Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

In this study, we employed a combination of genome mining and heteronuclear single quantum coherence (HSQC)-based small molecule accurate recognition technology (SMART) technology to search for fernane-type triterpenoids. Initially, potential endophytic fungi were identified through genome mining. Subsequently, fine fractions containing various fernane-type triterpenoids were selected using HSQC data collection and SMART prediction. These triterpenoids were then obtained through targeted isolation and identification. Finally, their antifungal activity was evaluated. As a result, three fernane-type triterpenoids, including two novel compounds, along with two new sesquiterpenes and four known compounds were isolated from one potential strain, Diaporthe discoidispora. Their structures were elucidated through analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR) spectroscopic data. The absolute configurations were determined using single-crystal X-ray diffraction analysis and electron capture detector (ECD) analysis. Compound 3 exhibited moderate antifungal activity against Candida albicans CMCC 98001 and Aspergillus niger.
Triterpenes/isolation & purification* ; Antifungal Agents/isolation & purification* ; Molecular Structure ; Candida albicans/drug effects* ; Ascomycota/genetics* ; Magnetic Resonance Spectroscopy ; Aspergillus niger/drug effects* ; Genome, Fungal ; Microbial Sensitivity Tests

Objective:To describe the hotspots and application trends of artificial intelligence (AI) in epidemiology in the past decade and analyze its advantages and challenges.Methods:The literatures with AI and epidemiology related keywords were systematically retrieved from Web of Science and China National Knowledge Infrastructure from 2014 to 2024. CiteSpace was used for bibliometric analysis of publication volume, keyword co-occurrence, clustering, emergence and cited literature co-occurrence analysis.Results:A total of 5 389 English papers and 1 659 Chinese papers were included, showing an increasing publication trend. High-frequency Chinese keywords included prediction, influencing factor, and machine learning, while English keywords frequently used were machine learning, prediction, and artificial intelligence. The Chinese keywords formed 14 clusters such as epidemiological characteristic, dietary pattern, and elderly individual, and the English keywords formed 21 clusters including prediction model, risk factor, and adult. In international studies, health policy, COVID-19, and digital health were the emerging frontier keywords. Eleven core papers were selected, covering key areas like traffic accident risk assessment, public health big data application, and deep learning in medical diagnosis.Conclusions:This study systematically summarized the research hotspots and development trends of AI applications in epidemiology over the past decade by using bibliometric methods, which indicated that current AI-based epidemiological studies are still in the exploratory phase, with the coexisting of both advantages and challenges. Continued attention should be paid to the future development of this field.

Objective:To investigate the molecular epidemiological characteristics of norovirus (NoV) among infectious diarrhea patients in Linyi from 2021 to 2023, and provide the scientific evidence for norovirus control and prevention.Methods:The epidemiological information and fecal samples of patients with infectious diarrhea in Linyi from 2021 to 2023 were collected and detected by real-time fluorescent quantitative PCR. The RdRp and capsid gene VP1 region of norovirus-positive specimens were amplified and sequenced used to analyze their genotype, phylogeny and homology.Results:Among the 2 311specimens, 123 (5.32%) were positive of NoV, with GI/GII group infection accounted for 17.07% (21/123) and 77.24% (95/123), respectively, GI/GII group mixed infection accounted for 5.69% (7/123). The detection rate of <1 year age group was the highest (8.86%), followed by the 1-3 years group (7.11%, 30/422) and the over 60 years group (5.29%, 23/123). The highest NoV detection rate was 7.96% (45/565) in the urban area, and the most abundant genotypes were found in the northern mountainous area. Sequence analysis showed that 61 identified NoV strains could be divided into 12 genotypes, with 4 NoV GI and 8 NoV GII. The dominant genotype differed during the 3 years, with GII.4 Sydney [P16] in 2021, GII.4 Sydney [P31] in 2022, and GII.2[P16] in 2023.Conclusions:NoV GII group was the main NoV infection in Linyi from 2021-2023 and genotypes were diverse. Children under 3 years of age and elderly people over 60 years old as susceptible groups should be given special protection. In addition, the monitoring of NoV genotype diversification should be strengthened in northern mountainous areas.

