Both type 2 diabetes mellitus (T2DM) and metabolic associated fatty liver disease (MAFLD) fall within the spectrum of metabolic diseases, and they exhibit a bi-directional causal relationship and robust reciprocal association. Their shared pathological cornerstone is insulin resistance (IR), which involves the interplay of mitochondrial dysfunction and chronic inflammation, forming a cascading pathological process of “IR-mitochondrial dysfunction-inflammation”. This largely explains the notable upward trend in T2DM-MAFLD co-occurrence observed over recent years. Exercise intervention, as a safe and effective non-pharmacological approach, can improve the pathological progression of these patients at multiple levels. Following the logical framework of “pathogenesis-efficacy comparison-molecular mechanisms-clinical translation”, this article systematically compares the efficacy and molecular mechanisms of moderate-intensity continuous training (MICT), resistance exercise, high-intensity interval training (HIIT), and combined training. MICT reduces intrahepatic triglycerides by promoting lipolysis and improving cardiorespiratory fitness; resistance exercise increases muscle mass and basal metabolic rate, offering unique advantages in preserving muscle while reducing fat and improving insulin sensitivity; HIIT is a time-efficient exercise modality that enhances patients’ cardiorespiratory fitness and insulin sensitivity by alternating brief periods of vigorous exertion with recovery periods, with a prominent short-term triglyceride-lowering effect; combined training produces synergistic effects, comprehensively improving glucolipid metabolism and showing the best long-term adherence. Mechanistically, exercise exerts its beneficial effects through three common pathways: (1) AMPK-mediated lipid oxidation and mitochondrial biogenesis; (2) IRS/PI3K/Akt-mediated insulin signaling sensitization; and (3) Nrf2/ARE anti-oxidation and TGF-β/Smads anti-fibrosis regulation. Different exercise modalities activate these pathways with distinct emphases: MICT most directly and persistently activates the AMPK pathway; resistance exercise uniquely improves IRS/PI3K/Akt signaling through muscle mass gain; HIIT induces the highest AMPK activation intensity and triggers unique lactate-mediated signaling regulation; combined training integrates the above multiple mechanistic advantages. For clinical translation, multidisciplinary team collaboration is essential to ensure safety and adherence. Individualized prescriptions should be formulated according to the FITT-VP principle and patient phenotypes—frequency of 3-5 sessions/week of aerobic exercise combined with 2-3 sessions/week of resistance exercise; intensity of moderate-intensity (40%-60% heart rate reserve (HRR))aerobic exercise and 60%-80% of one-repetition maximum (1-RM) for resistance exercise; time of at least 150 min/week of moderate-intensity aerobic exercise, 30-60 min per session; type of combined training as the preferred modality; total volume of≥500-1 000 MET-min/week; and progression adjusted every 4-6 weeks—with real-time adjustments supported by wearable devices, ultimately forming a closed-loop management system from initial assessment to long-term follow-up. Notably, current studies have limitations such as small sample sizes and short intervention periods. Future research should focus on long-term follow-up, multi-omics biomarkers, and combined exercise-drug strategies. In conclusion, the systematic integration of structured, individualized, and sustainable exercise interventions into the multidisciplinary management pathway for patients with T2DM complicated by MAFLD is an urgent need in current clinical practice.

ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.

