OBJECTIVE To explore the influencing factors for immune-related endocrine toxicity in the treatment of malignant solid tumors with sintilimab， aiming to provide a reference for rational drug use. METHODS Case data were collected from patients with malignant solid tumors， who were treated with sintilimab at the First Affiliated Hospital of Jinzhou Medical University from January 1， 2020 to December 31， 2024， using the electronic medical record system. The patients were divided into an endocrine immune-related adverse events （irAEs） group and a non-endocrine irAEs group based on whether they developed immune-related endocrine toxicity after sintilimab administration. The statistical significance of predictive variables was examined through univariate and multivariate Logistic regression methods. RESULTS A total of 224 patients were enrolled， including 138 cases （61.6%） in the non-endocrine irAEs group and 86 cases （38.4%） in the endocrine irAEs group. After univariate and multivariate Logistic regression analysis， a treatment period of 1-12 cycles was identified as an independent influencing factor for immune-related endocrine toxicity [OR＝7.175， 95%CI （1.239， 41.563）， P ＜0.05 ] ， immune-related hyperglycemia [OR＝6.600， 95%CI （1.053， 41.359）， P ＜0.05 ] ， and immune-related subclinical hypothyroidism [OR＝20.200， 95%CI （3.224， 126.558）， P ＜0.05 ] . The combination with paclitaxel-based drugs was identified as an independent influencing factor for immune-related subclinical hyperthyroidism [OR＝6.410， 95%CI （1.790， 22.955）， P ＜0.05 ] . CONCLUSIONS Among patients treated with sintilimab， the treatment cycle is a risk factor for immune-related endocrine toxicity， immune-related hyperglycemia and immune-related subclinical hypothyroidism. The combination of paclitaxel-based drugs is a risk factor for immune-related subclinical hyperthyroidism. It is recommended that when applying sintilimab in clinical practice， especially during the first few treatment cycles， the relevant endocrine indicators should be dynamically monitored in a standardized manner. In addition， special attention should be paid to patients treated with the combination of paclitaxel-based drugs to be vigilant against the occurrence of endocrine adverse events.

Objective To determine the effects of Bushen Huoxue Formula(BHF),a clinically vali-dated traditional Chinese herbal compound,on myelin integrity and cognitive function in mice with chronic cerebral hypoperfusion(CCH).Methods A total of 30 SPF male C57BL/6J mice were randomly divided into sham operation group(n=8)and model group(n=22).Bilateral com-mon carotid artery stenosis was inflicted to establish a mouse model of CCH,while the mice in the sham operation group only received separation of bilateral vagus nerves.In the model group,6 mice died in 2 d after surgery,the left 16 mice were then randomly divided into a model group and a treatment group,with 8 animals in each group.In 2 weeks after surgery,BHF(0.2 ml/d)or pure water was administered via gavage for 60 d to the corresponding groups.Cognitive function was assessed using the Morris water maze(MWM)test.White matter lesions were evaluated by diffu-sion tensor imaging-fractional anisotropy(DTI-FA).Demyelination in the corpus callosum was visualized using Luxol fast blue(LFB)staining,while neuronal damage in the hippocampal CA1 region was analyzed with Nissl staining.Results Compared to the sham group,the model group exhibited significantly prolonged swimming distance and escape latency on day 5 and reduced platform crossings on day 6 in Morris water maze test,decreased DTI-FA value,lower absorbance value of myelin in LFB staining,and fewer Nissl-stained neurons in the hippocampal region(P＜0.05,P＜0.01).In contrast,the treatment group showed significantly shorter swimming distance[188.14(105.19,342.00)cm vs 280.22(168.47,501.37)cm,P＜0.05]and escape latency[10.22(5.77,19.47)s vs 19.39(13.57,31.09)s,P＜0.01]on day 5,increased platform crossings on day 6[3.00(2.00,4.00)times vs 2.00(1.00,3.00)times,P＜0.05],elevated DTI-FA value(0.340±0.014 vs 0.313±0.012,P＜0.01),enhanced absorbance value of myelin[0.353(0.328,0.364)vs 0.305(0.290,0.350),P＜0.05],and greater neuronal counts(9.94±2.22 cells vs 7.11±2.02 cells,P＜0.01)when compared to the model group.Conclusion BHF can alleviate CCH-induced cogni-tive deficits in mice by promoting repair of white matter microstructure and rescue of neuronal loss.