Objective:To compare the effects of erector spinae plane block at T 2 (T 2-ESPB) and nerve root block at C 5 (C 5-NRB) in patients undergoing arthroscopic shoulder surgery with general anesthesia. Methods:This was a randomized, controlled, non-inferiority study. Sixty American Society of Anesthesiologists Physical Status classification I or Ⅱ patients, aged 45-75 yr, with body mass index ≤35 kg/m 2, scheduled for elective arthroscopic shoulder surgery at Jining No. 1 People′s Hospital from April 2023 to February 2024, were included and divided into 2 groups ( n=30 each) using a random number table method: C 5-NRB group (group C) and T 2-ESPB group (group T). In group C, C 5-NRB was carried out by injecting 0.5% ropivacaine 5 ml. In group T, T 2-ESPB was performed by injecting 0.25% ropivacaine 30 ml. The efficacy of nerve block was assessed using a prick test at 30 min after administration, and then total intravenous anesthesia was performed in both groups. The time to first rescue analgesia (the non-inferiority boundary Δ =2 h), requirement for rescue analgesia within 24 h after operation and intraoperative consumption of anesthetics were recorded. The motor function of the affected limb during shoulder abduction, elbow flexion and elbow extension was assessed and scored using the modified Bromage scale (MBS) at 30 min and 4 and 12 h after nerve block. The diaphragmatic excursion was measured and recorded using M-mode ultrasound before nerve block and at 30 min after nerve block to evaluate the occurrence of diaphragmatic paralysis. Complications such as local anesthetic toxicity, recurrent laryngeal nerve block and pneumothorax were also recorded. Results:The mean difference (95% confidence interval) for the time to first rescue analgesia between the two groups was 5.551 (1.875-9.148) h, with the upper limit exceeding the non-inferiority boundary. Compared with group T, the intraoperative consumption of remifentanil was significantly reduced, the time to first rescue analgesia was prolonged, the consumption of morphine for rescue analgesia was decreased, MBS scores during shoulder abduction, elbow flexion and elbow extension were decreased at 30 min after block, and MBS scores during shoulder abduction and elbow flexion were decreased at 4 and 12 h after block in group C ( P<0.05). There was no significant difference in the diaphragmatic excursion, incidence of diaphragm paralysis and incidence of complications before and after block in the two groups ( P>0.05). Conclusions:C 5-NRB provides superior efficacy compared to T 2-ESPB when used for arthroscopic shoulder surgery under general anesthesia.

In January 2021, a young male patient was admitted to the Department of Hand Surgery, Suzhou Ruihua Orthopeadic Hospital for a soft tissue degloving defect of distal segment of right thumb caused by machine compression. The thumb defect was reconstructed using a tiled flap with a right hallux nail flap and a lateral flap of left second toe. Donor site of the hallux nail flap was reconstructed by a lateral flap of right second toe, while the donor site of lateral flap of left second toe was covered by a skin graft of abdomen. At 1-year follow-up, the reconstructed nail was found excellent according to the established criteria. Two-point discrimination (TPD) was measured at 5 mm, and the affected thumb exhibited satisfactory flexion and extension and functions of thumb-to-palm and thumb-to-fingers oppositions. Donor sites in both feet achieved favorable appearance and function, with a Maryland foot score of 96. Only a linear scar was in abdominal donor site.

Human herpesvirus-6B (HHV-6B) reactivation is a significant contributor to nonrelapse mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective analysis describes three cases of HHV-6B reactivation following allo-HSCT, all of which achieved viral clearance with maribavir treatment following failure or intolerance to first-line antiviral therapy with foscarnet sodium. One patient diagnosed with HHV-6B encephalitis recovered without neurological sequelae. No adverse drug reactions to maribavir were observed. These findings provide preliminary evidence that maribavir may serve as an effective and safe salvage therapy for HHV-6B reactivation in patients receiving allo-HSCT.