Objective:The clinical significance of aural fullness in patients with vestibular migraine（VM） remains unclear, and it is yet to be determined whether VM with aural fullness represents a distinct subtype of VM; this study aimed to compare differences in demographic characteristics, clinical manifestations, audiological findings, and vestibular function tests between VM patients with and without aural fullness, and explore whether the former is a subtype of VM and whether it requires differentiated treatment. Methods:A total of 174 VM patients were enrolled, including 75 with aural fullness（aural fullness group） and 99 without aural fullness（non-aural fullness group）; demographic data, vertigo characteristics, medical history, family history, pure-tone audiometry, and vestibular function tests were thoroughly recorded, and independent samples t-test and chi-square test were used for inter-group comparisons. Results:①Regarding demographic characteristics, the age of the aural fullness group was significantly lower than that of the non-aural fullness group[（44.08±13.97） years vs. （49.45±16.05） years, P=0.020）, while the two groups showed consistent gender distribution（more females than males） with no statistically significant difference. ②For aural fullness characteristics, unilateral aural fullness accounted for 65.0% in the aural fullness group, significantly higher than bilateral aural fullness（35.0%, P<0.001）. ③In terms of vertigo characteristics, there were no statistically significant inter-group differences in the nature of attacks（rotational vertigo: 36.0% vs. 41.4%, P=0.463; dizziness: 21.3% vs. 11.1%, P=0.064; rotational vertigo or dizziness: 29.3% vs. 25.3%, P=0.548; dizziness with unsteady gait: 9.3% vs. 11.1%, Fisher P=0.806; visual oscillation with unsteady gait: 4.0% vs. 11.1%, Fisher P=0.086）, duration（several hours: 34.7% vs. 33.3%, P=0.841; several minutes: 22.7% vs. 21.2%, P=0.808; several seconds: 5.3% vs. 8.1%, Fisher P=0.557; several days: 9.3% vs. 9.1%, Fisher P=1.000; multiple combined patterns: 17.3% vs. 15.2%, P=0.686）, or incidence of nausea and vomiting（84.0% vs. 72.7%, P=0.071, no statistical significance）. ④No statistically significant inter-group differences were found in medical history and family history, including motion sickness history（8.0% vs. 4.0%, Fisher P=0.337）, headache history（22.7% vs. 34.3%, P=0.084）, and family history of dizziness（12.0% vs. 14.1%, P=0.666）. ⑤For audiological characteristics, 21.3%（16/75） of patients in the aural fullness group had low-frequency hearing loss, significantly higher than 5.1% in the non-aural fullness group（χ²=10.66, P=0.001）; among patients with unilateral aural fullness, 28.6%（14/49） had ipsilateral low-frequency hearing loss, significantly higher than 7.7%（2/26） of those with bilateral aural fullness（χ²=4.41, P=0.036）; however, there was no statistically significant difference in the rate of bilateral high-frequency hearing loss between the two groups（54.7%[41/75]vs. 50.5%[50/99], χ²=0.30, P=0.586）. ⑥In vestibular function tests, no statistically significant inter-group differences were observed in smooth pursuit type Ⅲ/Ⅳ（12.5% vs. 13.1%, P=0.913）, caloric test with CP>25%（31.2% vs. 37.4%, P=0.411）, abnormal video head impulse test（vHIT） rate（30.8% vs. 32.6%, P=0.865）, or abnormal vestibular evoked myogenic potential（VEMP） rate（53.8% vs. 38.9%, Fisher P=0.484）. Conclusion:VM patients with aural fullness have an earlier age of onset, with nearly 1/4 accompanied by low-frequency hearing loss; VM patients with and without aural fullness are highly consistent in gender distribution, nature/duration of vertigo, vestibular function impairment, and presence of bilateral high-frequency hearing loss, suggesting that the core clinical phenotypes of the two groups are consistent, while the former has an earlier age of onset and a higher proportion of unilateral hearing loss, which may be related to the pathological mechanism of VM and inner ear microcirculation disorders.
Humans ; Female ; Male ; Middle Aged ; Adult ; Migraine Disorders/classification* ; Young Adult ; Vertigo ; Age of Onset ; Aged ; Hearing Loss