Aim To investigate the association between cardiovascular health(CVH)score based on life's es-sential 8(LE8)on cognitive function and the mediation role of neutrophil-to-lymphocyte ratio(NLR)between them in ol-der adults,providing basis for the prevention and control of cognitive impairment.Methods The study population was selected from the National Health and Nutrition Examination Survey(NHANES)2011-2014 two cycles of 60 years and a-bove,demographic characteristics,medical history and other variables were collected,the participants'CVH scores were calculated according to LE8 defined by American Heart Association,and cognitive function was assessed using the digit symbol substitution test.The relationship between CVH and cognitive function was explored using a weighted linear re-gression analysis,and the dose-response relationship was analyzed using a restricted cubic spline.Moreover,mediation a-nalysis was used to explore the role of NLR in mediating the relationship between CVH score and cognitive function.Results A total of 2 510 participants were included in this study.After adjusting for relevant factors,cognitive function was positively associated with moderate CVH group score(β=3.36,95％CI:1.43～5.30)and high CVH group score(β=6.01,95％CI:2.89～9.13)compared with the low CVH group score.The LE8 single factor of diet score(β=0.04,95％CI:0.01～0.06),physical activity score(β=0.04,95％CI:0.02～0.05),tobacco exposure score(β=0.05,95％CI:0.02～0.08),blood pressure score(β=0.03,95％CI:0.01～0.05)and blood glucose score(β=0.06,95％CI:0.03～0.09)were positively correlated with cognitive function score.The results of restricted cubic splines showed that the score of CVH was linear positively correlated with the score of cognitive function.The indirect effect of CVH on cognitive function via NLR was 0.002(P＞0.05),and the proportion of mediating effect was 1.29％(P＞0.05),indicating the mediating effect of NLR on the relationship between CVH score and cognitive function was not signif-icant.Conclusions The CVH score based on the LE8 was positively correlated with cognitive function in older adults,underscoring the crucial role of maintaining optimal CVH levels in supporting cognitive health.However,the NLR,as an indicator of inflammation,did not exhibit a significant mediating effect between the CVH score and cognitive function.The relationship between these variables might be influenced by other mechanisms.

The development of traditional Chinese medicine (TCM) diagnosis and treatment has undergone multiple paradigms, evolving from sporadic experiential practices to systematic approaches in syndrome differentiation and treatment and further integration of disease and syndrome frameworks. TCM is a vital component of the medical system, valued alongside Western medicine. Treatment based on syndrome differentiation embodies both personalized treatment and holistic approaches; however, the inconsistency and lack of stability in syndrome differentiation limit clinical efficacy. The existing integration of diseases and syndromes primarily relies on patchwork and embedded systems, where the full advantages of synergy between Chinese and Western medicine are not fully realized. Recently, driven by the development of diagnosis and treatment concepts and advances in analytical technology, Western medicine has been rapidly transforming from a traditional biological model to a precision medicine model. TCM faces a similar need to progress beyond traditional syndrome differentiation and disease-syndrome integration toward a more precise diagnosis and treatment paradigm. Unlike the micro-level precision trend of Western medicine, precision diagnosis and treatment in TCM is primarily reflected in data-driven applications that incorporate information at various levels, including precise syndrome differentiation, medication, disease management, and efficacy evaluation. The current priority is to accelerate the development of TCM precision diagnosis and treatment technology platforms and advance discipline construction in this area.

