Objectives:To explore the relationship between carboxymethyl lysine (CML) and type 2 diabetes (T2DM) with myopenia, so as to provide some clinical reference for clinical prevention and early intervention of myopenia.Methods:A case-control study was conducted, selecting 142 T2DM patients admitted to the Endocrinology Department of the Affiliated Hospital of North China University of Science and Technology from November 2022 to November 2023. According to the diagnostic criteria of the 2019 consensus of experts on the diagnosis and treatment of sarcopenia, the patients were divided into a case group (T2DM with sarcopenia, 58 cases) and a control group (T2DM without sarcopenia, 84 cases). Collect and compare general information, serological data, and body composition data of two groups of patients. Two independent sample t-test is used for inter group comparison of metric data that conforms to normal distribution; Non parametric tests are used for inter group comparisons of non normally distributed quantitative data; The comparison of count data between groups is conducted using χ2 test. Multivariate logistic regression analysis was used to analyze the relationship between carboxymethyl lysine and type 2 diabetes with myopenia. Draw receiver operating characteristic (ROC) curves and analyze the efficacy of carboxymethyllysine in diagnosing T2DM with muscle atrophy. Results:Univariate analysis showed the BMI ((21.59±3.04) kg/m 2), FINS (4.49 (1.85,9.03) U/L), and FCP ((1.45±0.96) mg/L) levels of the patients in the case group were lower than those in the control group(27.32±3.74) kg/m 2, 6.91 (3.74, 11.99) U/L, (2.64±1.23) mg/L), while age, ((64.67±6.75) years old) of disease duration(12.16±6.69) years, and CML (5.70±2.14 μg/L) were higher than those in the control group ((62.23±7.33) years old, (8.70±8.01) years, (2.38±0.73) μg/L), and the differences were statistically significant (Statistical values were t=9.66, Z=2.86, t=6.46, t=2.02, t=2.70, t=13.17; P values were <0.001, 0.004, <0.001, 0.046, 0.008, <0.001). Multifactorial binary logistic regression analysis showed that CML ( OR(95%CI):3.242 (1.933-5.437)) and BMI ( OR(95%CI):0.636 (0.505-0.801)) were associated with T2DM combined with sarcopenia (all P<0.001). The results of the ROC curve showed that the area under the curve (AUC) of CML was 0.934, and the corresponding optimal cut-off value was 3.038 μg/L. The diagnostic efficacy of CML for the diagnosis of T2DM combined with myasthenia gravis was high, and the diagnostic results were in good agreement with the actual results. Conclusions:Carboxymethyl lysine is associated with T2DM combined with muscle atrophy. CML has a high diagnostic efficacy in diagnosing T2DM combined with muscle atrophy, and it has certain practical value in diagnosing T2DM combined with muscle atrophy.

The gut microbiota is of great significance for children's health.An increasing number of studies indicate that gut microbiota is one of the potential mediators affecting human neurodevelopment and neuropsychiatric dysbiosis.In early life，there is a significant overlap between the development window of gut microbiota and the nervous system.Premature infants are at high risk of developing gut microbiota dysbiosis and neurodevelopmental disorders.However，the connection between gut microbiota in early human life and neural development remains unclear.This article reviews the relationship between gut microbiota in early life and neurodevelopment in premature infants，with the aim of contributing to identify predictive biomarkers and potential therapeutic targets for healthy neurological development in premature infants.

Objectives:To explore the relationship between carboxymethyl lysine (CML) and type 2 diabetes (T2DM) with myopenia, so as to provide some clinical reference for clinical prevention and early intervention of myopenia.Methods:A case-control study was conducted, selecting 142 T2DM patients admitted to the Endocrinology Department of the Affiliated Hospital of North China University of Science and Technology from November 2022 to November 2023. According to the diagnostic criteria of the 2019 consensus of experts on the diagnosis and treatment of sarcopenia, the patients were divided into a case group (T2DM with sarcopenia, 58 cases) and a control group (T2DM without sarcopenia, 84 cases). Collect and compare general information, serological data, and body composition data of two groups of patients. Two independent sample t-test is used for inter group comparison of metric data that conforms to normal distribution; Non parametric tests are used for inter group comparisons of non normally distributed quantitative data; The comparison of count data between groups is conducted using χ2 test. Multivariate logistic regression analysis was used to analyze the relationship between carboxymethyl lysine and type 2 diabetes with myopenia. Draw receiver operating characteristic (ROC) curves and analyze the efficacy of carboxymethyllysine in diagnosing T2DM with muscle atrophy. Results:Univariate analysis showed the BMI ((21.59±3.04) kg/m 2), FINS (4.49 (1.85,9.03) U/L), and FCP ((1.45±0.96) mg/L) levels of the patients in the case group were lower than those in the control group(27.32±3.74) kg/m 2, 6.91 (3.74, 11.99) U/L, (2.64±1.23) mg/L), while age, ((64.67±6.75) years old) of disease duration(12.16±6.69) years, and CML (5.70±2.14 μg/L) were higher than those in the control group ((62.23±7.33) years old, (8.70±8.01) years, (2.38±0.73) μg/L), and the differences were statistically significant (Statistical values were t=9.66, Z=2.86, t=6.46, t=2.02, t=2.70, t=13.17; P values were <0.001, 0.004, <0.001, 0.046, 0.008, <0.001). Multifactorial binary logistic regression analysis showed that CML ( OR(95%CI):3.242 (1.933-5.437)) and BMI ( OR(95%CI):0.636 (0.505-0.801)) were associated with T2DM combined with sarcopenia (all P<0.001). The results of the ROC curve showed that the area under the curve (AUC) of CML was 0.934, and the corresponding optimal cut-off value was 3.038 μg/L. The diagnostic efficacy of CML for the diagnosis of T2DM combined with myasthenia gravis was high, and the diagnostic results were in good agreement with the actual results. Conclusions:Carboxymethyl lysine is associated with T2DM combined with muscle atrophy. CML has a high diagnostic efficacy in diagnosing T2DM combined with muscle atrophy, and it has certain practical value in diagnosing T2DM combined with muscle atrophy.

