OBJECTIVES: The integrated endoplasmic reticulum stress inhibitor (ISRIB) is a selective inhibitor of the protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway within endoplasmic reticulum stress (ERS) and can improve spatial and working memory in aged mice. Although ERS and oxidative stress are tightly interconnected, it remains unclear whether ISRIB alleviates cognitive impairment by restoring the balance between ERS and oxidative stress. This study aims to investigate the effects and mechanisms of ISRIB on lipopolysaccharide (LPS)-induced cognitive impairment in mice. METHODS: Eight-week-old male ICR mice were randomly divided into 3 groups: Normal saline (NS) group, LPS group, and ISRIB+LPS group. NS and LPS groups received daily intraperitoneal injections of normal saline for 7 days; on day 7, LPS group mice received intraperitoneal LPS (0.83 mg/kg) to establish a cognitive impairment model. ISRIB+LPS group received ISRIB (0.25 mg/kg) intraperitoneally for 7 days, with LPS injected 30 minutes after ISRIB on day 7. Cognitive ability was evaluated by the novel place recognition test (NPRT). Real-time fluorogenic quantitative PCR (RT-qPCR) was used to detect changes in nitric oxide synthase (NOS), superoxide dismutase-1 (SOD-1), and catalase (CAT) gene expression in the hippocampus and prefrontal cortex. Oxidative stress markers malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG), were measured in hippocampal and prefrontal cortex tissues. RESULTS: Compared with the NS group, mice in LPS group showed a significant reduction in novel place recognition ratio, upregulation of hippocampal NOS-1 and NOS-2 mRNA, downregulation of SOD-1 and CAT mRNA, increased MDA and GSSG, decreased GSH, and reduced GSH/GSSG ratio (all P<0.05). Compared with the LPS group, mice in ISRIB+LPS group exhibited significantly improved novel place recognition, downregulated NOS-1 and NOS-2 mRNA, upregulated SOD-1 and CAT mRNA, decreased MDA and GSSG, increased GSH, and an elevated GSH/GSSG ratio in the hippocampus (all P<0.05). No significant changes were observed in the prefrontal cortex. CONCLUSIONS ISRIB improves LPS-induced cognitive impairment in mice by restoring the oxidative/antioxidant balance in the hippocampus.
Animals ; Lipopolysaccharides ; Male ; Mice, Inbred ICR ; Cognitive Dysfunction/drug therapy* ; Mice ; Oxidative Stress/drug effects* ; Endoplasmic Reticulum Stress/drug effects* ; Hippocampus/drug effects* ; Nitric Oxide Synthase Type II/genetics* ; Guanidines/pharmacology* ; eIF-2 Kinase/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Superoxide Dismutase/metabolism*

BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

OBJECTIVE To analyze the clinical characteristics and the correlation between laboratory indicators and prognosis of severe Mycoplasma pneumoniae pneumonia(SMPP)in children.METHODS A total of 85 children with SMPP admitted to Anhui Provincial Children's Hospital from Nov.2021 to May 2024 were selected as the study subjects.Based on clinical typing at admission,they were divided into a high-risk group(n=59)and a low-risk group(n=26).The clinical manifestations,laboratory indicators and outcomes at 28 days of treatment were compared between the two groups.RESULTS The duration of fever and cough before admission in the high-risk group was(7.17±1.09)days and(6.79±1.25)days,respectively,which was longer than that in the low-risk group(P＜0.05).There were no statistically significant differences in pulmonary auscultation(wheezing rales,moist rales)and extrapulmonary complications between the two groups.The levels of C-reactive protein(CRP),serum amyloid A(SAA),platelets(PLT),fibrinogen(FIB),D-dimer(DD)and N-terminal pro-brain natriuretic peptide(NT-proBNP)in the high-risk group were(11.62±1.45)mg/L,(226.88±36.83)mg/L,(3 18.57±39.82)×109/L,(4.28±0.74)g/L,(0.81±0.12)μg/ml and(2 295.48±413.75)pg/ml,respectively,all of which were higher than those in the low-risk group(P＜0.05).Within 28 days after treatment of children in both groups,one patient in the high-risk group died.CONCLUSIONS Compared with children with SMPP in the low-risk group,those in the high-risk group have a higher risk of prognostic mor-tality,suggesting a correlation between the children's blood CRP,SAA,PLT,FIB,DD and NT-proBNP levels and the prognosis of children with SMPP.

This study examines the progress and application of Artificial Intelligence (AI) in the prevention and control of infectious diseases within Chinese healthcare institutions. It analyzes the difficulties and challenges encountered during implementation to promote the intelligent transformation and upgrading of infectious disease prevention and control. The results indicate that AI technology has made progress in areas such as infectious disease surveillance and early warning, risk assessment and emergency response, screening and detection, image-based diagnosis and analysis, and health management. Nevertheless, significant challenges remain, including limited application depth and breadth, issues with data quality and privacy protection, insufficient technological maturity and interpretability, potential legal risks, and a shortage of interdisciplinary professionals. To advance the application of AI technology in infectious disease prevention and control and support the modernization of China′s relevant systems, recommendations include strengthening policy support, establishing data standards and robust privacy protection mechanisms, increasing R&D investment, refining laws and regulations, and enhancing the training of interdisciplinary talent.