Objective : To investigate the effect of the miR-155-5p/silent information regulator 1(sirt1) signaling pathway on the immune function ofCandida albicansinduced Kawasaki disease model mice. Methods : C56BL/6 mice were separated into control group, Kawasaki disease group, antagonist control group, miR-155-5p antagonist group, miR-155-5p antagonist+si-NC group, and miR-155-5p antagonist+si-sirt1 group, with 12 mice in each group. Except for the control group, mice in all other groups were used to construct a Kawasaki disease model by intraperitoneal injection of water-solubleCandida albicans. After successful modeling, administration was performed once a day for 7 days. QRT-PCR was applied to detect the expression of miR-155-5p in coronary arteries. Western blot was applied to detect sirt1 protein in coronary arteries. HE staining was applied to detect pathological changes in coronary arteries. Mouse thymus index and spleen index were detected. Flow cytometry was applied to detect helper T cells 17(Th17)/regulatory T cells(Treg) in peripheral blood. ELISA was applied to detect the levels of interleukin(IL)-17 and IL-10 in mouse serum. The targeting relationship between sirt1 and miR-155-5p was validated. Results: Compared with the control group, there was a large amount of inflammatory cell infiltration in the coronary arteries of mice in the Kawasaki disease group. The miR-155-5p expression, Th17 ratio, Th17/Treg ratio, and IL-17 level increased. The sirt1 protein expression, thymus index, spleen index, Treg ratio, and IL-10 level decreased(P<0.05). Compared with the Kawasaki disease group, the inflammatory cell infiltration in the coronary arteries of mice in the miR-155-5p antagonist group was alleviated. The miR-155-5p expression, Th17 ratio, Th17/Treg ratio, and IL-17 level decreased. The sirt1 protein expression, thymus index, spleen index, Treg ratio, and IL-10 level increased(P<0.05). Si-sirt1 weakened the promoting effect of miR-155-5p inhibition on Th17/Treg balance and the inhibitory effect on vascular inflammation in Kawasaki disease mice, miR-155-5p targeted and regulated sirt1. Conclusion The mechanism by which inhibiting miR-155-5p promotes Th17/Treg balance and inhibits vascular inflammation in Kawasaki disease mice may be related to the upregulation of sirt1 expression.

Objective To elucidate the role of gut microbiota in cognitive impairment induced by adolescent social isolation(ASI)and identify key pathogenic microbial communities.Methods Sixteen male C57BL/6 mice(postnatal days 21～23)were randomly assigned to a control group(group-housed,4/cage,n=8)or an ASI group(single-housed,1/cage,n=8).After 5 weeks of ASI(5-ASI),fecal samples underwent 16S rRNA sequencing for microbiota analysis.Cognitive behavior was assessed using open field,Y-maze,novel object recognition tests.Correlation analysis integrated microbial abundance with behavioral parameters to screen cognition-associated taxa.Results(1)Behavior:5-ASI mice showed unchanged locomotion(open field)but significantly reduced spontaneous alternation(Y-maze,P<0.01)and lower cognitive index(novel object recognition,P<0.001),confirming spatial and recognition memory deficits.(2)Microbiota:5-ASI mice exhibited decreased α-diversity(P<0.05)and altered β-diversity(P<0.001).LEfSe analysis revealed depleted taxa(e.g.,Prevotellaceae_NK3B31_group,Tyzzerella,Allobaculum,Ruminococcus)and enriched taxa(e.g.,Butyricicoccus,Lachnoclostridium).(3)Correlations:Positive associations with cognitive performance were observed for Prevotellaceae_NK3B31_group,Allobaculum,and Ruminococcus(P<0.05),while Butyricicoccus and Lachnoclostridium showed negative correlations(P<0.05).Conclusion Adolescent social isolation induces spatial/recognition memory impairment and gut microbiota dysbio-sis.Specific microbial alterations(Prevotellaceae_NK3B31_group,Butyricicoccus)correlate with cognitive deficits,providing novel insights into microbiota-mediated mechanisms and potential therapeutic targets.

Objective To investigate the relationship between cognitive function and sleep quality in patients with Alzheimer's disease(AD).Methods A case-control trial was conducted on 151 patients admitted to our department from May 2024 to December 2024.The patients with mild-to-moderate AD were assigned into the AD group(59 cases),and the cognitively normal patients in-to the control group(92 cases).All patients received neuropsychological assessment and sleep quality evaluation,including mini-mental state examination(MMSE),Montreal cognitive assess-ment(MoCA)and Pittsburgh sleep quality index(PSQI).The general clinical data and sleep qual-ity were compared between the two groups.Spearman correlation analysis was applied to analyze the relationship between cognitive function and sleep quality in the AD patients.Results The education level,MMSE score,MoCA score,instant story recall(ISR)score,delayed story recall(DSR)score,clock dawning test(CDT)score and Boston naming test score were significantly lower,while the activity of daily living(ADL)score was obviously higher in the AD group than the cognitively normal group(P＜0.05,P＜0.01).The AD patients had notably higher total score of PSQI and scores of sleep efficiency,nocturnal sleep disturbance and daytime dysfunction than the cognitively normal patients(P＜0.05,P＜0.01).In the AD patients,the total sleep time was positively correlated with the DSR score and the CDT score(r=0.300,P=0.021;r=0.308,P=0.018);hypnotic medication was negatively correlated with MMSE score,ISR score,and DSR score,and positively with ADL score(r=-0.320,P=0.013;r=-0.400,P=0.002;r=-0.331,P=0.010;r=0.355,P=0.006).Multiple linear regression analysis showed that benzodiazepines use and education level were independent influencing factors for cognitive function in the AD patients(P＜0.05,P＜0.01).Conclusion In AD patients,sleep quality is closely associated with cognitive function,as manifested by decreased sleep quality,reduced sleep efficiency,and worsened nocturnal sleep disturbances and daytime dysfunction.Administration of benzodiazepines may exacerbate cognitive impairment in AD patients.So,it is recommended that AD patients should be cautious about taking such drugs.

