fused into 3 dimensional images for preoperative planning and intraoperative guidance of endoscopic hematoma removal in the MINS group. Clinical features, operative efficiency, perioperative complications, and prognoses between 2 groups were compared. Normally distributed data were analyzed using t-test of 2 independent samples, Nonnormally distributed data were compared using the Kruskal-Wallis test. Meanwhile categorical data were analyzed via the Chi-square test or Fisher’s exact test. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. Results::A total of 42 patients with ICH were enrolled, who underwent TC surgery or MINS. Patients who underwent MINS had shorter operative time ( p < 0.001), less blood loss ( p < 0.001), better hematoma evacuation ( p =0.003), and a shorter stay in the intensive care unit ( p =0.002) than patients who underwent TC. Based on clinical characteristics and analysis of perioperative complications, there is no significant difference between the 2 surgical methods. Modified Rankin scale scores at 180 days were better in the MINS than in the TC group ( p =0.014). Conclusions::Compared with TC for the treatment of ICH, MINS is safer and more efficient in cleaning ICH, which improved the prognosis of the patients. In the future, a larger sample size clinical trial will be needed to evaluate its efficacy.

Objective::Many studies have shown that blood glucose fluctuations (GFs) are more harmful to patients with diabetes mellitus (DM) than sustained hyperglycemia. However, the effect of GF on electrocardiogram (ECG) parameters and vulnerability to ventricular tachycardia/fibrillation (VT/VF) remains poorly characterized. This study aimed to assess the effect of GF on ECG parameters and induction of VT/VF in streptozotocin (STZ)-induced diabetic Sprague-Dawley rats.Methods::Male Sprague-Dawley rats were injected with STZ and randomly divided into 3 treatment groups: controlled STZ-induced diabetic rats (C-STZ) ( n = 10); uncontrolled STZ-induced diabetic rats (U-STZ) ( n = 10); and STZ-induced diabetic rats with glucose fluctuations (GF-STZ) ( n = 10). After 12 weeks, baseline ECG recordings were taken and a VT/VF test was performed with the administration of caffeine and dobutamine. Hematoxylin & eosin and masson staining were used to evaluate pathological cardiac changes after intervention. Results::No significant difference in heart rate, RR interval, P wave (duration and height), PR segment, PR interval, QRS wave duration, and T wave height was observed among the 3 groups ( P > 0.05). Compared with the C-STZ group, the U-STZ and GF-STZ groups both had a longer T wave duration ((62.41 ± 2.38) ms vs. (78.37 ± 4.64) ms and (96.06 ± 4.60) ms, P < 0.05), QT interval ((83.66 ± 2.31) ms vs. (101.75 ± 4.56) ms and (119.14 ± 4.88) ms, P < 0.05), and QTc interval ((77.45 ± 1.36) ms vs. (91.36 ± 3.49) ms and (104.55 ± 3.01) ms, P < 0.05), all of which were longest in the GF-STZ group ( P < 0.05). Additionally, the GF-STZ group had the highest VT/VF occurrence and duration and the highest arrhythmia score. Conclusion::This study revealed GF can significantly prolong the QT interval, QTc interval, and T wave duration, as well as increase vulnerability to VT/VF in rats, which may be an important electrophysiological mechanism of GF-related ventricular arrhythmia.

Objective::Many studies have shown that blood glucose fluctuations (GFs) are more harmful to patients with diabetes mellitus (DM) than sustained hyperglycemia. However, the effect of GF on electrocardiogram (ECG) parameters and vulnerability to ventricular tachycardia/fibrillation (VT/VF) remains poorly characterized. This study aimed to assess the effect of GF on ECG parameters and induction of VT/VF in streptozotocin (STZ)-induced diabetic Sprague-Dawley rats.Methods::Male Sprague-Dawley rats were injected with STZ and randomly divided into 3 treatment groups: controlled STZ-induced diabetic rats (C-STZ) ( n = 10); uncontrolled STZ-induced diabetic rats (U-STZ) ( n = 10); and STZ-induced diabetic rats with glucose fluctuations (GF-STZ) ( n = 10). After 12 weeks, baseline ECG recordings were taken and a VT/VF test was performed with the administration of caffeine and dobutamine. Hematoxylin & eosin and masson staining were used to evaluate pathological cardiac changes after intervention. Results::No significant difference in heart rate, RR interval, P wave (duration and height), PR segment, PR interval, QRS wave duration, and T wave height was observed among the 3 groups ( P > 0.05). Compared with the C-STZ group, the U-STZ and GF-STZ groups both had a longer T wave duration ((62.41 ± 2.38) ms vs. (78.37 ± 4.64) ms and (96.06 ± 4.60) ms, P < 0.05), QT interval ((83.66 ± 2.31) ms vs. (101.75 ± 4.56) ms and (119.14 ± 4.88) ms, P < 0.05), and QTc interval ((77.45 ± 1.36) ms vs. (91.36 ± 3.49) ms and (104.55 ± 3.01) ms, P < 0.05), all of which were longest in the GF-STZ group ( P < 0.05). Additionally, the GF-STZ group had the highest VT/VF occurrence and duration and the highest arrhythmia score. Conclusion::This study revealed GF can significantly prolong the QT interval, QTc interval, and T wave duration, as well as increase vulnerability to VT/VF in rats, which may be an important electrophysiological mechanism of GF-related ventricular arrhythmia.

Objective To explore the impact of empirical antibiotic treatment(EAT)on complications and mortality in patients with acute calculous cholecystitis(ACC).Methods This study retrospectively collected ACC patients from the department of general surgery of The 986th Hospital of Chinese People's Liberation Army Air Force from January 2016 to January 2022.According to the use of antibiotics,ACC patients were divided into an adequate EAT(AEAT)group and an insufficient EAT(IEAT)group.The incidence of complications and 30-day hospitalization mortality rate in two groups of ACC patients were observed and analyzied.Results A total of 504 ACC patients were included in this study.337(66.87％)ACC patients were included in the AEAT group,and 167(33.13％)ACC patients were included in the IEAT group.Multivariate Logistic regression analysis showed that AEAT was a protective factor for total complications[OR=0.625,95％CI(0.419,0.932),P=0.021]and infection complications[OR=0.512,95％CI(0.331,0.791),P=0.003].Multivariate COX risk proportional regression showed that AEAT was a protective factor for the 30-day mortality risk in ACC patients[OR=0.238,95％CI(0.070,0.810),P=0.022].Conclusion AEAT can reduce the incidence of complications and mortality in ACC patients.