In the era of evidence-based medicine， the progress of medical science and technology has enriched medical diagnostic tools and treatment methods， but it has also led to the loss of medical warmth and the alienation of the doctor-patient relationships. William Osler emphasized that while medical technology advances， attention should also be paid to the practice of narrative medicine and the development of physician’s narrative literacy. The view of the physician he advocated reminds us that the core of medicine still lies in the narrative connection between doctors and patients， as well as a deep understanding of human nature. By exploring the relationship between Osler’s view of the physician and narrative medicine as well as physician’s narrative literacy， this paper analyzed the methods of cultivating physician’s narrative literacy， providing references for modern medical education and practice， and assisting in the harmony and unity of science and technology and humanity.

Objective To investigate the therapeutic effects of a newly constructed Aβ25-35-based recombinant gene vaccine for Alzheimer's disease(AD).Methods The pcDNA-Aβ25-35-GRP94 recombinant gene vaccine was con-structed using Aβ25-35 as the epitope and pcDNA3.1 plasmid as the vector.Early APP/PS1 double-transgenic mice were selected as experimental subjects,including the AD control group and the pcDNA-Aβ25-35-GRP94 immunized group for regular immunization.ELISA was performed to detect the titers and isotypes of Aβ-specific antibodies;Morris Water Maze(MWM)Test and Open-Field Test(OFT)were performed to determine the changes in both cognitive ability and mental state of mice;Immunohistochemistry was used to assess the effects of the vac-cine on both Aβ plaques and glial cells in the brains of AD mouse models;ELISA kit was used to evaluate the level of inflammatory factors(TNF-α,IL-1β)in the mouse brain.Results Compared with the AD control group,the pcDNA-Aβ25-35-GRP94 vaccine induced APP/PS1 mice to produce higher levels of Aβ specific antibodies(P<0.05),and mainly induced IgG1 antibodies(P<0.01).The vaccine significantly reduced Aβ plaques in the brain tissue(P<0.05)and effectively alleviated learning memory impairment in APP/PS1 mice(P<0.05)without causing mental behavioral abnormalities.Moreover,the vaccine inhibited the abnormal proliferation of glial cells(P<0.05)and did not cause obvious inflammatory reactions in the brain,suggesting the vaccine was safe and effective.Conclusions Early vaccination with a Aβ25-35-based recombinant gene vaccine can induce the formation of high level of Aβ specific antibodies,effectively alleviate the learning memory impairment of AD and related neu-ro-pathological changes.It may be used to treat AD.

Objective To investigate the clinical diagnostic value of serum sTREM2 level in patients with cerebral small vessel disease(CSVD)and its correlation with depression and its severity.Methods A total of 208 CSVD inpatients admitted in Department of Neurology of the First Affiliated Hospital of Shihezi University from December 2023 to November 2024 were en-rolled,and according to their score of HAMD,they were divided into a depression group(CSVD+D group,112 cases)and a non-depression group(CSVD—D group,96 cases).According to the 17-item HAMD,the depression group(CSVD+D group)was further divided into mild(8-17,n=80),moderate(18-24,n=27)and severe depression(≥25,n=5)subgroups.Another 208 healthy individuals who taking health checkups in the same period were selected and served as the control group.The general clinical data were compared among the groups and subgroups,and mul-tivariate logistic regression analysis was applied to identify the risk factors for the occurrence of depression and the relationship between sTREM2 and depression severity in the CSVD patients.ROC curve was plotted to evaluate the predicative performance of serum sTREM2 level for the occurrence of depression in the CSVD patients.Results The serum sTREM2 level was remark-ably higher in the CSVD patients than the control group(5.95±3.82 μg/L vs 1.40±1.21 μg/L,P＜0.01).ROC curve analysis indicated that the AUC value of serum sTREM2 level in predicting CSVD was 0.917,with a sensitivity of 87.52％and a specificity of 85.64％,and an optimal cut-ff value of 2.272 μg/L.The CSVD+D group also had significantly higher serum sTREM2 level than the CSVD—D group(6.40±3.93 μg/L vs 5.01±2.87 μg/L,P＜0.01).Multivariate logistic regression analysis showed that serum sTREM2 level was an independent influencing factor for occurrence of depression in the CSVD patients(OR=1.115,95％CI:1.019-1.220,P=0.018).Statistical difference was also observed in the patients without and with mild,moderate and severe depression(P＜0.05).Multivariate ordinal logistic regression analysis revealed that serum sTREM2 level was an independent influencing factor for mild,moderate and severe depression(OR=1.113,95％CI:1.013-1.223,P=0.026;OR=1.135,95％CI:1.004-1.284,P=0.043).The AUC value of serum sTREM2 level in predicting depressive symptoms in CSVD patients was 0.603.Conclusion Serum sTREM2 is closely associated with CSVD patients.Its level may provide certain reference value for clinical diagnosis of CSVD,and has potentially predictive value for the occurrence of depression in the CSVD patients.

Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335^fl/fl FOXP3^creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4⁺ T cells, CD8⁺ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335^CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4⁺ and CD8⁺ T cells, along with their respective effector cells, was significantly higher in the Zfp335^CKO group than in the WT group. The proportions of CD4⁺ and CD8⁺ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335^CKO group compared to that of the WT group. In addition, the percentage of CD8⁺ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335^CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)⁺ Treg in the Zfp335^CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335^CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335^CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.
Animals ; T-Lymphocytes, Regulatory/metabolism* ; Mice ; CD8-Positive T-Lymphocytes/immunology* ; Neoplasms/genetics* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice, Knockout ; DNA-Binding Proteins/genetics* ; Female

Objective:To investigate the relationship between sarcopenic obesity(SO), defined by various obesity indicators, and mortality risk in older adults based on a prospective cohort from multiple nursing homes.Methods:Sarcopenia was diagnosed according to the 2019 consensus of the Asian Working Group for Sarcopenia.Obesity was defined using six different indicators: waist circumference(WC), waist-hip ratio(WHR), waist-height ratio(WHTR), body mass index(BMI), visceral fat area(VFA), and percentage of body fat(PBF).A prospective cohort of adults aged 60 and above was established across 15 nursing homes in Zigong City, with annual follow-ups on survival status conducted over two consecutive years.Cox proportional hazards regression models were employed to analyze the association between SO, defined by different obesity indicators, and mortality risk, calculating hazard ratios( HR)and their 95% confidence intervals( CI). Results:A total of 695 older adults were included in the study, of whom 67.1% were male.During the 2-year follow-up period, 88 participants died.The prevalence of SO as defined by WC, WHR, WHTR, BMI, VFA, PBF was found to be 17.6%, 30.1%, 48.9%, 3.0%, 28.3%, and 58.7%, respectively.When SO was defined using WC, WHR, WHTR, BMI, and VFA, there was no statistically significant difference in mortality rates between the SO and non-SO groups.However, when defined by PBF, the SO group exhibited a significantly higher mortality rate compared to the non-SO group(16.9% vs.6.6%, P<0.01).Cox proportional hazards regression analysis revealed that, compared to the non-SO group, the SO group defined by PBF had a significantly increased mortality risk( HR=2.81, 95% CI: 1.67-4.73, P<0.001).After adjusting for potential confounding factors, the mortality risk for the SO group remained significantly higher than that of the non-SO group( HR=1.97, 95% CI: 1.14-3.38, P=0.015). Conclusions:The prevalence of SO varies significantly across different obesity indicators.SO defined by PBF is significantly associated with mortality risk in nursing home residents.This study provides new evidence for further optimizing the diagnostic criteria for SO in this population.