Post-stroke cognitive impairment(PSCI)is a common complication after stroke,which significantly affects quality of life.However,the pathogenesis has not been fully explained.Increasing evidence has shown that the mechanism of programmed cell death(PCD)is related to PSCI,including apoptosis,necroptosis,pyroptosis,PANoptosis,parthanatos,and ferroptosis.Therefore,it is crucial to clearly understand the various mechanisms of PCD and their relationship with PSCI,and to elucidate the role of PCD in PSCI pathogenesis.The article reviews six PCD pathways related to PSCI,summarizes their mechanisms of action in PSCI,and elucidates the possible crosstalk among pathways to provide a basis for clinical targeting of regulatory factors in the PCD pathway for PSCI treatment.

Objective:To investigate the clinicopathological and molecular genetic characteristics of Crohn′s disease (CD).Methods:A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes.Results:Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium.Conclusions:CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

AIM:To study whether glycyrrhizic acid(GL)can resist the ototoxicity of cisplatin(CDDP)in mice and its molecular mechanism.METHODS:Male C57BL/6J mice were divided into 5 groups:control group,DMSO(5%)group,CDDP(4 mg/kg)group,CDDP+low-dose(50 mg/kg)GL group,and CDDP+high-dose(100 mg/kg)GL group(n=14).Auditory brainstem response(ABR)was used to detect hearing changes of mice.HE staining was used to observe the morphological change of cochlear stria vascular in mice.Evans blue(EB)staining was used to observe the per-meability change of the blood-labyrinth barrier(BLB).Immunohistochemical technique was used to detect the expression and distribution of adhesion protein VE-cadherin and tight junction protein ZO-1 on the cochlear stria.ELISA assay and immunofluorescence technology were employed to detect the expression of tumor necrosis factor-α(TNF-α)and interleu-kin-1β(1L-1β).RESULTS:In CDDP group,ABR waveforms of all frequencies were disturbed,the hearing threshold was significantly increased,and I wave latency was prolonged(P＜0.05).In CDDP+GL group,ABR waveforms of various frequencies were well differentiated,the hearing threshold was significantly decreased,and the latency of I-wave was shortened(P＜0.01).The disordered morphology and more vacuoles in the stria vascularis were observed by HE staining in CDDP group.The GL alleviated CDDP-induced damage in the stria vascularis.In EB staining,CDDP caused an increase in per-meability of BLB(P＜0.01),which was improved by GL treatment(P＜0.01).Immunohistochemical results showed that the expression of VE-cadherin and ZO-1 in CDDP group were decreased(P＜0.01),which was restored in CDDP+GL group(P＜0.01).The ELISA and immunofluorescence results showed that the expression of IL-1β and TNF-α was in-creased after CDDP treatment(P＜0.01),which was restored in CDDP+GL group(P＜0.01).CONCLUSION:The GL alleviates CDDP-induced hearing loss in mice by inhibiting CDDP-induced inflammation and reducing the permeability of BLB.

Cerebral organoids are three-dimensional nerve cultures induced by embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)that mimic the structure and function of human brain.With the continuous optimization of cerebral organoid culture technology and the combination with emerging technologies such as organ transplantation,gene editing and organoids-on-chip,complex brain tissue structures such as functional vascular structures and neural circuits have been produced,which provides new methods and ideas for studying human brain development and diseases.This article reviews the latest advances in brain organoid technology,describes its application in neurological diseases and advances in stroke modeling and transplantation treatment.

Post-stroke cognitive impairment(PSCI)is mainly manifested as learning and memory disorders.Highly enriched RNA m6A methylation modification in mammalian brain is involved in glial cell-mediated neuroinflammation.Given that neuroinflammation is the main mechanism for neural damage and spatial and memory impairment of PSCI,it is speculated that RNA m6A methylation modification can regulate the inflammatory response of glial cells after stroke to improve PSCI.This review summarizes and analyzes the role of RNA m6A methylation modification in the development of PSCI and analyzes its detailed mechanism of regulating glial cell-mediated inflammation,which will provide reference for researchers in this field.