OBJECTIVE: To construct a longitudinal trajectory model of arterial oxygen tension (PaO₂) within 24 hours after cardiac arrest (CA). METHODS: A retrospective cohort study was conducted. CA patients admitted to the ICU from 2014 to 2015 were selected from the eICU Collaborative Research Database (eICU-CRD). Data about patients' demographic characteristics, history of comorbidities, laboratory test indicators within 24 hours of intensive care unit (ICU) admission [including all PaO₂ data and arterial carbon dioxide tension (PaCO₂)], vasopressor use, and clinical outcomes were extracted from the database. The primary outcome variable was all-cause in-hospital mortality. Group-based trajectory model (GBTM) were built based on the changes in PaO₂ within 24 hours of ICU admission, and patients were grouped according to their initial static PaO₂ values upon ICU admission. Multivariable adjusted Poisson regression analysis was used to compare the in-hospital mortality risk among patients in different PaO₂ dynamic trajectory groups. Sensitivity analyses were performed using multivariable logistic regression and multivariable adjusted Poisson regression without imputation of missing values. RESULTS: A total of 3 866 CA patients were included. Three GBTM trajectory groups were identified based on PaO₂ changes within 24 hours of ICU admission: Group-1 (low level first increased then decreased, 148 cases), Group-2 (sustained low level, 3 040 cases), and Group-3 (first high level then decreased, 678 cases). Significant differences were found among the three groups in age, body weight, maximum serum potassium, maximum PaCO₂, minimum hemoglobin (Hb), vasopressor use, total hospitalization time, ICU stay, and hospital mortality. After incorporating variables with significant differences into the multivariable adjusted Poisson regression model, results showed that compared to Group-2 patients, patients in Group-1 and Group-3 had an increased risk of all-cause in-hospital mortality [Group-1 adjusted relative risk (aRR) = 1.20, 95% confidence interval (95%CI) was 1.02-1.41; Group-3 aRR = 1.11, 95%CI was 1.01-1.24]. Based on initial static PaO₂ values at ICU admission, patients were divided into four groups: PaO₂ < 100 mmHg (1 mmHg = 0.133 kPa; 1 217 cases), PaO₂ 100-200 mmHg (569 cases), PaO₂ 201-300 mmHg (547 cases), and PaO₂ > 300 mmHg (1 082 cases). Multivariable adjusted Poisson regression analysis indicated a significant upward trend in aRR for the latter three groups compared to the PaO₂ < 100 mmHg group. Sensitivity analyses revealed that compared to Group-2, patients in Group-1 and Group-3 had a significantly increased risk of all-cause in-hospital mortality (both P < 0.05). CONCLUSIONS Within 24 hours after return of spontaneous circulation in CA patients, PaO₂ exhibits different dynamic trajectories, and patients with hyperoxia have an increased risk of in-hospital mortality.
Humans ; Retrospective Studies ; Hospital Mortality ; Heart Arrest/blood* ; Prognosis ; Oxygen/blood* ; Intensive Care Units ; Cardiopulmonary Resuscitation ; Male ; Female ; Middle Aged

Objective To explore the effects and mechanisms of bone marrow mesenchymal stem cells(BMSCs)in regulating microglial polarization on neuropathic pain in rats with sciatic nerve branch-selective injury(SNI).Methods Fifty SD rats were randomly divided into five groups with ten rats in each group;sham group(rats only exposed sciatic nerve without ligation),SNI group(SNI model was estab-lished),BMSCs group[rats were injected with BMSCs(1×106)through the sheath for 3 days after SNI modeling],BMSCs+sh-NC group[rats were intrathecally injected with BMSCs(1×106)and intrathecally injected with knock-down control(adenovirus 2.5×107 IU)for 3 days after SNI modeling],and BMSCs+sh-YY1 group[rats were intrathecally injected with BMSCs(1×106)and intrathecally injected with YY1 knockdown adenovirus(2.5×107 IU)for 3 days after SNI modeling].Neuropathic pain was assessed using paw withdrawal threshold(PWT)and paw withdrawal thermal latency(PWTL)following mechanical stimulation.Immunofluorescence was used to detect the expression of CD86,CD206,iNOS,and Arg1 in the rat spinal cord tissues.Western blotting was used to measure the expression of YY1 and KLF4 in spinal cord tissue.Results Compared with sham group,the values of PWTL and PWT in the SNI group significantly reduced(both P<0.05).In spinal cord tissue,the positive rates of iNOS and CD86 protein increased,whereas the positive rates of CD206 and Arg1 protein and the expression of YY1 and KLF4 decreased(all P<0.05).Compared with the SNI group,the values of PWTL and PWT in the BMSCs and BMSCs+sh-NC groups increased(all P<0.05),the positive rate of CD86 protein in the spinal cord decreased,whereas the positive rate of CD206 protein and the expression of YY1 and KLF4 increased(all P<0.05).Also,the positive rate of iNOS protein in the spinal cord tissue decreased and the positive rate of Arg1 increased in the BMSCs group(all P<0.05).Compared with the BMSCs and BMSCs+sh-NC groups,the PWTL and PWT values in the BMSCs+sh-YY1 group decreased(all P<0.05).The positivity rate of CD86 protein increased,the positivity rate of CD206 protein decreased,and the expression of YY1 and KLF4 decreased in the spinal cord tissue(all P<0.05).Conclusion Intrathecal injection of BMSCs promotes M2 polarization of microglia in the spinal cord and relieves neuropathic pain in rats with SNI,and its mechanism may be related to the upregulation of KLF4 expression mediated by YY1.