Objective:To explore the risk factors of blood pressure fluctuations during the dialysis period in maintenance hemodialysis (MHD) patients and their impact on long-term survival.Methods:A total of 100 cases of MHD patients admitted to Anhui Linquan People′s Hospital from September 2020 to May 2022 were selected and divided into high fluctuation group (coefficient of variation in systolic blood pressure>8.64%) and non-high fluctuation group (coefficient of variation in systolic blood pressure ≤ 8.64%). The clinical data of the two groups were compared, and the LASSO model was used to conduct the preliminary screening for each risk factor. The nomogram prediction model of blood pressure fluctuation during the dialysis period was drawn, and the receiver operating characteristic (ROC) curve and calibration curve was drawn to obtain the prediction efficiency and calibration degree of the nomograph model. Kaplan-Meier survival curve was drawn to compare the 1-year survival status of the two groups.Results:The results of single factor analysis showed that body mass index, dialysis age, urea clearance index, ultrafiltration volume, serum calcium, serum albumin, serum phosphorus, serum sodium, total parathyroid hormone (iPTH), serum uric acid, serum creatinine, C-reactive protein, alkaline phosphatase, early diastolic maximum blood flow in the left ventricle (peak E)/atrial systolic maximum blood flow of mitral valve (peak A), and left ventricular ejection fraction (LVEF) were risk factors for blood pressure fluctuation during dialysis ( P<0.05). The prediction model of nomograph was drawn, and the consistency index (C-index) was 0.941, the prediction sensitivity was 88.40%, and the specificity was 91.20%. Kaplan-Meier survival curve analysis showed that the 1-year survival rate in the high fluctuation group was lower than that in the non-high fluctuation group ( P<0.05). Conclusions:Blood pressure fluctuation during dialysis in MHD patients is related to blood sodium, calcium and phosphorus, iPTH, blood uric acid, albumin, peak E/peak A, and LVEF, and can affect the prognosis of patients, and attention should be paid to the monitoring and control of above indexes of the patients in order to improve the prognosis.

Objective:To determine the prevalence of self-reported food allergies among children in the grasslands of North China and to analyze its associated risk factors.Methods:In this study, a cross-sectional epidemiological survey method was used to select children under 14 years old by multi-stage, stratified and random cluster sampling in the grassland ecological area of Zhangbei County, Hebei Province, China from May to July 2018. Face-to-face questionnaires were administered to gather food allergy-related information from the participants. Multivariate logistic regression analysis was used to analyze the risk factors associated with self-reported food allergy.Results:A total of 2 086 children completed the survey. The prevalence of self-reported food allergies was 22.0%(459/2 086). The prevalence of multiple food allergies (≥3 types) was 3.1%(64/2 086) versus 16.3% (341/2 086) for a single food allergy among all children. Mango allergy (6.1%, 127/2 086) was the most common, followed by peach allergy (4.1%, 85/2 086). Children who reported food allergies had a significantly higher prevalence of all 4 atopic disorders (eczema, asthma, allergic rhinitis, and allergic conjunctivitis than those without food allergies(35.73% vs. 20.65%, 5.88% vs. 2.77%, 17.86% vs. 7.38%, 16.78% vs. 10.45%, χ2 =44.663 1, 10.434 3, 45.038 3, 13.728 4, all P<0.001).Significantly associated risk factors of food allergy were found to be pollen allergy ( OR: 2.29; 95% CI: 1.80-2.92) and drug allergy ( OR: 1.53; 95% CI: 1.12-2.09). Conclusions:The prevalence of self-reported food allergies among children in the Zhangbei County area of the North China Grassland was relatively high. Pollen allergy and drug allergy are major risk factors.