Objective:To evaluate the clinical value of peripheral blood monocyte subset analysis in the diagnosis and treatment of chronic myelomonocytic leukemia (CMML) .Method:We retrospectively enrolled 51 patients newly diagnosed with CMML at Guangdong Provincial People's Hospital between June 1, 2020, and December 31, 2024, according to the WHO 2022 diagnostic criteria. Twenty-three patients with other myeloid neoplasms (excluding CMML) and peripheral monocytosis (absolute count ≥0.5×10 9/L and percentage ≥10%) were included as the control group. All patients underwent bone marrow aspiration for examinations including bone marrow smears, biopsies, cytogenetics, and gene mutation analysis to establish a definitive diagnosis. Concurrently, flow cytometry was used to determine the proportions of peripheral blood monocyte subsets: classical (MO1, CD14 +CD16 -) , intermediate (MO2, CD14 +CD16 +) , and non-classical (MO3, CD14 lowCD16 +) . Differences between the groups were compared, and diagnostic efficacy was evaluated using receiver operating characteristic (ROC) curves. Result:Among the 51 CMML patients, the proportion of the peripheral blood MO1 subset was significantly higher than that in patients with other myeloid neoplasms ( P=0.027) , whereas there were no significant differences in the MO2 and MO3 subsets (all P>0.05) . Further analysis revealed that 43 (84.31%) of the CMML patients met the WHO diagnostic threshold for the MO1 subset (≥94%) , while the remaining 8 patients did not; 46 patients (90.20%) had MO3 subset proportions below the threshold proposed by Hudson (≤1.13%) , while the remaining 5 patients were above this threshold. In-depth analysis showed that among the 8 patients who did not meet the WHO criteria, 7 were experiencing inflammation. Similarly, all 5 patients who did not meet the Hudson criteria were in an inflammatory state. Subsequent ROC curve analysis of this cohort identified a cut-off value for the MO1 subset of 97.55% [Area Under the Curve (AUC) =0.661, P=0.027], which aligns with the WHO criteria. Conclusion:Peripheral blood monocyte subset analysis, particularly MO1 subset analysis, can effectively assist in CMML diagnosis, but exclusion of inflammatory conditions is required.

Objective To investigate the correlation between perioperative oxygen concentration and postoperative organ injury and other adverse reactions in children undergoing neurosurgery.Methods This study is a single-center retrospective cohort study,including 512 children aged≤14 years and operating duration≥2 hours who were transferred after surgery to postanesthesia care unit(PACU),Department of Anesthesiology,Beijing Tiantan Hospital,Capital Medical University from October 2018 to September 2023.His electronic medical record system was used to review and collect the patient's medical records during hospitalization.Including baseline data,anesthetic use,duration of anesthesia,intraoperative oxygen concentration,postoperative diagnosis,and surgical method;blood pressure,heart rate,oxygen saturation,pain score and special conditions during anesthesia recovery;infection during postoperative hospitalization(including wound infection,intracranial infection),respiratory complications[confirmed by chest radiograph/chest computed tomography(CT)report],changes in renal function(first postoperative serum creatinine value-last preoperative serum creatinine value),and incidence of delirium during recovery period during anesthesia were recorded.The area under oxygen concentration-time curve area under curve AUCFiO2=the product of intraoperative oxygen concentration(%)and duration of anesthesia(min)was calculated,and then 512 children were divided into 3 groups according to the AUCFiO2 tripartite(group 1:AUCFiO2<8 720%min,group 2:8 720%·min≤AUCFiO2≤13 800%·min,group 3:AUCFiO2>13 800%·min)were included in the data analysis.Results The incidence of emergency delirium(ED)during postoperative recovery was 24%,26.9%and 19.4%,and the incidence of acute kidney injury(AKI)was 0.6%,2.3%and 0.6%,respectively.There was no significant difference between the three groups(P>0.05).The incidence of postoperative pulmonary complications in the three groups was 20.6%,20.8%and 31.5%,respectively,and there was significant statistical difference among the three groups(P<0.05).There were no significant differences in nausea,vomiting,hypoxemia,and PACU residence time among the three groups during anesthesia recovery room(P>0.05),and there were significant differences in intracranial infection,wound infection and hospital stay during hospitalization(P<0.05).Conclusion Although oxygen concentration AUCFiO2 has no correlation with the occurrence of postoperative AKI and ED,the longer the exposure time of conventional oxygen administration strategy,the higher the incidence of postoperative pulmonary complications and postoperative infection,and the longer the hospitalization time of children.

The tetraspanins are closely associated with the development and therapeutic prognosis of colorectal tumors. These proteins play a role in cell proliferation, metastasis, and invasion, regulate apoptosis and autophagy of colorectal tumor cells. affect immune escape by releasing exosomes, intervening the epithelial-mesenchymal transition process, and altering the tumor microenvironment, and enhance tumor stemness through specific pathways. This paper reviews the mechanisms and current research regarding the status of tetraspanins in colorectal cancer, aiming to improve early diagnosis and providing valuable insights for treatment strategies.