Objective·To explore the application effect of a new type of blepharoplasty with a lower eyelid margin incision in the mid-face rejuvenation.Methods·From September 2019 to September 2022,35 patients with lower eyelid pouches,eyelid-cheek junction depression,and mid-face sagging were treated in Department of Plastic Surgery,Tongren Hospital,Shanghai Jiao Tong University School of Medicine.The surgical procedure involved incising the lower eyelid margin of the patient,bluntly separating the orbital zygomatic space and maxillary space,and opening the orbital septum to release the orbital fat flap.Subsequently,the fat flap was spread downward to cover the infraorbital margin and fixed onto the zygomatic bone membrane.Then,the maxillary space was separated below the orbital zygomatic ligament,and the composite tissue in the infraorbital area was suspended and fixed outward and upward.The lateral orbicularis oculi muscle of the lower eyelid was suspended and fixed on the periosteum above the lateral orbital canthus,lifting the relaxed soft tissue in the mid-face.The upper and lower orbicularis oculi muscles were sutured to form a reclining silkworm,restoring the original tissue structure and morphology under the orbit.Outpatient follow-up visits were conducted at 1,3,and 6 months postoperatively,with digital cameras capturing frontal,left lateral and right lateral views.Postoperative complications were recorded,including subcutaneous bruising,swelling,conjunctival edema,hematoma,eyelid separation,lower eyelid eversion,diplopia,strabismus,dry eyeball,and tear overflow.The patients were followed up irregularly 6-12 months after surgery to observe the long-term effects.Results·All 35 patients were followed up for 6 to 12 months after surgery,with all incisions healing primarily.The blepharoplasty,palpebral sulcus depression,and nasolabial sulcus folds were significantly improved.The sagging tissue of the mid-face was reduced,and the effect was satisfactory.No complications,such as lower eyelid retraction,ectropion,or infection,occurred.Conclusion·The new type of eyelid blepharoplasty through the lower eyelid margin incision can significantly rejuvenate the lower eyelid and mid-face.This method has less trauma,less bleeding,reliable effect,and is easy to promote.

Objective By analyzing the causes of coding errors of lower extremity arteriosclerosis occlusion with throm-bosis and the endovascular intervention,explore the principle diagnosis and intervention coding rules to improve coding quality.Methods Inpatient medical records with the principle diagnosis codes of I70-I74 and I77 accompanied by endovascular interven-tional from January 1,2023 to December 31,2023 were retrieved from a tertiary hospital.A retrospective study was conducted to analyze the causes of coding errors.Results A total of 924 eligible cases were selected.There were 41 principle diagnosis cod-ing errors,with an error rate of 4.43％,among which the lower limb atherosclerosis coding had the highest error rate,accounting for 1.30％.There were 46 intervention coding errors,with an error rate of 4.98％,among which the percutaneous thrombectomy had the highest error rate.The main reason for coding errors was insufficient reading of medical record.Conclusion The coding error rate of the principle diagnosis of lower extremity arteriosclerosis occlusion and the endovascular intervention were relatively high.Therefore,it is necessary to continuously strengthen the training of clinicians and coders,including the coding rules and clinical knowledge of specialized disciplines,actively communicate between coders and clinicians,establish a quality control and assessment system,so as to improve the coding quality.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective:To investigate the mediating effect of psychological flexibility between recurrence risk perception and health behavior in stroke patients.Methods:From July to December 2024, 233 stroke patients at the First Affiliated Hospital of Zhengzhou University were selected using convenience sampling. Electronic questionnaires were used to collect patients' general information, perception of stroke recurrence risk, health behavior, and psychological flexibility.Results:The scores for recurrence risk perception, psychological flexibility, and health behavior of 233 stroke patients were (39.75±4.39), (47.45±4.19), and (54.04±3.78), respectively. Health behavior were positively correlated with recurrence risk perception ( r=0.495, P<0.01), and negatively correlated with psychological flexibility ( r=-0.367, P<0.01). Psychological flexibility partially mediated the relationship between recurrence risk perception and health behavior, with an effect value of 0.080 and an effect proportion of 17.5% (0.080/0.458) . Conclusions:Recurrence risk perception not only directly predicts health behavior in stroke patients but also indirectly influences their health behavior through psychological flexibility. Healthcare providers should enhance recurrence risk perception among stroke patients and incorporate the improvement of psychological flexibility as part of intervention strategies to improve patients' health behavior.

Objective To analyze the basic characteristics of patients with acute myocardial infarction in a tertiary hospi-tal from 2014 to 2023,and provide references for the prevention,treatment,management,and quality control of this disease.Methods Based on the data from the medical records of patients with acute myocardial infarction admitted to a tertiary hospital from January 1,2014,to December 31,2023,the basic characteristics of hospitalized patients and trends in hospitalization costs were analyzed to summarize the development patterns.Results Over the past decade,the number of hospitalized patients with a-cute myocardial infarction has been increasing,while the average length of hospital stay,average cost per hospitalization,and mortality rate have been decreasing.Among the 19 937 patients,there were 16 037 male patients(80.44％)and 3 900 female patients(19.56％),with a male-to-female ratio of 4.11∶1.The median age for male patients was 60 years,while for female patients it was 68 years,indicating that males tend to develop the disease approximately 10 years earlier than females.Among pa-tients aged 60 and above,the mortality rate is positively correlated with age,while among patients below 60,the mortality rate is negatively correlated with age.The decision to undergo surgery has a significant impact on hospitalization costs.From the per-spective of cost structure,the proportion of consumables has decreased from 69.81％to 54.60％in the past decade but remains relatively high.Conclusion With the advancement of hospital management and medical insurance policies,the diagnosis,treat-ment,and quality of care for acute myocardial infarction have significantly improved.However,consumables management remains a key focus.Men and individuals aged 50 and above should be given special attention.During the diagnosis and treatment process,greater attention should also be given to younger or older patients and female patients to reduce the mortality rate.