Objective:To report a Charcot-Marie-Tooth disease type 2 (CMT2) patient with SORD gene mutations, aiming to enhance the understanding of SORD gene-associated peripheral neuropathy. Methods:A CMT2 patient with SORD gene mutations was identified through whole exome sequencing in the Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in January 2024, and the patients′ clinical features were elaborated in detail. 31-Phosphorus magnetic resonance spectroscopy ( 31P-MRS) was employed to assess the phosphorus profile of the limbs, and real-time quantitative reverse transcription polymerase chain reaction was utilized to detect peripheral blood SORD gene mRNA expression levels in the patient, the family members, and the normal control. Additionally, the genetic and clinical characteristics of SORD gene mutation-related CMT2 and distal hereditary motor neuropathy (dHMN) were reviewed by searching the CNKI and PubMed databases. Results:The male CMT2 patient was 15 years old, presented with early-onset lower limb muscle weakness and atrophy, hypoesthesia, reduced tendon reflexes, and flat feet. 31P-MRS examination indicated that the pH of the patient′s leg was lower than that of the upper limb. Whole exome sequencing showed the patient carrying complex heterozygous mutations c.757delG (p.Ala253GlnfsTer27) and c.218C>T (P.Ser73Leu) in the SORD gene. The mRNA expression of the SORD gene of the patient′s mother [0.623(0.614, 0.645)] was lower than that of the patient′s father [0.961(0.888,1.020), H=13.330, P=0.007] and normal people [1.001(0.917, 1.092), H=14.830, P=0.002]. Through literature review, it is found that 31 SORD gene mutations have been reported worldwide, among which c.757delG (p.Ala253GlnfsTer27) was found to be a hotspot mutation, and all patients exhibited an autosomal recessive inheritance pattern. Conclusions:A patient with CMT2 caused by a compound heterozygous mutation c.757delG/c.218C>T in the SORD gene, with the main clinical symptoms of bilateral lower limb weakness, atrophy, sensory disturbance and reduced tendon reflexes is reported. Furthermore, 31P-MRS of the extremities is anticipated to both early and sensitively detect muscle lesions in patients with hereditary peripheral neuropathy.

Objective To investigate the protective effect of Liraglutide in rats with diabetic kidney disease(DKD)by regulating the nuclear factor E2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)ferroptosis signaling pathway.Methods Twelve male Sprague-Dawley(SD)rats were randomly divided into normal control(NC)group,DKD group,and Liraglutide treatment(Lir)group,with 4 rats in each group.The 24 hUAlb,TC,TG,LDL-C,serum creatinine(Scr),BUN,ferrous ion(Fe2+),the activity of glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)were detected in each group.Hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and periodic acid-silver methenamine-Masson(PASM-Masson)staining were used to observe the pathological changes of the kidneys.Immunofluorescence was performed to detect the localization and expression of reactive oxygen species(ROS)in the renal tissue.The protein expressions of Nrf2 and GPX4 were detected by Western blot.Results Compared with the NC group,the levels of 24 hUAlb,Scr,BUN,TC,TG,LDL-C,MDA,ROS,and Fe2+were increased(P＜0.05 or P＜0.01),while the expressions of GSH-Px,Nrf2,and GPX4 proteins were decreased in the DKD group(P＜0.01).Compared with the DKD group,the levels of 24 hUAlb,BUN,TC,TG,LDL-C,MDA,ROS,and Fe2+were decreased(P＜0.05 or P＜0.01),and the expressions of GSH-Px,Nrf2,and GPX4 proteins were increased in the Lir group(P＜0.01).Conclusions Liraglutide may exert a protective effect in DKD by upregulating the Nrf2/GPX4 signaling pathway and inhibiting ferroptosis.

Objective:To explore the relationship between programmed death-1(PD-1)inhibitors and cancer-related fatigue(CRF)in patients with malignant melanoma,and to identify associated influencing factors.Methods:A total of 100 patients with malignant melanoma treated at Jinan People's Hospital between April 2019 and April 2024 were included as study subjects.The Chinese version of the Piper Fatigue Scale was used to evaluate patients'fatigue levels within three months before and after the initiation of PD-1 inhibitor therapy.Results:There was a significant difference in CRF score before and after PD-1 inhibitor treatment(P<0.001).Univariate analysis showed no significant association between fatigue severity and factors such as gender,smoking history,tumor site,or PD-1 inhibitor type(all P>0.05).However,age,tumor stage,anemia,leukopenia,secondary hypothyroidism,secondary adrenal insufficiency(AI),and secondary adrenocorticotropic hormone deficiency(P<0.05 or P<0.01 or P<0.001)were significantly associated with CRF.Multivariate regression analysis identified secondary hypothyroidism,secondary AI,anemia,and leukopenia as independent risk factors for severe CRF in patients with malignant melanoma(all P<0.05).Conclusion:Adverse reactions of PD-1 inhibitors,including secondary hypothyroidism,secondary AI,anemia,and leukopenia,are independent risk factors for CRF in patients with malignant melanoma.