Objective To investigate the associations of immune cells,CD8+and CD4+T cells,and high-sensitivity C-reactive protein(hs-CRP)with cognitive function,and to explore the relation-ships among immunity,chronic inflammation,and Alzheimer's disease-related cognitive impair-ment.Methods A cross-sectional study was conducted on 101 patients with primary complaints of memory decline who visited the Alzheimer's Disease Clinic of Dongzhimen Hospital from June to December 2024.Mini-Mental State Examination(MMSE)and Delayed Story Recall Task(DSR)were performed to assess their cognitive function,and according to the results,they were divided into observation group(cognitively impaired,60 cases)and control group(cognitively normal,41 cases).Peripheral blood levels of CD8+T cells,CD4+T cells,and hs-CRP were compared between the two groups.Results The observation group exhibited significantly lower total scores and scores of different dimensions of MMSE and DSR scores,but notably higher activities of daily liv-ing scores than the control group(P＜0.05,P＜0.01).Serum hs-CRP level was obviously elevated in the observation group than the control group(P＜0.05).Binary logistic regression analysis revealed that CD8+T cells(OR=0.998,95％CI:0.996-1.000,P=0.038)and body mass index(OR=0.843,95％CI:0.719-0.990,P=0.037)were protective factors,while hs-CRP(OR=2.004,95％CI:1.215-3.306,P=0.006)was an independent risk factor for cognitive impairment.Spearman's rank correlation analysis showed a significant positive correlation between hs-CRP and CD4+T cells(P=0.011),but no significant association with CD8+T cells(P＞0.05).Conclusion Chronic inflammation and immune dysregulation synergistically contribute to cogni-tive decline.Hs-CRP may serve as a potential screening biomarker for cognitive impairment in pri-mary care settings.

Objective To investigate the relationship between cognitive function and sleep quality in patients with Alzheimer's disease(AD).Methods A case-control trial was conducted on 151 patients admitted to our department from May 2024 to December 2024.The patients with mild-to-moderate AD were assigned into the AD group(59 cases),and the cognitively normal patients in-to the control group(92 cases).All patients received neuropsychological assessment and sleep quality evaluation,including mini-mental state examination(MMSE),Montreal cognitive assess-ment(MoCA)and Pittsburgh sleep quality index(PSQI).The general clinical data and sleep qual-ity were compared between the two groups.Spearman correlation analysis was applied to analyze the relationship between cognitive function and sleep quality in the AD patients.Results The education level,MMSE score,MoCA score,instant story recall(ISR)score,delayed story recall(DSR)score,clock dawning test(CDT)score and Boston naming test score were significantly lower,while the activity of daily living(ADL)score was obviously higher in the AD group than the cognitively normal group(P＜0.05,P＜0.01).The AD patients had notably higher total score of PSQI and scores of sleep efficiency,nocturnal sleep disturbance and daytime dysfunction than the cognitively normal patients(P＜0.05,P＜0.01).In the AD patients,the total sleep time was positively correlated with the DSR score and the CDT score(r=0.300,P=0.021;r=0.308,P=0.018);hypnotic medication was negatively correlated with MMSE score,ISR score,and DSR score,and positively with ADL score(r=-0.320,P=0.013;r=-0.400,P=0.002;r=-0.331,P=0.010;r=0.355,P=0.006).Multiple linear regression analysis showed that benzodiazepines use and education level were independent influencing factors for cognitive function in the AD patients(P＜0.05,P＜0.01).Conclusion In AD patients,sleep quality is closely associated with cognitive function,as manifested by decreased sleep quality,reduced sleep efficiency,and worsened nocturnal sleep disturbances and daytime dysfunction.Administration of benzodiazepines may exacerbate cognitive impairment in AD patients.So,it is recommended that AD patients should be cautious about taking such drugs.