Natural human leukocyte antigen (HLA) antibodies refer to preformed antibodies present in the body that are not induced by prior exposure to allogeneic HLA antigens. In healthy individuals without a sensitization history, the detection rate of natural HLA antibodies is approximately 20%-29% when using screening assays with low sensitivity, and can reach up to 63% when more sensitive HLA-specific detection methods are employed. It is therefore inferred that natural HLA antibodies may also be present in transplant candidates with a similar prevalence. This review comprehensively discusses the potential mechanisms of natural HLA antibody generation, the characteristics of the recognized epitopes, detection techniques, clinical relevance in transplantation, their potential to confound therapeutic decisions, and approaches to distinguish and mitigate their impact. The goal is to raise clinician awareness of the objective existence of natural HLA antibodies, provide guidance on evaluating their association with allograft rejection, and inform appropriate clinical management strategies when encountering natural HLA antibody-positive transplant candidates.

Oral cancer(OC)is a common malignant tumor and its incidence and mortality rate is increasing year by year.According to statistics,there are over 500,000 new cases worldwide every year,and most patients face treatment challenges.Electrospinning technology(ES)is a method for preparing nanofibers by driving the polymer in solution to form nanoscale fibers through an electric field.Since its discovery in the 1930s,it has received widespread attention and application.This article reviews the application of ES in the treatment of OC.The principles and preparation process of ES are induced,its application research in treating OC is elaborated,and the challenges faced by ES in OC treatment research are analyzed.Finally,the future development is discussed.

Objective To explore the effects and mechanisms of bone marrow mesenchymal stem cells(BMSCs)in regulating microglial polarization on neuropathic pain in rats with sciatic nerve branch-selective injury(SNI).Methods Fifty SD rats were randomly divided into five groups with ten rats in each group;sham group(rats only exposed sciatic nerve without ligation),SNI group(SNI model was estab-lished),BMSCs group[rats were injected with BMSCs(1×106)through the sheath for 3 days after SNI modeling],BMSCs+sh-NC group[rats were intrathecally injected with BMSCs(1×106)and intrathecally injected with knock-down control(adenovirus 2.5×107 IU)for 3 days after SNI modeling],and BMSCs+sh-YY1 group[rats were intrathecally injected with BMSCs(1×106)and intrathecally injected with YY1 knockdown adenovirus(2.5×107 IU)for 3 days after SNI modeling].Neuropathic pain was assessed using paw withdrawal threshold(PWT)and paw withdrawal thermal latency(PWTL)following mechanical stimulation.Immunofluorescence was used to detect the expression of CD86,CD206,iNOS,and Arg1 in the rat spinal cord tissues.Western blotting was used to measure the expression of YY1 and KLF4 in spinal cord tissue.Results Compared with sham group,the values of PWTL and PWT in the SNI group significantly reduced(both P<0.05).In spinal cord tissue,the positive rates of iNOS and CD86 protein increased,whereas the positive rates of CD206 and Arg1 protein and the expression of YY1 and KLF4 decreased(all P<0.05).Compared with the SNI group,the values of PWTL and PWT in the BMSCs and BMSCs+sh-NC groups increased(all P<0.05),the positive rate of CD86 protein in the spinal cord decreased,whereas the positive rate of CD206 protein and the expression of YY1 and KLF4 increased(all P<0.05).Also,the positive rate of iNOS protein in the spinal cord tissue decreased and the positive rate of Arg1 increased in the BMSCs group(all P<0.05).Compared with the BMSCs and BMSCs+sh-NC groups,the PWTL and PWT values in the BMSCs+sh-YY1 group decreased(all P<0.05).The positivity rate of CD86 protein increased,the positivity rate of CD206 protein decreased,and the expression of YY1 and KLF4 decreased in the spinal cord tissue(all P<0.05).Conclusion Intrathecal injection of BMSCs promotes M2 polarization of microglia in the spinal cord and relieves neuropathic pain in rats with SNI,and its mechanism may be related to the upregulation of KLF4 expression mediated by YY1.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.