BACKGROUND:Long non-coding RNAs(lncRNAs),as important regulators of the inflammatory response,are involved in the immune-inflammation-brain crosstalk mechanism after ischemic stroke and have the potential to become a therapeutic agent for neurological dysfunction after ischemic stroke. OBJECTIVE:To analyze and summarize the molecular mechanism of lncRNA acting on glial cells involved in the neuroimmuno-inflammatory cascade response after ischemic stroke and the associated signaling pathways,pointing out that lncRNAs have the potential to regulate inflammation after ischemic stroke. METHODS:PubMed was searched using the search terms of"ischemic stroke,long non-coding RNA,neuroinflammation,immune function,signal pathway,microglia,astrocytes,oligodendrocyte,mechanism,"and 63 relevant documents were finally included for review. RESULTS AND CONCLUSION:In the early stage of ischemic stroke,the death of nerve cells due to ischemia and hypoxia activates the innate immune response of the brain,promoting the secretion of inflammatory factors and inducing blood-brain barrier damage and a series of inflammatory cascades responses.As an important pathogenesis factor in ischemic stroke,the neuroimmuno-inflammatory cascade has been proved to seriously affect the prognosis of patients with ischemic stroke,and it needs to be suppressed promptly in the early stage.Neuroinflammation after ischemic stroke usually induces abnormal expression of a large number of lncRNAs that mediate a series of neuro-immune-inflammatory crosstalk mechanisms through regulating the polarization of microglia,astrocytes and oligodendrocytes to exert post-stroke neuroprotective effects.LncRNAs,as important regulatory factors of the inflammatory response,inhibit the neuroimmuno-inflammatory cascade response after ischemic stroke through regulating nuclear factor-κB,lncRNA-miRNA-mRNA axis,Rho-ROCK,MAPK,AKT,ERK and other signaling pathways to effectively improve neurological impairment after ischemic stroke.Most of experimental studies on the interaction between lncRNAs and ischemic stroke are based on a middle cerebral artery occlusion model or a cerebral ischemia-reperfusion injury model,but no clinical trials have been conducted.Therefore,it remains to be further explored about whether lncRNAs can be safely applied in clinical practice.At present,there are many therapeutic drugs for the treatment of ischemic stroke,but there are relatively few studies on the application of lncRNAs,exosomes and other transplantation technologies for the treatment of ischemic stroke using tissue engineering technology,which need to be further explored.lncRNA has become an important target for the treatment of ischemic stroke with its relative stability and high specificity.In future studies,more types of inflammatory lncRNAs that function under ischemic-hypoxia conditions should continue to be explored,in order to provide new research directions for the treatment of neuroinflammation after ischemic stroke.

Background Heavy metals may play an important role in environmental risk factors associated disorders of activities of daily living (ADL) in older adults. Objective To investigate the associations between plasma levels of six heavy metals (zinc, arsenic, cadmium, lead, manganese, and copper) and ADL disorders in older adults. Methods A cross-sectional survey was conducted from 2018 to 2019 among 1412 rural elderly people in Gongcheng Yao Autonomous County, Guangxi Zhuang Autonomous Region. The plasma metal concentrations were detected by inductively coupled plasma mass spectrometry (ICP-MS), and subsequently classified into three groups (T1-T3) based on tertiles, with the T1 group as the reference. The samples were assessed for ADL disorders using the ADL scale. Logistic regression and restricted cubic spline model (RCS) were used to estimate the odds ratio (OR) and 95% confidence interval (CI) to assess the associations between heavy metals and the prevalence of reporting ADL disorders. Results The mean age of the study population was (68.52 ± 5.92) years, 825 (58.4%) female and 587 (41.6%) male. Of these, 372 (26.34%) subjects reported ADL disorders, and most of them were female (74.30%). The results of logistic regression showed that the participants in the cadmium T2 group (0.15-0.25 µg·L⁻¹) had a higher risk of ADL disorders compared to the T1 group (≤0.15 μg·L⁻¹) (OR=1.552, 95%CI: 1.086, 2.134). After stratification by sex, the relative risk of ADL disorders was lower in the plasma copper T3 group (>1019.58 µg·L⁻¹) compared to the T1 group (≤868.12 μg·L⁻¹) in men (OR=0.481, 95%CI: 0.232, 0.998). The relative risk of ADL disorders was higher in the plasma cadmium T2 group (0.15-0.25 µg·L⁻¹) compared to the T1 group (≤0.15 μg·L⁻¹) in women (OR=1.758, 95%CI: 1.182, 2.616). The RCS results showed that the risk of ADL disorders in men was nonlinearly associated with copper (P_nonlinear=0.011, P_overall<0.05). Conclusion High levels of cadmium are positively associated with the risk of reporting ADL disorders, while high levels of copper are negatively associated with the risk of reporting ADL disorders in men.